article: Between 2000–2007, the Global Programme to Eliminate Lymphatic Filariasis (GPELF) delivered more than 1. 9 billion treatments to nearly 600 million individuals via annual mass drug administration (MDA) of anti-filarial drugs (albendazole, ivermectin, diethylcarbamazine) to all at-risk for 4–6 years. Quantifying the resulting economic benefits of this significant achievement is important not only to justify the resources invested in the GPELF but also to more fully understand the Programme' s overall impact on some of the poorest endemic populations. To calculate the economic benefits, the number of clinical manifestations averted was first quantified and the savings associated with this disease prevention then analyzed in the context of direct treatment costs, indirect costs of lost-labor, and costs to the health system to care for affected individuals. Multiple data sources were reviewed, including published literature and databases from the World Health Organization, International Monetary Fund, and International Labour Organization An estimated US$21. 8 billion of direct economic benefits will be gained over the lifetime of 31. 4 million individuals treated during the first 8 years of the GPELF. Of this total, over US$2. 3 billion is realized by the protection of nearly 3 million newborns and other individuals from acquiring lymphatic filariasis as a result of their being born into areas freed of LF transmission. Similarly, more than 28 million individuals already infected with LF benefit from GPELF' s halting the progression of their disease, which results in an associated lifetime economic benefit of approximately US$19. 5 billion. In addition to these economic benefits to at-risk individuals, decreased patient services associated with reduced LF morbidity saves the health systems of endemic countries approximately US$2. 2 billion. MDA for LF offers significant economic benefits. Moreover, with favorable program implementation costs (largely a result of the sustained commitments of donated drugs from the pharmaceutical industry) it is clear that the economic rate of return of the GPELF is extremely high and that this Programme continues to prove itself an excellent investment in global health.
  As a leading cause of permanent and long-term disability worldwide, the parasitic infection lymphatic filariasis (LF) imposes a severe physical and socioeconomic burden on 1. 3 billion at-risk persons in 83 endemic countries. An estimated 120 million people are already infected with LF, with about 40 million suffering from overt clinical disease manifested as painful severe swelling due to lymphedema (generally an accumulation of lymphatic fluid in the limbs) and hydrocele (fluid accumulation in the scrotal sac). To rid the world of this debilitating disease, the Global Programme to Eliminate Lymphatic Filariasis (GPELF) was begun in 2000 to guide endemic countries in implementing single-dose, once-yearly mass drug administration (MDA) using a combination of either albendazole+ivermectin or albendazole+diethylcarbamazine (DEC) for an anticipated 4–6 years. Use of this effective strategy for LF elimination has become feasible because of the drug donations of albendazole and ivermectin from their pharmaceutical manufacturers, GlaxoSmithKline and Merck & Co. , Inc, respectively. Over the first 8 operational years of the GPELF (2000–2007), more than 1. 9 billion MDA treatments were administered to approximately 570 million individuals in 48 countries. This significant programmatic achievement has resulted in a notably beneficial impact on the health of endemic populations [1]. More than 6 million cases of hydrocele and 4 million cases of lymphedema have been prevented, resulting in over 32 million disability-adjusted life years (DALYs) averted and numerous quality-of-life benefits attained. What remains relatively undefined, however, is the economic significance of these achievements. Specifically, how much financial cost and loss of income is prevented over the lifetimes of individuals protected from LF due to the first 8 years of the GPELF? And, what cost savings do national health systems realize from the reduction in LF infection and morbidity? To date, few attempts have been made to examine LF from an economic perspective, particularly on a global level. Such data, however, is invaluable to policymakers, public health administrators, and program funders who may already be convinced that LF is a ‘best buy’ in global health but who lack precise estimates to support their conviction. This study offers such an economic analysis and estimates that following the first 8 years of the GPELF, US$21. 8 billion of economic benefits will be gained by LF infected and non-infected individuals in MDA-treated areas, in addition to US$2. 2 billion in health systems savings. Furthermore, though this economic assessment has not included the value of the many ancillary benefits on other concurrent infections that are effectively treated by the anti-LF drug regimens, it still leads to a far better understanding of the GPELF' s true overall impact on one of society' s most debilitating and widespread tropical diseases.
