Rabies Control: Could Innovative Financing Break the Deadlock?

The neglected zoonotic diseases (NZDs) have been all but eradicated in wealthier countries but remain major causes of ill-health and mortality in over 80 countries across Africa, Asia, and Latin America. The nature of neglect for the NZDs has been ascribed, in part, to underreporting resulting in an underestimation of their global burden that, together with a lack of advocacy, downgrades their relevance to policy-makers and funding agencies. While this may be the case for many NZDs, for rabies this is not the case. The global burden estimates for rabies (931,600 DALYs) more than justify prioritizing rabies control building on the strong advocacy platforms, functioning at local, regional, and global levels (including the Global Alliance for Rabies Control), and commitments from WHO, OIE, and FAO. Simple effective tools for rabies control exist together with blueprints for operationalizing control, yet, despite elimination targets being set, no global affirmative action has been taken. Rabies control demands activities both in the short term and over a long period of time to achieve the desired cumulative gains. Despite the availability of effective vaccines and messaging tools, rabies will not be sustainably controlled in the near future without long-term financial commitment, particularly as disease incidence decreases and other health priorities take hold. While rabies control is usually perceived as a public good, public private partnerships could prove equally effective in addressing endemic rabies through harnessing social investment and demonstrating the cost-effectiveness of control. It is acknowledged that greater attention to navigating local realities in planning and implementation is essential to ensuring that rabies, and other neglected diseases, are controlled sustainably. In the shadows of resource and institutional limitations in the veterinary sector in low- and middle-income countries, sufficient funding is required so that top-down interventions for rabies can more explicitly engage with local project organization capacity and affected communities in the long term. Development Impact Bonds have the potential to secure the financing required to deliver effective rabies control.

Cost-estimate and proposal for a development impact bond for canine rabies elimination by mass vaccination in Chad.

Close to 69,000 humans die of rabies each year, most of them in Africa and Asia. Clinical rabies can be prevented by post-exposure prophylaxis (PEP). However, PEP is commonly not available or not affordable in developing countries. Another strategy besides treating exposed humans is the vaccination of vector species. In developing countries, the main vector is the domestic dog, that, once infected, is a serious threat to humans. After a successful mass vaccination of 70% of the dogs in N'Djaména, we report here a cost-estimate for a national rabies elimination campaign for Chad. In a cross-sectional survey in four rural zones, we established the canine : human ratio at the household level. Based on human census data and the prevailing socio-cultural composition of rural zones of Chad, the total canine population was estimated at 1,205,361 dogs (95% Confidence interval 1,128,008-1,736,774 dogs). Cost data were collected from government sources and the recent canine mass vaccination campaign in N'Djaména. A Monte Carlo simulation was used for the simulation of the average cost and its variability, using probability distributions for dog numbers and cost items. Assuming the vaccination of 100 dogs on average per vaccination post and a duration of one year, the total cost for the vaccination of the national Chadian canine population is estimated at 2,716,359 Euros (95% CI 2,417,353-3,035,081) for one vaccination round. A development impact bond (DIB) organizational structure and cash flow scenario were then developed for the elimination of canine rabies in Chad. Cumulative discounted cost of 28.3 million Euros over ten years would be shared between the government of Chad, private investors and institutional donors as outcome funders. In this way, the risk of the investment could be shared and the necessary investment could be made available upfront - a key element for the elimination of canine rabies in Chad.

Estimating the burden of rhodesiense sleeping sickness during an outbreak in Serere, eastern Uganda.

BACKGROUND: Zoonotic sleeping sickness, or HAT (Human African Trypanosomiasis), caused by infection with Trypanosoma brucei rhodesiense, is an under-reported and neglected tropical disease. Previous assessments of the disease burden expressed as Disability-Adjusted Life Years (DALYs) for this infection have not distinguished T.b. rhodesiense from infection with the related, but clinically distinct Trypanosoma brucei gambiense form. T.b. rhodesiense occurs focally, and it is important to assess the burden at the scale at which resource-allocation decisions are made. METHODS: The burden of T.b. rhodesiense was estimated during an outbreak of HAT in Serere, Uganda. We identified the unique characteristics affecting the burden of rhodesiense HAT such as age, severity, level of under-reporting and duration of hospitalisation, and use field data and empirical estimates of these to model the burden imposed by this and other important diseases in this study population. While we modelled DALYs using standard methods, we also modelled uncertainty of our parameter estimates through a simulation approach. We distinguish between early and late stage HAT morbidity, and used disability weightings appropriate for the T.b. rhodesiense form of HAT. We also use a model of under-reporting of HAT to estimate the contribution of un-reported mortality to the overall disease burden in this community, and estimate the cost-effectiveness of hospital-based HAT control. RESULTS: Under-reporting accounts for 93% of the DALY estimate of rhodesiense HAT. The ratio of reported malaria cases to reported HAT cases in the same health unit was 133:1, however, the ratio of DALYs was 3:1. The age productive function curve had a close correspondence with the HAT case distribution, and HAT cases occupied more patient admission time in Serere during 1999 than all other infectious diseases other than malaria. The DALY estimate for HAT in Serere shows that the burden is much greater than might be expected from its relative incidence. Hospital based control in this setting appears to be highly cost-effective, highlighting the value of increasing coverage of therapy and reducing under-reporting. CONCLUSION: We show the utility of calculating DALYs for neglected diseases at the local decision making level, and emphasise the importance of improved reporting systems for acquiring a better understanding of the burden of neglected zoonotic diseases.

