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Varella K, Andrade-Silva BED, Costa-Neto SFD, Oliveira Cruz BAD, Maldonado Junior A, Gentile R. Helminth community of Nectomys squamipes naturally infected by Schistosoma mansoni in an endemic area in Brazil: A comparison of 22 years apart. Int J Parasitol Parasites Wildl 2024; 24:100941. [PMID: 38807751 PMCID: PMC11131069 DOI: 10.1016/j.ijppaw.2024.100941] [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: 03/13/2024] [Revised: 05/06/2024] [Accepted: 05/07/2024] [Indexed: 05/30/2024]
Abstract
The municipality of Sumidouro in the state of Rio de Janeiro, southeastern Brazil, is considered an area with low endemicity of Schistosoma mansoni. In this municipality, the wild water rat Nectomys squamipes is a wild reservoir of S. mansoni. A helminth community survey was carried out on N. squamipes populations in Sumidouro from 1997 to 1999. In the present study, we compared the helminth fauna and the helminth community structure of N. squamipes with a recent survey after a 22-year time interval, considering that the prevalence of S. mansoni infection in humans remained stable and that the area showed the same environmental characteristics. Seventy-three host specimens of N. squamipes collected between 1997 and 1999 and 21 specimens collected in 2021 were analyzed in this study. Seven helminth species were found in each collection period. The nematode Syphacia evaginata was recorded for the first time in N. squamipes in 2021. Syphacia venteli was the most abundant species in both periods and the most prevalent in 2021. During the period from 1997 to 1999, the most prevalent species was Hassalstrongylus epsilon. Significant differences in prevalence and abundance in relation to host sex were observed only for S. mansoni in 1997-1999. Significant differences in the abundance of the helminth species over time were observed only in Physaloptera bispiculata. Hassalstrongylus epsilon, S. venteli and S. mansoni were the dominant species in both periods. Litomosoides chagasfilhoi, Echinostoma paraensei paraensei and P. bispiculata became dominant, codominant and subordinate, respectively, over time. In conclusion, the helminth community of N. squamipes remained stable, with similar species richness, prevalence and abundance values and low beta-diversity over time. The occurrence of S. mansoni in the water rat has remained stable for decades, highlighting its importance for schistosomiasis control.
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Affiliation(s)
- Karina Varella
- Laboratório de Biologia e Parasitologia de Mamíferos Silvestres Reservatórios, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
- Programa de Pós-Graduação em Biologia Parasitária, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Beatriz Elise de Andrade-Silva
- Pós-Doutorado Nota 10 – 2021, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | | | - Brena Aparecida de Oliveira Cruz
- Laboratório de Biologia e Parasitologia de Mamíferos Silvestres Reservatórios, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
- Programa de Pós-Graduação em Biologia Parasitária, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Arnaldo Maldonado Junior
- Laboratório de Biologia e Parasitologia de Mamíferos Silvestres Reservatórios, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Rosana Gentile
- Laboratório de Biologia e Parasitologia de Mamíferos Silvestres Reservatórios, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
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Gerber DJF, Dhakal S, Islam MN, Al Kawsar A, Khair MA, Rahman MM, Karim MJ, Rahman MS, Aktaruzzaman MM, Tupps C, Stephens M, Emerson PM, Utzinger J, Vounatsou P. Distribution and treatment needs of soil-transmitted helminthiasis in Bangladesh: A Bayesian geostatistical analysis of 2017-2020 national survey data. PLoS Negl Trop Dis 2023; 17:e0011656. [PMID: 37930980 PMCID: PMC10662736 DOI: 10.1371/journal.pntd.0011656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 11/21/2023] [Accepted: 09/11/2023] [Indexed: 11/08/2023] Open
Abstract
BACKGROUND In Bangladesh, preventive chemotherapy targeting soil-transmitted helminth (STH) infections in school-age children has been implemented since 2008. To evaluate the success of this strategy, surveys were conducted between 2017 and 2020 in 10 out of 64 districts. We estimate the geographic distribution of STH infections by species at high spatial resolution, identify risk factors, and estimate treatment needs at different population subgroups. METHODOLOGY Bayesian geostatistical models were fitted to prevalence data of each STH species. Climatic, environmental, and socioeconomic predictors were extracted from satellite images, open-access, model-based databases, and demographic household surveys, and used to predict the prevalence of infection over a gridded surface at 1 x 1 km spatial resolution across the country, via Bayesian kriging. These estimates were combined with gridded population data to estimate the number of required treatments for different risk groups. PRINCIPAL FINDINGS The population-adjusted prevalence of Ascaris lumbricoides, Trichuris trichiura, and hookworm across all ages is estimated at 9.9% (95% Bayesian credible interval: 8.0-13.0%), 4.3% (3.0-7.3%), and 0.6% (0.4-0.9%), respectively. There were 24 out of 64 districts with an estimated population-adjusted STH infection prevalence above 20%. The proportion of households with improved sanitation showed a statistically important, protective association for both, A. lumbricoides and T. trichiura prevalence. Precipitation in the driest month of the year was negatively associated with A. lumbricoides prevalence. High organic carbon concentration in the soil's fine earth fraction was related to a high hookworm prevalence. Furthermore, we estimated that 30.5 (27.2; 36.0) million dosages of anthelmintic treatments for school-age children were required per year in Bangladesh. CONCLUSIONS/SIGNIFICANCE For each of the STH species, the prevalence was reduced by at least 80% since treatment was scaled up more than a decade ago. The current number of deworming dosages could be reduced by up to 61% if the treatment strategy was adapted to the local prevalence.
