Diagnostic challenges in monitoring and evaluating annual ivermectin (Mectizan^®) treatment intervention strategy to determine onchocerciasis elimination status

Abstract

Ability to accurately detect an active infection depends largely on the high accuracy (sensitivity and specificity) of a diagnostic test. There is no single diagnostic tool that meets the criteria of been simple, measurable, accurate, repeatable and timely (SMART). Combining the screening and confirmation tests have been relied upon in determining the true epidemiological situation of ongoing ivermectin or Mectizan® treatment intervention strategy. Antibody detection assays have been evaluated as screening tools using various formats like different types of agglutination protocol, enzyme linked immunosorbent assays (ELISA) and nucleic acid amplification tests (NAAT). Despite these developments, presence of any stage of the parasite antigen, microfilaria (fourth larva, L4) and macrofilaria (adult worm) confirms active infection. The standard microscopic examination of skin snips for emerged microfilaria obtained with a scleral biopsy punch is capable of spreading blood viral diseases. The sensitivity of the test has decreased following post-treatment with ivermectin and surveillance for recrudescence is inevitable. On one hand, the time preceding when parasite materials liberated as against when detectable immune responses were invoked decreases the sensitivity of serological tests. The DNA molecular based tests with the attendant complexity of protocol remained a technical barrier that has been surmounted with the development of loop- mediated isothermal amplification (LAMP). This technique amplifies DNA with high specificity, sensitivity and rapidity under isothermal conditions. It will serve as alternative definitive diagnostic test to skin microfilaria detection. A combination of LAMP with IgG4 antibodies against O. volvulus 16 kiloDalton (Ov16) antigen is used as a rapid qualitative test of human finger-prick blood, serum and plasma now widely applied in disease endemic countries. Also, diethyl carbamazine (DEC) patch skin test for popular eruption indicative of positive infection attracted further re-evaluation as non-invasive screening tool devoid of skin biopsy and blood sample collection.