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

Abstract

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 co-endemic) East Region in Cameroon were tested for: i) Loa MFD in blood samples; ii) O. volvulus presence by SST, and iii) Ig[immunoglobulin]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 0–85200mf/mL. The CART model subdivided the sample into two Loa MFD classes with a discrimination threshold of 4080 (95% CI: 2180–12240) mf/mL. The probability of being SST positive exceeded 27% when Loa MFD was >4080mf/mL. Conclusions The probability of finding L. loa mf by SST increases significantly with Loa MFD. Skin-snip polymerase chain reaction (PCR) would be useful when monitoring onchocerciasis prevalence by SST in onchocerciasis–loiasis co-endemic areas.

Historical overview and geographical distribution of neglected tropical diseases amenable to preventive chemotherapy in the Republic of the Congo: A systematic review

“…Indeed, recent studies found that high L . loa microfilaremia can lead to false-positive results for the RDTs used for LF [ 124 – 126 ] and skin snips for onchocerciasis diagnosis [ 127 , 128 ]. Current mapping of onchocerciasis and LF in central Africa should be interpreted with caution in L .…”

“…While the diagnostic performance of some RDTs is good [122,123], improvements are still needed. Indeed, recent studies found that high L. loa microfilaremia can lead to false-positive results for the RDTs used for LF [124][125][126] and skin snips for onchocerciasis diagnosis [127,128]. Current mapping of onchocerciasis and LF in central Africa should be interpreted with caution in L. loa coendemic areas, and further mapping should jointly assess L. loa microfilarial density during these surveys.…”