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Affiliation(s)
- Daniel J. F. Gerber
- Swiss Tropical and Public Health Institute, Allschwil, Switzerland
- University of Basel, Basel, Switzerland
| | - Sanjaya Dhakal
- Children Without Worms, Task Force for Global Health, Decatur, Georgia, United States of America
| | - Md. Nazmul Islam
- Communicable Disease Control Unit, Directorate General of Health Services, Ministry of Health & Family Welfare, Dhaka, Bangladesh
| | - Abdullah Al Kawsar
- Communicable Disease Control Unit, Directorate General of Health Services, Ministry of Health & Family Welfare, Dhaka, Bangladesh
| | - Md. Abul Khair
- Communicable Disease Control Unit, Directorate General of Health Services, Ministry of Health & Family Welfare, Dhaka, Bangladesh
| | - Md. Mujibur Rahman
- Communicable Disease Control Unit, Directorate General of Health Services, Ministry of Health & Family Welfare, Dhaka, Bangladesh
| | - Md. Jahirul Karim
- Communicable Disease Control Unit, Directorate General of Health Services, Ministry of Health & Family Welfare, Dhaka, Bangladesh
| | - Md. Shafiqur Rahman
- Communicable Disease Control Unit, Directorate General of Health Services, Ministry of Health & Family Welfare, Dhaka, Bangladesh
| | - M. M. Aktaruzzaman
- Communicable Disease Control Unit, Directorate General of Health Services, Ministry of Health & Family Welfare, Dhaka, Bangladesh
| | - Cara Tupps
- Children Without Worms, Task Force for Global Health, Decatur, Georgia, United States of America
| | - Mariana Stephens
- Children Without Worms, Task Force for Global Health, Decatur, Georgia, United States of America
| | - Paul M. Emerson
- Children Without Worms, Task Force for Global Health, Decatur, Georgia, United States of America
| | - Jürg Utzinger
- Swiss Tropical and Public Health Institute, Allschwil, Switzerland
- University of Basel, Basel, Switzerland
| | - Penelope Vounatsou
- Swiss Tropical and Public Health Institute, Allschwil, Switzerland
- University of Basel, Basel, Switzerland
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Emadi M, Delavari S, Bayati M. Global socioeconomic inequality in the burden of communicable and non-communicable diseases and injuries: an analysis on global burden of disease study 2019. BMC Public Health 2021; 21:1771. [PMID: 34583668 PMCID: PMC8480106 DOI: 10.1186/s12889-021-11793-7] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 09/15/2021] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Examining the distribution of the burden of different communicable and non-communicable diseases and injuries worldwide can present proper evidence to global policymakers to deal with health inequality. The present study aimed to determine socioeconomic inequality in the burden of 25 groups of diseases between countries around the world in 2019. METHODS In the current study data according to 204 countries in the world was gathered from the Human Development Report and the Global Burden of Diseases study. Variables referring to incidence, prevalence, years of life lost (YLL), years lived with disability (YLD) and disability adjusted life years (DALY) resulting by 25 groups of diseases and injuries also human development index was applied for the analysis. For measurement of socioeconomic inequality, concentration index (CI) and curve was applied. CI is considered as one of the popular measures for inequality measurement. It ranges from - 1 to + 1. A positive value implies that a variable is concentrated among the higher socioeconomic status population and vice versa. RESULTS The findings showed that CI of the incidence, prevalence, YLL, YLD and DALY for all causes were - 0.0255, - 0.0035, - 0.1773, 0.0718 and - 0.0973, respectively. CI for total Communicable, Maternal, Neonatal, and Nutritional Diseases (CMNNDs) incidence, prevalence, YLL, YLD and DALY were estimated as - 0.0495, - 0.1355, - 0.5585, - 0.2801 and - 0.5203, respectively. Moreover, estimates indicated that CIs of incidence, prevalence, YLL, YLD and DALY for Non-Communicable Diseases (NCDs) were 0.1488, 0.1218, 0.1552, 0.1847 and 0.1669, respectively. Regarding injuries, the CIs of incidence, prevalence, YLL, YLD and DALY were determined as 0.0212, 0.1364, - 0.1605, 0.1146 and 0.3316, respectively. In the CMNNDs group, highest and lowest CI of DALY were related to the respiratory infections and tuberculosis (- 0.4291) and neglected tropical diseases and malaria (- 0.6872). Regarding NCDs, the highest and lowest CI for DALY is determined for neoplasms (0.3192) and other NCDs (- 0.0784). Moreover, the maximum and minimum of CI of DALY for injuries group were related to the transport injuries (0.0421) and unintentional injuries (- 0.0297). CONCLUSIONS The distribution of all-causes and CMNNDs burden were more concentrated in low-HDI countries and there are pro-poor inequality. However, there is a pro-rich inequality for NCDs' burden i.e. it was concentrated in high-HDI countries. On the other hand, the concentration of DALY, YLD, prevalence, and incidence in injuries was observed in the countries with higher HDI, while YLL was concentrated in low-HDI countries.
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Affiliation(s)
- Mehrnoosh Emadi
- Health Human Resources Research Center, School of Health Management and Information Sciences, Shiraz University of Medical Sciences, Almas Building, Alley 29, Qasrodasht Ave, Shiraz, Iran
| | - Sajad Delavari
- Health Human Resources Research Center, School of Health Management and Information Sciences, Shiraz University of Medical Sciences, Almas Building, Alley 29, Qasrodasht Ave, Shiraz, Iran
| | - Mohsen Bayati
- Health Human Resources Research Center, School of Health Management and Information Sciences, Shiraz University of Medical Sciences, Almas Building, Alley 29, Qasrodasht Ave, Shiraz, Iran.
