Relationship between skin snip and Ov16 ELISA: Two diagnostic tools for onchocerciasis in a focus in Cameroon after two decades of ivermectin-based preventive chemotherapy.

Background: Onchocerciasis elimination currently relies on repeated ivermectin-based preventive chemotherapy. Current World Health Organization's guidelines strongly recommend, though with low evidence of certainty, the use of Ov16 serology testing in children younger than 10 years old to assess whether mass drugs administration can be safely stopped. Therefore, more evidences are needed to support the use of this marker as sero-evaluation tool. This study aimed at determining the relationship between microfilaridermia and anti-Ov16 IgG4, and their variation according to age, gender and ivermectin intake history. Methodology: A cross-sectional survey was conducted in an area where ivermectin-based MDA has been implemented since more than 20 years. A questionnaire was used to record ivermectin intake history for the last 5 years. All volunteers aged ≥2 years were tested for microfilaridermia. IgG4 antibodies against Ov16 antigen were determined using the Standard Diagnostic Ov16 IgG4 ELISA kits and the recombinant anti-Ov16 AbD19432 antibodies. Prevalences, microfilaridermia counts and IgG4 concentrations were compared with regards to age, gender and history of ivermectin intake. Principal findings: The prevalence of skin microfilariae was 23.4% (95% CI: 23.4–30.8), whereas Ov16 seroprevalence was 53.2% (95% CI: 47.9–58.4). A moderate positive percentage agreement (50.4%) and a high negative percentage agreement (69.2%) was found between skin snip and Ov16 serology in the whole population, while in children aged <10 years, the agreements were higher (positive percentage agreement: 62.6%; negative percentage agreement: 83.5%). In addition, no associations were found between ivermectin intake, Mf counts and estimated IgG4 concentration of participants. Anti-Ov16 IgG4 were higher in individuals harboring microfilariae than their negative counterparts (p<0.0001), though a negative correlation was found between skin microfilarial counts and anti-Ov16 IgG4 levels (r = -0.2400; p = 0.03). No variation in microfilarial counts according to age and gender was observed. Though positively correlated with age (r = 0.4020; p<0.0001), IgG4 was significantly different between the different age classes (p<0.0001). Conclusion/Significance: Our results revealed moderate positive and negative agreements between parasitological and immunological parameters of onchocerciasis infection after several rounds MDA. Anti-Ov16 IgG4 levels increased with age but decreased with microfilarial counts, suggesting a variation of anti-Ov16 IgG4 as a result of constant exposure and accumulation of infection. This brings evidence sustaining the use of Ov16 serology in children as evaluation tool. However, additional investigations are needed to further reshape the appropriate age range among children aged <10 years old. Author summary: The elimination of onchocerciasis places high demands on monitoring and evaluation. The current WHO's guidelines recommend the use of serological test (ELISA) to determine the presence of IgG4 antibodies to the O. volvulus specific antigen Ov16 among children aged <10 years old, thought with low evidence of certainty. In this paper, we explored the relationship between anti-Ov16 IgG4 antibodies and microfilaridermia counts, and assessed their variation according to age, gender and history of ivermectin intake. Our findings revealed no variation of Mf count and IgG4 with ivermectin intake. However, we observed that anti-Ov16 IgG4 decrease with microfilaridermia counts, but an increasing trend was observed with age. This brings evidence sustaining the use of Ov16 serology testing as exposition marker in children younger than 10 years. However, children age 2 to 4 years seem to have a very low anti-Ov16 IgG4 concentration, this finding should be considered when defining the age class for seroprevalence evaluation. [ABSTRACT FROM AUTHOR]