Modelling the impact of ivermectin on River Blindness and its burden of morbidity and mortality in African Savannah: EpiOncho projections.

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.

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

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: We have shown a direct relation between O volvulus microfilarial load and host mortality in a comprehensive dataset and in both sexes.

Excess mortality associated with blindness in the onchocerciasis focus of the Mbam Valley, Cameroon.

The association between blindness, mortality and nutritional status was investigated in a retrospective cohort study in villages of central Cameroon where onchocerciasis is hyper-endemic. Overall, 101 blind subjects and 101 non-blind controls matched with the blind for age, sex and (generally) village of residence were followed for 10 years. Blindness gave rise to a significant increase in mortality (relative risk = 2.3; P = 0.012), the life expectancy of the blind adults being reduced by 4 years compared with that of their controls. For a given age, excess mortality was found to be associated with a late onset of blindness. The causes of death were similar for the blind and the controls but blind subjects had relatively low body mass indices, which may lead to relatively early fatal disease outcomes. These results are similar to those obtained in other parts of Africa and emphasise, once more, the demographic impact of blindness in developing countries.

Application of the verbal autopsy during a clinical trial.

During a community-based treatment trial of onchocerciasis with ivermectin, verbal autopsies were employed as one method to assess the safety of the drug. The verbal autopsy questionnaire was designed to determine causes of death and mortality differentials in the treated population. During the 8 months of surveillance here reported, 25 individuals died, yet only 9 of these deaths were certified. Seven of the deaths occurred to individuals who had been treated with ivermectin and the majority of the deaths occurred to children under 5, who were excluded from treatment. The verbal autopsy method was evaluated and validated by comparing the verbal autopsy diagnosis of cause of death to death certificate diagnosis, when available. In addition, verbal autopsies were retrospectively performed for all deaths which had occurred at the hospital during the 6 months preceding the start of the study, if these deaths were traceable to households in the surveillance population. We found that in 80% of the adult deaths, the verbal autopsy and death certificate diagnoses of underlying cause of death agreed. The verbal autopsy was less accurate in diagnosing child deaths which we attribute to the design of the verbal autopsy (being to detect potential drug related deaths in adults) and to the delay between death and interview. We conclude that verbal autopsies are an important addition to surveillance systems in remote areas where the absence or inadequacy of health information systems does not allow a thorough follow-up of all subjects in drug studies.