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Thomas CM, Timson DJ. The Mechanism of Action of Praziquantel: Can New Drugs Exploit Similar Mechanisms? Curr Med Chem 2020; 27:676-696. [DOI: 10.2174/0929867325666180926145537] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Revised: 04/06/2018] [Accepted: 08/20/2018] [Indexed: 11/22/2022]
Abstract
Praziquantel (PZQ) is the drug of choice for treating infection with worms from the
genus Schistosoma. The drug is effective, cheap and has few side effects. However, despite its
use in millions of patients for over 40 years its molecular mechanism of action remains elusive.
Early studies demonstrated that PZQ disrupts calcium ion homeostasis in the worm and
the current consensus is that it antagonises voltage-gated calcium channels. It is hypothesised
that disruption of these channels results in uncontrolled calcium ion influx leading to uncontrolled
muscle contraction and paralysis. However, other experimental studies have suggested
a role for myosin regulatory light chains and adenosine uptake in the drug’s mechanism of
action. Assuming voltage-gated calcium channels do represent the main molecular target of
PZQ, the precise binding site for the drug remains to be identified. Unlike other commonly
used anti-parasitic drugs, there are few definitive reports of resistance to PZQ in the literature.
The lack of knowledge about PZQ’s molecular mechanism(s) undermines our ability to predict
how resistance might arise and also hinder our attempts to develop alternative antischistosomal
drugs which exploit the same target(s). Some PZQ derivatives have been identified
which also kill or paralyse schistosomes in culture. However, none of these are in widespread
clinical use. There is a pressing need for fundamental research into the molecular mechanism(
s) of action of PZQ. Such research would enable new avenues for antischsistosomal
drug discovery.
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Affiliation(s)
- Charlotte M. Thomas
- School of Biological Sciences, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom
| | - David J. Timson
- School of Biological Sciences, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom
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Saenz V, Mazzanti di Ruggiero MDLA. Propuestas bioéticas frente a los problemas sociales y éticos que generan las enfermedades infecciosas desatendidas. PERSONA Y BIOÉTICA 2019. [DOI: 10.5294/pebi.2019.23.1.6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Este artículo de revisión se centra en el tema de las enfermedades infecciosas desatendidas (EID), grupo de 18 patologías de carácter incapacitante, a veces mortales y frecuentemente deformantes, que prevalecen en poblaciones de Asia, África y en las zonas tropicales de Sur América. Mediante una revisión bibliográfica se plantean los elementos que se relacionan con estas enfermedades, se categorizan y se analizan a la luz de la Declaración Universal sobre Bioética y Derechos Humanos de 2005, en cuanto a igualdad, justicia y equidad, el enfoque de no discriminación y estigmatización, responsabilidad social y salud. A lo largo de la revisión se concluye que la problemática alrededor de las EID es multifactorial y se presentan propuestas, desde una mirada de la bioética centrada en el respeto por la dignidad de la persona y de las poblaciones afectadas, para mitigar y solucionar la atención a partir de estrategias posibles que aborden determinantes sociales. Se propone incluir la bioética en el debate sobre la atención de las EID para analizar los problemas y examinar soluciones por medio de proyectos de investigación transdisciplinaria que impliquen un trabajo colaborativo y formativo entre las comunidades afectadas, entidades gubernamentales y profesionales de la salud y de las ciencias veterinarias.
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Wang L, Sloan MA, Ligoxygakis P. Intestinal NF-κB and STAT signalling is important for uptake and clearance in a Drosophila-Herpetomonas interaction model. PLoS Genet 2019; 15:e1007931. [PMID: 30822306 PMCID: PMC6415867 DOI: 10.1371/journal.pgen.1007931] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Revised: 03/13/2019] [Accepted: 01/03/2019] [Indexed: 12/18/2022] Open
Abstract
Dipteran insects transmit serious diseases to humans, often in the form of trypanosomatid parasites. To accelerate research in more difficult contexts of dipteran-parasite relationships, we studied the interaction of the model dipteran Drosophila melanogaster and its natural trypanosomatid Herpetomonas muscarum. Parasite infection reduced fecundity but not lifespan in NF-κB/Relish-deficient flies. Gene expression analysis implicated the two NF-κB pathways Toll and Imd as well as STAT signalling. Tissue specific knock-down of key components of these pathways in enterocytes (ECs) and intestinal stem cells (ISCs) influenced initial numbers, infection dynamics and time of clearance. Herpetomonas triggered STAT activation and proliferation of ISCs. Loss of Relish suppressed ISCs, resulting in increased parasite numbers and delayed clearance. Conversely, overexpression of Relish increased ISCs and reduced uptake. Finally, loss of Toll signalling decreased EC numbers and enabled parasite persistence. This network of signalling may represent a general mechanism with which dipteran respond to trypanosomatids.
