A refined and updated health impact assessment of the Global Programme to Eliminate Lymphatic Filariasis (2000-2020).

BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease (NTD). In 2000 the World Health Organization (WHO) established the Global Programme to Eliminate Lymphatic Filariasis (GPELF). A key component of this programme is mass drug administration (MDA). Between 2000 and 2020, the GPELF has delivered over 8.6 billion treatments to at-risk populations. The last impact assessment of the programme evaluated the treatments provided between 2000-2014. The goal of this analysis is to provide an updated health impact assessment of the programme, based on the numbers treated between 2000-2020. METHODS: We updated and refined a previously established model that estimates the number of clinical manifestations and disability-adjusted life years (DALYs) averted by the treatments provided by the GPELF. The model comprises three different population cohorts that can benefit from MDA provided (those protected from acquiring infection, those with subclinical morbidity prevented from progressing and those with clinical disease alleviated). The treatment numbers were updated for all participating countries using data from the WHO. In addition, data relating to the estimated number of individuals initially at risk of LF infection were updated where possible. Finally, the DALY calculations were refined to use updated disability weights. RESULTS: Using the updated model and corresponding treatment data, we projected that the total benefit cohort of the GPELF (2000-2020) would consist of approximately 58.5 million individuals and the programme would avert 44.3 million chronic LF cases. Over the lifetime of the benefit cohorts, this corresponded to 244 million DALYs being averted. CONCLUSION: This study indicates that substantial health benefits have resulted from the first 20 years of the GPELF. It is important to note that the GPELF would have both additional benefits not quantified by the DALY burden metric as well as benefits on other co-endemic diseases (such as soil-transmitted helminths, onchocerciasis and scabies)-making the total health benefit underestimated. As with the past impact assessments, these results further justify the value and importance of continued investment in the GPELF.

The Health and Economic Burdens of Lymphatic Filariasis Prior to Mass Drug Administration Programs.

BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was launched in 2000 with the goal of eliminating lymphatic filariasis (LF) as a public health problem by 2020. Despite considerable progress, the current prevalence is around 60% of the 2000 figure, with the deadline looming a year away. Consequently, there is a continued need for investment in both the mass drug administration (MDA) and morbidity management programs, and this paper aims to demonstrate that need by estimating the health and economic burdens of LF prior to MDA programs starting in GPELF areas. METHODS: A previously developed model was used to estimate the numbers of individuals infected and individuals with symptomatic disease, along with the attributable number of disability-adjusted life years (DALYs). The economic burden was calculated by quantifying the costs incurred by the health-care system in managing clinical cases, the patients' out-of-pocket costs, and their productivity costs. RESULTS: Prior to the MDA program, approximately 129 million people were infected with LF, of which 43 million had clinical disease, corresponding to a DALY burden of 5.25 million. The average annual economic burden per chronic case was US $115, the majority of which resulted from productivity costs. The total economic burden of LF was estimated at US $5.8 billion annually. CONCLUSIONS: These results demonstrate the magnitude of the LF burden and highlight the continued need to support the GPELF. Patients with clinical disease bore the majority of the economic burden, but will not benefit much from the current MDA program, which is aimed at reducing transmission. This assessment further highlights the need to scale up morbidity management programs.

Economic evaluations of lymphatic filariasis interventions: a systematic review and research needs.

In 2000, the World Health Organization established the Global Programme to Eliminate Lymphatic Filariasis (GPELF), with the goal of eliminating the disease as a public health problem by 2020. Since the start of the programme, a cumulative total of 6.2 billion treatments have been delivered to affected populations - with more than 556 million people treated in 2015 alone. In this paper, we perform a rigorous systematic review of the economic evaluations of lymphatic filariasis interventions have been conducted. We demonstrate that the standard interventions to control lymphatic filariasis are consistently found to be highly cost-effective. This finding has important implications for advocacy groups and potential funders. However, there are several important inconsistencies and research gaps that need to be addressed as we move forward towards the 2020 elimination goals. One of the most important identified research gaps was a lack of evaluation of new interventions specifically targeting areas co-endemic with onchocerciasis and Loa loa - which could become a major barrier to achieving elimination.

Investment Success in Public Health: An Analysis of the Cost-Effectiveness and Cost-Benefit of the Global Programme to Eliminate Lymphatic Filariasis.

