1
|
Harutyunyan H, Hovhannisyan A, Torosyan H, Hakobjanyan G, Grigoryan A, Petrosyan G, Movsisyan M, Poland D, Monkel R, Lommen J, Tuaillon E, Yenkoyan K. Clinical performance and application of novel serum collection "Ser-Col" device in the practice of laboratory diagnosis of infection diseases and several other immunochemical tests. Clin Chim Acta 2025; 565:119970. [PMID: 39313064 DOI: 10.1016/j.cca.2024.119970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Revised: 09/06/2024] [Accepted: 09/12/2024] [Indexed: 09/25/2024]
Abstract
BACKGROUND Dried blood collection devices might be beneficial for diagnosing infectious diseases in areas far from the medical facilities and in lockdown situations. There are several reports on the efficacy of such applications for qualitative tests. Here we demonstrated the feasibility of a novel Ser-Col blood collection device as a standardized approach for qualitative and quantitative detection of infectious markers and several over immunochemical tests. METHODS In the current study, we included 395 adult participants, 191 men and 204 women, with a median age of 41 years, as well as 75 children with a median age of 3 years. Serological status was determined by testing serum samples for three groups of infection diseases: hepatitis A and C, SARS-CoV-2, and herpes family viruses, as well as for thyroid peroxidase (TPO), prolactin, vitamin B12, and folate. Blood collected on the Ser-Col device (Labonovum) was eluted using an automated system (SCAUT Ser-Col automation, Blok System Supply) and manually. Ser-Col results were compared with serum sampled via standard venipuncture considered as the reference. RESULTS High correlation coefficients (r = 0.95-0.99) were observed between serum samples collected with Ser-Col and via standard venipuncture for the following tests: anti-HCV, anti-SARS-CoV-2 IgG, anti-HSV-2 IgG, and anti-CMV IgM. Correlation coefficients between Ser-Col and standard venipuncture serum for anti-HSV-1 IgG, anti-CMV IgG, and anti-EBV tests were relatively low (r = 0.73-0.77). Correlation coefficients for anti-TPO, prolactin, vitamin B12, and folate were also characterized with high values (r = 0.97-0.99). CONCLUSIONS High accuracy and quantitative correlation were demonstrated between Ser-Col and samples collected by standard venipuncture. Hence, the Ser-Col blood collection device should be considered as a promising alternative for blood collection, storage, and transportation in both adult and pediatric populations.
Collapse
Affiliation(s)
- Hayk Harutyunyan
- Neuroscience Laboratory, Cobrain Center, Yerevan State Medical University named after Mkhitar Heratsi, Yerevan, Armenia
| | - Alvard Hovhannisyan
- Department of Infectious Diseases, Yerevan State Medical University named after Mkhitar Heratsi, Yerevan, Armenia
| | - Hamlet Torosyan
- Neuroscience Laboratory, Cobrain Center, Yerevan State Medical University named after Mkhitar Heratsi, Yerevan, Armenia
| | - Gohar Hakobjanyan
- Laboratory-Diagnostic Center of Heratsi Clinical Hospital, Yerevan State Medical University named after Mkhitar Heratsi, Yerevan, Armenia
| | - Ani Grigoryan
- Neuroscience Laboratory, Cobrain Center, Yerevan State Medical University named after Mkhitar Heratsi, Yerevan, Armenia
| | - Gayane Petrosyan
- Laboratory-Diagnostic Center of Heratsi Clinical Hospital, Yerevan State Medical University named after Mkhitar Heratsi, Yerevan, Armenia
| | - Mariam Movsisyan
- Neuroscience Laboratory, Cobrain Center, Yerevan State Medical University named after Mkhitar Heratsi, Yerevan, Armenia; Department of Allergology and Clinical Immunology, Yerevan State Medical University named after Mkhitar Heratsi, Yerevan, Armenia
| | | | | | | | - Edouard Tuaillon
- Pathogenesis and Control of Chronic and Emerging Infections, Montpellier University, INSERM, Établissement Français du Sang, Antilles University, Montpellier University Hospital, Montpellier, France
| | - Konstantin Yenkoyan
- Neuroscience Laboratory, Cobrain Center, Yerevan State Medical University named after Mkhitar Heratsi, Yerevan, Armenia; Department of Biochemistry, Yerevan State Medical University named after Mkhitar Heratsi, Yerevan, Armenia.
| |
Collapse
|
2
|
Sun W, Nan J, Xu H, Wang L, Niu J, Zhang J, Yang B. Neural Network Enables High Accuracy for Hepatitis B Surface Antigen Detection with a Plasmonic Platform. NANO LETTERS 2024; 24:8784-8792. [PMID: 38975746 DOI: 10.1021/acs.nanolett.4c02860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/09/2024]
Abstract
The detection of hepatitis B surface antigen (HBsAg) is critical in diagnosing hepatitis B virus (HBV) infection. However, existing clinical detection technologies inevitably cause certain inaccuracies, leading to delayed or unwarranted treatment. Here, we introduce a label-free plasmonic biosensing method based on the thickness-sensitive plasmonic coupling, combined with supervised deep learning (DL) using neural networks. The strategy of utilizing neural networks to process output data can reduce the limit of detection (LOD) of the sensor and significantly improve the accuracy (from 93.1%-97.4% to 99%-99.6%). Compared with widely used emerging clinical technologies, our platform achieves accurate decisions with higher sensitivity in a short assay time (∼30 min). The integration of DL models considerably simplifies the readout procedure, resulting in a substantial decrease in processing time. Our findings offer a promising avenue for developing high-precision molecular detection tools for point-of-care (POC) applications.
Collapse
Affiliation(s)
- Weihong Sun
- Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun 130021, P. R. China
- State Key Laboratory of Supramolecular Structure and Materials, Center for Supramolecular Chemical Biology, College of Chemistry, Jilin University, Changchun 130012, P. R. China
| | - Jingjie Nan
- Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun 130021, P. R. China
- State Key Laboratory of Supramolecular Structure and Materials, Center for Supramolecular Chemical Biology, College of Chemistry, Jilin University, Changchun 130012, P. R. China
| | - Hongqin Xu
- Department of Hepatology, Center of Infectious Diseases and Pathogen Biology, The First Hospital of Jilin University, Changchun 130021, P. R. China
| | - Lei Wang
- Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun 130021, P. R. China
- State Key Laboratory of Supramolecular Structure and Materials, Center for Supramolecular Chemical Biology, College of Chemistry, Jilin University, Changchun 130012, P. R. China
| | - Junqi Niu
- Department of Hepatology, Center of Infectious Diseases and Pathogen Biology, The First Hospital of Jilin University, Changchun 130021, P. R. China
| | - Junhu Zhang
- Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun 130021, P. R. China
- State Key Laboratory of Supramolecular Structure and Materials, Center for Supramolecular Chemical Biology, College of Chemistry, Jilin University, Changchun 130012, P. R. China
| | - Bai Yang
- Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun 130021, P. R. China
- State Key Laboratory of Supramolecular Structure and Materials, Center for Supramolecular Chemical Biology, College of Chemistry, Jilin University, Changchun 130012, P. R. China
| |
Collapse
|
3
|
Mane A, Agarwal R, Bajpai M, Sane S, Vidhate P, Rakshit P, Madan P, Gogia H, Abraham P, Kabra S, Gupta E. Validation of dried blood spot for serological diagnosis of Hepatitis B and C: a multicentric study. Diagn Microbiol Infect Dis 2024; 108:116108. [PMID: 38000329 DOI: 10.1016/j.diagmicrobio.2023.116108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Revised: 10/06/2023] [Accepted: 10/12/2023] [Indexed: 11/26/2023]
Abstract
The present study aimed to determine diagnostic performance of dried blood spot (DBS) for the detection of Hepatitis B surface antigen (HBsAg) and Hepatitis C virus antibodies (anti-HCV) using CLIA at 3 different laboratories across India. DBS can serve as a simple and convenient alternative to plasma/serum for HBsAg detection. However for anti-HCV, site-specific validation of the assay is warranted.
Collapse
Affiliation(s)
- Arati Mane
- Division of Microbiology, ICMR- NARI, Pune, India
| | - Reshu Agarwal
- Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Meenu Bajpai
- Department of Transfusion Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Suvarna Sane
- Division of Epidemiology and Biostatistics, ICMR- NARI, Pune, India
| | - Pallavi Vidhate
- Division of Epidemiology and Biostatistics, ICMR- NARI, Pune, India
| | | | - Preeti Madan
- National Centre for Disease Control, New Delhi, India
| | - Hema Gogia
- National Centre for Disease Control, New Delhi, India
| | - Priya Abraham
- Department of Virology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Sandhya Kabra
- National Centre for Disease Control, New Delhi, India
| | - Ekta Gupta
- Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi, India.
| |
Collapse
|
4
|
McAuliffe G, Gerber A, Chhibber A, Fisher M, Saxton P, Fisher T, Blakiston M, Forster R. Evaluating the sensitivity and specificity of dried blood spots for serological testing of HIV, syphilis, hepatitis B and C Elecsys assays on the Roche Cobas system. Pathology 2023; 55:1000-1003. [PMID: 37690864 DOI: 10.1016/j.pathol.2023.06.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 06/05/2023] [Accepted: 06/16/2023] [Indexed: 09/12/2023]
Abstract
This study was performed to validate a dried blood spot (DBS) method for the serological screening of HIV, syphilis, hepatitis B and C. It included 250 paired DBS and serum samples and 116 unpaired DBS samples from 366 unique patients from two laboratories between 8 October and 2 November 2021. As determined by original test request, these were tested using a DBS method for HIV Ag/Ab (n=216), anti-treponemal Ab (n=166), hepatitis B sAg (n=100), and hepatitis C Ab (n=100) Elecsys assays on the Roche Cobas automated platform. Using the manufacturer's (serum) cut-off for reactivity ('positivity'), the sensitivity and specificity of DBS testing compared with serum were: for HIV Ag/Ab 100% and 100%, for anti-treponemal Ab 68.3% and 100%, for hepatitis B sAg 95.9% and 100%, and for hepatitis C Ab 84.0% and 100%, respectively. Adjusting the assay cut-off using receiver operator curve analysis increased sensitivity of DBS testing for anti-treponemal Ab to 90.0%, hepatitis B sAg to 97.9% and hepatitis C Ab to 94.0% whilst maintaining specificity of 98.8%, 100% and 100%, respectively. With optimisation of assay cut-off, DBS can perform comparably with serum for serological testing for HIV, syphilis, hepatitis B and C and may be a valuable tool in increasing access to testing in New Zealand.
Collapse
Affiliation(s)
- Gary McAuliffe
- Labtests, Carbine Road, Mount Wellington, Auckland, New Zealand; LabPLUS, Te Whatu Ora, Te Toka Tumai, Grafton, Auckland, New Zealand.
| | - Adri Gerber
- Labtests, Carbine Road, Mount Wellington, Auckland, New Zealand
| | - Aakash Chhibber
- LabPLUS, Te Whatu Ora, Te Toka Tumai, Grafton, Auckland, New Zealand
| | | | - Peter Saxton
- University of Auckland, Grafton, Auckland, New Zealand
| | - Tony Fisher
- University of Auckland, Grafton, Auckland, New Zealand
| | - Matt Blakiston
- Labtests, Carbine Road, Mount Wellington, Auckland, New Zealand; LabPLUS, Te Whatu Ora, Te Toka Tumai, Grafton, Auckland, New Zealand
| | - Rose Forster
- Labtests, Carbine Road, Mount Wellington, Auckland, New Zealand; University of Auckland, Grafton, Auckland, New Zealand
| |
Collapse
|
5
|
Sciortino S, Graham S, Fillman T, Kandasamy H, Cooley R, Hanson C, Eckert V, Tang H, Yang J, Seftel D, Tsai CT, Robinson P. Shadow of a Pandemic: Persistence of Prenatal SARS-CoV-2 Antibodies in Newborn Blood Spots. Int J Neonatal Screen 2023; 9:43. [PMID: 37606480 PMCID: PMC10443380 DOI: 10.3390/ijns9030043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 07/25/2023] [Accepted: 07/31/2023] [Indexed: 08/23/2023] Open
Abstract
To investigate COVID-19 surveillance among pregnant women, the California Genetic Disease Screening Program conducted a screening performance and seroprevalence evaluation of maternal SARS-CoV-2 antibodies detected in banked newborn dried blood spots (DBS). We obtained seropositive results for 2890 newborn DBS from cohorts in 2020 and 2021 using Enable Bioscience's Antibody Detection by Agglutination-PCR (ADAP) assay for SARS-CoV-2 antibodies. To infer maternal infection, we linked 312 women with a known laboratory-confirmed COVID-19 episode with their newborn's DBS SARS-CoV02 antibody result. Among 2890 newborns, we detected 453 (15.7%) with SARS-CoV-2 antibodies in their DBS. Monthly snapshot statewide seroprevalence among neonates was 12.2% (95% CI 10.3-14.1%, n =1156) in December 2020 and 33.3% (95% CI 29.1-37.4%, n = 26) in March 2021. The longest time recorded from COVID-19 infection to a seropositive neonatal result was 11.7 months among the 312 mothers who had an available SARS-CoV-2 PCR test result. Approximately 94% (153/163) of DBS were seropositive when a known maternal infection occurred earlier than 19 days before birth. The estimated relative sensitivity of DBS to identify prevalent maternal infection was 85.1%, specificity 98.5% and PPV 99.2% (n = 312); the sensitivity was lowest during the December 2021 surge when many infections occurred within 19 days of birth. Fifty pre-pandemic specimens (100% seronegative) and 23 twin-pair results (100% concordant) support an intrinsic specificity and PPV of ADAP approaching 100%. Maternal infection surveillance is limited by a time lag prior to delivery, especially during pandemic surges.
Collapse
Affiliation(s)
- Stanley Sciortino
- Genetic Disease Screening Program, California Department of Public Health, Richmond, CA 94804, USA (H.K.)
| | - Steve Graham
- Genetic Disease Screening Program, California Department of Public Health, Richmond, CA 94804, USA (H.K.)
| | - Toki Fillman
- Genetic Disease Screening Program, California Department of Public Health, Richmond, CA 94804, USA (H.K.)
| | - Hari Kandasamy
- Genetic Disease Screening Program, California Department of Public Health, Richmond, CA 94804, USA (H.K.)
| | - Robin Cooley
- Genetic Disease Screening Program, California Department of Public Health, Richmond, CA 94804, USA (H.K.)
| | - Carl Hanson
- Viral and Rickettsial Disease Laboratory, California Department of Public Health, Richmond, CA 94804, USA
| | - Valorie Eckert
- Genetic Disease Screening Program, California Department of Public Health, Richmond, CA 94804, USA (H.K.)
| | - Hao Tang
- Genetic Disease Screening Program, California Department of Public Health, Richmond, CA 94804, USA (H.K.)
| | - Juan Yang
- Genetic Disease Screening Program, California Department of Public Health, Richmond, CA 94804, USA (H.K.)
| | - David Seftel
- Enable Biosciences, South San Francisco, CA 94080, USA
| | | | | |
Collapse
|
6
|
Kouamé DR, Aboli RA, Kabran M, Adiko AC, Coulibaly M, Dembele B, Inwoley A. Validation of dried blood spots samples for the screening of hepatitis B virus surface by enzyme immunoassay method. J Immunol Methods 2023; 513:113412. [PMID: 36586510 DOI: 10.1016/j.jim.2022.113412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 12/26/2022] [Accepted: 12/27/2022] [Indexed: 12/29/2022]
Abstract
Dried Blood Spots (DBS) are blood collection carriers that facilitate the storage and transport of samples. Used for quality control during sero-epidemiological investigations, DBS eluate are not the conventional specimen indicated by manufacturers for enzyme immunoassay method (EIA) for hepatitis B virus surface (HBs antigen). The aim of our study was to evaluate DBS eluates used as a matrix for EIA of HBs antigen in a reference laboratory. This study took place from August 2016 to November 2017 at the Centre for Diagnosis and Research on AIDS and other infectious diseases (CeDReS) in Abidjan, Côte d'Ivoire. We used a panel of 149 whole blood samples from blood donors. The DBS performed with these samples were analyzed after elution with the HBsAg (version ULTRA) ELISA, Dia.Pro Diagnostic Bioprobes S.R.L., Sesto San Giovanni, Italy. The technical performance (sensitivity and specificity and kappa coefficient) of the test performed on DBS was determined for different ratios (optical density/threshold value) compared to the results obtained on the plasma used as reference. We obtained a sensitivity of 100% with DBS for all ratios. The specificity increased according to the ratio of optical density of the individual EIA reaction to the threshold value, with 6.09%, 47.0%, and 83.0%, respectively, for ratios of 1.0, 3.0, and 5.0. Best performance was observed at ratio of 10.0 with a sensitivity and specificity of 100%. In conclusion, DBS eluate can be used for the diagnosis of viral hepatitis B and would be useful for conducting sero-epidemiological investigations. However, ratio giving best performance must be determined for each enzyme immunoassay method kits.