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Affiliation(s)
- Lihui Wang
- Laboratory of Cell Biology, Development and Genetics, Department of Biochemistry, University of Oxford, Oxford, United Kingdom
| | - Megan A Sloan
- Laboratory of Cell Biology, Development and Genetics, Department of Biochemistry, University of Oxford, Oxford, United Kingdom
| | - Petros Ligoxygakis
- Laboratory of Cell Biology, Development and Genetics, Department of Biochemistry, University of Oxford, Oxford, United Kingdom
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Lass A, Karanis P, Korzeniewski K. First detection and genotyping of Giardia intestinalis in stool samples collected from children in Ghazni Province, eastern Afghanistan and evaluation of the PCR assay in formalin-fixed specimens. Parasitol Res 2017; 116:2255-2264. [PMID: 28612148 PMCID: PMC5529491 DOI: 10.1007/s00436-017-5529-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Accepted: 06/01/2017] [Indexed: 02/07/2023]
Abstract
It is estimated that faecal-orally transmitted diseases are common in Afghanistan, as a consequence of poor hygienic standards of life and widespread contamination of water and food with both human and animal faeces. However, there is little information in the literature concerning infections caused by intestinal parasites in the Afghan population. In this study, we report the occurrence of Giardia intestinalis assemblages (A and B) in formalin-fixed stool samples collected from 245 Afghan schoolchildren living in Ghazni Province in eastern Afghanistan. Detection of the parasite’s DNA and genotyping was performed using real-time PCR, specific to the β-giardin gene of G. intestinalis. Positive results were recorded in 52 (21.2%) samples. Genotyping was successful in 39 faecal samples and showed the predominance of assemblage B of G. intestinalis in this population (15 assemblage A and 24 assemblage B). Co-infection with both genotypes A and B was detected in four samples. Additionally, we evaluated the effect of 10% buffered formalin fixative on the detection of G. intestinalis DNA using real-time PCR and nested PCR characterised by different lengths of PCR products (74 and 479 bp, respectively). The human faeces containing the Giardia cysts were tested for 16 weeks. Amplification of G. intestinalis DNA with real-time PCR was possible up to 6 weeks of preservation of stool sample in formalin, compared to only 2 weeks with nested PCR. This suggests that real-time PCR is a more suitable tool in cases where stool samples have to be kept in formalin for longer periods of time.
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Affiliation(s)
- Anna Lass
- Department of Tropical Parasitology, Institute of Maritime and Tropical Medicine in Gdynia, Medical University of Gdansk, 9b Powstania Styczniowego Str, 81-519, Gdynia, Poland.
| | - Panagiotis Karanis
- State Key Laboratory of Plateau Ecology and Agriculture, Center for Biomedicine and Infectious Disease, Qinghai Academy of Animal Sciences and Veterinary Medicine, Qinghai University, Xining, 1#Wei'er Road, Qinghai Biological Scientific Estate Garden, Xining, 810016, People's Republic of China
| | - Krzysztof Korzeniewski
- Epidemiology and Tropical Medicine Department in Gdynia, Military Institute of Medicine in Warsaw, Grudzinskiego St. 4, 81-103, Gdynia, Poland
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Ayukekbong JA, Oyero OG, Nnukwu SE, Mesumbe HN, Fobisong CN. Value of routine dengue diagnosis in endemic countries. World J Virol 2017; 6:9-16. [PMID: 28239567 PMCID: PMC5303857 DOI: 10.5501/wjv.v6.i1.9] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2016] [Revised: 11/24/2016] [Accepted: 12/09/2016] [Indexed: 02/05/2023] Open
Abstract
Dengue is one of the most common arthropod-borne viral diseases in humans and it is a leading cause of illness and death in the tropical and subtropical regions of the world. It is thought to account for 400 million cases annually among approximately 3.97 billion people at risk of infection in 128 endemic countries. Despite the global prevalence of the disease, the availability of a vaccine is limited in most countries in the endemic areas. Most endemic countries in South America, South East Asia and Africa serve as attractive touristic sites for people from non-endemic countries who become infected and export the virus to dengue-free regions. Dengue fever typically resembles malaria and in endemic countries most cases of dengue are treated as presumptive malaria. Consequently, routine dengue diagnosis among persons with fever will offer early treatment and reduce the burden of the disease. Also, routine testing among travellers from endemic countries will reduce importation and prevent the geographical expansion of dengue. In this essay, we seek to highlight the usefulness of routine dengue testing in endemic countries.
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Affiliation(s)
- Peter J. Hotez
- Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of America
- James A Baker III Institute for Public Policy, Rice University, Houston, Texas, United States of America
- Department of Biology, Baylor University, Waco, Texas, United States of America
- Scowcroft Institute for International Affairs, The Bush School of Government and Public Service, Texas A&M University, College Station, Texas, United States of America
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Hotez PJ, Herricks JR. Impact of the Neglected Tropical Diseases on Human Development in the Organisation of Islamic Cooperation Nations. PLoS Negl Trop Dis 2015; 9:e0003782. [PMID: 26606509 PMCID: PMC4659667 DOI: 10.1371/journal.pntd.0003782] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Affiliation(s)
- Peter J. Hotez
- Department of Pediatrics and Molecular Virology and Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of America
- Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development, Houston, Texas, United States of America
- James A. Baker III Institute for Public Policy, Rice University, Houston, Texas, United States of America
- Department of Biology, Baylor University, Waco, Texas, United States of America
| | - Jennifer R. Herricks
- Department of Pediatrics and Molecular Virology and Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of America
- James A. Baker III Institute for Public Policy, Rice University, Houston, Texas, United States of America
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Muhanguzi D, Picozzi K, Hattendorf J, Thrusfield M, Kabasa JD, Waiswa C, Welburn SC. The burden and spatial distribution of bovine African trypanosomes in small holder crop-livestock production systems in Tororo District, south-eastern Uganda. Parasit Vectors 2014; 7:603. [PMID: 25532828 PMCID: PMC4300167 DOI: 10.1186/s13071-014-0603-6] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2014] [Accepted: 12/11/2014] [Indexed: 11/10/2022] Open
Abstract
Background African animal trypanosomiasis (AAT) is considered to be one of the greatest constraints to livestock production and livestock-crop integration in most African countries. South-eastern Uganda has suffered for more than two decades from outbreaks of zoonotic Human African Trypanosomiasis (HAT), adding to the burden faced by communities from AAT. There is insufficient AAT and HAT data available (in the animal reservoir) to guide and prioritize AAT control programs that has been generated using contemporary, sensitive and specific molecular techniques. This study was undertaken to evaluate the burden that AAT presents to the small-scale cattle production systems in south-eastern Uganda. Methods Randomised cluster sampling was used to select 14% (57/401) of all cattle containing villages across Tororo District. Blood samples were taken from all cattle in the selected villages between September-December 2011; preserved on FTA cards and analysed for different trypanosomes using a suite of molecular techniques. Generalized estimating equation and Rogen-Gladen estimator models were used to calculate apparent and true prevalences of different trypanosomes while intra cluster correlations were estimated using a 1-way mixed effect analysis of variance (ANOVA) in R statistical software version 3.0.2. Results The prevalence of all trypanosome species in cattle was 15.3% (95% CI; 12.2-19.1) while herd level trypanosome species prevalence varied greatly between 0-43%. Trypanosoma vivax (17.4%, 95% CI; 10.6-16.8) and Trypanosoma brucei rhodesiense (0.03%) were respectively, the most, and least prevalent trypanosome species identified. Conclusions The prevalence of bovine trypanosomes in this study indicates that AAT remains a significant constraint to livestock health and livestock production. There is need to implement tsetse and trypanosomiasis control efforts across Tororo District by employing effective, cheap and sustainable tsetse and trypanosomiasis control methods that could be integrated in the control of other endemic vector borne diseases like tick-borne diseases.