Background: It has been estimated that $154 million per year will be required during 2015-2020 to continue the Global Programme to Eliminate Lymphatic Filariasis (GPELF). In light of this, it is important to understand the program's current value. Here, we evaluate the cost-effectiveness and cost-benefit of the preventive chemotherapy that was provided under the GPELF between 2000 and 2014. In addition, we also investigate the potential cost-effectiveness of hydrocele surgery. Methods: Our economic evaluation of preventive chemotherapy was based on previously published health and economic impact estimates (between 2000 and 2014). The delivery costs of treatment were estimated using a model developed by the World Health Organization. We also developed a model to investigate the number of disability-adjusted life years (DALYs) averted by a hydrocelectomy and identified the cost threshold under which it would be considered cost-effective. Results: The projected cost-effectiveness and cost-benefit of preventive chemotherapy were very promising, and this was robust over a wide range of costs and assumptions. When the economic value of the donated drugs was not included, the GPELF would be classed as highly cost-effective. We projected that a typical hydrocelectomy would be classed as highly cost-effective if the surgery cost less than $66 and cost-effective if less than $398 (based on the World Bank's cost-effectiveness thresholds for low income countries). Conclusions: Both the preventive chemotherapy and hydrocele surgeries provided under the GPELF are incredibly cost-effective and offer a very good investment in public health.

The health and economic benefits of the global programme to eliminate lymphatic filariasis (2000-2014).

BACKGROUND: Lymphatic filariasis (LF), also known as elephantiasis, is a neglected tropical disease (NTD) targeted for elimination through a Global Programme to Eliminate LF (GPELF). Between 2000 and 2014, the GPELF has delivered 5.6 billion treatments to over 763 million people. Updating the estimated health and economic benefits of this significant achievement is important in justifying the resources and investment needed for eliminating LF. METHOD: We combined previously established models to estimate the number of clinical manifestations and disability-adjusted life years (DALYs) averted from three benefit cohorts (those protected from acquiring infection, those with subclinical morbidity prevented from progressing and those with clinical disease alleviated). The economic savings associated with this disease prevention was then analysed in the context of prevented medical expenses incurred by LF clinical patients, potential income loss through lost-labour, and prevented costs to the health system to care for affected individuals. The indirect cost estimates were calculated using the human capital approach. A combination of four wage sources was used to estimate the fair market value of time for an agricultural worker with LF infection (to ensure a conservative estimate, the lowest wage value was used). RESULTS: We projected that due to the first 15 years of the GPELF 36 million clinical cases and 175 (116-250) million DALYs will potentially be averted. It was estimated that due to this notable health impact, US$100.5 billion will potentially be saved over the lifetimes of the benefit cohorts. This total amount results from summing the medical expenses incurred by LF patients (US$3 billion), potential income loss (US$94 billion), and costs to the health system (US$3.5 billion) that were projected to be prevented. The results were subjected to sensitivity analysis and were most sensitive to the assumed percentage of work hours lost for those suffering from chronic disease (changing the total economic benefit between US$69.30-150.7 billion). CONCLUSIONS: Despite the limitations of any such analysis, this study identifies substantial health and economic benefits that have resulted from the first 15 years of the GPELF, and it highlights the value and importance of continued investment in the GPELF.

Multidimensional complexities of filariasis control in an era of large-scale mass drug administration programmes: a can of worms.

The impact of control and elimination programmes by mass drug administration (MDA) targeting onchocerciasis and lymphatic filariasis (LF) in sub-Saharan Africa over the last two decades has resulted in significantly reduced prevalence and intensity of infection, with some areas interrupting transmission. However, given that these infections are often co-endemic and the drugs (either ivermectin alone or combined with albendazole) also impact on soil transmitted helminths (STH), the importance of this, in terms of reaching the global goals has not been assessed. The additional problem posed by Loa loa, where ivermectin cannot be safely administered due to the risk of serious adverse events compounds this situation and has left populations drug naïve and an alternative strategy to eliminate LF is yet to be initiated at scale. Here, we present a series of operational research questions, which must be addressed if the effectiveness of integrated control of filarial and helminth infections is to be understood for the endgame. This is particularly important in the diverse and dynamic epidemiological landscape, which has emerged as a result of the long-term large-scale mass drug administration (or not). There is a need for a more holistic approach to address these questions. Different programmes should examine this increased complexity, given that MDA has multiple impacts, drugs are given over different periods, and programmes have different individual targets.

Knowledge and practice related to compliance with mass drug administration during the Egyptian national filariasis elimination program.

