The new World Health Organization (WHO) guidelines for stopping mass drug administration (MDA) and verification of elimination of human onchocerciasis require evaluating children under the age of 10 years using a serologic test for the detection of IgG4 antibody to the Ov-16 antigen. The designated sampling frame is designed to provide a 95% confidence interval (CI) that excludes 0.1%, and it assumes that the test is 100% sensitive and 100% specific. Recently, a rapid diagnostic test (RDT) for IgG4 antibody to Ov-16 became commercially available. Although the Ov-16 enzyme-linked immonusorbent assay (ELISA) has been used to make stopping decisions in the Americas and several foci in Africa, the RDT has not. It will be important understand how the RDT performs in comparison to the ELISA format in order to appropriately use the RDT for important programmatic decisions. The performance of the RDT has been compared to the ELISA in controlled setting using panels of samples with known infection status and in a programmatic setting in Togo. Both of these settings are more reflective of the hyper/mesoendemic setting. Little is known about how the RDT performs in settings with little to no transmission. According to the WHO guidelines, an operational research priority is to validate the use of the Ov-16 RDT for making the decision to stop mass drug administration for onchocerciasis (see section 220.127.116.11).
An additional research question specified in the new guidelines is the need to understand the rate of sero-reversion of the Ov-16 antibody response. This information could be used by modelers to help determine potential new thresholds for stopping MDA. More importantly, understanding the dynamics of the antibody response may make it possible to use Ov-16 serology in community-wide or school-based evaluations (potentially added on to evaluations for other purposes) for post-treatment surveillance (PTS) or post-elimination surveillance (PES). Finally, despite the successes in the Americas, it is not really possible to measure a 0.1% threshold using the currently available diagnostic tests (both ELISA and RDT) as neither test is 100% specific. Although the new guidelines allow programs to use skin snip polymerase chain reaction (PCR) to evaluate potential false positive Ov-16 reactivity, it is counterintuitive to use a test that is less sensitive than the initial test used to exclude a diagnosis. In the absence of a confirmatory serologic test, the most likely way forward is to identify more realistic, evidence-based thresholds and sampling frames that allow for some potential false positives.
Because of these needs, the Ov-16 meeting was convened in order to examine several issues of programmatic importance.
Specific objectives were:
1) To examine the currently available data in which the Ov-16 RDT was compared to Ov-16 ELISA or skin snip in a variety of epidemiologic settings in Africa
2) To begin to examine the appropriate serologic threshold and age group for determining that it is safe to stop MDA for onchocerciasis
3) To examine what is currently known about the rate of Ov-16 sero-reversion
Access key findings and discussion points in the PDF report attached to this page.