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Affiliation(s)
- Dennis Muhanguzi
- Department of Biomolecular and Biolaboratory Sciences, School of Biosecurity, Biotechnical and Laboratory Sciences, College of Veterinary Medicine Animal Resources and Biosecurity, Makerere University, P.O. Box 7062, Kampala, Uganda. .,Division of Infection & Pathway Medicine, Centre for Infectious Diseases, School of Biomedical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
| | - Kim Picozzi
- Division of Infection & Pathway Medicine, Centre for Infectious Diseases, School of Biomedical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
| | - Jan Hattendorf
- Department of Public Health and Epidemiology, Swiss Tropical Institute, Socinstrasse 57, CH-4002, Basel, Switzerland. .,University of Basel, Petersplatz 1, 4003, Basel, Switzerland.
| | - Michael Thrusfield
- Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Edinburgh, EH25 9RG, UK.
| | - John David Kabasa
- Department of Biosecurity, Ecosystems & Veterinary Public Health, School of Biosecurity, Biotechnical and Laboratory Sciences, College of Veterinary Medicine Animal Resources and Biosecurity, Makerere University, P.O. Box 7062, Kampala, Uganda.
| | - Charles Waiswa
- Department of Pharmacy, Clinical and Comparative Medicine, School of Veterinary Medicine and Animal Resources, College of Veterinary Medicine Animal Resources and Biosecurity, Makerere University, P.O. Box 7062, Kampala, Uganda.
| | - Susan Christina Welburn
- Division of Infection & Pathway Medicine, Centre for Infectious Diseases, School of Biomedical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
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Muhanguzi D, Picozzi K, Hatendorf J, Thrusfield M, Welburn SC, Kabasa JD, Waiswa C. Improvements on restricted insecticide application protocol for control of Human and Animal African Trypanosomiasis in eastern Uganda. PLoS Negl Trop Dis 2014; 8:e3284. [PMID: 25356758 PMCID: PMC4214683 DOI: 10.1371/journal.pntd.0003284] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2014] [Accepted: 09/22/2014] [Indexed: 11/21/2022] Open
Abstract
Background African trypanosomes constrain livestock and human health in Sub-Saharan Africa, and aggravate poverty and hunger of these otherwise largely livestock-keeping communities. To solve this, there is need to develop and use effective and cheap tsetse control methods. To this end, we aimed at determining the smallest proportion of a cattle herd that needs to be sprayed on the legs, bellies and ears (RAP) for effective Human and Animal African Trypanosomiasis (HAT/AAT) control. Methodology/Principal finding Cattle in 20 villages were ear-tagged and injected with two doses of diminazene diaceturate (DA) forty days apart, and randomly allocated to one of five treatment regimens namely; no treatment, 25%, 50%, 75% monthly RAP and every 3 month Albendazole drench. Cattle trypanosome re-infection rate was determined by molecular techniques. ArcMap V10.3 was used to map apparent tsetse density (FTD) from trap catches. The effect of graded RAP on incidence risk ratios and trypanosome prevalence was determined using Poisson and logistic random effect models in R and STATA V12.1 respectively. Incidence was estimated at 9.8/100 years in RAP regimens, significantly lower compared to 25.7/100 years in the non-RAP regimens (incidence rate ratio: 0.37; 95% CI: 0.22–0.65; P<0.001). Likewise, trypanosome prevalence after one year of follow up was significantly lower in RAP animals than in non-RAP animals (4% vs 15%, OR: 0.20, 95% CI: 0.08–0.44; P<0.001). Contrary to our expectation, level of protection did not increase with increasing proportion of animals treated. Conclusions/significance Reduction in RAP coverage did not significantly affect efficacy of treatment. This is envisaged to improve RAP adaptability to low income livestock keepers but needs further evaluation in different tsetse challenge, HAT/AAT transmission rates and management systems before adopting it for routine tsetse control programs. Poverty, hunger and human ill-health aggravated by trypanosomiasis in Sub-Saharan Africa can only be reduced by developing and using cheap and effective tsetse control methods. To further reduce the cost of tsetse control by restricting insecticides to the legs, belly and ears (RAP) we set out to determine the lowest RAP coverage that can effectively control tsetse. Cattle in 20 south-eastern Uganda villages were randomly allocated to 5 treatment groups, ear-tagged for ease of follow-up and treated twice forty days apart with a trypanocide at the beginning of the trial. Cattle in regimens 2–4 received monthly graded RAP (25%, 50% and 75% of village herd respectively), while those in regimens 1 and 5 received no more treatment and deworming once every three months respectively. Molecular techniques were used to check for trypanosome infections, while tsetse apparent density was determined by traps at 161 locations in the district. About 25% RAP coverage was effective at controlling T. brucei s.l. while 50–75% RAP coverage would need to be used for effective T.vivax and T.congolense nagana control. Use of RAP at lower herd coverage is envisaged to reduce its cost, damage to the environment and improve its uptake in resource poor communities.