Collapse
Affiliation(s)
- Denis Rodrigue Kouamé
- Immunology Unit, UFR Pharmaceuticals and Biological Sciences, Félix Houphouët-Boigny University, BPV 34 Abidjan 01, Abidjan, Ivory Coast
| | - Roseline Affi Aboli
- Immunology Unit, UFR Pharmaceuticals and Biological Sciences, Félix Houphouët-Boigny University, BPV 34 Abidjan 01, Abidjan, Ivory Coast; Research and Diagnosis Center for AIDS and other infectious diseases (CeDReS), CHU (University Hospital) of Treichville, BP V3 Abidjan 01, Abidjan, Ivory Coast
| | - Mathieu Kabran
- Immunology Unit, UFR Pharmaceuticals and Biological Sciences, Félix Houphouët-Boigny University, BPV 34 Abidjan 01, Abidjan, Ivory Coast; Research and Diagnosis Center for AIDS and other infectious diseases (CeDReS), CHU (University Hospital) of Treichville, BP V3 Abidjan 01, Abidjan, Ivory Coast
| | - Aimé Cézaire Adiko
- Immunology Unit, UFR Pharmaceuticals and Biological Sciences, Félix Houphouët-Boigny University, BPV 34 Abidjan 01, Abidjan, Ivory Coast; Research and Diagnosis Center for AIDS and other infectious diseases (CeDReS), CHU (University Hospital) of Treichville, BP V3 Abidjan 01, Abidjan, Ivory Coast
| | - Mabarakissa Coulibaly
- Immunology Unit, UFR Pharmaceuticals and Biological Sciences, Félix Houphouët-Boigny University, BPV 34 Abidjan 01, Abidjan, Ivory Coast
| | - Bamory Dembele
- Immunology Unit, UFR Pharmaceuticals and Biological Sciences, Félix Houphouët-Boigny University, BPV 34 Abidjan 01, Abidjan, Ivory Coast; Laboratory of NBTS (National Blood Transfusion Center), BP V15 Abidjan 01, Ivory Coast.
| | - Andre Inwoley
- Immunology Unit, UFR Pharmaceuticals and Biological Sciences, Félix Houphouët-Boigny University, BPV 34 Abidjan 01, Abidjan, Ivory Coast; Research and Diagnosis Center for AIDS and other infectious diseases (CeDReS), CHU (University Hospital) of Treichville, BP V3 Abidjan 01, Abidjan, Ivory Coast
| |
Collapse
|
7
|
Pisoni A, Reynaud E, Douine M, Hureau L, Alcocer Cordellat C, Schaub R, Poland D, Monkel R, Lommen J, Yenkoyan K, Vreden S, Nacher M, Tuaillon E. Automated and combined HIV, HBV, HCV, and syphilis testing among illegal gold miners in French Guiana using a standardized dried blood device. Acta Trop 2023; 238:106731. [PMID: 36395882 DOI: 10.1016/j.actatropica.2022.106731] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 09/28/2022] [Accepted: 10/22/2022] [Indexed: 11/16/2022]
Abstract
Blood spotted onto filter paper can be easily collected outside healthcare facilities and shipped to a central laboratory for serological testing. However, dried blood testing generally requires manual processing for pre-analytical steps. In this study, we used a standardized blood collection device combined with an automated elution system to test illegal gold miners living in French Guiana for human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis. We included 378 participants, 102 females and 266 males, in three illegal gold mining resting sites. Blood collected on the Ser-Col device (Labonovum) was eluted using an automated system (SCAUT Ser-Col automation, Blok System Supply) and an automated analyzer (Alinity i, Abbott). Ser-Col results were compared to both plasma results, considered the gold standard, and to Dried blood Spot (DBS) results, considered the reference sampling method using dried blood. In plasma samples, two participants (0.5%) tested positive for HIV, six (1.5%) tested positive for hepatitis B surface antigen (HBsAg), eight were weakly positive for anti-HCV antibodies but negative for HCV RNA, and 47 tested positive for treponemal antibodies (12.4%), including 20 females (19.6%) and 27 males (9.8%, p= 0.010179). We observed a full concordance of Ser-Col and DBS results for HIV diagnosis compared to plasma results. Ser-Col and DBS samples tested positive in five HBsAg carriers and negative for one participant with a low HBsAg level in plasma (0.5 IU/mL). All participants tested negative for HCV in Ser-Col and DBS samples, including the eight participants who tested low positive for HCV antibodies and HCV RNA negative in plasma. Among syphilis seropositive participants, 41 (87.2%) and 40 (85.1%) tested positive for treponemal antibodies in Ser-Col and DBS samples, respectively. The Ser-Col method allows automated dried blood testing of HIV, HBV, HCV and syphilis with performances comparable to DBS. Automated approaches to test capillary blood transported on dried blood devices may facilitate large-scale surveys and improve testing of populations living in remote areas.
Collapse
Affiliation(s)
- Amandine Pisoni
- Pathogenesis and Control of Chronic and Emerging Infections, Montpellier University, INSERM, Établissement Français du Sang, Antilles University, Montpellier University Hospital, Montpellier, France
| | - Elisa Reynaud
- Montpellier University Hospital, Montpellier, France
| | - Maylis Douine
- Centre d'Investigation Clinique Antilles-Guyane (Inserm 1424), Cayenne Hospital, Epidemiology of Tropical Parasitoses, Universite de Guyane, EA 3593, Cayenne, French Guiana
| | - Louise Hureau
- Centre d'Investigation Clinique Antilles-Guyane (Inserm 1424), Cayenne Hospital, Epidemiology of Tropical Parasitoses, Universite de Guyane, EA 3593, Cayenne, French Guiana
| | | | - Roxane Schaub
- Centre d'Investigation Clinique Antilles-Guyane (Inserm 1424), Cayenne Hospital, Epidemiology of Tropical Parasitoses, Universite de Guyane, EA 3593, Cayenne, French Guiana
| | | | | | | | - Konstantin Yenkoyan
- Department of Biochemistry, Neuroscience Laboratory, Cobrain Center Yerevan State Medical University named after M. Heratsi, Yerevan, Armenia
| | - Stephen Vreden
- Foundation for Scientific Research of Suriname, Paramaribo, Suriname
| | - Mathieu Nacher
- Centre d'Investigation Clinique Antilles-Guyane (Inserm 1424), Cayenne Hospital, Epidemiology of Tropical Parasitoses, Universite de Guyane, EA 3593, Cayenne, French Guiana
| | - Edouard Tuaillon
- Pathogenesis and Control of Chronic and Emerging Infections, Montpellier University, INSERM, Établissement Français du Sang, Antilles University, Montpellier University Hospital, Montpellier, France.
| |
Collapse
|
8
|
Miyano S, Pathammavong C, Ichimura Y, Sugiyama M, Phounphenghack K, Tengbriacheu C, Khamphaphongphane B, Nouanthong P, Franzel L, Yang TU, Raaijimakers H, Ota T, Funato M, Komada K, Hachiya M. Prevalence of hepatitis B and C virus infections in Lao People's Democratic Republic: The first national population-based cross-sectional survey. PLoS One 2022; 17:e0278933. [PMID: 36584043 PMCID: PMC9803141 DOI: 10.1371/journal.pone.0278933] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 11/23/2022] [Indexed: 12/31/2022] Open
Abstract
Population-based seroprevalence of chronic hepatitis B and C infections has not been examined in Lao People's Democratic Republic (PDR). Therefore, this study aimed to estimate the seroprevalence of these infections in the general population of Lao PDR and perform subgroup analysis. A nationwide seroprevalence survey was conducted in Lao PDR in June 2019 using the multistage cluster sampling method. Dried blood spot samples were collected onto WhatmanTM 903 filter paper by finger prick. A chemiluminescent microparticle immunoassay was used to measure the levels of hepatitis B surface antigen (HBsAg) and hepatitis C antibody (HCV-Ab). Samples in which the HBsAg level was above 0.05 IU/ml and HCV-Ab was above the signal/cutoff ratio of 1.0 were considered positive based on comparisons with the relative light unit value of a calibration sample. A total of 1,927 samples (male: 47.3%, mean age: 23.0 years) were included in the analysis. The prevalence was estimated to be 4.2% (95% confidence interval [CI]: 2.7-6.3) for HBsAg and 1.6% (95% CI: 0.5-5.3) for HCV-Ab. Multivariable analysis revealed that those aged 20-24 years (adjusted odds ratio (AOR): 2.3, 95% CI: 1.1-4.6), those aged 25-29 years (AOR: 2.7, 95% CI: 1.3-5.6), those from the Northern region (AOR: 2.8, 95% CI: 1.2-6.6), and those who were Khmu (AOR: 3.6, 95% CI: 2.0-6.8) or Hmong (AOR: 5.0, 95% CI: 3.3-7.5) were significantly more likely to be positive for HBsAg. Although there were no statistically significant differences in the HCV-Ab prevalence according to each variable, males (2.9%, 95% CI: 0.7-10.7), those aged ≥40 years (6.1%, 95% CI: 2.1-16.8), and those from the Southern region (3.3%, 95% CI: 0.6-15.3) tended to have a higher prevalence. This novel population-based survey found differences in the prevalence of chronic hepatitis B and hepatitis C virus infections in Lao PDR according to sex, age group, region, and ethnicity; however, the results of this study should be confirmed in future studies, and relevant responses tailored for each target also need to be determined to control the transmission of hepatitis B and C infections.
Collapse
Affiliation(s)
- Shinsuke Miyano
- Bureau of International Health Cooperation and WHO Collaborating Center for Health Systems Development, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan
- * E-mail:
| | - Chansay Pathammavong
- National Immunization Program, Mother and Child Health Center, Ministry of Health, Lao People’s Democratic Republic (Lao PDR), Vientiane Capital, Lao PDR
| | - Yasunori Ichimura
- Bureau of International Health Cooperation and WHO Collaborating Center for Health Systems Development, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan
| | - Masaya Sugiyama
- Genome Medical Science Project, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikwa, Chiba, Japan
| | - Kongxay Phounphenghack
- National Immunization Program, Mother and Child Health Center, Ministry of Health, Lao People’s Democratic Republic (Lao PDR), Vientiane Capital, Lao PDR
| | | | | | - Phonethipsavanh Nouanthong
- Institute Pasteur du Laos, National Immunization Technical Advisory Group, Ministry of Health, Vientiane Capital, Lao PDR
| | - Lauren Franzel
- Vaccine-Preventable Diseases and Immunization Team, WHO Lao PDR, Vientiane Capital, Lao PDR
| | - Tae Un Yang
- Vaccine-Preventable Diseases and Immunization Team, WHO Lao PDR, Vientiane Capital, Lao PDR
| | | | - Tomomi Ota
- Bureau of International Health Cooperation and WHO Collaborating Center for Health Systems Development, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan
| | - Masafumi Funato
- Bureau of International Health Cooperation and WHO Collaborating Center for Health Systems Development, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan
| | - Kenichi Komada
- Bureau of International Health Cooperation and WHO Collaborating Center for Health Systems Development, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan
| | - Masahiko Hachiya
- Bureau of International Health Cooperation and WHO Collaborating Center for Health Systems Development, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan
| |
Collapse
|
9
|
Nicolás Pérez D, Morales Arráez DE, Castilla Rodríguez I, Gutiérrez Nicolás F, Díaz-Flores Estévez F, de Vera González A, Nazco Casariego GJ, Hernández Guerra M. Hepatitis C virus infection screening reduces mortality and is cost-effective independently of the intervention test. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS : ORGANO OFICIAL DE LA SOCIEDAD ESPANOLA DE PATOLOGIA DIGESTIVA 2022; 114:731-737. [PMID: 35285662 DOI: 10.17235/reed.2022.8609/2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
INTRODUCTION Chronic infection due to hepatitis C virus (HCV) is frequently asymptomatic even in advanced stages of liver disease. Implementation of a screening program based on different HCV tests may enable an earlier diagnosis of HCV liver disease and subsequent application of highly effective treatment. PATIENTS AND METHODS A Markov model which compares three different screening strategies for hepatitis C versus no screening in low-risk prevalence (general population) and high-risk prevalence population (people who inject drugs or prison population) was designed, taking into account age at the start of screening and participation. The three strategies were: 1) serological detection of antibodies against the HCV, 2) dried blood spot test (DBS) to detect antibodies against HCV and 3) detection of RNA from HCV. Quality-adjusted life-years (QALY) were taken as a measurement of effectiveness. The incremental cost-effectiveness ratio (ICER) was calculated and a deterministic and probabilistic sensitivity analysis was performed. RESULTS All three screening strategies were found to be cost-effective with an ICER of €13,633, €12,015 and €12,328/QALY for AntiHCV, DBS-AntiHCV and DBS-RNA HCV, respectively. There was a decrease in mortality due to liver disease in comparison to no screening for AntiHCV (40.7% and 52%), DBS-AntiHCV (45% and 80%) and DBS-RNA HCV (45.2% and 80%) for low-prevalence and high-prevalence populations, respectively. CONCLUSION All test interventions for HCV screening are cost-effective for the early detection of HCV infection, also achieving a reduction in mortality. Thus, implementation of screening programs for HCV should not be halted by decisions on monetary policy.
Collapse
|
10
|
Myring G, Lim AG, Hollingworth W, McLeod H, Beer L, Vickerman P, Hickman M, Radley A, Dillon JF. Cost-effectiveness of pharmacy-led versus conventionally delivered antiviral treatment for hepatitis C in patients receiving opioid substitution therapy: An economic evaluation alongside a pragmatic cluster randomised trial. J Infect 2022; 85:676-682. [PMID: 36170895 DOI: 10.1016/j.jinf.2022.09.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 09/20/2022] [Accepted: 09/21/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND Elimination targets for hepatitis C have been set across the world. In the UK almost 90% of infections are in people who inject drugs. Evidence shows community case-finding is effective at identifying and treating undiagnosed patients. The aim of this analysis was to assess, from a healthcare provider perspective, the cost-effectiveness of a new pharmacist-led test and treat pathway for hepatitis C in opioid agonist treatment (OAT) patients attending community pharmacies compared to conventional care. METHODS In a cluster randomised controlled trial, pharmacies were randomised to the pharmacist-led or conventional care pathway. Mean cost per OAT patient and per patient initiating treatment was identified for each pathway. A Markov model tracking disease progression was developed, with a 50-year time horizon and 3·5% time discount rate, to estimate the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained and the probability of being cost-effective at a £30,000 per QALY willingness-to-pay threshold. Probabilistic sensitivity analysis was performed for a range of drug discounts, re-infection rates, and model assumptions. FINDINGS Mean cost per OAT patient (£3,674 vs £1,965) and per patient initiating treatment (£863 vs £404) was higher in the pharmacist-led pathway, due to higher uptake of testing and pharmacist time requirements. Over a 50-year time horizon the ICER per QALY gained was £31,612 at NHS indicative price for treatment (£38,979 for 12 weeks) and 12·1/100 person-years re-infection rate, reducing to £21,027/£10,220/-£501 per QALY gained with 30%/60%/90% drug price discounts and £25,373/£21,738/£14,912 per QALY gained at re-infection rates of 8/5/2 per 100 person-years. At 30%/60%/90% drug discount rates, the pharmacist-led pathway has an 80%/98%/100% probability of being cost-effective. INTERPRETATION The pharmacist-led pathway is effective at increasing testing and treatment uptake, with cost-effectiveness being highly dependent on drug price discounts. FUNDING Trial funding provided by the Scottish Government, Gilead Sciences, and Bristol-Myers Squibb.
Collapse
Affiliation(s)
- G Myring
- Population Health Sciences, Bristol Medical School, University of Bristol, BS8 1UD, UK; The National Institute for Health Research Applied Research Collaboration West (NIHR ARC West) at University Hospitals Bristol and Weston NHS Foundation Trust, Bristol BS1 2NT, UK.
| | - A G Lim
- Population Health Sciences, Bristol Medical School, University of Bristol, BS8 1UD, UK
| | - W Hollingworth
- Population Health Sciences, Bristol Medical School, University of Bristol, BS8 1UD, UK; The National Institute for Health Research Applied Research Collaboration West (NIHR ARC West) at University Hospitals Bristol and Weston NHS Foundation Trust, Bristol BS1 2NT, UK
| | - H McLeod
- Population Health Sciences, Bristol Medical School, University of Bristol, BS8 1UD, UK; The National Institute for Health Research Applied Research Collaboration West (NIHR ARC West) at University Hospitals Bristol and Weston NHS Foundation Trust, Bristol BS1 2NT, UK
| | - L Beer
- Tayside Clinical Trials Unit, Tayside Medical Science Centre, University of Dundee, Dundee DD1 9SY, UK
| | - P Vickerman
- Population Health Sciences, Bristol Medical School, University of Bristol, BS8 1UD, UK
| | - M Hickman
- Population Health Sciences, Bristol Medical School, University of Bristol, BS8 1UD, UK
| | - A Radley
- Hepatology & Gastroenterology, Clinical & Molecular Medicine, School of Medicine, University of Dundee, Dundee DD1 9SY, UK
| | - J F Dillon
- Hepatology & Gastroenterology, Clinical & Molecular Medicine, School of Medicine, University of Dundee, Dundee DD1 9SY, UK
| |
Collapse
|
11
|
Okawa S, Komada K, Ichimura Y, Sugiyama M, Do HT, Le HX, Hoang TT, Nguyen TB, Huynh MK, Hoang HTH, Tran NAT, Le TH, Ngo QT, Miyano S, Yokobori Y, Inoue Y, Mizoue T, Hachiya M. Comparison between a rapid diagnostic test and dried blood spot-based immunoassay for hepatitis B surface antigen testing: Performance and cost implications in a population-based serosurvey in Vietnam. Int J Infect Dis 2022; 125:51-57. [PMID: 36241163 DOI: 10.1016/j.ijid.2022.10.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 10/01/2022] [Accepted: 10/06/2022] [Indexed: 11/06/2022] Open
Abstract
OBJECTIVES This study aimed to determine the agreement between a rapid diagnostic test (RDT) and a dried blood spot (DBS)-based electrochemiluminescence immunoassay (ECLIA) of hepatitis B surface antigen and to compare the costs of conducting serosurveys using RDTs and DBS in a field setting. METHODS A serosurvey was conducted in the South Central Coast region of Vietnam in May 2019. Participants aged 1-39 years were recruited using a four-stage random sampling method and tested for hepatitis B surface antigen using an RDT kit (Alere Determine) and a DBS-based ECLIA. The agreement between the RDT and the DBS-based ECLIA was assessed using cross-tabulation and Cohen kappa. Cost data were categorized by input (personnel, transportation, field consumables, laboratory consumables, and capital item/overhead) and survey phase (survey preparation, data/biospecimen collection, laboratory testing, and coordination). RESULTS A total of 2072 participants were analyzed. There was a 99% agreement between the RDT and the DBS-based ECLIA results, with a Cohen kappa of 0.9. The estimated cost of conducting a serosurvey by DBS was UD $75,291, whereas RDT was $53,182. CONCLUSION RDTs and DBS-based ECLIA provide test results with high agreements. RDTs are a better option in terms of cost, whereas the DBS-based ECLIA may be useful when evaluating multiple infectious diseases.
