Unusual Localization of Blood-Borne Loa loa Microfilariae in the Skin Depends on Microfilarial Density in the Blood: Implications for Onchocerciasis Diagnosis in Coendemic Areas

BACKGROUND: The diagnostic gold standard for onchocerciasis relies on identification and enumeration of (skin-dwelling) Onchocerca volvulus microfilariae (mf) using the skin snip technique (SST). In a recent study, blood-borne Loa loa mf were found by SST in individuals heavily infected with L. loa, and microscopically misidentified as O. volvulus due to their superficially similar morphology. This study investigates the relationship between L. loa microfilarial density (Loa MFD) and the probability of testing SST positive. METHODS: A total of 1053 participants from the (onchocerciasis and loiasis coendemic) East Region in Cameroon were tested for (1) Loa MFD in blood samples, (2) O. volvulus presence by SST, and (3) Immunoglobulin (Ig) G4 antibody positivity to Ov16 by rapid diagnostic test (RDT). A Classification and Regression Tree (CART) model was used to perform a supervised classification of SST status and identify a Loa MFD threshold above which it is highly likely to find L. loa mf in skin snips. RESULTS: Of 1011 Ov16-negative individuals, 28 (2.8%) tested SST positive and 150 (14.8%) were L. loa positive. The range of Loa MFD was 0–85 200 mf/mL. The CART model subdivided the sample into 2 Loa MFD classes with a discrimination threshold of 4080 (95% CI, 2180–12 240) mf/mL. The probability of being SST positive exceeded 27% when Loa MFD was >4080 mf/mL. CONCLUSIONS: The probability of finding L. loa mf by SST increases significantly with Loa MFD. Skin-snip polymerase chain reaction would be useful when monitoring onchocerciasis prevalence by SST in onchocerciasis–loiasis coendemic areas.