  Key data sources are listed below, though specific sources are cited throughout the paper: For this analysis, two broad groups of individuals are recognized as economically benefitting from the MDA treatment given during the first 8 years of the GPELF: Those protected from acquiring infection (and subsequent disease [specifically, hydrocele and/or lymphedema]); Those already infected but protected from disease progression. These two groups can be segmented into four sub-populations (detailed below and summarized in Table 1); together, they constitute the “benefit cohort population”. Population estimates for each sub-population were calculated using the same base figures and key assumptions as described previously [1]; namely that 10% of the at-risk population is actually infected with LF, that this ratio would remain constant in the absence of MDA, and that the relative frequency of the clinical disease syndromes will also remain stable among those infected individuals. The previous section defined a 4-part benefit cohort population as the group of protected individuals who will realize economic benefits as a result of MDA activity between 2000–2007. The total economic impact of the GPELF, however, extends over a much longer period than these first 8 years because protection from LF infection or disease progression is a lifelong benefit. It is therefore necessary to aggregate the total economic benefit gained over the projected remaining lifetime of the benefit cohort population. To estimate this total, a general formula (Figure 1) was applied and calculated independently for each country to accommodate country specific differences in several key variables (life expectancy, mortality rate, direct and indirect costs). All calculated costs and benefits are discounted to the base year of 2008. For this study, 2008 was used as the base year for calculating economic benefits. When calculating future benefits, however, it is necessary to discount values to a net present value (NPV) under the economic principle that a dollar earned in the present is worth more than one earned in the future. Therefore, all annual accumulated cost savings beyond 2008 are discounted at 3% per year in accordance to guidelines set by WHO-CHOICE [53]. GPELF program costs can be compared with the economic benefits calculated in this study through a cost-benefit analysis to evaluate the efficiency and practicality of implementing the Global Programme. Estimating program costs, however, is not the intent of this study and such data was, therefore, sourced through our previously published work [54]. On a macro-level, no study has yet been conducted to estimate the total cost of the GPELF over its first 8 years and as a result, a broader programmatic cost-benefit analysis cannot be calculated. It is possible, however, to estimate the cost-benefit on an individual-level using per person costs calculated in a multi-country study of national MDA program costs for LF including training, mapping, mobilization, distribution, monitoring, and surveillance [54]. In this study, Goldman et al. analyzed both the average annual economic cost per person treated (i. e. including the implied costs of donated materials and drugs – set at US$0. 19+$0. 0019 for shipping per 400mg tablet of albendazole and US$1. 50+$0. 0018 per 3mg tablet of ivermectin) and also the financial cost per person treated (i. e. excluding the costs of the donated materials and drugs) from data collected through questionnaires and adjusted for LF-specific activities. Donated ivermectin is used in combination with donated albendazole in areas co-endemic for onchocerciasis in Africa plus Yemen. DEC, which is not donated, is used in combination with donated albendazole in all other countries and must be purchased by national programs. In terms of per person economic benefits, the total economic benefits estimated over one year in this study was divided by the total number of people treated with MDA in that same year. For this analysis, per person economic benefits were only calculated for the 7 countries whose program costs were also evaluated in Goldman et al.' s study. Cost-benefit was then measured using benefit-cost ratios (BCR), which is the per person treated benefit divided by the per person treated cost. For standardization purposes, the BCR reflects costs, benefits, and currencies adjusted to the year of the most recent MDA round in Goldman et al.' s study.