Collapse
Affiliation(s)
- Sumiyo Okawa
- Bureau of International Health Cooperation, National Center for Global Health and Medicine, Sumiyo Okawa, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
| | - Kenichi Komada
- Bureau of International Health Cooperation, National Center for Global Health and Medicine, Sumiyo Okawa, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
| | - Yasunori Ichimura
- Bureau of International Health Cooperation, National Center for Global Health and Medicine, Sumiyo Okawa, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
| | - Masaya Sugiyama
- Genome Medical Science Project, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan
| | - Hung Thai Do
- Pasteur Institute in Nha Trang, Nha Trang, Khánh Hòa, Viet Nam
| | - Huy Xuan Le
- Medical Health Service Center, Pasteur Institute in Nha Trang, Nha Trang, Khánh Hòa, Viet Nam
| | - Thanh Tien Hoang
- Department of Infectious Disease Control and Prevention, Pasteur Institute in Nha Trang, Nha Trang, Khánh Hòa, Viet Nam
| | - Trieu Bao Nguyen
- Department of Microbiology and Immunology, Pasteur Institute in Nha Trang, Nha Trang, Khánh Hòa, Viet Nam
| | - Mai Kim Huynh
- Department of Microbiology and Immunology, Pasteur Institute in Nha Trang, Nha Trang, Khánh Hòa, Viet Nam
| | - Hang Thi Hai Hoang
- Department of Infectious Disease Control and Prevention, Pasteur Institute in Nha Trang, Nha Trang, Khánh Hòa, Viet Nam
| | - Nhu Anh Thi Tran
- Department of Microbiology and Immunology, Pasteur Institute in Nha Trang, Nha Trang, Khánh Hòa, Viet Nam
| | - Thieu Hoang Le
- Department of Infectious Disease Control and Prevention, Pasteur Institute in Nha Trang, Nha Trang, Khánh Hòa, Viet Nam
| | - Quyet Thi Ngo
- Department of Microbiology and Immunology, Pasteur Institute in Nha Trang, Nha Trang, Khánh Hòa, Viet Nam
| | - Shinsuke Miyano
- Bureau of International Health Cooperation, National Center for Global Health and Medicine, Sumiyo Okawa, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
| | - Yuta Yokobori
- Bureau of International Health Cooperation, National Center for Global Health and Medicine, Sumiyo Okawa, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
| | - Yosuke Inoue
- Department of Epidemiology and Prevention, National Center for Global Health and Medicine, Tokyo, Japan
| | - Tetsuya Mizoue
- Department of Epidemiology and Prevention, National Center for Global Health and Medicine, Tokyo, Japan
| | - Masahiko Hachiya
- Bureau of International Health Cooperation, National Center for Global Health and Medicine, Sumiyo Okawa, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
| |
Collapse
|
12
|
Villar LM, de Lima MP, Cruz HM, de Paula VS, Scalioni LDP, Flores GL, Carvalho-Costa FA, Parente CC, Coelho MRCD, de Albuquerque ACC, Milagres FAP, Cruz MS, Andrade TM, Motta-Castro ARC, da Mota JC, Lewis-Ximenez LL, Bastos FI. Feasibility of dried blood spot for hepatitis C diagnosis in vulnerable subjects and people living in remote areas from Brazil. BMC Infect Dis 2022; 22:804. [PMID: 36303137 PMCID: PMC9615222 DOI: 10.1186/s12879-022-07717-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Accepted: 09/01/2022] [Indexed: 11/10/2022] Open
Abstract
Background Agile, accessible and cheap diagnosis of hepatitis C virus (HCV) infection is essential to achieve the elimination of this infection, worldwide, as mandated by the World Health Organzation as part of its strategy for 2030. Dried blood spots (DBS) can be an attractive alternative for sample collection among people living in remote areas and vulnerable populations due to the less invasive collection, its biosafety, and storage & transportation of samples at room temperature.
Design This study aims to estimate the usefulness of dried blood spot samples for the diagnosis and the assessment of HCV infection rates in three different settings in Brazil. Cross-sectional analysis of a sample collection from different populations, aiming to assess the performance of the testing algorithms and respective procedures among different populations with diverse background infection rates. Methods We reported the evaluation of DBS as alternative samples for detecting anti-HCV in different groups in real life conditions: (I) Vulnerable subjects living in remote areas of Southeast, North and Northeast Brazil (n = 1464); (II) Beauticians (n = 288); (III) People who use non-injectable drugs (n = 201); (IV) patients referred to outpatient care (n = 275). Results General assay accuracy was 99%, with a weighted kappa value of 0.9, showing an excellent performance. Sensitivities ranged from 87.5% to 100.0% between groups and specificities were above 99.2%. A total of 194 individuals had HCV RNA in serum and concordance of anti-HCV detection in DBS was 98.4%. Conclusions DBS samples could be used for anti-HCV detection in different populations recruited in real life conditions and ambulatory settings, with a high overall sensitivity and specificity. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-022-07717-4.
Collapse
Affiliation(s)
- Livia Melo Villar
- Laboratory of Viral Hepatitis, Oswaldo Cruz Institute, FIOCRUZ, Helio and Peggy Pereira Pavillion, Ground Floor, Room B09, v. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil.
| | - Marjorie Parra de Lima
- Laboratory of Viral Hepatitis, Oswaldo Cruz Institute, FIOCRUZ, Helio and Peggy Pereira Pavillion, Ground Floor, Room B09, v. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil
| | - Helena Medina Cruz
- Laboratory of Viral Hepatitis, Oswaldo Cruz Institute, FIOCRUZ, Helio and Peggy Pereira Pavillion, Ground Floor, Room B09, v. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil.,Estácio de Sá University, Resende, Rio de Janeiro, Brazil
| | | | - Leticia de Paula Scalioni
- Laboratory of Viral Hepatitis, Oswaldo Cruz Institute, FIOCRUZ, Helio and Peggy Pereira Pavillion, Ground Floor, Room B09, v. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil
| | - Geane Lopes Flores
- Laboratory of Viral Hepatitis, Oswaldo Cruz Institute, FIOCRUZ, Helio and Peggy Pereira Pavillion, Ground Floor, Room B09, v. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil
| | | | | | | | | | | | - Marcelo Santos Cruz
- Institute of Psychiatry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Tarcisio Matos Andrade
- Department of Community and Family Health, Federal University of Bahia, SalvadorBahia, 40110-100, Brazil
| | | | - Jurema Corrêa da Mota
- Institute of Communication and Scientific Information and Technology for Health, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Lia Laura Lewis-Ximenez
- Laboratory of Viral Hepatitis, Oswaldo Cruz Institute, FIOCRUZ, Helio and Peggy Pereira Pavillion, Ground Floor, Room B09, v. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil
| | - Francisco Inácio Bastos
- Institute of Communication and Scientific Information and Technology for Health, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| |
Collapse
|
13
|
Modified ARCHITECT ® serologic assays enable plasma-level performance from dried blood spot samples. Biotechniques 2022; 73:193-203. [PMID: 36240056 DOI: 10.2144/btn-2022-0082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Dried blood spots (DBSs) provide an alternative sample input for serologic testing. We evaluated DBSs for the ARCHITECT® hepatitis B surface antigen (HBsAg) NEXT, hepatitis B e-antigen (HBeAg), anti-hepatitis B core antigen (anti-HBc II), HIV antigen/antibody (Ag/Ab) Combo and AdviseDx SARS-CoV-2 IgG II assays. Assay performance with DBSs was assessed with or without assay modification and compared with on-market assay with plasma samples. DBS stability was also determined. HBsAg NEXT and HIV Ag/Ab Combo assays using DBSs showed sensitivity and specificity comparable to that of on-market assays. Modified HBeAg, anti-HBc II and SARS-CoV-2 IgG II DBS assays achieved performance comparable to on-market assays. Use of DBSs as input for high-throughput serologic assays is expected to have significant implications for improving population surveillance and increasing access to diagnostic testing.
Collapse
|
14
|
Kikuchi M, Lindstrom P, Tejada-Strop A, Mixson-Hayden T, Kamili S, Sawabe M. Dried blood spot is the feasible matrix for detection of some but not all hepatitis B virus markers of infection. BMC Res Notes 2022; 15:287. [PMID: 36064629 PMCID: PMC9446784 DOI: 10.1186/s13104-022-06178-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 08/25/2022] [Indexed: 11/30/2022] Open
Abstract
Objective Use of dried blood spots (DBS) for detection of hepatitis B virus (HBV) markers of infection has the potential to facilitate diagnosis of HBV infection especially in resource-limited countries. The aim of this study was to evaluate the feasibility of DBS for detection of various markers of HBV infections. Results Fifty-four DBS samples were engineered from well-characterized plasma samples. All DBS samples were tested for HBsAg, total anti-HBc and HBV DNA, 20 of 54 samples were also tested for HBeAg using commercially available assays. HBsAg was detected in 24 of 25 (96%), HBV DNA in 22 of 25 (88%), total anti-HBc in all 9 (100%), and HBeAg in all 7 (100%) DBS samples. The average difference in HBV DNA levels between DBS eluates and corresponding plasma samples was 2.7 log10 IU/mL. Fifteen DBS eluates positive for HBV DNA were sequenced and all of them belonged to HBV genotype A. Thirteen samples which were negative for all HBV markers showed HBeAg false positivity. Therefore, DBS is a reliable sample matrix for detection of HBsAg, total anti-HBc and HBV DNA, but not HBeAg. Further feasibility studies of DBS for diagnostic purposes and epidemiologic studies are warranted. Supplementary Information The online version contains supplementary material available at 10.1186/s13104-022-06178-x.
Collapse
Affiliation(s)
- Minami Kikuchi
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA, 30329, USA.,Department of Molecular Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo, 113-8519, Japan
| | - Patrick Lindstrom
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA, 30329, USA
| | - Alexandra Tejada-Strop
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA, 30329, USA
| | - Tonya Mixson-Hayden
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA, 30329, USA
| | - Saleem Kamili
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA, 30329, USA
| | - Motoji Sawabe
- Department of Molecular Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo, 113-8519, Japan.
| |
Collapse
|
15
|
Said ZNA, El-Sayed MH. Challenge of managing hepatitis B virus and hepatitis C virus infections in resource-limited settings. World J Hepatol 2022; 14:1333-1343. [PMID: 36158908 PMCID: PMC9376770 DOI: 10.4254/wjh.v14.i7.1333] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 01/30/2022] [Accepted: 06/13/2022] [Indexed: 02/06/2023] Open
Abstract
The global burden of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and coinfection represents a major public health concern, particularly in resource-limited settings. Elimination of HCV by 2030 has become foreseeable, with effective direct-acting antiviral oral therapies and the availability of affordable generics in low-and-middle-income countries (LMICs). However, access to oral nucleos(t)ide therapy for HBV remains critical and is limited outside the existing global HIV program platforms despite affordable prices. Prevention of mother-to-child transmission of HBV through scaling up of birth dose implementation in LMICs is essential to achieve the 2030 elimination goal. Most individuals living with HBV and/or HCV in resource-limited settings are unaware of their infection, and with improved access to medications, the most significant barrier remains access to affordable diagnostics and preventive strategies. The coronavirus disease 2019 pandemic interrupted hepatitis elimination programs, albeit offered opportunities for improved diagnostic capacities and raised political awareness of the critical need for strengthening health care services and universal health coverage. This review underpins the HBV and HCV management challenges in resource-limited settings, highlighting the current status and suggested future elimination strategies in some of these countries. Global efforts should continue to improve awareness and political commitment. Financial resources should be secured to access and implement comprehensive strategies for diagnosis and linkage to care in resource-constrained settings to fulfill the 2030 elimination goal.
Collapse
Affiliation(s)
- Zeinab Nabil Ahmed Said
- Department of Microbiology & Immunology, Faculty of Medicine for Girls Al-Azhar University, Cairo, Egypt.
| | - Manal Hamdy El-Sayed
- Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| |
Collapse
|
16
|
Development and Implementation of Dried Blood Spot-Based COVID-19 Serological Assays for Epidemiologic Studies. Microbiol Spectr 2022; 10:e0247121. [PMID: 35612315 PMCID: PMC9241704 DOI: 10.1128/spectrum.02471-21] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Serological surveillance studies of infectious diseases provide population-level estimates of infection and antibody prevalence, generating crucial insight into population-level immunity, risk factors leading to infection, and effectiveness of public health measures. These studies traditionally rely on detection of pathogen-specific antibodies in samples derived from venipuncture, an expensive and logistically challenging aspect of serological surveillance. During the COVID-19 pandemic, guidelines implemented to prevent the spread of SARS-CoV-2 infection made collection of venous blood logistically difficult at a time when SARS-CoV-2 serosurveillance was urgently needed. Dried blood spots (DBS) have generated interest as an alternative to venous blood for SARS-CoV-2 serological applications due to their stability, low cost, and ease of collection; DBS samples can be self-generated via fingerprick by community members and mailed at ambient temperatures. Here, we detail the development of four DBS-based SARS-CoV-2 serological methods and demonstrate their implementation in a large serological survey of community members from 12 cities in the East Bay region of the San Francisco metropolitan area using at-home DBS collection. We find that DBS perform similarly to plasma/serum in enzyme-linked immunosorbent assays and commercial SARS-CoV-2 serological assays. In addition, we show that DBS samples can reliably detect antibody responses months postinfection and track antibody kinetics after vaccination. Implementation of DBS enabled collection of valuable serological data from our study population to investigate changes in seroprevalence over an 8-month period. Our work makes a strong argument for the implementation of DBS in serological studies, not just for SARS-CoV-2, but any situation where phlebotomy is inaccessible. IMPORTANCE Estimation of community-level antibody responses to SARS-CoV-2 from infection or vaccination is critical to inform public health responses. Traditional studies of antibodies rely on collection of blood via venipuncture, an invasive procedure not amenable to pandemic-related social-distancing measures. Dried blood spots (DBS) are an alternative to venipuncture, since they can be self-collected by study participants at home and do not require refrigeration for shipment or storage. However, DBS-based assays to measure antibody levels to SARS-CoV-2 have not been widely utilized. Here, we show that DBS are comparable to blood as a sampling method for antibody responses to SARS-CoV-2 infection and vaccination over time measured using four distinct serological assays. The DBS format enabled antibody surveillance in a longitudinal cohort where study participants self-collected samples, ensuring the participants’ safety during an ongoing pandemic. Our work demonstrates that DBS are an excellent sampling method for measuring antibody responses whenever venipuncture is impractical.
Collapse
|
17
|
Alinity m, a Random-Access System, for Hepatitis B Virus DNA Quantification in Plasma and Whole Blood Collected on Dried Blood Spots. mSphere 2022; 7:e0008222. [PMID: 35477312 PMCID: PMC9241498 DOI: 10.1128/msphere.00082-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
The International Liver Association recommends the use of accurate and sensitive molecular methods for determination of hepatitis B virus (HBV) DNA levels in plasma or serum of chronic HBsAg carriers. The level of HBV replication represents the strongest predictive biomarker associated with disease progression and long-term outcome of chronic HBV infection. The purpose of this study was to evaluate the ability to the new Alinity m System to detect and quantify HBV DNA in plasma and whole blood collected on dried blood spots (DBS). Paired plasma and DBS samples from patients chronically infected with various HBV genotypes were tested in parallel for HBV DNA detection and quantification. There is a linear relationship between HBV DNA levels measured in plasma samples using the Alinity m HBV assay and the Xpert HBV viral load assay, used for comparison. A slight deviation (0.03 ± 0.31 log IU/mL) was observed within the quantitative range. In DBS, HBV DNA levels closely correlated with levels measured in plasma. All patients had detectable and quantifiable HBV DNA by DBS testing, except for one patient with a plasma HBV DNA level above 2,000 IU/mL. In conclusion, the newly developed real-time PCR-based assay Alinity m HBV assay can correctly detect HBV DNA in DBS, especially for patients with blood HBV DNA levels above 2,000 IU/mL, and also accurately quantify HBV DNA in plasma samples. IMPORTANCE Hepatitis B virus is one of the most prevalent blood-borne viruses affecting the liver and causing acute and chronic hepatitis. Only a small proportion of people with HBV infection are diagnosed. HBV DNA measurement is critical in clinical practice for the diagnosis and treatment decisions of patients requiring antiviral therapy. Dried blood spot (DBS) collection provides a simple, practical, and acceptable alternative to venous blood collection, especially in community settings. We have demonstrated high sensitivity and specificity for HBV DNA detection in DBS compared to plasma samples, especially when using clinically relevant cutoffs of 2,000 and 20,000 IU/mL. Results support the use of DBS in community-based settings.
Collapse
|
18
|
Performance of Immunoglobulin G Serology on Finger Prick Capillary Dried Blood Spot Samples to Detect a SARS-CoV-2 Antibody Response. Microbiol Spectr 2022; 10:e0140521. [PMID: 35266818 PMCID: PMC9045222 DOI: 10.1128/spectrum.01405-21] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
We investigate the diagnostic accuracy and predictive value of finger prick capillary dried blood spot (DBS) samples tested by a quantitative multiplex anti-immunoglobulin G (IgG) assay to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies after infection or vaccination. This cross-sectional study involved participants (n = 6,841) from several serological surveys conducted in nonhospitalized children and adults throughout 2020 and 2021 in British Columbia (BC), Canada. Analysis used paired DBS and serum samples from a subset of participants (n = 642) prior to vaccination to establish signal thresholds and calculate diagnostic accuracy by logistic regression. Discrimination of the logistic regression model was assessed by receiver operator curve (ROC) analysis in an n = 2,000 bootstrap of the paired sample (n = 642). The model was cross-validated in a subset of vaccinated persons (n = 90). Unpaired DBS samples (n = 6,723) were used to evaluate anti-IgG signal distributions. In comparison to paired serum, DBS samples from an unvaccinated population possessed a sensitivity of 79% (95% confidence interval [95% CI]: 58 to 91%) and specificity of 97% (95% CI: 95 to 98%). ROC analysis found that DBS samples accurately classify SARS-CoV-2 seroconversion at an 88% percent rate (area under the curve [AUC] = 88% [95% CI: 80 to 95%]). In coronavirus disease 2019 (COVID-19) vaccine dose one or two recipients, the sensitivity of DBS testing increased to 97% (95% CI: 83 to 99%) and 100% (95% CI: 88 to 100%). Modeling found that DBS testing possesses a high positive predictive value (98% [95% CI: 97 to 98%]) in a population with 75% seroprevalence. We demonstrate that DBS testing should be considered to reliably detect SARS-CoV-2 seropositivity from natural infection or vaccination. IMPORTANCE Dried blood spot samples have comparable diagnostic accuracy to serum collected by venipuncture when tested by an electrochemiluminescent assay for antibodies and should be considered to reliably detect seropositivity following SARS-CoV-2 infection and/or vaccination.
Collapse
|
19
|
Evaluation of hepatitis C virus antibody assay using dried blood spot samples. Sci Rep 2022; 12:3763. [PMID: 35260691 PMCID: PMC8904514 DOI: 10.1038/s41598-022-07821-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 02/22/2022] [Indexed: 01/05/2023] Open
Abstract
Early diagnosis of hepatitis C virus (HCV) infection is essential for prompt initiation of treatment and prevention of transmission, yet several logistical barriers continue to limit access to HCV testing. Dried blood spot (DBS) technology involves a simple fingerstick that eliminates the need for trained personnel, and DBS can be stored and transported at room temperature. We evaluated the use of DBS whole blood samples in the modified Abbott ARCHITECT anti-HCV assay, comparing assay performance against the standard assay run using DBS and venous plasma samples. 144 HCV positive and 104 HCV negative matched venous plasma and whole blood specimens were selected from a retrospective study with convenience sampling in Cameroon. Results obtained using a modified volume DBS assay were highly correlated to the results of the standard assay run with plasma on clinical samples and dilution series (R2 = 0.71 and 0.99 respectively). The ARCHITECT Anti-HCV assay with input volume modification more accurately detects HCV antibodies in DBS whole blood samples with 100% sensitivity and specificity, while the standard assay had 90.97% sensitivity. The use of DBS has the potential to expand access to HCV testing to underserved or marginalized populations with limited access to direct HCV care.
