Onchocerciasis in Yemen: moving forward towards an elimination program.

The onchocerciasis focus in Yemen has been known for many years as an endemic area with unique characteristics, notably the atypical and most severe form of onchodermatitis, known as sowda or reactive onchodermatitis (ROD). The national effort to control the disease began in 1992 as an individual case treatment program by administering ivermectin to those presenting with ROD. The challenging geography of the endemic area and the current political and military unrest both underscore a need for special approaches when attempting to eliminate onchocerciasis from this country. An assessment of the national situation regarding this disease was carried out in 2011-2013 aimed at defining the best approach for moving from individual clinical case treatment to elimination of transmission. The history of the control efforts and the current status of the disease are reviewed and the essential changes needed to a mass drug administration (MDA) approach are identified as the national program addresses elimination. Yemen, despite the current troubles, has shown that it can successfully implement MDA programs despite many difficulties and therefore should be supported in its efforts towards countrywide elimination of this infection; however, success will need renewed national and international efforts.

Absence of an association between Plasmodium falciparum infection and post-ivermectin Loa-related non-neurologic serious adverse events.

Although ivermectin treatment can induce serious adverse events (SAEs) in individuals harboring high Loa loa microfilaremia (mf), not all patients with high mf levels develop such reactions, suggesting that cofactors may be involved. A study was conducted in Cameroon to investigate the possible role of Plasmodium coinfection at the time of ivermectin treatment in the development of SAEs. Before their first ivermectin treatment, thick smears were obtained from 4,175 individuals to determine the burden of Plasmodium sp., L. loa, and Mansonella perstans. After treatment, 18 (4.3 per 1,000) patients developed a non-neurologic SAE. Logistic regression analysis, adjusting for age, sex, P. falciparum infection, and M. perstans infection intensities, confirmed that L. loa mf was the main risk factor for SAEs. We found no evidence that coinfection with P. falciparum at the time of ivermectin treatment was associated with the occurrence of Loa-related SAEs in this population.

A controlled trial to assess the effect of quinine, chloroquine, amodiaquine, and artesunate on Loa loa microfilaremia.

Onchocerciasis control is currently based on mass ivermectin treatment. Unfortunately, this drug can induce serious adverse events (SAEs) in persons with high levels of Loa loa microfilaremia (> 30,000 microfilaria/mL). A means of preventing SAEs would be to treat at risk populations with a drug that would progressively reduce the microfilarial loads before administering ivermectin. Antimalarial drugs are a potential solution because they have shown some activity against various filarial species. A controlled trial was conducted to assess the effect of standard doses of quinine, chloroquine, amodiaquine, and artesunate on L. loa microfilaremia. Ninety-eight patients were randomly allocated into five groups (one for each drug and a control group) after stratification on microfilarial load. Loa loa microfilaremia was monitored on days 0, 3, 7, 15, 30, 60, and 90. No significant change in the loads was recorded in any of the treatment groups. A comprehensive review of the effects of antimalarial drugs against filariae is also provided.

Loa loa microfilarial periodicity in ivermectin-treated patients: comparison between those developing and those free of serious adverse events.

The main risk factor of post-ivermectin serious adverse events (SAEs) is the presence of a high Loa loa microfilaremia. However, the majority of patients with such high loads do not develop SAEs, suggesting that co-factors may be involved. An infection with simian Loa parasites, whose microfilariae show a nocturnal periodicity, might be such a co-factor. The periodicity of Loa microfilariae was compared, using cosinor methodology, in 4 patients who had developed a post-ivermectin neurologic SAE, 4 patients who had experienced a non-neurologic SAE, and 14 control individuals. The periodicity was similar in all three groups, with a peak of microfilaremia occurring between 12:30 and 2:00 PM. The results of this study, which for the first time characterizes the periodicity of Loa microfilariae mathematically, suggest that post-ivermectin SAEs are not related to an infection with a Loa simian strain.

Encephalopathy after ivermectin treatment in a patient infected with Loa loa and Plasmodium spp.