  During the first 8 years of LF MDA, the Global Programme delivered nearly 2 billion treatments and reached almost 570 million individuals in 48 of the 83 identified endemic countries (Table 4). As a result of these program achievements, 31. 4 million individuals – defined in this study as the benefit cohort population – will gain economic benefits over their lifetime from averting direct treatment costs and indirect lost-labor costs. Of these 31. 4 million individuals in the benefit cohort population, 2. 7 million (8. 6%) would have acquired LF and subsequently progressed to clinical disease but were protected from infection altogether because of interruption of the transmission cycle by MDA. This group comprises the proportion of newborns (2. 2 million) that are protected by virtue of being born in MDA-treated areas, as well as other individuals in the general population (0. 5 million) protected because LF transmission has been interrupted. The remaining 28. 7 million (91. 4%) individuals are those who were already infected at the time of MDA treatment but benefit from halted disease progression. This population group comprises individuals at the subclinical disease stage (9. 4 million, [29. 9%]) who avoid clinical disease altogether and individuals at the clinical disease stage (19. 3 million [61. 6%]) whose conditions may improve following MDA. As seen in Table 5, the efforts in reaching and administering MDA to such a large population have produced extraordinary economic benefits over the first 8 years of the GPELF. An estimated US$21. 8 billion will be saved over the lifetimes of the 31. 4 million individuals who have or would have acquired clinical disease during this timeframe. This total amount results from summing the direct treatment costs ($1. 4b) and indirect lost wages ($20. 4b) prevented over the lifetime of each of the population groups under the assumptions and estimates previously outlined in Table 3. Direct costs for acute disease were calculated based on the aggregate number of ADL episodes expected in the absence of MDA and the average cost incurred per episode. Chronic disease direct costs were derived from the percentage and total number of patients seeking treatment multiplied by the average cost spent per treatment. Indirect costs for both acute and chronic disease were calculated by accruing the equivalent workdays lost to LF and multiplying this total by the average daily wage. All average costs and rate of disease estimates were weighted annually by country-specific estimates and with respect to total number of person-years. On average, each individual of the benefit cohort population will avoid nearly $700 in LF-associated costs that would have accrued over his/her lifetime. This equates to the amount earned for 19 working days per person-year, thus preventing the loss of approximately 6. 3% of annual income (Table 6). These sums and averages are even greater when considered in a single year-to-year perspective, since beyond 2008, each year of economic benefit is discounted by 3% per year. Table 6 also shows that the infected patient sub-population groups (i. e. clinical and subclinical) have the greatest total lifetime benefits based on their larger proportion of the total benefit cohort population. On a per person lifetime average, however, subclinical (Group 2a) and ‘other protected individuals’ (Group 1b) benefits are larger. Figure 3 highlights the total economic benefit segmented by cost, morbidity, and clinical presentation. Economic benefits to national health systems resulting from reduced LF infections derive particularly from patient service costs averted in the public sector. Approximately US$2. 2 billion in health system costs will be saved over the lifetime of the benefit cohort population (Table 8). Combined with the US$21. 8 billion savings for individuals, the total economic benefit following the first 8 years of the GPELF is estimated at an extraordinary US$24. 0 billion (Figure 4). This overall economic analysis of the GPELF' s first 8 years does have notable limitations due to the lack of regionalized primary data concerning both epidemiological and socioeconomic factors associated with LF. Indeed, two sections of the model remain with particular uncertainty: 1) The degree to which MDA can reverse or return an individual with overt clinical disease to regular productivity, and 2) The relationship between hours lost and output/productivity lost due to disease. The total estimated economic impact is particularly sensitive to these variables because of the large number of clinical disease patients receiving MDA and the high proportion of total prevented costs that come from indirect labor costs. As a result, sensitivity analyses were carried out to assess the range of economic benefits that can be achieved under varying estimates of each variable. Secondary sensitivity analyses investigating the frequency and duration of ADL episodes, and direct treatment costs indicated less variability of economic benefits when adjusting these parameters. Goldman et al. found the average annual economic cost per person treated (i. e. including the implied costs of donated materials and drugs – set at US$0. 19+$0. 0019 for shipping per 400mg tablet of albendazole and US$1. 50+$0. 0018 per 3mg tablet of ivermectin) ranged from US$0. 40 in Philippines to $5. 82 in Tanzania. The average annual financial cost per person treated (i. e. excluding the costs of the donated materials and drugs) ranged from US$0. 06 in Burkina Faso to US$1. 34 in Haiti [54]. One-year economic benefits per person treated in this study ranged from US$1. 00 in Burkina Faso to US$4. 56 in the Dominican Republic. Table 10 compares these economic benefit estimates with the economic and financial costs from Goldman et al.' s study to calculate country-specific BCRs. The economic cost BCR for the three African countries using the ivermectin+albendazole regimen are lower (0. 21–0. 37) than those in countries using DEC+albendazole (1. 23–8. 59). Since the drugs, however, are available at no cost to the GPELF, BCRs calculated using financial costs are more favorable, ranging from 1. 64 in Egypt to 18. 07 in the Philippines.
