Positivity of Antigen Tests Used for Diagnosis of Lymphatic Filariasis in Individuals Without Wuchereria bancrofti Infection But with High Loa loa Microfilaremia

Abstract

Since the mid-2000s, the immunochromatographic card test (ICT), a point-of-care test for detecting Wuchereria bancrofti circulating filarial antigens (CFAs), has been the backbone for mapping and monitoring lymphatic filariasis (LF) worldwide. Recently, there have been instances in which CFA positivity has been associated with Loa loa microfilaremia. Here, we examined the association, at both the community and individual levels, between L. loa and CFA using additional diagnostic tools (quantitative polymerase chain reaction [qPCR], Og4C3 enzyme-linked immunosorbent assay, and IgG4 antibodies to Wb123 assays) to demonstrate the relationship between L. loa microfilaremia and ICT positivity. In May 2013, peripheral blood was collected during the day from 1,812 individuals living in southern Cameroon. ICT tests were done on the spot, and positive individuals were resampled at night. Results of qPCR and Wb123 assays concurred proving the absence of W. bancrofti infection. Og4C3 assays indicate a quantitative relationship between the level of L. loa microfilaremia and that of CFA. This was confirmed by epidemiological analyses, which reveal a strong association between L. loa microfilaremia and ICT positivity, with 50% of ICT reacting to L. loa when its microfilarial density exceeds 30,000 microfilariae/mL. At the community level, the proportion of positive ICT would exceed 2% when the prevalence of L. loa microfilaremia in the total population is above 20%. This has significant implications in terms of mapping and control of LF caused by W. bancrofti in Loa-endemic areas. Cross-reactivity of ICT with L. loa has to be considered in the context of both individual and community diagnostics.

Mapping lymphatic filariasis in Loa loa endemic health districts naïve for ivermectin mass administration and situated in the forested zone of Cameroon

“…Analysis with microscopy using night blood TBF and qPCR, indicated zero presence of W. bancrofti but a high L loa density. The absence of W. bancrofti in night blood smears and qPCR, confirm previous findings [15,17], that high L loa mf was probably the cause of FTS positivity, as earlier observed with ICT due to cross-reaction, since FTS was developed with the same reagents as ICT [16].…”

“…Discrepancies were noticed between FTS results with those obtained from microscopy and qPCR respectively. However, previous works [15] reported high L loa mf to be associated with false positivity of the ICT test. Due to suspicion that FTS positivity could be caused by a possible cross-reaction between L. loa and W. bancrofti infection, two methods (Microscopy and qPCR), confirmed the absence of W. bancrofti and demonstrated the presence of L. loa.…”

“…In the past, epidemiological mapping used ICT cards to assess the prevalence of LF but recent findings in Democratic Republic of the Congo (DRC) and Cameroon reported cross reactivity of this tool with high L loa Mf load in blood [12][13][14]. Another study demonstrated the loss of sensitivity of the ICT test in detecting W. bancrofti in low prevalence settings [15,16]. Recently, a new strategy was developed to assess LF in co-endemic areas with other filariae [17].…”

Lymphatic Filariasis: An Overview

“…[TropBio, Australia], immunochromatographic card test), antibody assays, and polymerase chain reaction [5,7,8,9,15,24,30,37,38].…”

Loa loa vectors Chrysops spp.: perspectives on research, distribution, bionomics, and implications for elimination of lymphatic filariasis and onchocerciasis

“…The epidemiological complexity of these problems has been highlighted by Molyneux et al [13], and more recently by the observations that there is cross-reactivity of the rapid antigen diagnostic BinaxNOW Filariasis immunochromatographic test (ICT), where positive ICT positive cases have been shown to be the result of infection with L. loa , thus complicating the diagnostic and monitoring assessments required of LF programmes [14–17]. …”