Collapse
|
20
|
Carty PG, McCarthy M, O'Neill SM, De Gascun CF, Harrington P, O'Neill M, Smith SM, Teljeur C, Ryan M. Laboratory-based testing for hepatitis C infection using dried blood spot samples: A systematic review and meta-analysis of diagnostic accuracy. Rev Med Virol 2021; 32:e2320. [PMID: 34957630 DOI: 10.1002/rmv.2320] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 12/11/2021] [Accepted: 12/13/2021] [Indexed: 11/10/2022]
Abstract
The use of dried blood spot (DBS) samples can facilitate the implementation of reflex testing by circumventing the need for centrifugation and freezing of venous blood samples. This systematic review assessed the accuracy of using DBS samples to diagnose chronic hepatitis C virus (HCV) infection. A comprehensive search was undertaken to identify articles published up to July 2020 evaluating the diagnostic accuracy of anti-HCV, HCV-RNA and HCV core antigen tests using DBS. Screening, data extraction, quality appraisal and Grading of Recommendations, Assessment, Development and Evaluations certainty of the evidence assessment were performed independently by two reviewers. Meta-analysis, meta-regression and sensitivity analyses were conducted. The evidence demonstrates that laboratory-based anti-HCV and HCV-RNA tests using DBS samples have high diagnostic accuracy. All comparisons were between DBS and venous samples. For the detection of anti-HCV, sensitivity was 95% (95% CI: 92%-97%) and specificity was 99% ([95% CI: 98%-99%]; n = 25; I2 = 81%; moderate certainty). For the detection of HCV-RNA, the sensitivity was 95% (95% CI: 93%-97%) and specificity was 97% ([95% CI: 94%-98%]; n = 20; I2 = 52%; moderate certainty). The sensitivity of HCV core antigen tests was 86% (95% CI: 79%-91%) and specificity was 98% ([95% CI: 94%-99%]; n = 5; I2 = 37%; low certainty) compared with HCV-RNA (the gold standard for detecting chronic HCV). DBS samples could facilitate diagnosis of chronic HCV infection as the necessary sequential tests (anti-HCV and then HCV-RNA or HCV core antigen) can be undertaken using the same blood sample. This could reduce loss of patient follow-up and support international efforts towards HCV elimination in both high and low prevalence settings.
Collapse
Affiliation(s)
- Paul G Carty
- Faculty of Medicine & Health Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland.,Health Information and Quality Authority, Dublin, Ireland
| | | | | | - Cillian F De Gascun
- National Virus Reference Laboratory, University College Dublin, Dublin, Ireland
| | | | | | - Susan M Smith
- Department of General Practice, Health Research Board Centre for Primary Care Research, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Conor Teljeur
- Health Information and Quality Authority, Dublin, Ireland
| | - Mairin Ryan
- Health Information and Quality Authority, Dublin, Ireland.,Department of Pharmacology & Therapeutics, Trinity College Dublin, Trinity Health Sciences, St James's Hospital, Dublin, Ireland
| |
Collapse
|
21
|
Périères L, Protopopescu C, Lo G, Marcellin F, Ba EH, Coste M, Touré Kane C, Diallo A, Sokhna C, Boyer S. Sibling status, home birth, tattoos and stitches are risk factors for chronic hepatitis B virus infection in Senegalese children: A cross-sectional survey. J Viral Hepat 2021; 28:1515-1525. [PMID: 34355470 DOI: 10.1111/jvh.13589] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 07/12/2021] [Accepted: 07/22/2021] [Indexed: 12/14/2022]
Abstract
Sub-Saharan Africa's hepatitis B virus (HBV) burden is primarily due to infection in infancy. However, data on chronic HBV infection prevalence and associated risk factors in children born post-HBV vaccination introduction are scarce. We estimated hepatitis B surface antigen (HBsAg) prevalence and risk factors in Senegalese children born during the HBV vaccination era. In 2018-2019, a community-based cross-sectional survey was conducted in Senegal among children born between 2004 and 2015 (ie after the three-dose HBV vaccine series was introduced (2004) but before the birth dose's introduction (2016)). HBsAg-positive children were identified using dried blood spots. A standardized questionnaire collected socioeconomic information. Data were age-sex weighted and calibrated to be representative of children living in the study area. Risk factors associated with HBsAg positivity were identified using negative binomial regression. Among 1,327 children, 17 were HBsAg-positive (prevalence = 1.23% (95% confidence interval [CI] 0.61-1.85)). Older age (adjusted incidence-rate ratio [aIRR] 1.31 per one-year increase, 95% CI 1.10-1.57), home vs healthcare facility delivery (aIRR 3.55, 95% CI 1.39-9.02), stitches (lifetime) (aIRR 4.79; 95% CI 1.84-12.39), tattoos (aIRR 8.97, 95% CI 1.01-79.11) and having an HBsAg-positive sibling with the same mother (aIRR 3.05, 95% CI 1.09-8.57) were all independently associated with HBsAg positivity. The low HBsAg prevalence highlights the success of the Senegalese HBV vaccination program. To further reduce HBV acquisition in children, high-risk groups, including pregnant women and siblings of HBsAg-positive individuals, must be screened. Vital HBV infection prevention measures include promoting delivery in healthcare facilities, and increasing awareness of prevention and control procedures.
Collapse
Affiliation(s)
| | - Camelia Protopopescu
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France
| | - Gora Lo
- Institut de Recherche en Santé de Surveillance Epidémiologique et de Formation, Dakar, Senegal
| | - Fabienne Marcellin
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France
| | | | - Marion Coste
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France.,Aix Marseille Univ, CNRS, EHESS, Centrale Marseille, AMSE, Marseille, France
| | - Coumba Touré Kane
- Institut de Recherche en Santé de Surveillance Epidémiologique et de Formation, Dakar, Senegal
| | | | - Cheikh Sokhna
- VITROME, IRD, AMU, AP-HM, SSA, IHU-MI, Marseille, France
| | - Sylvie Boyer
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France
| | | |
Collapse
|
22
|
Shahid I, Alzahrani AR, Al-Ghamdi SS, Alanazi IM, Rehman S, Hassan S. Hepatitis C Diagnosis: Simplified Solutions, Predictive Barriers, and Future Promises. Diagnostics (Basel) 2021; 11:1253. [PMID: 34359335 PMCID: PMC8305142 DOI: 10.3390/diagnostics11071253] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 07/02/2021] [Accepted: 07/05/2021] [Indexed: 12/14/2022] Open
Abstract
The simplification of current hepatitis C diagnostic algorithms and the emergence of digital diagnostic devices will be very crucial to achieving the WHO's set goals of hepatitis C diagnosis (i.e., 90%) by 2030. From the last decade, hepatitis C diagnosis has been revolutionized by the advent and approval of state-of-the-art HCV diagnostic platforms which have been efficiently implemented in high-risk HCV populations in developed nations as well as in some low-to-middle income countries (LMICs) to identify millions of undiagnosed hepatitis C-infected individuals. Point-of-care (POC) rapid diagnostic tests (RDTs; POC-RDTs), RNA reflex testing, hepatitis C self-test assays, and dried blood spot (DBS) sample analysis have been proven their diagnostic worth in real-world clinical experiences both at centralized and decentralized diagnostic settings, in mass hepatitis C screening campaigns, and hard-to-reach aboriginal hepatitis C populations in remote areas. The present review article overviews the significance of current and emerging hepatitis C diagnostic packages to subvert the public health care burden of this 'silent epidemic' worldwide. We also highlight the challenges that remain to be met about the affordability, accessibility, and health system-related barriers to overcome while modulating the hepatitis C care cascade to adopt a 'test and treat' strategy for every hepatitis C-affected individual. We also elaborate some key measures and strategies in terms of policy and progress to be part of hepatitis C care plans to effectively link diagnosis to care cascade for rapid treatment uptake and, consequently, hepatitis C cure.
Collapse
Affiliation(s)
- Imran Shahid
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, P.O. Box 13578, Makkah 21955, Saudi Arabia; (A.R.A.); (S.S.A.-G.); (I.M.A.)
| | - Abdullah R. Alzahrani
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, P.O. Box 13578, Makkah 21955, Saudi Arabia; (A.R.A.); (S.S.A.-G.); (I.M.A.)
| | - Saeed S. Al-Ghamdi
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, P.O. Box 13578, Makkah 21955, Saudi Arabia; (A.R.A.); (S.S.A.-G.); (I.M.A.)
| | - Ibrahim M. Alanazi
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, P.O. Box 13578, Makkah 21955, Saudi Arabia; (A.R.A.); (S.S.A.-G.); (I.M.A.)
| | - Sidra Rehman
- Functional Genomics Laboratory, Department of Biosciences, COMSATS University Islamabad (CUI), Islamabad 45550, Pakistan;
| | - Sajida Hassan
- Viral Hepatitis Program, Laboratory of Medicine, University of Washington, Seattle, WA 98195, USA;
| |
Collapse
|
23
|
Stockdale AJ, Silungwe NM, Shawa IT, Kreuels B, Gordon MA, Geretti AM. Diagnostic performance evaluation of hepatitis B e antigen rapid diagnostic tests in Malawi. BMC Infect Dis 2021; 21:487. [PMID: 34044776 PMCID: PMC8157469 DOI: 10.1186/s12879-021-06134-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 04/19/2021] [Indexed: 12/18/2022] Open
Abstract
Background The World Health Organization (WHO) has targeted a reduction in viral hepatitis-related mortality by 65% and incidence by 90% by 2030, necessitating enhanced hepatitis B treatment and prevention programmes in low- and middle-income countries. Hepatitis B e antigen (HBeAg) status is used in the assessment of eligibility for antiviral treatment and for prevention of mother-to-child transmission (PMTCT). Accordingly, the WHO has classified HBeAg rapid diagnostic tests (RDTs) as essential medical devices. Methods We assessed the performance characteristics of three commercially available HBeAg RDTs (SD Bioline, Alere, South Africa; Creative Diagnostics, USA; and Biopanda Reagents, UK) in two hepatitis B surface antigen-positive cohorts in Blantyre, Malawi: participants of a community study (n = 100) and hospitalised patients with cirrhosis or hepatocellular carcinoma (n = 94). Two investigators, blinded to the reference test result, independently assessed each assay. We used an enzyme-linked immunoassay (Monolisa HBeAg, Bio-Rad, France) as a reference test and quantified HBeAg concentration using dilutions of the WHO HBeAg standard. We related the findings to HBV DNA levels, and evaluated treatment eligibility using the TREAT-B score. Results Among 194 HBsAg positive patients, median age was 37 years, 42% were femaleand 26% were HIV co-infected. HBeAg prevalence was 47/194 (24%). The three RDTs showed diagnostic sensitivity of 28% (95% CI 16–43), 53% (38–68) and 72% (57–84) and specificity of 96–100% for detection of HBeAg. Overall inter-rater agreement κ statistic was high at 0.9–1.0. Sensitivity for identifying patients at the threshold where antiviral treatment is recommended for PMTCT, with HBV DNA > 200,000 IU/ml (39/194; 20%), was 22, 49 and 54% respectively. Using the RDTs in place of the reference HBeAg assay resulted in 3/43 (9%), 5/43 (12%) and 8/43 (19%) of patients meeting the TREAT-B treatment criteria being misclassified as ineligible for treatment. A relationship between HBeAg concentration and HBeAg detection by RDT was observed. A minimum HBeAg concentration of 2.2–3.1 log10IU/ml was required to yield a reactive RDT. Conclusions Commercially available HBeAg RDTs lack sufficient sensitivity to accurately classify hepatitis B patients in Malawi. This has implications for hepatitis B public health programs in sub-Saharan Africa. Alternative diagnostic assays are recommended. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-021-06134-3.
Collapse
Affiliation(s)
- Alexander J Stockdale
- Malawi-Liverpool-Wellcome Programme, Blantyre, Malawi. .,Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Ronald Ross Building, 8 West Derby Street, Liverpool, L69 7BE, UK.
| | | | - Isaac Thom Shawa
- Malawi-Liverpool-Wellcome Programme, Blantyre, Malawi.,University of Malawi College of Medicine, Blantyre, Malawi
| | - Benno Kreuels
- University of Malawi College of Medicine, Blantyre, Malawi.,Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.,First Department of Medicine, University Medical Centre, Hamburg-Eppendorf, Hamburg, Germany
| | - Melita A Gordon
- Malawi-Liverpool-Wellcome Programme, Blantyre, Malawi.,Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Ronald Ross Building, 8 West Derby Street, Liverpool, L69 7BE, UK
| | - Anna Maria Geretti
- Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Ronald Ross Building, 8 West Derby Street, Liverpool, L69 7BE, UK
| |
Collapse
|
24
|
Anderson M, Holzmayer V, Vallari A, Taylor R, Moy J, Cloherty G. Expanding access to SARS-CoV-2 IgG and IgM serologic testing using fingerstick whole blood, plasma, and rapid lateral flow assays. J Clin Virol 2021; 141:104855. [PMID: 34144453 PMCID: PMC8111886 DOI: 10.1016/j.jcv.2021.104855] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 04/22/2021] [Accepted: 05/04/2021] [Indexed: 12/31/2022]
Abstract
Serologic testing for SARS-CoV-2 antibodies can be used to confirm diagnosis, estimate seroprevalence, screen convalescent plasma donors, and assess vaccine efficacy. Dried blood spot (DBS) samples have been used for serology testing of various diseases in resource-limited settings. We examined the use of DBS samples and capillary blood (fingerstick) plasma collected in Microtainer tubes for SARS-CoV-2 testing with the automated Abbott ARCHITECT™ SARS-CoV-2 IgG and IgM assays and use of venous whole blood with a prototype PANBIO™ rapid point-of-care lateral flow SARS-CoV-2 IgG assay. The ARCHITECT™ SARS-CoV-2 IgG assay was initially optimized for use with DBS, venous and capillary plasma, and venous whole blood collected from patients with symptoms and PCR-confirmed COVID-19 and negative asymptomatic controls. Linearity and reproducibility was confirmed with 3 contrived DBS samples, along with sample stability and signal recovery after 14 days. ARCHITECT™ SARS-CoV-2 IgG and IgM assay results showed high concordance between fingerstick DBS and venous DBS samples, and between fingerstick DBS and venous whole blood samples (n = 61). Fingerstick plasma collected in Microtainer tubes (n = 109) showed 100% concordant results (R2=0.997) with matched patient venous plasma on the ARCHITECT™ SARS-CoV-2 IgG assay. High concordance of assay results (92.9% positive, 100% negative) was also observed for the PANBIO™ SARS-CoV-2 IgG assay compared to the ARCHITECT™ SARS-CoV-2 IgG assay run with matched venous plasma (n = 61). Fingerstick DBS and plasma samples are easy and inexpensive to collect and, along with the use of rapid point-of-care testing platforms, will expand access to SARS-CoV-2 serology testing, particularly in resource-limited areas.
Collapse
Affiliation(s)
- Mark Anderson
- Abbott Laboratories, Abbott Diagnostics Division, 100 Abbott Park Road, Bldg. AP20, Abbott Park, IL 60064-3500, United States
| | - Vera Holzmayer
- Abbott Laboratories, Abbott Diagnostics Division, 100 Abbott Park Road, Bldg. AP20, Abbott Park, IL 60064-3500, United States
| | - Ana Vallari
- Abbott Laboratories, Abbott Diagnostics Division, 100 Abbott Park Road, Bldg. AP20, Abbott Park, IL 60064-3500, United States
| | - Russell Taylor
- Abbott Laboratories, Abbott Diagnostics Division, 100 Abbott Park Road, Bldg. AP20, Abbott Park, IL 60064-3500, United States
| | - James Moy
- Rush University Medical Center, Chicago, Illinois, United States
| | - Gavin Cloherty
- Abbott Laboratories, Abbott Diagnostics Division, 100 Abbott Park Road, Bldg. AP20, Abbott Park, IL 60064-3500, United States.
| |
Collapse
|
25
|
Shimakawa Y, Vernoux L, Gabassi A, Mercier‐Delarue S, Vincent JP, Simon F, Maylin S. Analytical validation of hepatitis B core-related antigen (HBcrAg) using dried blood spots (DBS). J Viral Hepat 2021; 28:837-843. [PMID: 33599049 PMCID: PMC8247985 DOI: 10.1111/jvh.13489] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 02/05/2021] [Accepted: 02/09/2021] [Indexed: 12/11/2022]
Abstract
Limited access to nucleic acid testing (NAT) to quantify HBV DNA levels, an essential tool to determine anti-HBV treatment eligibility, represents a significant barrier to scale up HBV diagnostic services in resource-limited countries. Hepatitis B core-related antigen (HBcrAg) has the potential to become an affordable alternative because of its low cost (US$ <15/assay) and strong correlation with HBV DNA levels in treatment-naïve patients. However, the current assay requires plasma or serum. To further facilitate its application to decentralized settings, we developed and evaluated a standardized procedure to quantify HBcrAg using dried blood spots as a tool to diagnose HBV-infected people with high viraemia. We evaluated the following elution method optimized to quantify HBcrAg: suspension of a punched blood-soaked disc (11 mm) of Whatman 903 Protein Saver Card in 450 µL of PBS 0.05% Tween 20, followed by an incubation for 4 h at room temperature and a centrifugation at 10,000 g for 10 minutes. 150 µL of DBS eluate was used to quantify HBcrAg using chemiluminescent enzyme immunoassay (LUMIPULSE® G600II, Fujirebio). The limit of detection of dried blood spot HBcrAg in relation with HBV DNA levels was 19,115 IU/mL across the five major HBV genotypes (A/B/C/D/E). A strong linear correlation was confirmed between dried blood spot HBcrAg and HBV DNA levels (r = 0.94, p < 0.0001) in samples with high viral loads (range: 3.7-7.0 log IU/mL). The coefficient of variation ranged between 4.0-11.2% for repeatability and 3.9-12.2% for reproducibility. Analytical specificity was 100% (95% CI: 83.9-100%) in HBV-negative samples. Using our elution method, it may be possible to identify HBV-infected patients with high viraemia who need antiviral therapy using dried blood spot and HBcrAg. A large-scale clinical validation is warranted in resource-limited countries.
