Paul G. Coleman

Re-evaluating the burden of rabies in Africa and Asia

OBJECTIVE To quantify the public health and economic burden of endemic canine rabies in Africa and Asia. METHODS Data from these regions were applied to a set of linked epidemiological and economic models. The human population at risk from endemic canine rabies was predicted using data on dog density, and human rabies deaths were estimated using a series of probability steps to determine the likelihood of clinical rabies developing in a person after being bitten by a dog suspected of having rabies. Model outputs on mortality and morbidity associated with rabies were used to calculate an improved disability-adjusted life year (DALY) score for the disease. The total societal cost incurred by the disease is presented. FINDINGS Human mortality from endemic canine rabies was estimated to be 55 000 deaths per year (90% confidence interval (CI) = 24 000-93 000). Deaths due to rabies are responsible for 1.74 million DALYs lost each year (90% CI = 0.75-2.93). An additional 0.04 million DALYs are lost through morbidity and mortality following side-effects of nerve-tissue vaccines. The estimated annual cost of rabies is USD 583.5 million (90% CI = USD 540.1-626.3 million). Patient-borne costs for post-exposure treatment form the bulk of expenditure, accounting for nearly half the total costs of rabies. CONCLUSION Rabies remains an important yet neglected disease in Africa and Asia. Disparities in the affordability and accessibility of post-exposure treatment and risks of exposure to rabid dogs result in a skewed distribution of the disease burden across society, with the major impact falling on those living in poor rural communities, in particular children.

Late-acting dominant lethal genetic systems and mosquito control

BackgroundReduction or elimination of vector populations will tend to reduce or eliminate transmission of vector-borne diseases. One potential method for environmentally-friendly, species-specific population control is the Sterile Insect Technique (SIT). SIT has not been widely used against insect disease vectors such as mosquitoes, in part because of various practical difficulties in rearing, sterilization and distribution. Additionally, vector populations with strong density-dependent effects will tend to be resistant to SIT-based control as the population-reducing effect of induced sterility will tend to be offset by reduced density-dependent mortality.ResultsWe investigated by mathematical modeling the effect of manipulating the stage of development at which death occurs (lethal phase) in an SIT program against a density-dependence-limited insect population. We found late-acting lethality to be considerably more effective than early-acting lethality. No such strains of a vector insect have been described, so as a proof-of-principle we constructed a strain of the principal vector of the dengue and yellow fever viruses, Aedes (Stegomyia) aegypti, with the necessary properties of dominant, repressible, highly penetrant, late-acting lethality.ConclusionConventional SIT induces early-acting (embryonic) lethality, but genetic methods potentially allow the lethal phase to be tailored to the program. For insects with strong density-dependence, we show that lethality after the density-dependent phase would be a considerable improvement over conventional methods. For density-dependent parameters estimated from field data for Aedes aegypti, the critical release ratio for population elimination is modeled to be 27% to 540% greater for early-acting rather than late-acting lethality. Our success in developing a mosquito strain with the key features that the modeling indicated were desirable demonstrates the feasibility of this approach for improved SIT for disease control.

Cost-effectiveness of malaria control in sub-Saharan Africa

BACKGROUND Information on the cost-effectiveness of malaria control is needed for the WHO Roll Back Malaria campaign, but is sparse. We used mathematical models to calculate cost-effectiveness ratios for the main prevention and treatment interventions in sub-Saharan Africa. METHODS We analysed interventions to prevent malaria in childhood (insecticide-treated nets, residual spraying of houses, and chemoprophylaxis) and pregnancy (chloroquine chemoprophylaxis and sulfadoxine-pyrimethamine intermittent treatment), and to improve malaria treatment (improved compliance, improved availability of second-line and third-line drugs, and changes in first-line drug). We developed models that included probabilistic sensitivity analysis to calculate ranges for the cost per disability-adjusted life year (DALY) averted for each intervention in three economic strata. Data were obtained from published and unpublished sources, and consultations with researchers and programme managers. FINDINGS In a very-low-income country, for insecticide treatment of existing nets, the cost-effectiveness range was US

Estimating human rabies mortality in the United Republic of Tanzania from dog bite injuries

4-10 per DALY averted; for provision of nets and insecticide treatment

Immunization coverage required to prevent outbreaks of dog rabies

19-85; for residual spraying (two rounds per year)

Identification of human-infective trypanosomes in animal reservoir of sleeping sickness in Uganda by means of serum-resistance-associated (SRA) gene

32-58; for chemoprophylaxis for children

Cost-effectiveness of malaria diagnostic methods in sub-Saharan Africa in an era of combination therapy

3-12 (assuming an existing delivery system); for intermittent treatment of pregnant women

The origins of a new Trypanosoma brucei rhodesiense sleeping sickness outbreak in eastern Uganda

4-29; and for improvement in case management

A dominant lethal genetic system for autocidal control of the Mediterranean fruitfly

1-8. Although some interventions are inexpensive, achieving high coverage with an intervention to prevent childhood malaria would use a high proportion of current health-care expenditure. INTERPRETATION Cost-effective interventions are available. A package of interventions to decrease the bulk of the malaria burden is not, however, affordable in very-low-income countries. Coverage of the most vulnerable groups in Africa will require substantial assistance from external donors.

Sleeping sickness: a tale of two diseases

OBJECTIVE To make quantitative predictions about the magnitude of underreporting of human rabies deaths in the United Republic of Tanzania. METHODS Human rabies deaths were estimated by using a series of probability steps to calculate the likelihood of rabies developing after the bite of a suspected rabid dog, incorporating field data on the incidence of animal bite injuries, the accuracy of rabies recognition, the distribution of bite wounds, and post-exposure treatment. FINDINGS Predicted human rabies mortality was estimated to be (a) 1499 deaths per year (95% confidence interval 891-2238), equivalent to an annual incidence of 4.9 (2.9-7.2) deaths/100,000, when active surveillance data on bite incidence were used, and (b) 193 deaths per year (32-409), corresponding to an annual incidence of 0.62 (0.1-1.32) deaths/100,000, when national bite statistics were used. The annual mean number of rabies deaths officially recorded for the same period was 10.8 (7.7-14.0). CONCLUSION In the United Republic of Tanzania, cases of rabies in humans have been greatly underreported. Dog bite injuries are an accessible source of epidemiological data that may be used to estimate the public health burden of rabies and to monitor epidemiological trends in developing countries.