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Affiliation(s)
- Dennis Muhanguzi
- Department of Biomolecular and Biolaboratory Sciences, College of Veterinary Medicine Animal Resources and Biosecurity, Makerere University, Kampala, Uganda
- Division of Pathway Medicine, Centre for Infectious Diseases, School of Biomedical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, United Kingdom
- * E-mail:
| | - Kim Picozzi
- Division of Pathway Medicine, Centre for Infectious Diseases, School of Biomedical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, United Kingdom
| | - Jan Hatendorf
- Department of Public Health and Epidemiology, Swiss Tropical Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Michael Thrusfield
- Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Edinburgh, United Kingdom
| | - Susan Christina Welburn
- Division of Pathway Medicine, Centre for Infectious Diseases, School of Biomedical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, United Kingdom
| | - John David Kabasa
- Department of Biomolecular and Biolaboratory Sciences, College of Veterinary Medicine Animal Resources and Biosecurity, Makerere University, Kampala, Uganda
| | - Charles Waiswa
- Department of Biomolecular and Biolaboratory Sciences, College of Veterinary Medicine Animal Resources and Biosecurity, Makerere University, Kampala, Uganda
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13
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Asojo OA, Ceccarelli C. Structure of glutathione S-transferase 1 from the major human hookworm parasite Necator americanus (Na-GST-1) in complex with glutathione. Acta Crystallogr F Struct Biol Commun 2014; 70:1162-6. [PMID: 25195885 PMCID: PMC4157412 DOI: 10.1107/s2053230x1401646x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2014] [Accepted: 07/15/2014] [Indexed: 11/10/2022] Open
Abstract
Glutathione S-transferase 1 from Necator americanus (Na-GST-1) is a vaccine candidate for hookworm infection that has a high affinity for heme and metal porphyrins. As part of attempts to clarify the mechanism of heme detoxification by hookworm GSTs, co-crystallization and soaking studies of Na-GST-1 with the heme-like molecules protoporphyrin IX disodium salt, hematin and zinc protoporphyrin were undertaken. While these studies did not yield the structure of the complex of Na-GST-1 with any of these molecules, co-crystallization experiments resulted in the first structures of the complex of Na-GST-1 with the substrate glutathione. The structures of the complex of Na-GST-1 with glutathione were solved from pathological crystalline aggregates comprising more than one crystal form. These first structures of the complex of Na-GST-1 with the substrate glutathione were solved by molecular replacement from data collected with a sealed-tube home source using the previously reported apo structure as the search model.
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Affiliation(s)
- Oluwatoyin A. Asojo
- National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA
| | - Christopher Ceccarelli
- National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA
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14
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Affiliation(s)
- Peter J. Hotez
- Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Departments of Pediatrics and Molecular Virology and Microbiology, National School of Tropical Medicine at Baylor College of Medicine, Houston, Texas, United States of America
- Departments of Medical Humanities and Biology, Baylor University, Waco, Texas, United States of America
- James A. Baker III Institute for Public Policy, Rice University, Houston, Texas, United States of America
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15
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Affiliation(s)
- Peter J. Hotez
- National School of Tropical Medicine at Baylor College of Medicine, Houston, Texas, United States of America
- Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Houston, Texas, United States of America
- James A. Baker III Institute at Rice University, Houston, Texas, United States of America
- * E-mail:
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16
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Chacha M, Yohana C, Nkwengulila G. Indigenous Knowledge, Practices, Beliefs and Social Impacts of Porcine Cysticercosis and Epilepsy in Iringa Rural. Health (London) 2014. [DOI: 10.4236/health.2014.621328] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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17
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Kelleher A, Zhan B, Asojo OA. Structure of monomeric Na-GST-3, a glutathione S-transferase from the major human hookworm parasite Necator americanus. Acta Crystallogr Sect F Struct Biol Cryst Commun 2013; 69:839-43. [PMID: 23908024 PMCID: PMC3729155 DOI: 10.1107/s1744309113017661] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2013] [Accepted: 06/26/2013] [Indexed: 11/10/2022]
Abstract
Necator americanus is the major cause of human hookworm infection, which is a global cause of anemia in the developing world. Ongoing efforts to control hookworm infection include the identification of candidate vaccine antigens as well as potential therapeutic targets from the infective L3 larval stages and adult stages of the parasite. One promising family of proteins are the adult-stage-secreted cytosolic glutathione S-transferases (GSTs). Nematode GSTs facilitate the inactivation and degradation of a variety of electrophilic substrates (drugs) via the nucleophilic addition of reduced glutathione. Parasite GSTs also play significant roles in multi-drug resistance and the modulation of host immune defense mechanisms. Here, the structure of Na-GST-3, one of three GSTs secreted by adult-stage N. americanus, is reported. Unlike most GST structures, the Na-GST-3 crystal contains a monomer in the asymmetric unit. However, the monomer forms a prototypical GST dimer across the crystallographic twofold. A glutathione from the fermentation process is bound to the monomer. The overall binding cavity of Na-GST-3 is reminiscent of that of other N. americanus GSTs and is larger and capable of binding a wider array of ligands than GSTs from organisms that have other major detoxifying mechanisms. Furthermore, despite having low sequence identity to the host GST, Na-GST-3 has a greater tertiary-structure similarity to human sigma-class GST than was observed for the other N. americanus GSTs.