Collapse
Affiliation(s)
- Yusuke Shimakawa
- Unité d'Épidémiologie des Maladies ÉmergentesInstitut PasteurParisFrance
| | | | - Audrey Gabassi
- Laboratoire de VirologieHôpital Saint‐LouisAP‐HPParisFrance
| | | | | | - François Simon
- Laboratoire de VirologieHôpital Saint‐LouisAP‐HPParisFrance
| | - Sarah Maylin
- Laboratoire de VirologieHôpital Saint‐LouisAP‐HPParisFrance
| |
Collapse
|
26
|
Barr DB, Kannan K, Cui Y, Merrill L, Petrick LM, Meeker JD, Fennell TR, Faustman EM. The use of dried blood spots for characterizing children's exposure to organic environmental chemicals. ENVIRONMENTAL RESEARCH 2021; 195:110796. [PMID: 33508256 PMCID: PMC7988293 DOI: 10.1016/j.envres.2021.110796] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Revised: 01/02/2021] [Accepted: 01/20/2021] [Indexed: 05/05/2023]
Abstract
Biomonitoring is a commonly used tool for exposure assessment of organic environmental chemicals with urine and blood samples being the most commonly used matrices. However, for children's studies, blood samples are often difficult to obtain. Dried blood spots (DBS) represent a potential matrix for blood collection in children that may be used for biomonitoring. DBS are typically collected at birth to screen for several congenital disorders and diseases; many of the states that are required to collect DBS archive these spots for years. If the archived DBS can be accessed by environmental health researchers, they potentially could be analyzed to retrospectively assess exposure in these children. Furthermore, DBS can be collected prospectively in the field from children ranging in age from newborn to school-aged with little concern from parents and minimal risk to the child. Here, we review studies that have evaluated the measurement of organic environmental toxicants in both archived and prospectively collected DBS, and where available, the validation procedures that have been performed to ensure these measurements are comparable to traditional biomonitoring measurements. Among studies thus far, the amount of validation has varied considerably with no studies systematically evaluating all parameters from field collection, shipping and storage contamination and stability to laboratory analysis feasibility. These validation studies are requisite to ensure reliability of the measurement and comparability to more traditional matrices. Thus, we offer some recommendations for validation studies and other considerations before DBS should be adopted as a routine matrix for biomonitoring.
Collapse
Affiliation(s)
- Dana Boyd Barr
- Emory University, Rollins School of Public Health, Gangarosa Department of Environmental Health, Atlanta, GA, USA.
| | - Kurunthachalam Kannan
- Department of Pediatrics and Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA
| | - Yuxia Cui
- National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
| | | | - Lauren M Petrick
- The Senator Frank R. Lautenberg Environmental Health Sciences Laboratory, Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - John D Meeker
- School of Public Health, University of Michigan, Ann Arbor, MI, USA
| | | | - Elaine M Faustman
- University of Washington, School of Public Health, Department of Environmental and Occupational Health, Seattle, WA, USA
| |
Collapse
|
27
|
Bajis S, Applegate TL, Grebely J, Matthews GV, Dore GJ. Novel Hepatitic C Virus (HCV) Diagnosis and Treatment Delivery Systems: Facilitating HCV Elimination by Thinking Outside the Clinic. J Infect Dis 2021; 222:S758-S772. [PMID: 33245354 DOI: 10.1093/infdis/jiaa366] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The World Health Organization has set a goal to eliminate hepatitis C virus (HCV) infection as public health threat by 2030. Although the advent of highly effective and tolerable direct-acting antiviral therapy has paved the way for HCV elimination, most people with HCV infection remain undiagnosed and untreated globally, with striking disparities between high-income and low- to middle-income countries. Novel decentralized and cost-effective "test-and-treat" strategies are critically needed to identify the millions of people unaware of their status and link them to treatment.
Collapse
Affiliation(s)
- Sahar Bajis
- The Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia
| | - Tanya L Applegate
- The Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia
| | - Jason Grebely
- The Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia
| | - Gail V Matthews
- The Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia
| | - Gregory J Dore
- The Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia
| |
Collapse
|
28
|
Cohen JF, Deeks JJ, Hooft L, Salameh JP, Korevaar DA, Gatsonis C, Hopewell S, Hunt HA, Hyde CJ, Leeflang MM, Macaskill P, McGrath TA, Moher D, Reitsma JB, Rutjes AWS, Takwoingi Y, Tonelli M, Whiting P, Willis BH, Thombs B, Bossuyt PM, McInnes MDF. Preferred reporting items for journal and conference abstracts of systematic reviews and meta-analyses of diagnostic test accuracy studies (PRISMA-DTA for Abstracts): checklist, explanation, and elaboration. BMJ 2021; 372:n265. [PMID: 33722791 PMCID: PMC7957862 DOI: 10.1136/bmj.n265] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
For many users of the biomedical literature, abstracts may be the only source of information about a study. Hence, abstracts should allow readers to evaluate the objectives, key design features, and main results of the study. Several evaluations have shown deficiencies in the reporting of journal and conference abstracts across study designs and research fields, including systematic reviews of diagnostic test accuracy studies. Incomplete reporting compromises the value of research to key stakeholders. The authors of this article have developed a 12 item checklist of preferred reporting items for journal and conference abstracts of systematic reviews and meta-analyses of diagnostic test accuracy studies (PRISMA-DTA for Abstracts). This article presents the checklist, examples of complete reporting, and explanations for each item of PRISMA-DTA for Abstracts.
Collapse
Affiliation(s)
- Jérémie F Cohen
- Department of Pediatrics and Inserm UMR 1153 (Centre of Research in Epidemiology and Statistics), Necker - Enfants Malades Hospital, Assistance Publique - Hôpitaux de Paris, Université de Paris, Paris, France
| | - Jonathan J Deeks
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK
| | - Lotty Hooft
- Cochrane Netherlands, Julius Center for Health Sciences and Primary Care, Utrecht University, University Medical Center Utrecht, Utrecht, Netherlands
| | - Jean-Paul Salameh
- The Ottawa Hospital Research Institute Clinical Epidemiology Program, Ottawa, ON, Canada
- Faculty of Medicine, Queen's University, Kingston, ON, Canada
| | - Daniël A Korevaar
- Department of Respiratory Medicine, Academic Medical Centers, Amsterdam, Netherlands
| | | | - Sally Hopewell
- Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Harriet A Hunt
- Exeter Test Group, College of Medicine and Health, University of Exeter, Exeter, UK
| | - Chris J Hyde
- Exeter Test Group, College of Medicine and Health, University of Exeter, Exeter, UK
| | - Mariska M Leeflang
- Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam Public Health, Academic Medical Centers, Amsterdam, Netherlands
| | | | - Trevor A McGrath
- Department of Radiology, University of Ottawa, Ottawa, ON, Canada
| | - David Moher
- Centre for Journalology, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Johannes B Reitsma
- Cochrane Netherlands, Julius Center for Health Sciences and Primary Care, Utrecht University, University Medical Center Utrecht, Utrecht, Netherlands
| | - Anne W S Rutjes
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
| | - Yemisi Takwoingi
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK
| | - Marcello Tonelli
- Department of Medicine, University of Calgary, Calgary, AB, Canada
| | - Penny Whiting
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Brian H Willis
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Brett Thombs
- Lady Davis Institute of the Jewish General Hospital and Department of Psychiatry, McGill University, Montréal, QC, Canada
| | - Patrick M Bossuyt
- Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam Public Health, Academic Medical Centers, Amsterdam, Netherlands
| | - Matthew D F McInnes
- University of Ottawa, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada
| |
Collapse
|
29
|
Carrasco T, Barquín D, Ndarabu A, Fernández-Alonso M, Rubio-Garrido M, Carlos S, Makonda B, Holguín Á, Reina G. HCV Diagnosis and Sequencing Using Dried Blood Spots from Patients in Kinshasa (DRC): A Tool to Achieve WHO 2030 Targets. Diagnostics (Basel) 2021; 11:522. [PMID: 33804260 PMCID: PMC8002119 DOI: 10.3390/diagnostics11030522] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 03/09/2021] [Accepted: 03/11/2021] [Indexed: 12/11/2022] Open
Abstract
The World Health Organization has established an elimination plan for hepatitis C virus (HCV) by 2030. In Sub-Saharan Africa (SSA) access to diagnostic tools is limited, and a number of genotype 4 subtypes have been shown to be resistant to some direct-acting antivirals (DAAs). This study aims to analyze diagnostic assays for HCV based on dried blood spots (DBS) specimens collected in Kinshasa and to characterize genetic diversity of the virus within a group of mainly HIV positive patients. HCV antibody detection was performed on 107 DBS samples with Vidas® anti-HCV and Elecsys anti-HCV II, and on 31 samples with INNO-LIA HCV. Twenty-six samples were subjected to molecular detection. NS3, NS5A, and NS5B regions from 11 HCV viremic patients were sequenced. HCV seroprevalence was 12.2% (72% with detectable HCV RNA). Both Elecsys Anti-HCV and INNO-LIA HCV were highly sensitive and specific, whereas Vidas® anti-HCV lacked full sensitivity and specificity when DBS sample was used. NS5B/NS5A/NS3 sequencing revealed exclusively GT4 isolates (50% subtype 4r, 30% 4c and 20% 4k). All 4r strains harbored NS5A resistance-associated substitutions (RAS) at positions 28, 30, and 31, but no NS3 RAS was detected. Elecsys Anti-HCV and INNO-LIA HCV are reliable methods to detect HCV antibodies using DBS. HCV subtype 4r was the most prevalent among our patients. RASs found in subtype 4r in NS5A region confer unknown susceptibility to DAA.
Collapse
Affiliation(s)
- Teresa Carrasco
- Microbiology Department, Clínica Universidad de Navarra, 31008 Pamplona, Spain; (T.C.); (D.B.); (M.F.-A.)
| | - David Barquín
- Microbiology Department, Clínica Universidad de Navarra, 31008 Pamplona, Spain; (T.C.); (D.B.); (M.F.-A.)
| | - Adolphe Ndarabu
- Department of Internal Medicine, Centre Hospitalier Monkole, 4484 Kinshasa, Democratic Republic of the Congo; (A.N.); (B.M.)
| | - Mirian Fernández-Alonso
- Microbiology Department, Clínica Universidad de Navarra, 31008 Pamplona, Spain; (T.C.); (D.B.); (M.F.-A.)
- ISTUN, Institute of Tropical Health, Universidad de Navarra, 31008 Pamplona, Spain;
- IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain
| | - Marina Rubio-Garrido
- HIV-1 Molecular Epidemiology Laboratory, Microbiology and Parasitology Department and Instituto Ramón y Cajal para la Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, CIBER en Epidemiología y Salud Pública (CIBERESP), Red en Investigación Translacional en Infecciones Pediátricas (RITIP), 28034 Madrid, Spain; (M.R.-G.); (Á.H.)
| | - Silvia Carlos
- ISTUN, Institute of Tropical Health, Universidad de Navarra, 31008 Pamplona, Spain;
- IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain
- Department Preventive Medicine and Public Health, Universidad de Navarra, 31008 Pamplona, Spain
| | - Benit Makonda
- Department of Internal Medicine, Centre Hospitalier Monkole, 4484 Kinshasa, Democratic Republic of the Congo; (A.N.); (B.M.)
| | - África Holguín
- HIV-1 Molecular Epidemiology Laboratory, Microbiology and Parasitology Department and Instituto Ramón y Cajal para la Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, CIBER en Epidemiología y Salud Pública (CIBERESP), Red en Investigación Translacional en Infecciones Pediátricas (RITIP), 28034 Madrid, Spain; (M.R.-G.); (Á.H.)
| | - Gabriel Reina
- Microbiology Department, Clínica Universidad de Navarra, 31008 Pamplona, Spain; (T.C.); (D.B.); (M.F.-A.)
- ISTUN, Institute of Tropical Health, Universidad de Navarra, 31008 Pamplona, Spain;
- IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain
| |
Collapse
|
30
|
Velásquez-Orozco F, Rando-Segura A, Martínez-Camprecios J, Salmeron P, Najarro-Centeno A, Esteban À, Quer J, Buti M, Pumarola-Suñe T, Rodríguez-Frías F. Utility of the Cobas ® Plasma Separation Card as a Sample Collection Device for Serological and Virological Diagnosis of Hepatitis C Virus Infection. Diagnostics (Basel) 2021; 11:diagnostics11030473. [PMID: 33800211 PMCID: PMC7998864 DOI: 10.3390/diagnostics11030473] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 03/01/2021] [Accepted: 03/04/2021] [Indexed: 02/07/2023] Open
Abstract
Diagnosis and clinical management of people infected with hepatitis C virus (HCV) relies on results from a combination of serological and virological tests. The aim of this study was to compare the performance of dried plasma spots (DPS), prepared using the cobas® Plasma Separation Card (PSC), to plasma and serum from venipuncture, for HCV diagnosis. We carried out a prospective study using DPS and paired plasma or serum samples. Serum and DPS samples were analyzed by immunoassay using Elecsys® Anti-HCV II (Roche). Plasma and DPS samples were analyzed using the cobas® HCV viral load and cobas® HCV genotyping tests (Roche). All DPS samples that had high anti-HCV antibody titers in serum were also antibody-positive, as were five of eight samples with moderate titers. Eight samples with low titers in serum were negative with DPS. Among 80 samples with plasma HCV viral loads between 61.5 and 2.2 × 108 IU/mL, 74 were RNA-positive in DPS. The mean viral load difference between plasma and DPS was 2.65 log10 IU/mL. The performance of DPS for detection of serological and virological markers of hepatitis C virus infection was comparable to that of the conventional specimen types. However, the limits of detection were higher for DPS.
Collapse
Affiliation(s)
- Fernando Velásquez-Orozco
- Department of Microbiology, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain; (F.V.-O.); (P.S.); (T.P.-S.)
- Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain;
| | - Ariadna Rando-Segura
- Department of Microbiology, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain; (F.V.-O.); (P.S.); (T.P.-S.)
- Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain;
- Liver Pathology Unit, Department of Microbiology and Biochemistry, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain; (A.N.-C.); (À.E.)
- Correspondence:
| | - Joan Martínez-Camprecios
- Department of Internal Medicine, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain; (J.M.-C.); (M.B.)
| | - Paula Salmeron
- Department of Microbiology, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain; (F.V.-O.); (P.S.); (T.P.-S.)
- Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain;
| | - Adrián Najarro-Centeno
- Liver Pathology Unit, Department of Microbiology and Biochemistry, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain; (A.N.-C.); (À.E.)
- Liver Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hberon Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain;
- Department of Biochemistry, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
| | - Àngels Esteban
- Liver Pathology Unit, Department of Microbiology and Biochemistry, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain; (A.N.-C.); (À.E.)
- Liver Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hberon Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain;
- Department of Biochemistry, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
| | - Josep Quer
- Liver Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hberon Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain;
| | - María Buti
- Department of Internal Medicine, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain; (J.M.-C.); (M.B.)
- Liver Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hberon Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain;
- CIBER de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Avenida de Monforte de Lemos 3-5, 28029 Madrid, Spain
| | - Tomás Pumarola-Suñe
- Department of Microbiology, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain; (F.V.-O.); (P.S.); (T.P.-S.)
- Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain;
| | - Francisco Rodríguez-Frías
- Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain;
- Liver Pathology Unit, Department of Microbiology and Biochemistry, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain; (A.N.-C.); (À.E.)
- Liver Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hberon Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain;
- Department of Biochemistry, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
- CIBER de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Avenida de Monforte de Lemos 3-5, 28029 Madrid, Spain
| |
Collapse
|
31
|
Prospective evaluation of hepatitis C virus antibody detection in whole blood collected on dried blood spots with the INNOTEST® HCV Ab IV enzyme immunoassay. J Clin Virol 2021; 137:104783. [PMID: 33711695 DOI: 10.1016/j.jcv.2021.104783] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 02/25/2021] [Accepted: 02/28/2021] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Dried blood spots (DBS) have potential to improve access to screening for antibodies to hepatitis C virus (HCV). However, although several studies on off-label use of DBS have been performed, to date no HCV antibody serology test is formally approved for use with DBS. This study evaluated the performance of the INNOTEST® HCV Ab IV enzyme immunoassay in paired DBS and plasma samples, to determine whether DBS may be added to the intended use. METHODS Adults with no history of HCV treatment were prospectively enrolled from two sites in Ukraine. DBS were prepared from fingerstick whole blood (fDBS) and venous whole blood (vDBS) samples. Undiluted and serially diluted DBS and plasma samples were tested. RESULTS Samples from 149 HCV positive and 151 HCV negative participants were included. Sensitivity and specificity of the INNOTEST® HCV Ab IV assay were both 100 % (95 % confidence intervals 95.7-100) for samples collected on fDBS or vDBS compared with plasma as the reference standard. In all undiluted samples, negative and positive percentage agreement and overall rate of agreement were 100 % between all sample types (Cohen's kappa coefficient of 1). In serially diluted samples, agreement was high (>95 %) between fDBS and vDBS, and as expected, positive percentage agreement between both DBS sample types and plasma was lower (>66 %). CONCLUSIONS Performance of the INNOTEST® HCV Ab IV assay in DBS was acceptable, thus whole blood collected on DBS may represent an alternative sample type for this assay in settings where venous blood collection is not possible.
Collapse
|
32
|
Moat SJ, Zelek WM, Carne E, Ponsford MJ, Bramhall K, Jones S, El-Shanawany T, Wise MP, Thomas A, George C, Fegan C, Steven R, Webb R, Weeks I, Morgan BP, Jolles S. Development of a high-throughput SARS-CoV-2 antibody testing pathway using dried blood spot specimens. Ann Clin Biochem 2021; 58:123-131. [PMID: 33269949 PMCID: PMC7844389 DOI: 10.1177/0004563220981106] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/24/2020] [Indexed: 01/17/2023]
Abstract
BACKGROUND Serological assays for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) have roles in seroepidemiology, convalescent plasma-testing, antibody durability and vaccine studies. Currently, SARS-CoV-2 serology is performed using serum/plasma collected by venepuncture. Dried blood spot (DBS) testing offers significant advantages as it is minimally invasive, avoids venepuncture with specimens being mailed to the laboratory. METHODS A pathway utilizing a newborn screening laboratory infrastructure was developed using an enzyme-linked immunosorbent assay to detect IgG antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein in DBS specimens. Paired plasma and DBS specimens from SARS-CoV-2 antibody-positive and -negative subjects and polymerase chain reaction positive subjects were tested. DBS specimen stability, effect of blood volume and punch location were also evaluated. RESULTS DBS specimens from antibody-negative (n = 85) and -positive (n = 35) subjects and polymerase chain reaction positive subjects (n = 11) had a mean (SD; range) optical density (OD) of 0.14 (0.046; 0.03-0.27), 0.98 (0.41; 0.31-1.64) and 1.12 (0.37; 0.49-1.54), respectively. An action value OD >0.28 correctly assigned all cases. The weighted Deming regression for comparison of the DBS and the plasma assay yielded: y = 0.004041 + 1.005x, r = 0.991, Sy/x 0.171, n = 82. Extraction efficiency of antibodies from DBS specimens was >99%. DBS specimens were stable for at least 28 days at ambient room temperature and humidity. CONCLUSIONS SARS-CoV-2 IgG receptor-binding domain antibodies can be reliably detected in DBS specimens. DBS serological testing offers lower costs than either point of care or serum/plasma assays that require patient travel, phlebotomy and hospital/clinic resources; the development of a DBS assay may be particularly important for resource poor settings.
