A Test-and-Not-Treat Strategy for Onchocerciasis inLoa loa–Endemic Areas

Abstract

Background:The most important risk encountered in distributing Mectizan® for the control of onchocerciasis in areas where Loa loa is co-endemic is the development of an encephalopathic syndrome in people with very high levels of L. loa [> 30,000 microfilariae/milliliter blood (mf/ml)] following treatment with Mectizan®. This syndrome, which occurs rarely, is characterized by symptoms such as confusion, lethargy, coma, and urinary incontinence.The reason this syndrome develops is that Mectizan®, in addition to being an effective drug against the microfilariae of Onchocerca volvulus (the causative agent of onchocerciasis), is also effective against L. loa microfilariae, the rapid killing of which has been associated with this encephalopathy. Like all serious illnesses, this encephalopathy requires prompt medical and nursing care to provide supportive treatment and to prevent nosocomial infections. With competent and timely medical care, patients usually recover fully. The pathogenesis of this encephalopathy remains unknown.L. loa is known, or suspected, to be endemic in humid forest areas of Central and East Africa. The precise distribution of L. loa is still being defined and mapped. Methodologies for mapping include parasitologic surveys, rapid assessment of L. loa based on the restricted definition of eye worm passage (RAPLOA), and predicted prevalence based on environmental factors conducive to the breeding of the vector of L. loa, Chrysops spp.Recent epidemiologic studies have shown that in areas where the prevalence of L. loa microfilaremia in adults exceeds 20%, the percentage of adults with L. loa microfilaremia greater than 30,000 mf/ml is about 1%.1 The threshold for increased community risk of L. loa encephalopathy following Mectizan® treatment has been defined as 20% microfilaremia prevalence which corresponds to a 40% prevalence of history of eye worm passage as measured by RAPLOA.

The Population Biology and Transmission Dynamics of Loa loa

“…proportion of individuals who exhibit these heavy microfilaraemia levels typically represents 1-2% of the population) [92,93]. Without suitably constructed mathematical models, the impact of these strategies on the transmission dynamics of loiasis will remain unclear and amenable only to informal and less rigorous analysis.…”

In Southern Nigeria Loa loa Blood Microfilaria Density is Very Low Even in Areas with High Prevalence of Loiasis: Results of a Survey Using the New LoaScope Technology

“…In Cameroon, the LoaScope has been successfully used to determine each individual's treatment eligibility based on his/ her L. loa density, excluding those with microfilaremia exceeding 20,000 mf/mL. 21,23 This strategy, called "Test and not Treat," is proposed as a possible way forward for onchocerciasis programs in L. loa-endemic areas. In this report we used the LoaScope as a survey technology to judge village (rather than individual) risk for CNS-AEs.…”

“…Very high-density L. loa infection was defined as ³ 20,000 mf/mL because the lower 95% confidence intervals from LoaScope readings of ³ 30,000 included 20,000 mf/mL. 23 Prevalence of very highdensity infection was calculated as the number of persons with ³ 20,000 mf/mL divided by the total number of persons examined overall, by age group (adult or children), and in the subset of villages having RAPLOA prevalence ³ 40%. Two percent very high-density infection was assumed to be at a CNS-AE risk threshold at or above which ivermectin MDA should not be given.…”

Reduction of Loa loa Microfilaremia with Imatinib — A Case Report

“…1 The pathogenesis of these serious adverse events after ivermectin treatment (or after diethylcarbamazine treatment) is believed to involve an inflammatory response to the massive release of parasite antigens that occurs with the rapid death of L. loa microfilariae. 2 Recently, elimination efforts have begun to focus on screening potential recipients of ivermectin and excluding from drug treatment those who have high levels of L. loa microfilariae to avoid these adverse effects — a strategy that is termed “test and not treat.” 3 We have previously reported in the L. loa genome the presence of a homologue of the human c-Abl tyrosine kinase. 4 The inhibition of this L. loa c-Abl–like tyrosine kinase with imatinib led to the slow death of microfilariae in vitro, 4 probably because imatinib targets the tyrosine kinase expression in the nuclei of the microfilariae.…”