Gautam Biswas

The Global Programme to Eliminate Lymphatic Filariasis: Health Impact after 8 Years

Background In its first 8 years, the Global Programme to Eliminate Lymphatic Filariasis (GPELF) achieved an unprecedentedly rapid scale-up: >1.9 billion treatments with anti-filarial drugs (albendazole, ivermectin, and diethylcarbamazine) were provided via yearly mass drug administration (MDA) to a minimum of 570 million individuals living in 48 of the 83 initially identified LF-endemic countries. Methodology To assess the health impact that this massive global effort has had, we analyzed the benefits accrued first from preventing or stopping the progression of LF disease, and then from the broader anti-parasite effects (‘beyond-LF’ benefits) attributable to the use of albendazole and ivermectin. Projections were based on demographic and disease prevalence data from publications of the Population Reference Bureau, The World Bank, and the World Health Organization. Result Between 2000 and 2007, the GPELF prevented LF disease in an estimated 6.6 million newborns who would otherwise have acquired LF, thus averting in their lifetimes nearly 1.4 million cases of hydrocele, 800,000 cases of lymphedema and 4.4 million cases of subclinical disease. Similarly, 9.5 million individuals—previously infected but without overt manifestations of disease—were protected from developing hydrocele (6.0 million) or lymphedema (3.5 million). These LF-related benefits, by themselves, translate into 32 million DALYs (Disability Adjusted Life Years) averted. Ancillary, ‘beyond-LF’ benefits from the >1.9 billion treatments delivered by the GPELF were also enormous, especially because of the >310 million treatments to the children and women of childbearing age who received albendazole with/without ivermectin (effectively treating intestinal helminths, onchocerciasis, lice, scabies, and other conditions). These benefits can be described but remain difficult to quantify, largely because of the poorly defined epidemiology of these latter infections. Conclusion The GPELF has earlier been described as a ‘best buy’ in global health; this present tally of attributable health benefits from its first 8 years strengthens this notion considerably.

Treatment strategies underpinning the global programme to eliminate lymphatic filariasis

Lymphatic filariasis (LF) is a disease targeted for elimination. The global strategy is a once-yearly, single-dose, two-drug regimen utilised by communities at risk for LF, with the goal of reaching 80% population coverage yearly, for at least 5years, in order to interrupt transmission of LF. Where onchocerciasis is co-endemic, the regimen is ivermectin 200 – 400 μg/kg plus albendazole 400mg; elsewhere, the regimen should be diethylcarbamazine 6mg/kg plus albendazole 400mg. This paper reviews in detail the evidence for the efficacy and safety of these two-drug regimens underpinning the global strategy and makes recommendations for future developments in chemotherapy for LF, focusing on unresolved issues. These include optimal frequency, duration and end point of treatment, tools for monitoring successful therapy and means for detecting the potential development of resistance to any of the three antifilarial drugs on which the Global Programme to Eliminate LF depends.

The use of spatial analysis in mapping the distribution of bancroftian filariasis in four West African countries

Abstract The geographical distribution of human infection with Wuchereria bancrofti was investigated in four West African countries (Benin, Burkina Faso, Ghana and Togo), using a commercial immunochromatographic test for filarial antigen. Efforts were made to cover each health-system implementation unit and to ensure no sampling point was >50km from another, but otherwise the 401 study communities were selected at random. The aim was to enable spatial analysis of the data, to provide a prediction of the overall spatial relationships of the infection. The results, which were subjected to an independent random validation in Burkina Faso and Ghana, revealed that prevalence in the adult population of some communities exceeded 70% and that, over large areas of Burkina Faso, community prevalences were between 30% and 50%. Most of Togo, southern Benin and much of southern Ghana appeared completely free of the infection. Although there were foci on the Ghanaian coast with prevalences of 10%-30%, such high prevalences did not extend into coastal Togo or costal Benin. The prevalence map produced should be useful in prioritizing areas for filariasis control, identifying potential overlap with ivermectin-distribution activities undertaken by onchocerciasis-control programmes, and enabling inter-country and sub-regional planning to be initiated. The results indicate that bancroftian filariasis is more widely distributed in arid areas of Burkina Faso than hitherto recognized and that the prevalences of infection have remained fairly stable for at least 30 years. The campaign to eliminate lymphatic filariasis as a public-health problem in Africa will require significantly more resources (human, financial, and logistic) than previously anticipated.

Triple co-administration of ivermectin, albendazole and praziquantel in zanzibar: a safety study.

Background Public health interventions based on distribution of anthelminthic drugs against lymphatic filariasis (LF), onchocerciasis, soil-transmitted helminthiasis (STH) and schistosomiasis have been implemented separately to date. A better use of available resources might be facilitated by a more coordinated approach to control such infections, including the possibility of co-administering the three recommended anthelminthic drugs through a single, large-scale intervention. Methodology/Principal Findings Ivermectin, albendazole and praziquantel were co-administered to 5,055 children and adults living in areas endemic for LF, STH and schistosomiasis in Zanzibar, United Republic of Tanzania, during a pilot intervention aimed at elucidating and quantifying possible side-effects. Subsequently, these drugs were co-administered to about 700,000 individuals during a countrywide intervention targeting a large part of the total population of Zanzibar. Passive and active surveillance measures carried out during both interventions showed that side-effects attributable to the three drugs given at the same time were mild and self-limiting events. Conclusions/Significance Our data suggest that co-administration of ivermectin, albendazole and praziquantel is safe in areas where lymphatic filariasis, soil-transmitted helminthiasis and schistosomiasis are co-endemic and where several rounds of treatment with one or two drugs have been implemented in the past. Passive surveillance measures, however, should be continued and detection, management and reporting of possible side-effects should be considered a key component of any health intervention administering drugs.