Collapse
Affiliation(s)
- Stuart J Moat
- Wales Newborn Screening Laboratory, Department of Medical Biochemistry, Immunology and Toxicology, University Hospital of Wales, Cardiff, Wales, UK
- School of Medicine, Cardiff University, Cardiff, Wales, UK
| | - Wioleta M Zelek
- Systems Immunity University Research Institute and Dementia Research Institute, Cardiff University, Cardiff, UK
| | - Emily Carne
- Immunodeficiency Centre for Wales, University Hospital of Wales, Cardiff, UK
| | - Mark J Ponsford
- Immunodeficiency Centre for Wales, University Hospital of Wales, Cardiff, UK
- Division of Infection, Inflammation and Immunity, School of Medicine, Cardiff University, Cardiff, UK
| | - Kathryn Bramhall
- Immunodeficiency Centre for Wales, University Hospital of Wales, Cardiff, UK
| | - Sara Jones
- Weqas, Cardiff and Vale University Health Board, Cardiff, UK
| | - Tariq El-Shanawany
- Immunodeficiency Centre for Wales, University Hospital of Wales, Cardiff, UK
| | - Matt P Wise
- Adult Critical Care, University Hospital of Wales, Cardiff, UK
| | - Annette Thomas
- Weqas, Cardiff and Vale University Health Board, Cardiff, UK
| | - Chloe George
- Welsh Blood Service, Ely Valley Road, Talbot Green, Pontyclun, UK
| | - Christopher Fegan
- Department of Haematology, University Hospital of Wales, Cardiff, Wales, UK
| | - Rachael Steven
- Immunodeficiency Centre for Wales, University Hospital of Wales, Cardiff, UK
| | - Russell Webb
- Immunodeficiency Centre for Wales, University Hospital of Wales, Cardiff, UK
| | - Ian Weeks
- College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK
| | - B Paul Morgan
- Systems Immunity University Research Institute and Dementia Research Institute, Cardiff University, Cardiff, UK
| | - Stephen Jolles
- Immunodeficiency Centre for Wales, University Hospital of Wales, Cardiff, UK
| |
Collapse
|
33
|
Martínez-Campreciós J, Rando-Segura A, Buti M, Rodrigo-Velásquez F, Riveiro-Barciela M, Barreira-Díaz A, Álvarez-López P, Salmerón P, Palom A, Tabernero D, Palomo N, Nindia A, Barbosa G, López E, Ferreira V, Saiago N, Kuchta A, Ferrer-Costa R, Esteban R, Molina I, Rodríguez-Frías F. Reflex viral load testing in dried blood spots generated by plasma separation card allows the screening and diagnosis of chronic viral hepatitis. J Virol Methods 2021; 289:114039. [PMID: 33338545 DOI: 10.1016/j.jviromet.2020.114039] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 12/03/2020] [Accepted: 12/06/2020] [Indexed: 02/07/2023]
Abstract
Dried blood spots (DBS) have been proposed as an alternative diagnostic technique for chronic viral hepatitis. The aim of this observational study was to correlate serologic HBV, HCV, and HDV status and reflex the respective viral load testing by PSC-DBS samples from capillary blood vs conventional plasma samples in patients with chronic viral hepatitis. Besides, we apply these tests in a prospective study for chronic viral hepatitis diagnosis in a rural region of sub-Saharan Africa. In total, 124 HBsAg-positive patients, 75 anti-HCV positive, 2 with HBV-HCV coinfection, and 13 anti-HDV positive were included. PSC-DBS sensitivity/specificity was 98.4 %/96.2 % for HBsAg detection, 98.7 %/100 % for anti-HCV, and 84.6 %/100 % for anti-HDV. HCV-RNA was quantified in all viremic patients using DBS. Only 42 of 78 (53.8 %) samples with HBV-DNA viremia were quantifiable by DBS. Sensitivity increased to 95.7 % in patients with HBV-DNA levels >2000 IU/mL. There was a high correlation between DBS and venous blood. The prevalence of HBsAg among the 93 individuals tested in Angola was 11 %, and 60 % of cases had detectable HBV-DNA viremia. As a conclusion, PSC-DBS is useful for chronic viral hepatitis screening and reflex molecular diagnosis showing globally high sensitivities and correlation with conventional blood samples.
Collapse
Affiliation(s)
- Joan Martínez-Campreciós
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 080335 Barcelona, Spain; Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain
| | - Ariadna Rando-Segura
- Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 080335 Barcelona, Spain; Department of Microbiology, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain
| | - María Buti
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 080335 Barcelona, Spain; CIBERehd, Instituto Carlos II, Spain.
| | - Fernando Rodrigo-Velásquez
- Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 080335 Barcelona, Spain; Department of Microbiology, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain
| | - Mar Riveiro-Barciela
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 080335 Barcelona, Spain; CIBERehd, Instituto Carlos II, Spain
| | - Ana Barreira-Díaz
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 080335 Barcelona, Spain
| | - Patricia Álvarez-López
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 080335 Barcelona, Spain
| | - Paula Salmerón
- Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 080335 Barcelona, Spain; Department of Microbiology, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain
| | - Adriana Palom
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 080335 Barcelona, Spain
| | - David Tabernero
- CIBERehd, Instituto Carlos II, Spain; Liver Pathology Unit, Biochemistry and Microbiology Departments, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - Nieves Palomo
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 080335 Barcelona, Spain
| | | | | | - Eva López
- Hospital Nossa Senhora da Paz, Cubal, Angola
| | - Vicelma Ferreira
- Hospital General de Benguela, Universidade Katyavla Bwila, Benguela, Angola
| | - Nelsa Saiago
- Hospital General de Benguela, Universidade Katyavla Bwila, Benguela, Angola
| | | | - Roser Ferrer-Costa
- Biochemistry Department, Clinical Laboratories Hospital Universitari Vall d'Hebron, Spain
| | - Rafael Esteban
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 080335 Barcelona, Spain; CIBERehd, Instituto Carlos II, Spain
| | - Israel Molina
- Infectious Diseases Department, Hospital Universitari Vall d'Hebron, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Francisco Rodríguez-Frías
- CIBERehd, Instituto Carlos II, Spain; Biochemistry Department, Clinical Laboratories Hospital Universitari Vall d'Hebron, Spain; Liver Pathology Unit, Biochemistry and Microbiology Departments, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| |
Collapse
|
34
|
Prabdial‐Sing N, Gaelejwe L, Makhathini L, Thaver J, Manamela MJ, Malfeld S, Spearman CW, Sonderup M, Scheibe A, Young K, Hausler H, Puren AJ. The performance of hepatitis C virus (HCV) antibody point-of-care tests on oral fluid or whole blood and dried blood spot testing for HCV serology and viral load among individuals at higher risk for HCV in South Africa. Health Sci Rep 2021; 4:e229. [PMID: 33614978 PMCID: PMC7876859 DOI: 10.1002/hsr2.229] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 11/10/2020] [Accepted: 12/04/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND AND AIMS To enhance screening and diagnosis in those at-risk of hepatitis C virus (HCV), efficient and improved sampling and testing is required. We investigated the performance of point-of-care (POC) tests and dried blood spots (DBS) for HCV antibody and HCV RNA quantification in individuals at higher risk for HCV (people who use and inject drugs, sex workers and men who have sex with men) in seven South African cities. METHODS Samples were screened on the OraQuick HCV POC test (471 whole blood and 218 oral fluid); 218 whole blood and DBS paired samples were evaluated on the ARCHITECT HCV antibody (Abbott) and HCV viral load (COBAS Ampliprep/COBAS TaqMan version 2) assays. For HCV RNA quantification, 107 dB were analyzed with and without normalization coefficients. RESULTS POC on either whole blood or oral fluid showed an overall sensitivity of 98.5% (95% CI 97.4-99.5), specificity of 98.2% (95% CI 98.8-100) and accuracy of 98.4% (95% CI 96.5-99.3). On the antibody immunoassay, DBS showed a sensitivity of 96.0% (95% CI 93.4-98.6), specificity of 97% (95% CI 94.8-99.3) and accuracy of 96.3% (95% CI 93.8-98.8). A strong correlation (R 2 = 0.90) between viral load measurements for DBS and plasma samples was observed. After normalization, DBS viral load results showed an improved bias from 0.5 to 0.16 log10 IU/mL. CONCLUSION The POC test performed sufficiently well to be used for HCV screening in at-risk populations. DBS for diagnosis and quantification was accurate and should be considered as an alternative sample to test. POC and DBS can help scale up hepatitis services in the country, in light of our elimination goals.
Collapse
Affiliation(s)
- Nishi Prabdial‐Sing
- Centre for Vaccines and ImmunologyNational Institute for Communicable DiseasesJohannesburgSouth Africa
- Faculty of Health SciencesUniversity of WitwatersrandJohannesburgSouth Africa
| | - Lucinda Gaelejwe
- Centre for Vaccines and ImmunologyNational Institute for Communicable DiseasesJohannesburgSouth Africa
- Faculty of Health SciencesUniversity of WitwatersrandJohannesburgSouth Africa
| | - Lillian Makhathini
- Centre for Vaccines and ImmunologyNational Institute for Communicable DiseasesJohannesburgSouth Africa
| | - Jayendrie Thaver
- Centre for Vaccines and ImmunologyNational Institute for Communicable DiseasesJohannesburgSouth Africa
| | - Morubula Jack Manamela
- Centre for Vaccines and ImmunologyNational Institute for Communicable DiseasesJohannesburgSouth Africa
| | - Susan Malfeld
- Centre for Vaccines and ImmunologyNational Institute for Communicable DiseasesJohannesburgSouth Africa
| | - C. Wendy Spearman
- Division of Hepatology, Department of Medicine, Faculty of Health SciencesUniversity of Cape TownCape TownSouth Africa
| | - Mark Sonderup
- Division of Hepatology, Department of Medicine, Faculty of Health SciencesUniversity of Cape TownCape TownSouth Africa
| | - Andrew Scheibe
- TB HIV CareCape TownSouth Africa
- Department of Family MedicineUniversity of PretoriaPretoriaSouth Africa
| | | | | | - Adrian J. Puren
- Centre for Vaccines and ImmunologyNational Institute for Communicable DiseasesJohannesburgSouth Africa
- Faculty of Health SciencesUniversity of WitwatersrandJohannesburgSouth Africa
| |
Collapse
|
35
|
Kim JU, Ingiliz P, Shimakawa Y, Lemoine M. Improving care of migrants is key for viral hepatitis elimination in Europe. Bull World Health Organ 2021; 99:280-286. [PMID: 33953445 PMCID: PMC8085634 DOI: 10.2471/blt.20.260919] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 10/03/2020] [Accepted: 10/07/2020] [Indexed: 02/08/2023] Open
Abstract
By 2040, deaths from chronic viral hepatitis worldwide are projected to exceed those from human immunodeficiency virus infection, tuberculosis and malaria combined. The burden of this disease is predominantly carried by low-resource countries in Africa and Asia. In resource-rich countries, the epidemiological spread of viral hepatitis is partially driven by migrant movements from areas of high endemicity. In the last decade, Member States of the European Union and the European Economic Area have experienced an unprecedented influx of migrants, which has resulted in the polarization of political views about migration. In addition, the coronavirus disease 2019 pandemic has worsened the economic and health conditions of migrants and contributed to hostility to ensuring their health rights. Moreover, the implementation of hostile laws in some host nations has increased the vulnerability of marginalized migrant subgroups, such as asylum seekers and undocumented individuals. These developments have complicated the historical challenge of identifying high-risk migrant groups for screening and treatment. However, if European countries can apply the simplified assessment tools and diagnostic tests for viral hepatitis that have been used for decentralized screening and monitoring in resource-poor countries, the uptake of care by migrants could be dramatically increased. Given the global calls for the elimination of viral hepatitis, European nations should recognize the importance of treating this vulnerable migrant population. Political and health strategies need to be adapted to meet this challenge and help eliminate viral hepatitis globally.
Collapse
Affiliation(s)
- Jin Un Kim
- Hepatology Section, Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, 10th Floor QEQM Wing, St Mary's Hospital Campus, Imperial College London, South Wharf Street, London W2 1NY, England
| | - Patrick Ingiliz
- Department of Gastroenterology and Hepatology, Charité University Medical Center, Berlin, Germany
| | - Yusuke Shimakawa
- Unité d'Épidémiologie des Maladies Émergentes, Institut Pasteur, Paris, France
| | - Maud Lemoine
- Hepatology Section, Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, 10th Floor QEQM Wing, St Mary's Hospital Campus, Imperial College London, South Wharf Street, London W2 1NY, England
| |
Collapse
|
36
|
Nasir S, Majeed MI, Nawaz H, Rashid N, Ali S, Farooq S, Kashif M, Rafiq S, Bano S, Ashraf MN, Abubakar M, Ahmad S, Rehman A, Amin I. Surface enhanced Raman spectroscopy of RNA samples extracted from blood of hepatitis C patients for quantification of viral loads. Photodiagnosis Photodyn Ther 2020; 33:102152. [PMID: 33348077 DOI: 10.1016/j.pdpdt.2020.102152] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 11/23/2020] [Accepted: 12/14/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND Raman spectroscopy is a promising technique to analyze the body fluids for the purpose of non-invasive disease diagnosis. OBJECTIVES To develop a surface-enhanced Raman spectroscopy (SERS) based method for qualitative and quantitative analysis of HCV from blood samples. METHODS SERS was employed to characterize the Hepatitis C viral RNA extracted from different blood samples of hepatitis C virus (HCV) infected patients with predetermined viral loads in comparison with total RNA of healthy individuals. The SERS measurements were performed on 27 extracted RNA samples including low viral loads, medium viral loads, high viral loads and healthy/negative viral load samples. For this purpose, silver nanoparticles (Ag NPs) were used as SERS substrates. Furthermore, multivariate data analysis technique, Principal Component Analysis (PCA) and Partial Least Square Regression (PLSR) were also performed on SERS spectral data. RESULTS The SERS spectral features due to biochemical changes in the extracted RNA samples associated with the increasing viral loads were established which could be employed for HCV diagnostic purpose. PCA was found helpful for the differentiation between Raman spectral data of RNA extracted from hepatitis infected and healthy blood samples. PLSR model is established for the determination of viral loads in HCV positive RNA samples with 99 % accuracy. CONCLUSION SERS can be employed for qualitative and quantitative analysis of HCV from blood samples.
Collapse
Affiliation(s)
- Saira Nasir
- Department of Chemistry, University of Agriculture Faisalabad, 38040, Pakistan
| | | | - Haq Nawaz
- Department of Chemistry, University of Agriculture Faisalabad, 38040, Pakistan.
| | - Nosheen Rashid
- Department of Chemistry, University of Central Punjab, Lahore, Faisalabad Campus, Pakistan
| | - Saqib Ali
- Department of Chemistry, University of Agriculture Faisalabad, 38040, Pakistan
| | - Sidra Farooq
- Department of Chemistry, University of Agriculture Faisalabad, 38040, Pakistan
| | - Muhammad Kashif
- Department of Chemistry, University of Agriculture Faisalabad, 38040, Pakistan
| | - Sidra Rafiq
- Department of Chemistry, University of Agriculture Faisalabad, 38040, Pakistan
| | - Saira Bano
- Department of Chemistry, University of Agriculture Faisalabad, 38040, Pakistan
| | | | - Muhammad Abubakar
- Department of Chemistry, University of Agriculture Faisalabad, 38040, Pakistan
| | - Shamsheer Ahmad
- Department of Chemistry, University of Agriculture Faisalabad, 38040, Pakistan
| | - Asma Rehman
- National Institute for Biotechnology and Genetic Engineering (NIBGE), P. O. Box 577, Jhang Road Faisalabad, Pakistan
| | - Imran Amin
- PCR Laboratory, PINUM Hospital, Faisalabad, Pakistan
| |
Collapse
|
37
|
Carty PG, McCarthy M, O'Neill S, Harrington P, O'Neill M, Teljeur C, Smith SM, Ryan M. Laboratory-based dried blood spot testing for hepatitis C: A protocol for systematic review and meta-analysis of diagnostic accuracy. HRB Open Res 2020; 3:78. [PMID: 34957372 PMCID: PMC8666990 DOI: 10.12688/hrbopenres.13166.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/20/2020] [Indexed: 12/29/2022] Open
Abstract
Background: Diagnosis of chronic hepatitis C virus (HCV) infection typically involves collection of venous blood samples prior to serological investigation of an antibody response followed by a confirmatory viral load or antigen test to verify active HCV infection. This conventional pathway poses logistical challenges for the implementation of reflex testing, whereby the confirmatory test is performed on the same sample used for serological investigation. Dried blood spot (DBS) testing, in which capillary blood is deposited on filter paper, is a less invasive alternative that can enable reflex testing without the need for venepuncture, centrifugation and freezing of samples. Methods: This systematic review aims to assess the diagnostic accuracy of DBS compared with venous blood samples for diagnosis of chronic HCV infection. Observational studies which compare diagnostic tests using DBS with those using serum, plasma or whole blood in patients with chronic or resolved HCV infection will be included. Electronic searches will be conducted in PubMed, Embase, Scopus, Web of Science, Lilacs and the Cochrane library. Citation screening, data extraction and quality appraisal of included studies will be performed in duplicate using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. A meta-analysis will be conducted to derive pooled estimates of sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, and diagnostic odds ratios. Sensitivity analyses and meta-regression will also be performed. Quality of the evidence will be evaluated using the GRADE criteria. Discussion: Identifying and linking people with currently undiagnosed chronic HCV infection to care is pivotal to attaining global viral hepatitis elimination targets. The use of DBS could simplify diagnostic testing strategies by integrating reflex testing into the care pathway and reducing drop-off along the cascade of care. Registration: PROSPERO, CRD42020205204. Registered 19 th September 2020.
