A novel rapid test for detecting antibody responses to Loa loa infections

Ivermectin-based mass drug administration (MDA) programs have achieved remarkable success towards the elimination of onchocerciasis and lymphatic filariasis. However, their full implementation has been hindered in Central Africa by the occurrence of ivermectin-related severe adverse events (SAEs) in a subset of individuals with high circulating levels of Loa loa microfilariae. Extending MDA to areas with coincident L. loa infection is problematic, and inexpensive point-of-care tests for L. loa are acutely needed. Herein, we present a lateral flow assay (LFA) to identify subjects with a serological response to Ll-SXP-1, a specific and validated marker of L. loa. The test was evaluated on serum samples from patients infected with L. loa (n = 109) and other helminths (n = 204), as well as on uninfected controls (n = 77). When read with the naked eye, the test was 94% sensitive for L. loa infection and was 100% specific when sera from healthy endemic and non-endemic controls or from those with S. stercoralis infections were used as the comparators. When sera of patients with O. volvulus, W. bancrofti, or M. perstans were used as the comparators, the specificity of the LFA was 82%, 87%, and 88%, respectively. A companion smartphone reader allowed measurement of the test line intensities and establishment of cutoff values. With a cutoff of 600 Units, the assay sensitivity decreased to 71%, but the specificity increased to 96% for O. volvulus, 100% for W. bancrofti, and 100% for M. perstans-infected individuals. The LFA may find applications in refining the current maps of L. loa prevalence, which are needed to eliminate onchocerciasis and lymphatic filariasis from the African continent.
Author summary Loiasis affects over 10 million people in sub-Saharan Africa, and there are no commercial assays to detect Loa loa infection. New diagnostics for L. loa are urgently needed for two different purposes. First, although L. loa is generally a relatively asymptomatic infection, it has been associated with serious renal, cardiac, and neurological complications. Second, L. loa infection represents a major obstacle to the MDA-based elimination of river blindness and, to a lesser extent, of lymphatic filariasis. The programs to control and eliminate these parasites rely on mass administrations of ivermectin, a drug that has been associated with neurologic adverse events and sometimes death in patients with high levels of L. loa microfilariae. Herein, we present a novel lateral flow assay for L. loa infection. It is hoped that this test will help refine the current maps of loiasis, which will in turn allow optimization of programmatic decisions in the fight against O. volvulus and W. bancrofti, and ultimately against L. loa itself.