If ivermectin-based programmes for the control of human onchocerciasis are to be successful, the drug must remain effective for as long as necessary. In an open, case-control study, an attempt was made to determine if the persistent, significant, Onchocerca volvulus microfilaridermias seen in some individuals who had received at least nine treatments with ivermectin were the result of the development of drug resistance in the parasite. Twenty-one of these 'sub-optimal' responders (cases) were matched, by age, weight, number of treatments, locality and skin microfilarial counts, with seven amicrofilaridermic responders and 14 ivermectin-naive subjects. The number of treatments taken, any potential drug interactions and significant underlying disease were determined from detailed clinical and laboratory studies. Each subject was treated with ivermectin during the study, so that plasma concentrations of the drug could be determined for 72 h from the time of dosage. The microfilarial and adult-worm responses to this treatment were assessed from skin microfilarial counts (obtained before the treatment and at days 8, 90 and 365 post-treatment), day-90 embryogrammes, and the results of fly-feeding experiments. Parasite-sensitivity criteria for various time-points were derived from earlier data on skin microfilaridermias and the effects of ivermectin on the adult worms. The results indicate that the significant microfilaridermias that persist despite multiple treatments with ivermectin are mainly attributable to the non-response of the adult female worms and not to inadequate drug exposure or other factors. The possibility that some adult female worms have developed resistance to ivermectin cannot be excluded. These results justify the routine monitoring of treatment efficacy in any ivermectin-based programme of disease control.

BackgroundIn 2007, various countries around the world notified 178677 cases of cholera and 4033 cholera deaths to the World Health Organization (WHO). About 62% of those cases and 56.7% of deaths were reported from the WHO African Region alone. To date, no study has been undertaken in the Region to estimate the economic burden of cholera for use in advocacy for its prevention and control. The objective of this study was to estimate the direct and indirect cost of cholera in the WHO African Region.MethodsDrawing information from various secondary sources, this study used standard cost-of-illness methods to estimate: (a) the direct costs, i.e. those borne by the health-care system and the family in directly addressing cholera; and (b) the indirect costs, i.e. loss of productivity caused by cholera, which is borne by the individual, the family or the employer. The study was based on the number of cholera cases and deaths notified to the World Health Organization by countries of the WHO African Region.ResultsThe 125018 cases of cholera notified to WHO by countries of the African Region in 2005 resulted in a real total economic loss of US$39 million, US$ 53.2 million and US$64.2 million, assuming a regional life expectancies of 40, 53 and 73 years respectively. The 203,564 cases of cholera notified in 2006 led to a total economic loss US$91.9 million, US$128.1 million and US$156 million, assuming life expectancies of 40, 53 and 73 years respectively. The 110,837 cases of cholera notified in 2007 resulted in an economic loss of US$43.3 million, US$60 million and US$72.7 million, assuming life expectancies of 40, 53 and 73 years respectively.ConclusionThere is an urgent need for further research to determine the national-level economic burden of cholera, disaggregated by different productive and social sectors and occupations of patients and relatives, and national-level costs and effectiveness of alternative ways of scaling up population coverage of potable water and clean sanitation facilities.

Objective: To identify key data sources of health information and describe their availability in countries of the World Health Organization (WHO) African Region. Methods: An analytical review on the availability and quality of health information data sources in countries; from experience, observations, literature and contributions from countries. Setting: Forty-six Member States of the WHO African Region. Participants: No participants. Main outcome measures: The state of data sources, including censuses, surveys, vital registration and health care facility-based sources. Results: In almost all countries of the Region, there is a heavy reliance on household surveys for most indicators, with more than 121 household surveys having been conducted in the Region since 2000. Few countries have civil registration systems that permit adequate and regular tracking of mortality and causes of death. Demographic surveillance sites function in several countries, but the data generated are not integrated into the national health information system because of concerns about representativeness. Health management information systems generate considerable data, but the information is rarely used because of concerns about bias, quality and timeliness. To date, 43 countries in the Region have initiated Integrated Disease Surveillance and Response. Conclusions: A multitude of data sources are used to track progress towards health-related goals in the Region, with heavy reliance on household surveys for most indicators. Countries need to develop comprehensive national plans for health information that address the full range of data needs and data sources and that include provision for building national capacities for data generation, analysis, dissemination and use.

BackgroundThe 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 FindingsData 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/SignificanceIncorporation 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.

The relation between the number of microfilariae (mf) ingested by host-seeking vectors of human onchocerciasis and skin mf load is an important component of the population biology of Onchocerca volvulus, with implications for disease control and evaluation of the risk of transmission recrudescence. The microsimulation model ONCHOSIM has been used to assess such risk in the area of the Onchocerciasis Control Program (OCP) in West Africa, based on a strongly nonlinear relation between vector mf uptake and human mf skin density previously published. However, observed levels of recrudescence have exceeded predictions, warranting a recalibration of the model. To this end, we present the results of a series of fly-feeding experiments carried out in savanna and forest localities of West Africa. Flies belonging to Simulium damnosum s.s., S. sirbanum, S. soubrense, and S. leonense were fed on mf carriers and dissected to assess the number of ingested mf escaping imprisonment by the peritrophic matrix (the number of exo-peritrophic mf), a predictor of infective larval output. The method of instrumental variables was used to obtain (nearly) unbiased estimates of the parameters of interest, taking into account error in the measurement of skin mf density. This error is often neglected in these types of studies, making it difficult to ascertain the degree of density-dependence truly present in the relation between mf uptake and skin load. We conclude that this relation is weakly (yet significantly) nonlinear in savanna settings but indistinguishable from linearity in forest vectors. Exo-peritrophic mf uptake does not account for most of the density dependence in the transmission dynamics of the parasite as previously thought. The number of exo-mf in forest simuliids is at least five times higher than in the savanna vectors. Parasite abundance in human onchocerciasis is regulated by poorly known mechanisms operating mainly on other stages of the lifecycle.