Collapse
Affiliation(s)
- Paul G Carty
- Health Information and Quality Authority, Dublin, D07 E98Y, Ireland
| | - Michael McCarthy
- Health Information and Quality Authority, Dublin, D07 E98Y, Ireland
| | - Sinead O'Neill
- Health Information and Quality Authority, Dublin, D07 E98Y, Ireland
| | | | - Michelle O'Neill
- Health Information and Quality Authority, Dublin, D07 E98Y, Ireland
| | - Conor Teljeur
- Health Information and Quality Authority, Dublin, D07 E98Y, Ireland
| | - Susan M Smith
- Department of General Practice, Royal College of Surgeons in Ireland, Dublin, D02 YN77, Ireland
| | - Máirín Ryan
- Health Information and Quality Authority, Dublin, D07 E98Y, Ireland
- Department of Pharmacology & Therapeutics, Trinity College Dublin, Dublin, D02 PN40, Ireland
| |
Collapse
|
38
|
Evaluation of dried blood spot testing using the Abbott Alinity i. J Clin Virol 2020; 132:104638. [PMID: 33049642 DOI: 10.1016/j.jcv.2020.104638] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 09/03/2020] [Accepted: 09/06/2020] [Indexed: 11/23/2022]
Abstract
BACKGROUND The West of Scotland Specialist Virology Centre currently uses the Abbott Architect for DBS serology. The new Abbott Alinity i will replace the Architect in our laboratory. In this study, mock and stored patient DBS samples were tested on both platforms and results compared. STUDY DESIGN Mock DBS were made from whole blood where patient results were known (38 negative samples and 141 positive samples; 39 HIV Antigen/Antibody (Ag/Ab), 35 HCV IgG antibody (HCVG), 34 HBV core IgG (HBCG) and 33 HBsAg). Mock DBS were tested on both Abbott platforms. Stored patient DBS samples (132 negative and 263 positive: 9 HIVAg/Ab, 10 HBsAg, 52 HBCG and 60 HCVG) previously tested on the Architect were retested on the Alinity i. RESULTS Mock DBS showed good correlation between the Architect and Alinity i for the HIV Ag/Ab,HBCG and HCVG assays. A poorer correlation occurred with HBsAg, the Alinity i reported HBsAg positives at a lower value compared to the Architect. The coefficient of variation for intra-assay variation was 1.69 % (HIVAg/Ab), 3.25 % (HCVG), 1.68 % (HBsAg) and 1.95 % (HBCG). The sensitivity and specificity was determined based on results from the mock and patient samples. At S/Co cut-off 1.0 both HIV and HBsAg had a sensitivity of 100 %. A cut-off 0.8 gave a sensitivity of 95.83 % (95 % CI 89.67%-98.85%) for HCVG and 0.3 gave a sensitivity of 98.8 % (CI 93.69%-99.97%) for HBCG. DISCUSSION The alinity i compared well against the architect and can be used to test DBS samples.
Collapse
|
39
|
Doornekamp L, Embregts CWE, Aron GI, Goeijenbier S, van de Vijver DAMC, van Gorp ECM, GeurtsvanKessel CH. Dried blood spot cards: A reliable sampling method to detect human antibodies against rabies virus. PLoS Negl Trop Dis 2020; 14:e0008784. [PMID: 33048925 PMCID: PMC7584180 DOI: 10.1371/journal.pntd.0008784] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 10/23/2020] [Accepted: 09/08/2020] [Indexed: 01/21/2023] Open
Abstract
Background Although preventable by vaccination for more than a century, rabies virus still causes numerous fatalities every year. To determine antibody levels in humans, blood collected with a finger prick and applied on dried blood spot (DBS) cards is an alternative for venipuncture. The use of DBS is specifically valuable in remote areas, as it is easy to perform, store and transport. Therefore, the technique is frequently used for epidemiological studies of tropical diseases. Up to present, determination of rabies virus antibody levels on human DBS has not been validated. Methodology/Principal findings We evaluated the use of human DBS for rabies serology and analyzed 99 pre- or post-vaccination serum and DBS samples with a fluorescent antibody virus neutralization test (FAVNt), which is the gold standard to detect protective antibody levels, and a Bio-Rad Platelia Rabies II ELISA. Sensitivity and specificity of DBS eluates tested with the FAVNt were 97% and 92%, respectively and 87% and 96% when tested with the Platelia-II ELISA. Antibody levels measured in serum with the FAVNt, correlated best with antibody levels measured in DBS with the FAVNt (R = 0.88). Conclusions/Significance This is the first study that applies DBS for reliable detection of human antibodies against rabies virus. Both the FAVNt and Platelia-II ELISA demonstrate an acceptable performance on DBS, providing opportunities for rabies serology in remote areas. This technique could drastically ease studies evaluating (novel) rabies vaccination strategies and monitoring persisting immunity in humans at risk, living in rabies endemic regions. Rabies is a nearly 100% fatal disease in humans. However, available vaccines are effective in preventing rabies infection. To investigate if a person is protected against rabies, rabies virus neutralizing antibody levels in the blood are determined. The World Health Organization defines protective immunity as a rabies virus antibody concentration of at least 0.5 IU/ml detected in serum using a virus neutralization test. Yet, in remote areas serum may be rather difficult to collect, process and transport. Whole blood collected with a finger prick and applied on filter paper cards, also known as dried blood spots (DBS), are an easier alternative. This collection method is frequently used for serology of several tropical infectious diseases, but never studied for rabies serology in humans. Therefore, we compared antibody levels measured in serum with those measured in DBS eluates, using the gold standard FAVNt and related it to another commonly used test for human rabies serology, the Platelia-II ELISA. We found that both assays had a good performance on DBS eluates. The reported high specificities provide confidence that unprotected individuals will rarely be missed. Therefore, the DBS is a promising sampling technique for evaluations of vaccination strategies and monitoring persisting immunity after vaccination in populations at risk for rabies.
Collapse
Affiliation(s)
- Laura Doornekamp
- Department of Viroscience, Erasmus MC, University Medical Center Rotterdam, WHO Collaborating Centre–Emerging Viral Infections, Rotterdam, the Netherlands
- Travel Clinic, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Carmen W. E. Embregts
- Department of Viroscience, Erasmus MC, University Medical Center Rotterdam, WHO Collaborating Centre–Emerging Viral Infections, Rotterdam, the Netherlands
| | - Georgina I. Aron
- Department of Viroscience, Erasmus MC, University Medical Center Rotterdam, WHO Collaborating Centre–Emerging Viral Infections, Rotterdam, the Netherlands
| | - Simone Goeijenbier
- Department of Viroscience, Erasmus MC, University Medical Center Rotterdam, WHO Collaborating Centre–Emerging Viral Infections, Rotterdam, the Netherlands
- Travel Clinic, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - David A. M. C. van de Vijver
- Department of Viroscience, Erasmus MC, University Medical Center Rotterdam, WHO Collaborating Centre–Emerging Viral Infections, Rotterdam, the Netherlands
| | - Eric C. M. van Gorp
- Department of Viroscience, Erasmus MC, University Medical Center Rotterdam, WHO Collaborating Centre–Emerging Viral Infections, Rotterdam, the Netherlands
- Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Corine H. GeurtsvanKessel
- Department of Viroscience, Erasmus MC, University Medical Center Rotterdam, WHO Collaborating Centre–Emerging Viral Infections, Rotterdam, the Netherlands
- * E-mail:
| |
Collapse
|
40
|
Xiao Y, Thompson AJ, Howell J. Point-of-Care Tests for Hepatitis B: An Overview. Cells 2020; 9:cells9102233. [PMID: 33023265 PMCID: PMC7650625 DOI: 10.3390/cells9102233] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 09/30/2020] [Accepted: 09/30/2020] [Indexed: 12/15/2022] Open
Abstract
Despite the heavy disease burden posed by hepatitis B, around 90% of people living with hepatitis B are not diagnosed globally. Many of the affected populations still have limited or no access to essential blood tests for hepatitis B. Compared to conventional blood tests which heavily rely on centralised laboratory facilities, point-of-care testing for hepatitis B has the potential to broaden testing access in low-resource settings and to engage hard-to-reach populations. Few hepatitis B point-of-care tests have been ratified for clinical use by international and regional regulatory bodies, and countries have been slow to adopt point-of-care testing into hepatitis B programs. This review presents currently available point-of-care tests for hepatitis B and their roles in the care cascade, reviewing evidence for testing performance, utility, acceptability, costs and cost-effectiveness when integrated into hepatitis B diagnosis and monitoring programs. We further discuss challenges and future directions in aspects of technology, implementation, and regulation when adopting point-of-care testing in hepatitis B programs.
Collapse
Affiliation(s)
- Yinzong Xiao
- Burnet Institute, 3004 Melbourne, VIC, Australia;
- Department of Gastroenterology, St Vincent’s Hospital, 3065 Fitzroy, VIC, Australia;
- Faculty of Medicine, University of Melbourne, 3010 Parkville, VIC, Australia
| | - Alexander J. Thompson
- Department of Gastroenterology, St Vincent’s Hospital, 3065 Fitzroy, VIC, Australia;
- Faculty of Medicine, University of Melbourne, 3010 Parkville, VIC, Australia
| | - Jessica Howell
- Burnet Institute, 3004 Melbourne, VIC, Australia;
- Department of Gastroenterology, St Vincent’s Hospital, 3065 Fitzroy, VIC, Australia;
- Faculty of Medicine, University of Melbourne, 3010 Parkville, VIC, Australia
- School of Public Health and Preventive Medicine, Monash University, 3004 Melbourne, VIC, Australia
- Correspondence:
| |
Collapse
|
41
|
Poljak M. Simplification of hepatitis C testing: a time to act. ACTA DERMATOVENEROLOGICA ALPINA PANNONICA ET ADRIATICA 2020. [DOI: 10.15570/actaapa.2020.27] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
|
42
|
Duchesne L, Hejblum G, Njouom R, Touré Kane C, Toni TD, Moh R, Sylla B, Rouveau N, Attia A, Lacombe K. Model-based cost-effectiveness estimates of testing strategies for diagnosing hepatitis C virus infection in Central and Western Africa. PLoS One 2020; 15:e0238035. [PMID: 32833976 PMCID: PMC7446873 DOI: 10.1371/journal.pone.0238035] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 08/07/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Whereas 72% of hepatitis C virus (HCV)-infected people worldwide live in low- and middle-income countries (LMICs), only 6% of them have been diagnosed. Innovative technologies for HCV diagnosis provide opportunities for developing testing strategies more adapted to resource-constrained settings. However, studies about their economic feasibility in LMICs are lacking. METHODS Adopting a health sector perspective in Cameroon, Cote-d'Ivoire, and Senegal, a decision tree model was developed to compare 12 testing strategies with the following characteristics: a one-step or two-step testing sequence, HCV-RNA or HCV core antigen as confirmative biomarker, laboratory or point-of-care (POC) tests, and venous blood samples or dried blood spots (DBS). Outcomes measures were the number of true positives (TPs), cost per screened individual, incremental cost-effectiveness ratios, and nationwide budget. Corresponding time horizon was immediate, and outcomes were accordingly not discounted. Detailed sensitivity analyses were conducted. FINDINGS In the base-case, a two-step POC-based strategy including anti-HCV antibody (HCV-Ab) and HCV-RNA testing had the lowest cost, €8.18 per screened individual. Assuming a lost-to-follow-up rate after screening > 1.9%, a DBS-based laboratory HCV-RNA after HCV-Ab POC testing was the single un-dominated strategy, requiring an additional cost of €3653.56 per additional TP detected. Both strategies would require 8-25% of the annual public health expenditure of the study countries for diagnosing 30% of HCV-infected individuals. Assuming a seroprevalence > 46.9% or a cost of POC HCV-RNA < €7.32, a one-step strategy based on POC HCV-RNA dominated the two-step POC-based strategy but resulted in many more false-positive cases. CONCLUSIONS POC HCV-Ab followed by either POC- or DBS-based HCV-RNA testing would be the most cost-effective strategies in the study countries. Without a substantial increase in funding for health or a dramatic decrease in assay prices, HCV testing would constitute an economic barrier to the implementation of HCV elimination programs in LMICs.
Collapse
Affiliation(s)
- Léa Duchesne
- Institut Pierre Louis d’Épidémiologie et de Santé Publique, Sorbonne Université, INSERM, Paris, France
| | - Gilles Hejblum
- Institut Pierre Louis d’Épidémiologie et de Santé Publique, Sorbonne Université, INSERM, Paris, France
| | - Richard Njouom
- Virology Department, Pasteur Centre of Cameroon, Yaoundé, Cameroon
| | - Coumba Touré Kane
- Laboratoire de Bactériologie Virologie, Centre Hospitalier Universitaire Aristide Le Dantec/ Université Cheikh Anta Diop de Dakar, Dakar, Senegal
| | - Thomas d’Aquin Toni
- Centre de Diagnostic et de Recherches sur le SIDA (CeDReS), Centre Hospitalier Universitaire de Treichville, Abidjan, Côte d’Ivoire
| | - Raoul Moh
- Programme PAC-CI, Abidjan, Côte d’Ivoire
- Unité de formation et de recherche de Sciences Médicales, Unité Pédagogique de Dermatologie et Infectiologie, Université Félix Houphouët Boigny, Abidjan
| | - Babacar Sylla
- Institut de Médecine et d'Epidémiologie Appliquée (IMEA), Paris, France
| | - Nicolas Rouveau
- International Research and Collaboration unit, Agence Nationale de Recherche sur le Sida et les hépatites virales (ANRS), Paris, France
| | - Alain Attia
- Service d’Hépatologie, Centre Hospitalier Universitaire de Yopougon, Abidjan, Côte d’Ivoire
| | - Karine Lacombe
- Institut Pierre Louis d’Epidémiologie et de Santé Publique, Sorbonne Université, INSERM, AP-HP, Hôpital Saint-Antoine, Service des Maladies Infectieuses et Tropicales, Paris, France
| |
Collapse
|
43
|
Besombes C, Njouom R, Paireau J, Lachenal G, Texier G, Tejiokem M, Cauchemez S, Pépin J, Fontanet A. The epidemiology of hepatitis delta virus infection in Cameroon. Gut 2020; 69:1294-1300. [PMID: 31907297 DOI: 10.1136/gutjnl-2019-320027] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 11/22/2019] [Accepted: 12/20/2019] [Indexed: 01/05/2023]
Abstract
OBJECTIVE To investigate the distribution and risk factors of hepatitis delta virus (HDV) infection in Cameroon. DESIGN We tested for hepatitis B virus (HBV) surface antigen (HBsAg) and anti-HDV antibody 14 150 samples collected during a survey whose participants were representative of the Cameroonian adult population. The samples had already been tested for hepatitis C virus and HIV antibodies. RESULTS Overall, 1621/14 150 (weighted prevalence=11.9%) participants were HBsAg positive, among whom 224/1621 (10.6%) were anti-HDV positive. In 2011, the estimated numbers of HBsAg positive and HDV seropositives were 1 160 799 and 122 910 in the 15-49 years age group, respectively. There were substantial regional variations in prevalence of chronic HBV infection, but even more so for HDV (from 1% to 54%). In multivariable analysis, HDV seropositivity was independently associated with living with an HDV-seropositive person (OR=8.80; 95% CI: 3.23 to 24.0), being HIV infected (OR=2.82; 95% CI: 1.32 to 6.02) and living in the South (latitude <4°N) while having rural/outdoor work (OR=15.2; 95% CI: 8.35 to 27.6, when compared with living on latitude ≥4°N and not having rural/outdoor work). CONCLUSION We found evidence for effective intra-household transmission of HDV in Cameroon. We also identified large differences in prevalence between regions, with cases concentrated in forested areas close to the Equator, as described in other tropical areas. The reasons underlying these geographical variations in HDV prevalence deserve further investigation.
Collapse
Affiliation(s)
- Camille Besombes
- Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France
| | - Richard Njouom
- Department of Virology, Centre Pasteur du Cameroun, Yaounde, Cameroon
| | - Juliette Paireau
- Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, Paris, France
| | | | - Gaëtan Texier
- Department of Epidemiology and Public Health, Centre Pasteur du Cameroun, Yaounde, Cameroon
| | - Mathurin Tejiokem
- Department of Epidemiology and Public Health, Centre Pasteur du Cameroun, Yaounde, Cameroon
| | - Simon Cauchemez
- Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, Paris, France.,UMR2000, CNRS, Paris, France
| | - Jacques Pépin
- Department of Microbiology and Infectious Diseases, Sherbrooke University, Sherbrooke, Quebec, Canada
| | - Arnaud Fontanet
- Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France .,PACRI Unit, Conservatoire National des Arts et Métiers, Paris, France
| |
Collapse
|
44
|
Tuaillon E, Kania D, Pisoni A, Bollore K, Taieb F, Ontsira Ngoyi EN, Schaub R, Plantier JC, Makinson A, Van de Perre P. Dried Blood Spot Tests for the Diagnosis and Therapeutic Monitoring of HIV and Viral Hepatitis B and C. Front Microbiol 2020; 11:373. [PMID: 32210946 PMCID: PMC7075356 DOI: 10.3389/fmicb.2020.00373] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 02/19/2020] [Indexed: 12/20/2022] Open
Abstract
Blood collected and dried on a paper card – dried blood spot (DBS) – knows a growing interest as a sampling method that can be performed outside care facilities by capillary puncture, and transported in a simple and safe manner by mail. The benefits of this method for blood collection and transport has recently led the World Health Organization to recommend DBS for HIV and hepatitis B and C diagnosis. The clinical utility of DBS sampling to improve diagnostics and care of HIV and hepatitis B and C infection in hard to reach populations, key populations and people living in low-income settings was highlighted. Literature about usefulness of DBS specimens in the therapeutic cascade of care – screening, confirmation, quantification of nucleic acids, and resistance genotyping -, was reviewed. DBS samples are suitable for testing antibodies, antigens, or nucleic acids using most laboratory methods. Good sensibility and specificity have been reported for infant HIV diagnosis and diagnosis of hepatitis B and C. The performance of HIV RNA testing on DBS to identified virological failure on antiretroviral therapy is also high but not optimal because of the dilution of dried blood in the elution buffer, reducing the analytical sensitivity, and because of the contamination by intracellular HIV DNA. Standardized protocols are needed for inter-laboratory comparisons, and manufacturers should pursue regulatory approval for in vitro diagnostics using DBS specimens. Despite these limitations, DBS sampling is a clinically relevant tool to improve access to infectious disease diagnosis worldwide.
