Association between microfilarial load and excess mortality in onchocerciasis: An epidemiological study

Department of Epidemiology and Public Health, Imperial College London, London, UK.
The Lancet (Impact Factor: 45.22). 05/2004; 363(9420):1514-1521. DOI: 10.1016/S0140-6736(04)16151-5
Source: PubMed


Infection with the parasitic filarial nematode Onchocerca volvulus can lead to severe visual impairment and ultimately blindness. Excess mortality has been noted among people with onchocerciasis, but it is not clear whether this effect is entirely due to blindness, or mediated by some more direct effects of the infection.
We assessed the relations between infection with O volvulus, visual acuity, and host mortality with data obtained by the Onchocerciasis Control Programme in West Africa from 2315 villages in 11 countries.
297,756 people were eligible for follow-up, and accumulated 2,579449 person-years of follow-up from 1971 through 2001. 24,517 people died during this period; 1283 (5.2%) of these deaths were due to onchocerciasis. Mortality of the human host was significantly and positively associated with increasing microfilarial burden (p<0.00001), but not with blindness after adjustment for microfilarial load and other variables. Overall, after adjustment for microfilarial load and other variables, female individuals had a risk of death about 7.5% lower than males (p<0.00001). Rates of mortality peaked in the mid 1980s but generally decreased thereafter.
We have shown a direct relation between O volvulus microfilarial load and host mortality in a comprehensive dataset and in both sexes.

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    • "The estimated DALYs include the excess mortality of sighted individuals with heavy microfilarial loads [8,9], which has not been considered elsewhere. At baseline, the contribution of this mortality associated with infection was greater than the mortality associated with vision loss, and the difference between these two components of premature death increased with increasing levels of pre-control endemicity. "
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    ABSTRACT: Background The African Programme for Onchocerciasis Control (APOC) has refocused its goals on the elimination of infection where possible, seemingly achievable by 15–17 years of annual mass distribution of ivermectin in some African foci. Previously, APOC had focused on the elimination of onchocerciasis as a public health problem. Timeframes have been set by the World Health Organization, the London Declaration on Neglected Tropical Diseases and the World Bank to achieve these goals by 2020–2025. Methods A novel mathematical model of the dynamics of onchocercal disease is presented which links documented associations between Onchocerca volvulus infection and the prevalence and incidence of morbidity and mortality to model outputs from our host age- and sex-structured onchocerciasis transmission framework (EpiOncho). The model is calibrated for African savannah settings, and used to assess the impact of long-term annual mass administration of ivermectin on infection and ocular and skin disease and to explore how this depends on epidemiological and programmatic variables. Results Current onchocerciasis disease projections, which do not account for excess mortality of sighted individuals with heavy microfilarial loads, underestimate disease burden. Long-term annual ivermectin treatment is highly effective at reducing both the morbidity and mortality associated with onchocerciasis, and this result is not greatly influenced by treatment coverage and compliance. By contrast, impact on microfilarial prevalence and intensity is highly dependent on baseline endemicity, treatment coverage and systematic non-compliance. Conclusions The goals of eliminating morbidity and infection with ivermectin alone are distinctly influenced by epidemiological and programmatic factors. Whilst the former goal is most certainly achievable, reaching the latter will strongly depend on initial endemicity (the higher the endemicity, the greater the magnitude of inter-treatment transmission), advising caution when generalising the applicability of successful elimination outcomes to other areas. The proportion of systematic non-compliers will become far more influential in terms of overall success in achieving elimination goals.
    Parasites & Vectors 05/2014; 7(1):241. DOI:10.1186/1756-3305-7-241 · 3.43 Impact Factor
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    • "coordinates the distribution of ivermectin ± albendazole to endemic populations. Because O. volvulus and L. loa can be co-endemic and treatment with ivermectin can lead to the rapid killing of L. loa larvae and induce severe adverse reactions (Anonymous, 2004; Gardon et al., 1997; Little et al., 2004), L. loa areas are first mapped and excluded from treatment (Wanji et al., 2005). In Latin America, the Onchocerciasis Elimination Program of the Americas (OEPA; "
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    ABSTRACT: Lymphatic filariasis and onchocerciasis are diseases of severe morbidity that affect the poorest of the poor in the world. The diseases are caused by filarial nematodes that are transmitted by mosquitoes or biting blackflies and are endemic to more than 80 countries worldwide, mainly in the tropics and sub-tropics. Current control programs aim to eliminate the diseases by distributing antifilarial drugs. However, the primary effect of the drugs is to kill the microfilariae in the blood or skin, thus preventing uptake by the obligate insect vector. Since the adult worms live 10 years or longer, drug distribution requires many years of treatment, which is a heavy burden on the burgeoning health care systems. Sub-optimal response, possible resistance and inadequate population coverage lessen the chances for successful elimination in all endemic areas. The search for new drugs that could enhance elimination by permanently sterilizing or killing adult worms has identified the Wolbachia intracellular bacteria of filarial nematodes as a target. Depleting the obligate endosymbionts from the worms with doxycycline or rifampicin causes a permanent block in oogenesis, embryogenesis and development, and in slow death of the adult worms. These two antibiotics are suitable for individual drug administration, but caveats exist for their inclusion in broader drug administration programs. Here we review Wolbachia as targets for antifilarial drug discovery and highlight the natural product corallopyronin A as an effective drug that is currently being developed specifically for use against filarial nematodes.
    International journal of medical microbiology: IJMM 09/2013; 304(1). DOI:10.1016/j.ijmm.2013.08.010 · 3.61 Impact Factor
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    • "The mf cause dermatitis, skin atrophy, and inflammation in the eyes, leading to reduced vision and blindness. Apart from blindness, a high mf load has been identified as a factor reducing the life span of infected people (Little et al. 2004). Vector control and mass treatment with ivermectin have been successfully used to regionally reduce the burden of this neglected disease. "
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    ABSTRACT: The effects of 5-week doxycycline treatment on the depletion of Wolbachia endobacteria from Onchocerca volvulus, on the interruption of embryogenesis and on microfilariae production, and with regard to macrofilaricidal activity were studied. In 2003, in an endemic area in Ghana, 22 onchocerciasis patients received 100 mg/day doxycycline for 5 weeks. Two years after the start of the study, 20 treated and ten untreated patients were nodulectomized and skin microfilariae were counted. The onchocercomas were examined by immunohistology for the presence of Wolbachia, embryogenesis, and vitality of adult filariae. The latter two parameters were further assessed by alternating logistic regression analysis, taking into account the dependency of worms and nodules in patients. Doxycycline resulted in depletion of Wolbachia and in complete interruption of embryogenesis in all worms that were assumed to have been present during treatment. In the treated patients, only 51% of the female worms were alive, compared to 84% in the untreated patients, indicating a moderate but distinct macrofilaricidal activity of doxycycline at this dose. It is concluded that, in areas with ongoing transmission, doxycycline cannot replace regular ivermectin mass treatment because new infections would require repeated rounds of doxycycline. However, doxycycline can be used for the treatment of individuals outside transmission areas, in foci where ivermectin resistance may occur, and in countries where onchocerciasis and loiasis are co-endemic.
    Parasitology Research 11/2008; 104(2):437-47. DOI:10.1007/s00436-008-1217-8 · 2.10 Impact Factor
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