Viral infections in orthopedics: A systematic review and classification proposal

Table 3 Study characteristics of the included articles dealing with Chikungunya virus infection

Author (year)	Virus information	Study design	Inoculated groups and number of subjects	Outcome measures	Follow-up
Chang (2017)	Colombian patients infected by CHIKV	Case-control study of 38 participants with CHIVK and chronic arthritis and 10 location-matched controls without CHIKV or arthritis	Group 1: Out of 907 patients who were clinically (424) and laboratory (483) confirmed for CHIKV, 38 individuals with chronic arthritis post-infection were selected; Group 2: 10 matched controls without CHIKV/arthritis were considered	Synovial fluid samples were analyzed by PCR, and mass spectrometry for viral proteins. No virus could be detected.	Not specified
Chen (2015)	Chikungunya virus from infected patients' serum. CHIKV-mCherry strain was also used	In vitro study utilizing serum from 14 CHIK patients and 7 healthy individuals; In vivo animal study utilizing 25 d-old C57BL/6 mice infected with CHIKV/mCherry	Group 1: Serum from 14 CHIKV patients (8F 6M) was collected between the 3rd and 22nd week post-infection; Group 2: Serum from 7 (4F and 3M) healthy individuals was also used; Group 1: 25 d-old mice were infected with 20 μL 105 PFU CHIKV-mCherry in the ventral side of the foot. Group 2: Consisted of the control group of mice.	For the in vitro study: Serum RANKL/OPG ratio was measured; For the in vivo study: Day 3 post-infection peak swelling was measured until day 10. Levels of RANKL and OPG were measured inside the joint during days 1, 3, 7 and 15 post-infection.	Days 1, 3, 7, and 15 post-infection
Goupil (2016)	Chikungunya virus SVO 476-96	In vivo animal study featuring IRF 3/7 C57BL/6 mice (M and F > 8 wk old) and C57BL/6J mice (> 8 wk old only F)	Group 1: 11 IRF mice were intradermally injected with 2 × 104 PFU; Group 2: 9 control C57BL/6j mice were injected with 2 × 104 PFU	Intact hindlimbs were collected and scanned μCT to evaluate the difference between the morphology of two types of mice (joint, trabecular bone). Histopathological evaluation was also performed. On day 5, post-infection 4 mice were euthanized due to being lethargic, and 6 mice died due to rapid progression of the illness	For the IRF mice 1, 2, 3, 5, 6, 7th day post-infection;For the C57BL/6J mice 7, 14, 21st day post-infection
Hawman (2013)	Chikungunya SL15649 from serum sample	In vivo animal study featuring 3-week-old C57BL/6J mice and congenial rag_/- mice	Group 1: 55 mice were inoculated in the left rear footpad with 103 PFU (10 μL). MAbs (200 μg each of CHK-152 and CHK-166) were administered intraperitoneally on days -1 and 3 for prophylaxis studies. For therapeutic studies, MAbs were administered on days 21 and 25 post-infection; Group 2: Control mice were subject to mock-infection	Duration of CHIKV infection in tissues was assessed, and associated histopathological changes were evaluated	Day 3 and weeks 1, 2, 4, 6, 12, 16

CHIKV: Chikungunya virus; PCR: Polymerase chain reaction; WT: Wild type; RT-PCR: Reverse transcription polymerase chain reaction; μCT: Micro-computed tomography; M: Male; F: Female; IL-6: Interleukin 6; PFU: Plaque-forming unit; MAbs: Monoclonal antibodies.