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Affiliation(s)
- Alan Kelleher
- Department of Pediatrics and National School of Tropical Medicine, Baylor College of Medicine, 1102 Bates Avenue BCM 320, Houston, TX 77030, USA
| | - Bin Zhan
- Department of Pediatrics and National School of Tropical Medicine, Baylor College of Medicine, 1102 Bates Avenue BCM 320, Houston, TX 77030, USA
| | - Oluwatoyin A. Asojo
- Department of Pediatrics and National School of Tropical Medicine, Baylor College of Medicine, 1102 Bates Avenue BCM 320, Houston, TX 77030, USA
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18
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Ajonina-Ekoti I, Kurosinski MA, Younis AE, Ndjonka D, Tanyi MK, Achukwi M, Eisenbarth A, Ajonina C, Lüersen K, Breloer M, Brattig NW, Liebau E. Comparative analysis of macrophage migration inhibitory factors (MIFs) from the parasitic nematode Onchocerca volvulus and the free-living nematode Caenorhabditis elegans. Parasitol Res 2013; 112:3335-46. [DOI: 10.1007/s00436-013-3513-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2013] [Accepted: 06/17/2013] [Indexed: 10/26/2022]
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19
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Hotez PJ. The Four Horsemen of the Apocalypse: Tropical Medicine in the Fight against Plague, Death, Famine, and War. Am J Trop Med Hyg 2012; 87:3-10. [PMID: 22764283 PMCID: PMC3391054 DOI: 10.4269/ajtmh.2012.11-0814] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Affiliation(s)
- Peter J. Hotez
- *Address correspondence to Peter J. Hotez, National School of Tropical Medicine, Baylor College of Medicine, 1 Baylor Plaza (Suite 164a), Houston, TX, 77030. E-mail:
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20
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El Ridi RAF, Tallima HAM. Novel therapeutic and prevention approaches for schistosomiasis: review. J Adv Res 2012; 4:467-78. [PMID: 25685454 PMCID: PMC4293887 DOI: 10.1016/j.jare.2012.05.002] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2012] [Revised: 05/12/2012] [Accepted: 05/15/2012] [Indexed: 01/23/2023] Open
Abstract
Schistosomiasis is a debilitating disease affecting approximately 600 million people in 74 developing countries, with 800 million, mostly children at risk. To circumvent the threat of having praziquantel (PZQ) as the only drug used for treatment, several PZQ derivatives were synthesized, and drugs destined for other parasites were used with success. A plethora of plant-derived oils and extracts were found to effectively kill juvenile and adult schistosomes, yet none was progressed to pre- and clinical studies except an oleo-gum resin extracted from the stem of Commiphora molmol, myrrh, which action was challenged in several trials. We have proposed an essential fatty acid, a component of our diet and cells, the polyunsaturated fatty acid arachidonic acid (ARA) as a remedy for schistosomiasis, due to its ability to activate the parasite tegument-bound neutral sphingomyelinase, with subsequent hydrolysis of the apical lipid bilayer sphingomyelin molecules, allowing access of specific antibody molecules, and eventual worm attrition. This concept was convincingly supported using larval and adult Schistosoma mansoni and Schistosoma haematobium worms in in vitro experiments, and in vivo studies in inbred mice and outbred hamsters. Even if ARA proves to be an entirely effective and safe therapy for schistosomiasis, it will not prevent reinfection, and accordingly, the need for developing an effective vaccine remains an urgent priority. Our studies have supported the status of S. mansoni calpain, glutathione-S-transferase, aldolase, triose phosphate isomerase, glyceraldehyde 3-phosphate dehydrogenase, enolase, and 2-cys peroxiredoxin as vaccine candidates, as they are larval excreted-secreted products and, contrary to the surface membrane molecules, are entirely accessible to the host immune system effector elements. We have proposed that the use of these molecules, in conjunction with Th2 cytokines-inducing adjuvants for recruiting and activating eosinophils and basophils, will likely lead to development and implementation of a sterilizing vaccine in a near future.
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Affiliation(s)
- Rashika A F El Ridi
- Zoology Department, Faculty of Science, Cairo University, Cairo 12613, Egypt
| | - Hatem A-M Tallima
- Zoology Department, Faculty of Science, Cairo University, Cairo 12613, Egypt
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21
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Liu GH, Gasser RB, Su A, Nejsum P, Peng L, Lin RQ, Li MW, Xu MJ, Zhu XQ. Clear genetic distinctiveness between human- and pig-derived Trichuris based on analyses of mitochondrial datasets. PLoS Negl Trop Dis 2012; 6:e1539. [PMID: 22363831 PMCID: PMC3283558 DOI: 10.1371/journal.pntd.0001539] [Citation(s) in RCA: 92] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2010] [Accepted: 01/11/2012] [Indexed: 01/15/2023] Open
Abstract
The whipworm, Trichuris trichiura, causes trichuriasis in ∼600 million people worldwide, mainly in developing countries. Whipworms also infect other animal hosts, including pigs (T. suis), dogs (T. vulpis) and non-human primates, and cause disease in these hosts, which is similar to trichuriasis of humans. Although Trichuris species are considered to be host specific, there has been considerable controversy, over the years, as to whether T. trichiura and T. suis are the same or distinct species. Here, we characterised the entire mitochondrial genomes of human-derived Trichuris and pig-derived Trichuris, compared them and then tested the hypothesis that the parasites from these two host species are genetically distinct in a phylogenetic analysis of the sequence data. Taken together, the findings support the proposal that T. trichiura and T. suis are separate species, consistent with previous data for nuclear ribosomal DNA. Using molecular analytical tools, employing genetic markers defined herein, future work should conduct large-scale studies to establish whether T. trichiura is found in pigs and T. suis in humans in endemic regions.
