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

Onchocerciasis, commonly known as river blindness, is a filarial nematode infection caused by Onchocerca volvulus, transmitted by certain insect vector species of the genus Simulium.1 This disease is of public health importance because of its associated visual impairment, blindness, stigmatizing skin disease, and debilitating itching. Human disease results from inflammation around microfilaria (mf) released from fertilized adult female worms residing in fibrous subcutaneous “nodules.” Disease is more severe in individuals who have high numbers (“intensities”) of mf. The Simulium black fly vectors breed in rapidly flowing rivers and streams and become infected when they ingest mf during a blood meal; mf develop into third stage larvae that can infect humans when the vector takes subsequent blood meals. The World Health Organization (WHO) estimates that about 198.2 million people are at risk of infection and that 99% of them reside in Africa.1–3 Nigeria is among the countries with the highest burden of onchocerciasis.4 Mass drug administration (MDA) with ivermectin (Mectizan®, an oral medication donated by Merck, Kenilworth, NJ) kills the mf stage of the parasite and prevents onchocerciasis-associated eye and skin disease. A global partnership against river blindness, which includes the endemic countries, nongovernmental organizations, the Mectizan® Donation Program, and the WHO, has given more than 1 billion treatments for onchocerciasis since 1987.5 If the coverage and duration of ivermectin MDA programs are sufficient, mf densities can be kept sufficiently low to prevent the vectors from transmitting the infection. Because there are no important animal reservoirs of O. volvulus to maintain the transmission cycle independent of the human population, permanent elimination of transmission of onchocerciasis can be achieved, such as in four countries in the Americas and in some parts of Africa.6,7 In 2014 the African Program for Onchocerciasis Control called for a new goal of onchocerciasis transmission elimination for Africa. As part of that policy, an expansion of ivermectin MDA into previously untreated areas was proposed. These areas (the so-called “hypoendemic” areas) are those with sufficient O. volvulus transmission to maintain the adult parasite population but very little morbidity due to the near absence of high mf density infections. Untreated areas bordering ivermectin MDA programs are those most likely to be hypoendemic and therefore newly targeted for MDA.8 Loa loa, another filarial parasite prevalent in central Africa, is complicating the MDA expansion plan under the new onchocerciasis elimination paradigm. Loa loa is transmitted by deerflies (Chrysops species) that breed in high canopy-forested areas in Africa. Adult L. loa worms may migrate under the eye’s conjunctiva and be recognized by the infected individual.9–11 Adult female L. loa worms produce mf that (unlike in onchocerciasis) enter the blood stream; circulating L. loa mf can reach extremely high densities in the blood. The abrupt death of mf after the administration of a microfilaricidal agent such as ivermectin can rarely result in central nervous system adverse events (CNS-AEs) shortly after treatment that include changes in consciousness and, rarely, coma. Deaths have resulted from complications arising from prolonged coma events.12 Only individuals with very high L. loa mf densities (≥ 30,000/mL of blood) are at risk of these CNS-AEs.13–15 A technique called the Rapid Assessment Procedure for L. loa (RAPLOA) was developed over a decade ago to quickly and noninvasively assess an area for the risk of L. loa–related CNS-AEs after ivermectin MDA. A sample of 80 residents aged 15 years and older are individually asked if they at some point in the past experienced a worm moving across the surface of their eye. During the interview the respondents are shown a photograph of a L. loa worm in the eye. A multi-country study showed a strong correlation with ≥ 40% of residents answering “yes” (e.g., a RAPLOA prevalence of ≥ 40%), a village prevalence of L. loa microfilaremia ≥ 20%, and the village prevalence of very high-density L. loa ≥ 2%.16–20 These critical and correlated thresholds (RAPLOA ≥ 40%, L. loa microfilaremia prevalence ≥ 20% and very high-density L. loa ≥ 2%) define an area at high risk for L. loa CNS-AEs. The magnitude of this risk is poorly defined.14 High RAPLOA determinations in onchocerciasis hypoendemic areas are roadblocks to the onchocerciasis elimination agenda in L. loa–endemic countries such as Nigeria. Expansion of MDA into these hypoendemic areas is difficult to justify because the benefit from MDA in reducing morbidity from onchocerciasis is low compared with the risk of CNS-AEs from L. loa treatment. We report a survey in just such an area in Nigeria where there is presumed hypoendemic onchocerciasis and hyperendemic L. loa. Our purpose was to reevaluate the relationships among RAPLOA, L. loa microfilaremia prevalence, and most importantly, very high-density L. loa. We also assessed for onchocerciasis endemicity using a rapid diagnostic test for OV16 IgG4 antibodies; the results of that study will be reported elsewhere.