Despite over 350 million people being safely treated with ivermectin, there have been rare cases of death post-treatment; these events are most often associated with high Loa loa microfilaremia. This first autopsy description of an encephalopathy case following the administration of ivermectin involves a 45-year-old male who became comatose 3 days after treatment. He slowly deteriorated over 5 weeks and died at 54 days after the anthelminthic treatment, probably as a result of a secondary skin or pulmonary infection exacerbated by malnutrition. The major pre- and post-autopsy findings included the presence of high loads of Loa loa, positivity for Plasmodium, the presence of a longstanding respiratory condition, and vascular pathology in the brain. The central nervous system lesions have similarities with those described in previously reported cases of Loa loa-associated death following diethylcarbamazine treatment.

Randomized, controlled, double-blind trial with ivermectin on Loa loa microfilaraemia: efficacy of a low dose (approximately 25 microg/kg) versus current standard dose (150 microg/kg).

Neurological serious adverse events (SAEs) following ivermectin treatment may occur in individuals harbouring high Loa loa microfilarial densities and are of major concern in the context of mass ivermectin distributions organized in Africa for onchocerciasis and lymphatic filariasis control. As those SAEs are induced by the rapid and massive microfilaricidal effect of a standard dose of ivermectin (150 microg/kg), we performed a randomized, controlled, double-blind trial to determine whether ivermectin given as: (a) a single low dose of 1.5mg (i.e. 25 microg/kg for a 60 kg person); or (b) two doses of 1.5mg given at a 2 week interval leads to a more progressive decrease in Loa microfilarial loads compared with the standard dosage. A low dose of ivermectin brought about a significantly smaller decrease in Loa microfilaraemia than the standard dose. However, this decrease was not sufficiently different from that obtained after the standard dose to be acceptable to public health programmes, which require a wide safety margin. A second low dose of ivermectin given 15 days after the first dose did not lead to a further decrease in Loa microfilaraemia. Lastly, the variability in the response observed in the group treated with 25 microg/kg suggests that even lower doses would have no effect on a significant number of patients. Ivermectin given at a low dose (

The Mectizan Donation Program - highlights from 2005.

Through the Mectizan Donation Program, Merck & Co., Inc. has donated Mectizan (ivermectin, MSD) for the treatment of onchocerciasis worldwide since 1987. Mectizan has also been donated for the elimination of lymphatic filariasis (LF) since 1998 in African countries and in Yemen where onchocerciasis and LF are co-endemic; for LF elimination programs, Mectizan is co-administered with albendazole, which is donated by GlaxoSmithKline. The Mectizan Donation Program works in collaboration with the Mectizan Expert Committee/Albendazole Coordination, its scientific advisory committee. In 2005, a total of 62,201,310 treatments of Mectizan for onchocerciasis were approved for delivery via mass treatment programs in Africa, Latin America, and Yemen. Seventy-seven percent and 20% of these treatments for onchocerciasis were for countries included in the African Programme for Onchocerciasis Control (APOC) and the former-Onchocerciasis Control Programme in West Africa (OCP), respectively. The remaining 3% of treatments approved were for the six onchocerciasis endemic countries in Latin America, where mass treatment is carried out twice-yearly with the goal of completely eliminating morbidity and eventually transmission of infection, and for Yemen. All 33 onchocerciasis endemic countries where mass treatment with Mectizan is indicated have ongoing mass treatment programs. In 2005, 42,052,583 treatments of co-administered albendazole and Mectizan were approved for national Programs to Eliminate LF (PELFs) in Africa and Yemen. There are ongoing PELFs using albendazole and Mectizan in nine African countries and Yemen; these represent 35% of the total number of countries expected to require the co-administration of these two chemotherapeutic agents for LF elimination. In Africa, the expansion of existing PELFs and the initiation of new ones have been hampered by lack of resources, technical difficulties with the mapping of LF endemicity, and the co-endemicity of LF and loiasis. Included in this review are recommendations recently put forward for the co-administration of albendazole and Mectizan in areas endemic for LF, loiasis, and onchocerciasis.