Tandem Use of OvMANE1 and Ov-16 ELISA Tests Increases the Sensitivity for the Diagnosis of Human Onchocerciasis

Abstract

The current serological test for human onchocerciasis relies on IgG4 reactivity against the parasite Ov-16 antigen, with reported sensitivities of only 60–80%. As control programs move from control to elimination, it is imperative to identify novel molecules that could improve the serodiagnosis reliability of this disease. In this study we compared the sensitivity of total IgG against OvMANE1—a chimeric antigen previously identified as a potential biomarker of human onchocerciasis—with that of an Ov-16 antibody test to detect an Onchocerca volvulus infection in persons presenting with microfilaria in skin snips. One hundred and ninety serum samples were obtained from persons with epilepsy in an onchocerciasis-endemic area at Ituri in the Democratic Republic of Congo where ivermectin has never been distributed. Fifty-nine (31.1%) samples were from individuals with a positive skin snip test; 41 (69.5%) of these 59 samples were positive with the OvMANE1 test and 41 (69.5%) with the Ov-16 test; 30 (50.8%) samples were positive for both tests and in 52 (88.1%) at least one of the tests was positive. Testing the 131 sera from persons with a negative skin snip result revealed that 63 (48.1%) were positive exclusively with the OvMANE1 test, 13 (9.9%) exclusively with the Ov-16 test and 25 (19.1%) with both tests. Nine European samples from individuals without past travel history in onchocerciasis endemic zones and 15 samples from Rwanda, a hypoendemic country for onchocerciasis were all negative for the OvMANE1 and Ov-16 tests. However, the specificity of both tests was difficult to determine due to the lack of a gold standard for antibody tests. In conclusion, the tandem use of OvMANE1 and Ov-16 tests improves the sensitivity of detecting Onchocerca volvulus seropositive individuals but, the OvMANE1 test needs to be further evaluated on samples from a population infected with other helminths to cautiously address its specificity.

Immunoinformatics Design and Assessment of a Multiepitope Antigen (OvMCBL02) for Onchocerciasis Diagnosis and Monitoring

“…Thus, new diagnostic tools are needed to effectively diagnose onchocerciasis in the era of onchocerciasis elimination in Africa. The value of developing tests that incorporate a wider range of antigens have been highlighted previously by our group [ 46 ] and in a study from Yemen [ 47 ], where the use of additional antigens increased the detection of individuals exposed to O. volvulus. Thus, in this study, nine linear B-epitopes from six proteins were fused to form a multiepitope antigen (OvMCBL02).…”

“…Currently, the preferred epidemiological approach to diagnose O. volvulus infection utilizing sera from humans relies on the detection of an antibody response to the Ov-16 antigen [ 44 , 45 ]. However, this test has moderate sensitivity ranging between 60%–80% [ 18 ] and cannot distinguish between current and past infections [ 46 ], which renders it limited in the diagnosis of onchocerciasis. Thus, new diagnostic tools are needed to effectively diagnose onchocerciasis in the era of onchocerciasis elimination in Africa.…”

“…The OvMCBL02 test is an antibody-based test which is unable to differentiate between past and current infection; thus, control samples were obtained from Rwanda and Europe rather than Cameroon to exclude the possibility of including healthy individuals that may have been infected with the parasite in the past. Consistently, we were unable during our previous research activities to identify individuals who fully responded negative to antibody tests using other antigens, which is the reason why serum samples from a country hypoendemic for onchocerciasis such as Rwanda was the best control option [ 46 ]. The OvMCBL02 multiepitope antigen was able to significantly differentiate between serum from infected and uninfected individuals.…”

Nanobody Technology and New Molecular Biology Methods to Advance Rapid Diagnostic Test for Neglected Tropical Diseases

“…As noted previously, ELISA is among those "dual-purpose" immunoassay methods in use either for antibody or antigen detection. Antibody detection ELISAs for diagnosis of NTDs are many but only a few examples are listed here; the Hemagen ELISA for chagas disease [39], MAC-ELISA for dengue [40], Em2-ELISA for echinococcosis [41], the anti-Mycobacterium leprae phenolic glycolipid I (PGL-I) IgM ELISA for leprosy [42], the Ov-16 ELISA for onchocerciasis [43], and the FAST-ELISA for schistosomiasis [44]. Unlike antibody detecting ELISA, fewer antigen detecting ELISAs for diagnosis of NTDs exist.…”

Onchocerciasis: Current knowledge and future goals

“…A study by Hotterbeekx et al made a comparison between the sensitivity of the Ov-16 test alone with the tandem use of OvMANE1 and Ov-16, assuming that the tandem use of OvMANE1 and Ov-16 tests may represent a more appropriate tool for onchocerciasis elimination mapping because of the improved sensitivity (42).…”