  In Table 10, the BCRs calculated with economic costs are low, particularly for the African countries using the ivermectin+albendazole regimen. In reality, however, the whole foundation of the GPELF is the long-term, sustained commitment of drug donations offered by GlaxoSmithKline for albendazole and Merck & Co. , Inc. for ivermectin for as long as needed until LF is eliminated [72], [73]. Because of this commitment, governments and donors will never have to finance these costs themselves; indeed, without these commitments there would be no GPELF. Therefore, understanding the financial costs (i. e. excluding the costs of the donated materials and drugs) to the GPELF is more relevant for policy- and decision-making than is the analysis of economic costs. When comparing financial costs to economic benefits, then, Table 10 shows very favorable BCRs, including up to 18. 07 in the Philippines. Whether examining financial or economic costs, the BCR becomes larger in the years beyond the recommended 5 rounds of MDA to achieve lifetime protection from LF. The Goldman et al. study [54] showed strong evidence that costs decrease after the initial year of implementation and after 5 rounds of MDA, the drug costs and majority of program activities would arguably subside dramatically as well. In the Philippines for example, by conservatively extrapolating the initial year' s annual economic cost over 5 years, the cost to lifetime benefit ratio indicates that a $1 investment leads to a sizable return of $60 per individual treated. While this analysis does not account for costs following the 5th round of MDA (e. g. post-MDA surveillance), it can be reasonably assumed that the BCR would still remain very significant. Indeed, even if annual economic costs were to persist at an equivalent rate for an additional 10 to 15 years, the economic rate of return per person treated is still approximately $20–$30 for every $1 invested. Comparing the cost-benefit of the GPELF to that of other NTD programs is difficult because there are few directly comparable analyses, particularly at a global level. A review of the African Programme for Onchocerciasis Control (APOC) projected an economic rate of return of 6% to 17% but did not factor in the implied economic cost of the donated drug [74]. This finding is less than the drug-excluded LF cost-benefit estimate presented here, however, several economic benefits apart from onchocercal blindness prevention were not analyzed in the APOC review. Cost-benefit analyses for trachoma have focused almost exclusively on trichiasis surgery in a localized context [75]. A broader array of cost-benefit studies has been carried out for malaria, although with differing scopes and outcome goals, making it challenging to compare results across the same disease, let alone between malaria and LF. In a review of several malaria costing studies, the BCR ranged from 1. 9 to 17. 1 using a variety of human capital and burden of disease methodologies [76]. Other approaches assessing a more macroeconomic impact of malaria [77], [78] have yet to be applied to NTDs but future research into such cost-benefit applications will be critical for validating the investment of the GPELF and stimulating likeminded investigations for related global NTD programs. There has been considerable movement – particularly in Sub-Saharan Africa – toward integrating preventive chemotherapy programs to target multiple NTDs (e. g. LF, onchocerciasis, schistosomiasis, soil-transmitted helminths [STH], trachoma) together. Although there is no clear verdict yet on the benefits of integrated NTD treatments versus standalone vertical programs, early assessments indicate potential savings of 25–47% for the entire group of NTDs can be achieved in Sub-Saharan Africa by packaging MDA interventions together [79]. These findings underlie an important concept of economic analysis, specifically that although an intervention (e. g. vertically integrated MDA programs for LF) may have a favorable BCR, there may be more cost-effective alternatives to achieving a similar outcome (e. g. the number of treatments administered, the total economic benefits of the GPELF). In this respect, the GPELF is well positioned to take advantage of synergistic opportunities with other disease program activities including vector control (malaria and dengue fever), surveillance (guinea worm, onchocerciasis), and distribution (integrated NTDs, Vitamin A) to maximize cost-effectiveness and economic impact [80]. Joint efforts with the private sector and drug development projects addressing improved sanitation and housing facilities could also contribute to greater cost-effectiveness for the GPELF [81]. While this study is not positioned to analyze cost-effectiveness in details, it is abundantly clear that under any joint or standalone scenario, the GPELF indeed represents an excellent buy in global health. The prevention of LF infection and clinical disease has led to additional benefits that are difficult or impossible to quantify in monetary terms. The true