Dracunculiasis (guinea worm disease): eradication without a drug or a vaccine

Dracunculiasis, commonly known as guinea worm disease, is a nematode infection transmitted to humans exclusively via contaminated drinking water. The disease prevails in the most deprived areas of the world. No vaccine or medicine is available against the disease: eradication is being achieved by implementing preventive measures. These include behavioural change in patients and communities—such as self-reporting suspected cases to health workers or volunteers, filtering drinking water and accessing water from improved sources and preventing infected individuals from wading or swimming in drinking-water sources—supplemented by active surveillance and case containment, vector control and provision of improved water sources. Efforts to eradicate dracunculiasis began in the early 1980s. By the end of 2012, the disease had reached its lowest levels ever. This paper reviews the progress made in eradicating dracunculiasis since the eradication campaign began, the factors influencing progress and the difficulties in controlling the pathogen that requires behavioural change, especially when the threat becomes rare. The challenges of intensifying surveillance are discussed, particularly in insecure areas containing the last foci of the disease. It also summarizes the broader benefits uniquely linked to interventions against dracunculiasis.

The Global Programme to Eliminate Lymphatic Filariasis: health impact during its first 8 years (2000-2007).

Abstract During its first 8 years, the Global Programme to Eliminate Lymphatic Filariasis provided more than 1900 million treatments with antifilarial drugs (albendazole, ivermectin and diethylcarbamazine) to at least 570 million people in 48 countries with endemic lymphatic filariasis (LF). As a result of this impressive global effort and an unprecedented public–private partnership, 8 years of mass drug administration (MDA) have prevented the spread of filarial infection to an estimated 6.6 million newborns, stopped the progression to clinical morbidity in 9.5 million individuals already infected with the parasites that cause LF, and drastically reduced the burden of several co-infections. The resulting health benefits of the MDA, in terms of reduced morbidity and disability-adjusted life-years, are thus enormous. The next step should be an analysis of the Global Programmes economic impact from its first 8 years of MDA.

Benchmarking the Cost per Person of Mass Treatment for Selected Neglected Tropical Diseases: An Approach Based on Literature Review and Meta-regression with Web-Based Software Application.

Background Advocacy around mass treatment for the elimination of selected Neglected Tropical Diseases (NTDs) has typically put the cost per person treated at less than US

The cost-effectiveness of an eradication programme in the end game: Evidence from guinea worm disease

0.50. Whilst useful for advocacy, the focus on a single number misrepresents the complexity of delivering “free” donated medicines to about a billion people across the world. We perform a literature review and meta-regression of the cost per person per round of mass treatment against NTDs. We develop a web-based software application (https://healthy.shinyapps.io/benchmark/) to calculate setting-specific unit costs against which programme budgets and expenditures or results-based pay-outs can be benchmarked. Methods We reviewed costing studies of mass treatment for the control, elimination or eradication of lymphatic filariasis, schistosomiasis, soil-transmitted helminthiasis, onchocerciasis, trachoma and yaws. These are the main 6 NTDs for which mass treatment is recommended. We extracted financial and economic unit costs, adjusted to a standard definition and base year. We regressed unit costs on the number of people treated and other explanatory variables. Regression results were used to “predict” country-specific unit cost benchmarks. Results We reviewed 56 costing studies and included in the meta-regression 34 studies from 23 countries and 91 sites. Unit costs were found to be very sensitive to economies of scale, and the decision of whether or not to use local volunteers. Financial unit costs are expected to be less than 2015 US

Monitoring equity in universal health coverage with essential services for neglected tropical diseases: an analysis of data reported for five diseases in 123 countries over 9 years

0.50 in most countries for programmes that treat 100 thousand people or more. However, for smaller programmes, including those in the “last mile”, or those that cannot rely on local volunteers, both economic and financial unit costs are expected to be higher. Discussion The available evidence confirms that mass treatment offers a low cost public health intervention on the path towards universal health coverage. However, more costing studies focussed on elimination are needed. Unit cost benchmarks can help in monitoring value for money in programme plans, budgets and accounts, or in setting a reasonable pay-out for results-based financing mechanisms.

Viewpoint on the review by Savioli and colleagues on the 2017 WHO guideline on soil-transmitted helminth infections in at-risk population groups

Background Of the three diseases targeted for eradication by WHO, two are so-called Neglected Tropical Diseases (NTDs)–guinea worm disease (GWD) and yaws. The Guinea Worm Eradication Programme (GWEP) is in its final stages, with only 25 reported in 2016. However, global eradication still requires certification by WHO of the absence of transmission in all countries. We analyze the cost-effectiveness of the GWEP in the end game, when the number of cases is lower and the cost per case is higher than at any other time. Ours is the first economic evaluation of the GWEP since a World Bank study in 1997. Methods Using data from the GWEP, we estimate the cost of the implementation, pre-certification and certification stages. We model cost-effectiveness in the period 1986–2030. We compare the GWEP to two alternative scenarios: doing nothing (no intervention since 1986) and control (only surveillance and outbreak response during 2016–2030). We report the cost per case averted, cost per disability adjusted life year (DALY) averted and cost per at-risk life year averted. We assess cost-effectiveness against a threshold of about one half GDP per capita (less than US