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Affiliation(s)
- Guo-Hua Liu
- State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province, People's Republic of China
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22
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Affiliation(s)
- Peter J. Hotez
- Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Baylor College of Medicine, Houston, Texas, United States of America
- National School of Tropical Medicine at Baylor College of Medicine, Houston, Texas, United States of America
- * E-mail: (PJH); (SA)
| | - Serap Aksoy
- Yale School of Public Health, New Haven, Connecticut, United States of America
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23
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Bethony JM, Cole RN, Guo X, Kamhawi S, Lightowlers MW, Loukas A, Petri W, Reed S, Valenzuela JG, Hotez PJ. Vaccines to combat the neglected tropical diseases. Immunol Rev 2011; 239:237-70. [PMID: 21198676 DOI: 10.1111/j.1600-065x.2010.00976.x] [Citation(s) in RCA: 120] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
The neglected tropical diseases (NTDs) represent a group of parasitic and related infectious diseases such as amebiasis, Chagas disease, cysticercosis, echinococcosis, hookworm, leishmaniasis, and schistosomiasis. Together, these conditions are considered the most common infections in low- and middle-income countries, where they produce a level of global disability and human suffering equivalent to better known conditions such as human immunodeficiency virus/acquired immunodeficiency syndrome and malaria. Despite their global public health importance, progress on developing vaccines for NTD pathogens has lagged because of some key technical hurdles and the fact that these infections occur almost exclusively in the world's poorest people living below the World Bank poverty line. In the absence of financial incentives for new products, the multinational pharmaceutical companies have not embarked on substantive research and development programs for the neglected tropical disease vaccines. Here, we review the current status of scientific and technical progress in the development of new neglected tropical disease vaccines, highlighting the successes that have been achieved (cysticercosis and echinococcosis) and identifying the challenges and opportunities for development of new vaccines for NTDs. Also highlighted are the contributions being made by non-profit product development partnerships that are working to overcome some of the economic challenges in vaccine manufacture, clinical testing, and global access.
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Affiliation(s)
- Jeffrey M Bethony
- Microbiology, Immunology, and Tropical Medicine, George Washington University Medical Center, Washington, DC 20037, USA.
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Hotez PJ. Unleashing "civilian power": a new American diplomacy through neglected tropical disease control, elimination, research, and development. PLoS Negl Trop Dis 2011; 5:e1134. [PMID: 21738802 PMCID: PMC3125138 DOI: 10.1371/journal.pntd.0001134] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Affiliation(s)
- Peter J. Hotez
- Sabin Vaccine Institute – Texas Children's Hospital – Baylor College of Medicine Center for Vaccine Development, Houston, Texas, United States of America
- Departments of Pediatrics and Molecular Virology & Microbiology, and National School of Tropical Medicine, Baylor College of Medicine, Houston Texas, United States of America
- * E-mail:
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Functional Diversity of the Schistosoma mansoni Tyrosine Kinases. JOURNAL OF SIGNAL TRANSDUCTION 2011; 2011:603290. [PMID: 21776387 PMCID: PMC3135232 DOI: 10.1155/2011/603290] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/02/2010] [Revised: 02/15/2011] [Accepted: 03/15/2011] [Indexed: 01/07/2023]
Abstract
Schistosoma mansoni, one of the causative agents of schistosomiasis, has a complex life cycle infecting over 200 million people worldwide. Such a successful and prolific parasite life cycle has been shown to be dependent on the adaptive interaction between the parasite and hosts. Tyrosine kinases (TKs) play a key role in signaling pathways as demonstrated by a large body of experimental work in eukaryotes. Furthermore, comparative genomics have allowed the identification of TK homologs and provided insights into the functional role of TKs in several biological systems. Finally, TK structural biology has provided a rational basis for obtaining selective inhibitors directed to the treatment of human diseases. This paper covers the important aspects of the phospho-tyrosine signaling network in S. mansoni, Caenorhabditis elegans, and humans, the main process of functional diversification of TKs, that is, protein-domain shuffling, and also discusses TKs as targets for the development of new anti-schistosome drugs.
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New antipoverty drugs, vaccines, and diagnostics: a research agenda for the US President's Global Health Initiative (GHI). PLoS Negl Trop Dis 2011; 5:e1133. [PMID: 21655348 PMCID: PMC3104954 DOI: 10.1371/journal.pntd.0001133] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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27
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Affiliation(s)
- Peter J. Hotez
- Sabin Vaccine Institute, Washington, D.C., United States of
America
- Department of Microbiology, Immunology, and Tropical Medicine, George
Washington University Medical Center, Washington, D.C., United States of
America
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28
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Affiliation(s)
- Peter J. Hotez
- Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, D.C., United States of America
- Sabin Vaccine Institute, Washington, D.C., United States of America
- * E-mail:
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29
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Hotez PJ. The neglected tropical diseases and their devastating health and economic impact on the member nations of the Organisation of the Islamic Conference. PLoS Negl Trop Dis 2009; 3:e539. [PMID: 19859530 PMCID: PMC2760759 DOI: 10.1371/journal.pntd.0000539] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Affiliation(s)
- Peter J. Hotez
- Department of Microbiology, Immunology, and Tropical Medicine, George Washington University Medical Center, Washington, D. C., United States of America
- Sabin Vaccine Institute, Washington, D. C., United States of America
- * E-mail:
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