Treating cutaneous leishmaniasis patients in Kabul, Afghanistan: cost-effectiveness of an operational program in a complex emergency setting.

BACKGROUND: Although Kabul city, Afghanistan, is currently the worldwide largest focus of cutaneous leishmaniasis (CL) with an estimated 67,500 cases, donor interest in CL has been comparatively poor because the disease is non-fatal. Since 1998 HealthNet TPO (HNTPO) has implemented leishmaniasis diagnosis and treatment services in Kabul and in 2003 alone 16,390 were treated patients in six health clinics in and around the city. The aim of our study was to calculate the cost-effectiveness for the implemented treatment regimen of CL patients attending HNTPO clinics in the Afghan complex emergency setting. METHODS: Using clinical and cost data from the on-going operational HNTPO program in Kabul, published and unpublished sources, and discussions with researchers, we developed models that included probabilistic sensitivity analysis to calculate ranges for the cost per disability adjusted life year (DALY) averted for implemented CL treatment regimen. We calculated the cost-effectiveness of intralesional and intramuscular administration of the pentavalent antimonial drug sodium stibogluconate, HNTPO's current CL 'standard treatment'. RESULTS: The cost of the standard treatment was calculated to be 27 US dollars (95% C.I. 20-36) per patient treated and cured. The cost per DALY averted per patient cured with the standard treatment was estimated to be approximately 1,200 US dollars (761-1,827). CONCLUSION: According to WHO-CHOICE criteria, treatment of CL in Kabul, Afghanistan, is not a cost-effective health intervention. The rationale for treating CL patients in Afghanistan and elsewhere is discussed.

Crisis, what crisis? Control of Rhodesian sleeping sickness.

There is an urgent need for cost-effective strategies for the sustainable control of Trypanosoma brucei rhodesiense (Rhodesian) sleeping sickness, which is a fatal zoonotic disease that has caused devastating epidemics during the past century. Sleeping sickness continues to be controlled by crisis management, using active case detection, treatment and vector control - activities that occur only during major epidemics; during the intervening periods, farmers and communities must fend for themselves. There are several methods for assessing the burden of this disease and there is a series of farmer-led methodologies that can be applied to reduce the burden of human and animal trypanosomiases.

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.

A threshold analysis of the cost-effectiveness of artemisinin-based combination therapies in sub-saharan Africa.

Artemisinin-based combination therapies (ACTs) are generally regarded as vital in addressing the growing problem posed by the development of antimalarial resistance across sub-Saharan Africa. However, the costs of the new ACTs are likely to be significantly higher than current therapies. Therefore, it is important to examine formally the cost-effectiveness of the more effective yet more expensive ACTs before advocating a switch in policy. Importantly, any such economic evaluation must consider the temporal dynamics of drug resistance, and not just focus on the static question of whether switching today would be cost-effective at current levels of resistance, particularly since the development of new antimalarials in the future is so uncertain. However, predicting the future changes in drug resistance is a major difficulty in accurately quantifying the relative costs and health outcomes associated with different drug therapies over time. Here, we use a simple decision tree model to estimate the incremental cost-effectiveness of using ACTs, compared with persisting with current therapies, over 5-, 10-, and 15-year periods. We describe the dynamics of drug resistance using a general logistic growth function, in which the starting frequency of resistance and maximum growth may be altered. However, rather than make assumptions about the absolute rate at which resistance to ACTs will progress, we allow the ratio of the growth rate of resistance to ACTs relative to that of current therapies to vary. Defining the growth rate of ACT resistance in this manner allows us to calculate the threshold ratio at which ACTs would no longer appear cost-effective, for any starting conditions of resistance to current therapies and ACTs, and over any time period. The influence of uncertainty in other decision tree parameters on the threshold ratio values is also quantified, using Monte Carlo simulation techniques. This analysis shows that ACTs are more than 95% likely to be cost-effective under most conditions, other than very low levels of initial resistance to sulfadoxine/pyrimethamine and a five-year time frame. These predictions are conservative in that 95% certainty is a stringent decision rule favoring the rejection of new policies. The importance of other variables not included in the analysis for the robustness of the findings are discussed (e.g., consideration of the entire population at risk for malaria, the affordability of ACTs in specific settings, and the growth of resistance modeled according to population genetic parameters).