Density-dependent mortality of the human host in onchocerciasis: relationships between microfilarial load and excess mortality.

BACKGROUND: The parasite Onchocerca volvulus has, until recently, been regarded as the cause of a chronic yet non-fatal condition. Recent analyses, however, have indicated that in addition to blindness, the parasite can also be directly associated with human mortality. Such analyses also suggested that the relationship between microfilarial load and excess mortality might be non-linear. Determining the functional form of such relationship would contribute to quantify the population impact of mass microfilaricidal treatment. METHODOLOGY/PRINCIPAL FINDINGS: Data from the Onchocerciasis Control Programme in West Africa (OCP) collected from 1974 through 2001 were used to determine functional relationships between microfilarial load and excess mortality of the human host. The goodness-of-fit of three candidate functional forms (a (log-) linear model and two saturating functions) were explored and a saturating (log-) sigmoid function was deemed to be statistically the best fit. The excess mortality associated with microfilarial load was also found to be greater in younger hosts. The attributable mortality risk due to onchocerciasis was estimated to be 5.9%. CONCLUSIONS/SIGNIFICANCE: Incorporation of this non-linear functional relationship between microfilarial load and excess mortality into mathematical models for the transmission and control of onchocerciasis will have important implications for our understanding of the population biology of O. volvulus, its impact on human populations, the global burden of disease due to onchocerciasis, and the projected benefits of control programmes in both human and economic terms.