Collapse
Affiliation(s)
- Edouard Tuaillon
- Pathogenèse et Contrôle des Infections Chroniques, INSERM U1058, Centre Hospitalier Universitaire de Montpellier, Montpellier, France
| | | | - Amandine Pisoni
- Pathogenèse et Contrôle des Infections Chroniques, INSERM U1058, Centre Hospitalier Universitaire de Montpellier, Montpellier, France
| | - Karine Bollore
- Pathogenèse et Contrôle des Infections Chroniques, INSERM U1058, Centre Hospitalier Universitaire de Montpellier, Montpellier, France
| | - Fabien Taieb
- Emerging Diseases Epidemiology Unit, Center for Translational Science, Institut Pasteur, Paris, France
| | - Esther Nina Ontsira Ngoyi
- Pathogenèse et Contrôle des Infections Chroniques, INSERM U1058, Centre Hospitalier Universitaire de Montpellier, Montpellier, France
| | - Roxane Schaub
- CIC AG/INSERM 1424, Centre Hospitalier de Cayenne, Cayenne, France
| | | | - Alain Makinson
- INSERM U1175/IRD UMI 233, IRD, CHU de Montpellier, Montpellier, France
| | - Philippe Van de Perre
- Pathogenèse et Contrôle des Infections Chroniques, INSERM U1058, Centre Hospitalier Universitaire de Montpellier, Montpellier, France
| |
Collapse
|
45
|
Thompson P, Parr JB, Holzmayer V, Carrel M, Tshefu A, Mwandagalirwa K, Muwonga J, Welo PO, Fwamba F, Kuhns M, Jhaveri R, Meshnick SR, Cloherty G. Seroepidemiology of Hepatitis B in the Democratic Republic of the Congo. Am J Trop Med Hyg 2020; 101:226-229. [PMID: 31074406 DOI: 10.4269/ajtmh.18-0883] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Hepatitis B virus (HBV) is endemic throughout Africa, but its prevalence in the Democratic Republic of the Congo (DRC) is incompletely understood. We used dried blood spot (DBS) samples from the 2013 to 2014 Demographic and Health Survey in the DRC to measure the prevalence of HBV using the Abbott ARCHITECT HBV surface antigen (HBsAg) qualitative assay. We then attempted to sequence and genotype HBsAg-positive samples. The weighted national prevalence of HBV was 3.3% (95% CI: 1.8-4.7%), with a prevalence of 2.2% (95% CI: 0.3-4.1%) among children. Hepatitis B virus cases occurred countrywide and across age strata. Genotype E predominated (60%), and we found a unique cluster of genotype A isolates (30%). In conclusion, DBS-based HBsAg testing from a nationally representative survey found that HBV is common and widely distributed among Congolese adults and children. The distribution of cases across ages suggests ongoing transmission and underscores the need for additional interventions to prevent HBV infection.
Collapse
Affiliation(s)
- Peyton Thompson
- Division of Infectious Diseases, Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina
| | - Jonathan B Parr
- Division of Infectious Diseases, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina
| | | | - Margaret Carrel
- Department of Geographical and Sustainability Sciences, University of Iowa, Iowa City, Iowa
| | - Antoinette Tshefu
- Kinshasa School of Public Health, Kinshasa, Democratic Republic of the Congo
| | | | - Jérémie Muwonga
- National AIDS Control Program, Kinshasa, Democratic Republic of the Congo
| | - Placide O Welo
- National AIDS Control Program, Kinshasa, Democratic Republic of the Congo
| | - Franck Fwamba
- National AIDS Control Program, Kinshasa, Democratic Republic of the Congo
| | - Mary Kuhns
- Abbott Laboratories, Abbott Park, Illinois
| | - Ravi Jhaveri
- Division of Infectious Diseases, Department of Pediatrics, Northwestern University, Evanston, Illinois
| | - Steven R Meshnick
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina
| | | |
Collapse
|
46
|
Catlett B, Lamoury FMJ, Bajis S, Hajarizadeh B, Martinez D, Mowat Y, Cunningham PH, Jacka BP, Cloherty GA, Marks P, Dore GJ, Grebely J, Applegate TL. Evaluation of a hepatitis C virus core antigen assay from venepuncture and dried blood spot collected samples: A cohort study. J Viral Hepat 2019; 26:1423-1430. [PMID: 31448470 DOI: 10.1111/jvh.13196] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 07/30/2019] [Accepted: 08/05/2019] [Indexed: 12/19/2022]
Abstract
The global scale-up of hepatitis C virus (HCV) diagnosis requires simplified and affordable HCV diagnostic pathways. This study evaluated the sensitivity and specificity of the HCV Architect core antigen (HCVcAg) assay for detection of active HCV infection in plasma and capillary whole blood dried blood spots (DBS) compared with HCV RNA testing in plasma (Abbott RealTime HCV Viral Load). Samples were collected from participants in an observational cohort enrolled at three sites in Australia (two-drug treatment and alcohol clinics and one homelessness service). Of 205 participants, 200 had results across all samples and assay types and 186 were included in this analysis (14 participants receiving HCV therapy were excluded). HCV RNA was detected in 29% of participants ([95% CI: 22.6-36.1], 54 of 186). The sensitivity of HCVcAg for detection of active HCV infection in plasma was 98.1% (95% CI: 90-100) and 100% (95% CI: 93-100) when compared to HCV RNA thresholds of ≥12 and ≥1000 IU/mL, respectively. The sensitivity of the HCVcAg assay for detection of active HCV infection in DBS was 90.7% (95% CI: 80-97) and 92.5% (95% CI: 82-98) when compared to HCV RNA thresholds of ≥12 and ≥1000 IU/mL, respectively. The specificity of HCV core antigen for detection of active infection was 100% (95% CI: 97-100) for all samples and RNA thresholds. These data indicate that the detection of HCVcAg is a useful tool for determining active HCV infection; to facilitate enhanced testing, linkage to care and treatment particularly when testing plasma samples are collected by venepuncture.
Collapse
Affiliation(s)
- Beth Catlett
- The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.,St Vincent's Centre for Applied Medical Research, Darlinghurst, Sydney, NSW, Australia
| | | | - Sahar Bajis
- The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia
| | | | | | - Yasmin Mowat
- The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia
| | - Philip H Cunningham
- The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.,St Vincent's Centre for Applied Medical Research, Darlinghurst, Sydney, NSW, Australia
| | - Brendan P Jacka
- The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.,Centre de recherche du CHUM, Montreal, QC, Canada
| | | | - Philippa Marks
- The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia
| | - Gregory J Dore
- The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia
| | - Jason Grebely
- The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia
| | | |
Collapse
|
47
|
Brouard C, Saboni L, Gautier A, Chevaliez S, Rahib D, Richard JB, Barin F, Larsen C, Sommen C, Pillonel J, Delarocque-Astagneau E, Lydié N, Lot F. HCV and HBV prevalence based on home blood self-sampling and screening history in the general population in 2016: contribution to the new French screening strategy. BMC Infect Dis 2019; 19:896. [PMID: 31660879 PMCID: PMC6819439 DOI: 10.1186/s12879-019-4493-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Accepted: 09/23/2019] [Indexed: 02/07/2023] Open
Abstract
Background The advent of effective direct-acting antivirals (DAAs), has prompted an assessment of the French Hepatitis C virus (HCV) screening strategy, which historically targeted high-risk groups. One of the options put forward is the implementation of combined (i.e., simultaneous) HCV, Hepatitis B virus (HBV) and HIV screening for all adults at least once during their lifetime (“universal combined screening”). However, recent national survey-based data are lacking to guide decision-making regarding which new strategy to implement. Accordingly, we aimed to provide updated data for both chronic hepatitis C (CHC) and B (CHB) prevalence and for HCV and HBV screening history, using data from the BaroTest and 2016 Health Barometer (2016-HB) studies, respectively. Methods 2016-HB was a national cross-sectional phone based health survey conducted in 2016 among 20,032 randomly selected individuals from the general population in mainland France. BaroTest was a virological sub-study nested in 2016-HB. Data collected for BaroTest were based on home blood self-sampling on dried blood spots (DBS). Results From 6945 analyzed DBS, chronic hepatitis C (CHC) and B (CHB) prevalence was estimated at 0.30% (95% Confidence Interval (CI): 0.13-0.70) and 0.30% (95% CI: 0.13-0.70), respectively. The proportion of individuals aware of their status was estimated at 80.6% (95% CI: 44.2-95.6) for CHC and 17.5% (95% CI: 4.9-46.4) for CHB. Universal combined screening would involve testing between 32.6 and 85.3% of 15-75 year olds according to whether we consider only individuals not previously tested for any of the three viruses, or also those already tested for one or two of the viruses. Conclusions Our data are essential to guide decision-making regarding which new HCV screening recommendation to implement in France. They also highlight that efforts are still needed to achieve the WHO’s targets for eliminating these diseases. Home blood self-sampling may prove to be a useful tool for screening and epidemiological studies.
Collapse
Affiliation(s)
- Cécile Brouard
- Santé publique France, the national public health agency, HIV, Hepatitis B/C and STI Unit, Saint-Maurice, France.
| | - Leïla Saboni
- Santé publique France, the national public health agency, HIV, Hepatitis B/C and STI Unit, Saint-Maurice, France
| | - Arnaud Gautier
- Santé publique France, the national public health agency, Surveys Unit, Saint-Maurice, France
| | - Stéphane Chevaliez
- National Reference Centre for Viral Hepatitis B, C and Delta, Department of Virology, Henri Mondor University Hospital, Créteil, France.,INSERM U955, Paris-Est University, Créteil, France
| | - Delphine Rahib
- Santé publique France, the national public health agency, Sexual Health Unit, Saint-Maurice, France
| | - Jean-Baptiste Richard
- Santé publique France, the national public health agency, Surveys Unit, Saint-Maurice, France
| | - Francis Barin
- National Reference Centre for HIV, Department of Virology, Bretonneau University Hospital, Tours, France.,INSERM U1259, François-Rabelais University, Tours, France
| | - Christine Larsen
- Santé publique France, the national public health agency, Sexual Health Unit, Saint-Maurice, France
| | - Cécile Sommen
- Santé publique France, the national public health agency, Biostatistics Unit, Saint-Maurice, France
| | - Josiane Pillonel
- Santé publique France, the national public health agency, HIV, Hepatitis B/C and STI Unit, Saint-Maurice, France
| | - Elisabeth Delarocque-Astagneau
- INSERM 1181, Biostatistics, Biomathematics, Pharmacoepidemiology, and Infectious Diseases (B2PHI), Paris, France.,Pasteur Institute, B2PHI, Paris, France.,Versailles Saint-Quentin University UMR 1181, B2PHI, Montigny-le-Bretonneux, France
| | - Nathalie Lydié
- Santé publique France, the national public health agency, Sexual Health Unit, Saint-Maurice, France
| | - Florence Lot
- Santé publique France, the national public health agency, HIV, Hepatitis B/C and STI Unit, Saint-Maurice, France
| | | |
Collapse
|
48
|
Villar LM, Cruz HM, Deodato RM, Miguel JC, da Silva EF, Flores GL, Lewis-Ximenez LL. Usefulness of automated assays for detecting hepatitis B and C markers in dried blood spot samples. BMC Res Notes 2019; 12:523. [PMID: 31429797 PMCID: PMC6700985 DOI: 10.1186/s13104-019-4547-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2019] [Accepted: 08/07/2019] [Indexed: 12/28/2022] Open
Abstract
Objective Dried blood spots (DBSs) can be used as an alternative to serum samples because they are easily collected and can be transported without refrigeration to reference laboratories for diagnosis. The present study was performed to evaluate the utility of electrochemiluminescence immunoassay “ECLIA” for anti-HCV, HBsAg and anti-HBc detection from DBS samples. Results Anti-HCV was detected in 103 DBS samples from 108 paired, positive serum and undetected in 364 DBS samples from 366 paired, negative specimens, giving a sensitivity of 95.4% and a specificity of 99.4%. HBsAg was detected in 67 DBS samples out of 71 positive, paired serum and was undetected among 295 DBS samples from 298 paired, negative specimens, giving a sensitivity and specificity of 94.4% and 99%, respectively. Anti-HBc was detected in 160 DBS samples from 185 paired, positive serum specimens and undetected in 349 DBS samples from 357 paired, negative serum specimens, giving a sensitivity of 86.5% and a specificity of 97.8%. Overall, the Kappa index indicated a high agreement between results obtained for the serum and DBS samples (k: 0.95, 0.93 and 0.86 for anti-HCV, HBsAg, anti-HBc, respectively). In conclusion, the ECLIA test could be used for detecting hepatitis B and C markers in DBS.
Collapse
Affiliation(s)
- Livia Melo Villar
- Viral Hepatitis Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Hélio and Peggy Pereira Pavilion - Ground Floor - Office B09, FIOCRUZ Av. Brasil, 4365 - Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil.
| | - Helena Medina Cruz
- Viral Hepatitis Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Hélio and Peggy Pereira Pavilion - Ground Floor - Office B09, FIOCRUZ Av. Brasil, 4365 - Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil
| | - Raissa Martins Deodato
- Viral Hepatitis Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Hélio and Peggy Pereira Pavilion - Ground Floor - Office B09, FIOCRUZ Av. Brasil, 4365 - Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil
| | - Juliana Custódio Miguel
- Viral Hepatitis Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Hélio and Peggy Pereira Pavilion - Ground Floor - Office B09, FIOCRUZ Av. Brasil, 4365 - Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil
| | - Elisangela Ferreira da Silva
- Viral Hepatitis Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Hélio and Peggy Pereira Pavilion - Ground Floor - Office B09, FIOCRUZ Av. Brasil, 4365 - Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil
| | - Geane Lopes Flores
- Viral Hepatitis Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Hélio and Peggy Pereira Pavilion - Ground Floor - Office B09, FIOCRUZ Av. Brasil, 4365 - Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil
| | - Lia Laura Lewis-Ximenez
- Viral Hepatitis Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Hélio and Peggy Pereira Pavilion - Ground Floor - Office B09, FIOCRUZ Av. Brasil, 4365 - Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil
| |
Collapse
|
49
|
Wilson P, Parr JB, Jhaveri R, Meshnick SR. Call to Action: Prevention of Mother-to-Child Transmission of Hepatitis B in Africa. J Infect Dis 2019; 217:1180-1183. [PMID: 29351639 DOI: 10.1093/infdis/jiy028] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2017] [Accepted: 01/16/2018] [Indexed: 12/24/2022] Open
Abstract
Hepatitis B virus (HBV) is a significant public health issue that has not been adequately addressed, especially in the high-prevalence region of Africa. Despite the incorporation of HBV vaccines into the Expanded Program on Immunization, children continue to be infected with HBV through maternal-to-child transmission (MTCT). The addition of a birth dose of HBV vaccine would be a cost-effective method to reduce MTCT. Birth-dose HBV vaccine policies have been adopted in the Western Pacific region but not yet in Africa. Even better protection against HBV MTCT can be achieved by treatment of pregnant women with high HBV viral loads with tenofovir. Tenofovir is already widely used in prevention of HIV MTCT (PMTCT) programs. We suggest that existing HIV PMTCT programs could be expanded to deliver care for HBV-infected pregnant women. With appropriate adoption of birth-dose vaccination policies and expansion of PMTCT programs, elimination of HBV MTCT in Africa is achievable.
Collapse
Affiliation(s)
- Peyton Wilson
- Department of Pediatrics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill
| | - Jonathan B Parr
- Department of Medicine, Division of Infectious Diseases, Gillings School of Global Public Health, University of North Carolina, Chapel Hill
| | - Ravi Jhaveri
- Department of Pediatrics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill
| | - Steve R Meshnick
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill
| |
Collapse
|
50
|
Vázquez-Morón S, Ardizone Jiménez B, Jiménez-Sousa MA, Bellón JM, Ryan P, Resino S. Evaluation of the diagnostic accuracy of laboratory-based screening for hepatitis C in dried blood spot samples: A systematic review and meta-analysis. Sci Rep 2019; 9:7316. [PMID: 31086259 PMCID: PMC6514168 DOI: 10.1038/s41598-019-41139-8] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2018] [Accepted: 02/27/2019] [Indexed: 12/25/2022] Open
Abstract
The dried blood spot (DBS) is increasingly used for the hepatitis C virus (HCV) screening. Our objective was to perform a meta-analysis of the methodology for HCV screening in DBS samples, particularly in the type of diagnostic assay used. We performed a meta-analysis of all eligible studies published to date (March 2018). The literature search revealed 26 studies: 21 for detection of anti-HCV antibodies and 10 for detection of HCV-RNA. Statistical analyses were performed using Meta-DiSc and STATA (MIDAS module). For detection of HCV antibodies, pooled diagnostic accuracy measures were as follows: sensitivity 96.1%, specificity 99.2%, positive likelihood ratio (PLR) 105, negative likelihood ratio (NLR) 0.04, diagnostic odds ratio (DOR) 2692.9, and summary receiver operating characteristic (SROC) 0.997 ± 0.001. For detection of HCV-RNA, the pooled diagnostic accuracy measures were as follows: sensitivity 97.8%, specificity 99.2%, PLR 44.8, NLR 0.04, DOR 1966.9, and SROC 0.996 ± 0.013. Similar values of pooled diagnostic accuracy measures were found according to the type of anti-HCV antibody detection assay (enzyme-linked immunosorbent assay, rapid diagnostic test, and chemiluminescence assays) and HCV-RNA detection assay (real-time polymerase chain reaction and transcription-mediated amplification). The analysis of external validity showed a high negative predicted value (NPV) for both approaches, but a low positive predicted value (PPV) when prevalence was < 10%, particularly in HCV-RNA tests. Finally, this meta-analysis is subject to limitations, especially publication bias and significant heterogeneity between studies. In conclusion, HCV screening in DBS samples has an outstanding diagnostic performance, with no relevant differences between the techniques used. However, external validity may be limited when the HCV prevalence is low.
Collapse
Affiliation(s)
- Sonia Vázquez-Morón
- Unidad de Infección Viral e Inmunidad. Centro Nacional de Microbiología - Instituto de Salud Carlos III, Majadahonda, Spain
| | - Beatriz Ardizone Jiménez
- Unidad de Infección Viral e Inmunidad. Centro Nacional de Microbiología - Instituto de Salud Carlos III, Majadahonda, Spain
| | - María A Jiménez-Sousa
- Unidad de Infección Viral e Inmunidad. Centro Nacional de Microbiología - Instituto de Salud Carlos III, Majadahonda, Spain
| | - José M Bellón
- Hospital General Universitario Gregorio Marañón, Madrid, Spain.,Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Pablo Ryan
- Hospital Universitario Infanta Leonor (HUIL). Vallecas, Madrid, Spain
| | - Salvador Resino
- Unidad de Infección Viral e Inmunidad. Centro Nacional de Microbiología - Instituto de Salud Carlos III, Majadahonda, Spain.
| |
Collapse
|