economic value of the GPELF is, therefore, arguably much higher based on the numerous quality-of-life benefits achieved through clinical disease aversion, as well as the economic impact that MDA has on other diseases and syndromes related to LF. A narrow range of country-specific primary data somewhat limits the breadth of economic analysis presented in this paper; however, much of the prevailing literature originates from India and Sub-Saharan African countries where over 75% of the benefit cohort population resides. Of significance, there is scarce regional data regarding treatment-seeking behavior for LF patients, but because this is a direct cost input, more exact data would result in only marginal changes to the overall economic impact. Similarly, LF disease-specific parameters (e. g. ADL frequency and duration, lost workdays) were attributed a global standardized estimate due to a lack of regional data. Sensitivity analyses conducted earlier in this study presented the resulting economic impact under differing degrees of pathology and indeed, a clearer understanding of regional variability would enrich future economic analyses. Other variables such as wages, health system costs, and direct treatment costs, however, were able to be made region- and country-specific with the aid of international databases from the ILO, WHO, and World Bank. Despite important limitations to our analysis, this study identifies a wide array of economic benefits that have resulted from the first 8 years of the GPELF – approximately US$21. 8 billion of direct and indirect patient costs will be prevented in the lifetimes of more than 31 million individuals, US$2. 2 billion of LF-associated patient services saved by national health systems over the lifetimes of the MDA-treated individuals, and additional quality-of-life benefits and treatment of co-morbidities such as STH that make the total economic value of the GPELF unquestionably far greater than the calculable estimate presented here. These achievements notwithstanding, it is clear that the economic impact will be even greater when the GPELF reaches the remaining endemic countries and at-risk populations. Currently, the GPELF has extended to 48 of the 83 endemic countries and treated nearly 570 million individuals – approximately 44% of the ∼1. 3 billion worldwide at-risk population [8]. Extrapolating this proportion with the US$24 billion lifetime economic benefit already achieved, the full potential economic benefit of the GPELF could be in excess of US$55 billion distributed over each of the endemic WHO regions (Figure 5). Reaching the remaining at-risk individuals presents notable challenges especially since much of the population not yet reached resides in some of the poorest countries in Africa. Additional resources and economic empowerment will be necessary to assist these countries in implementing programs for LF elimination [91]. The expansion of the GPELF will therefore be a critical building block in this effort and also an important driver for increased attention to NTDs and the continuation of integrated NTD programs. The recognition of the sizable monetary benefit already achieved after 8 years provides new confidence that it is an investment well worth undertaking.
summary: Lymphatic filariasis (LF), commonly known as ‘elephantiasis’, is one of the world' s most debilitating infectious diseases. In 83 countries worldwide, more than 1. 3 billion people are at risk of infection with an estimated 120 million individuals already infected. A recent publication reviewing the health impact of the first 8 years of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) demonstrated the enormous health benefits achieved in populations receiving annual mass drug administration (MDA), as a result of infection prevented, disease progression halted, and ancillary treatment of co-infections. To date, however, no studies have estimated the economic value of these health benefits, either to the individuals or the societies afflicted with LF. Our study estimates that US$21. 8 billion will be gained among individuals benefitting from just the first 8 years of the Global Programme, and an additional US$2. 2 billion will be saved by the health systems of endemic countries. Treating endemic populations is possible at very low cost – particularly because of the generous drug donations from two pharmaceutical companies – but results in enormous economic benefits. Findings from this study yield a much clearer understanding the GPELF' s full economic impact and strengthen the conviction that it is a ‘best buy’ in global health.
keywords: infectious diseases/neglected tropical diseases
  infectious diseases/helminth infections
  public health and epidemiology/global health
  public health and epidemiology/infectious diseases
  non-clinical medicine/health economics
  infectious diseases/epidemiology and control of infectious diseases
title: The Economic Benefits Resulting from the First 8 Years of the Global Programme to Eliminate Lymphatic Filariasis (2000–2007)