Lymphatic filariasis (LF) has been targeted for global elimination by 2020. The primary tool for the program is mass drug administration (MDA) with antifilarial medications to reduce the source of microfilariae required for mosquito transmission of the parasite. This strategy requires high MDA compliance rates. Egypt initiated a national filariasis elimination program in 2000 that targeted approximately 2.7 million persons in 181 disease-endemic localities. This study assessed factors associated with MDA compliance in year three of the Egyptian LF elimination program. 2,859 subjects were interviewed in six villages. The surveyed compliance rate for MDA in these villages was 85.3% (95% confidence interval = 83.9-86.5%). Compliance with MDA was positively associated with LF knowledge scores, male sex, and older age. Adverse events reported by 18.4% of participants were mild and more common in females. This study has provided new information on factors associated with MDA compliance during Egypt's successful LF elimination program.

The economic benefits resulting from the first 8 years of the Global Programme to Eliminate Lymphatic Filariasis (2000-2007).

BACKGROUND: 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. METHODOLOGY: 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 PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

Xenomonitoring of Wuchereria bancrofti and Dirofilaria immitis infections in mosquitoes from American Samoa: trapping considerations and a comparison of polymerase chain reaction assays with dissection.

Entomologic monitoring of filarial infections, xenomonitoring, may have advantages in certain epidemiologic situations to assess the presence of infections in humans. Hemalum staining and dissection and polymerase chain reaction (PCR) were compared to determine the filarial infection status of Aedes (Stegomyia) mosquitoes in American Samoa. The overall prevalences of Wuchereria bancrofti and Dirofilaria immitis infections in Ae. polynesiensis were, respectively, 0.16% and 1.06% by dissection and 0.69% and 1.77% by PCR. Human filarial worm DNA rates in Aedes aegypti and Aedes upolensis were 1.16% and 0.38%, respectively. The results suggest that W. bancrofti transmission to humans may be continuing at low levels in some villages despite recent completion of 5 years of mass drug administration. PCR testing of mosquitoes collected using the BG-Sentinel traps represents a promising alternative to landing catches for assessing the transmission of filariasis in areas where Ae. polynesiensis and related species are the primary vectors.

Determinants of success in national programs to eliminate lymphatic filariasis: a perspective identifying essential elements and research needs.

The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was launched in 2000. To understand why some national programs have been more successful than others, a panel of individuals with expertise in LF elimination efforts met to assess available data from programs in 8 countries. The goal was to identify: 1) the factors determining success for national LF elimination programs (defined as the rapid, sustained reduction in microfilaremia/antigenemia after repeated mass drug administration [MDA]); 2) the priorities for operational research to enhance LF elimination efforts. Of more than 40 factors identified, the most prominent were 1) initial level of LF endemicity; 2) effectiveness of vector mosquitoes; 3) MDA drug regimen; 4) population compliance. Research important for facilitating program success was identified as either biologic (i.e., [1] quantifying differences in vectorial capacity; [2] identifying seasonal variations affecting LF transmission) or programmatic (i.e., [1] identifying quantitative thresholds, especially the population compliance levels necessary for success, and the antigenemia or microfilaremia prevalence at which MDA programs can stop with minimal risk of resumption of transmission; [2] defining optimal drug distribution strategies and timing; [3] identifying those individuals who are "persistently non-compliant" during MDAs, the reasons for this non-compliance and approaches to overcoming it). While addressing these challenges is important, many key determinants of program success are already clearly understood; operationalizing these as soon as possible will greatly increase the potential for national program success.

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.

Test strip detection of Wuchereria bancrofti amplified DNA in wild-caught Culex pipiens and estimation of infection rate by a PoolScreen algorithm.

Bancroftian filariasis is targeted for elimination in the Nile Delta of Egypt. Improved simple methods are needed for monitoring Wuchereria bancrofti infection in the mosquito vector and thereby the success of elimination programmes. We evaluated the performance of the SspI-PCR assay combined with a DNA Detection Test StripTM method and used the PoolScreen algorithm method for estimating mosquito infection rates. A total of 769 indoor-resting Culex pipiens were captured in 79 randomly selected houses from a filaria-endemic village in the Nile Delta of Egypt (24.4% antigenaemia and 8.6% microfilaraemia). Collected mosquitoes were pooled by house, and assayed by the SspI-PCR. Amplified parasite DNA was detected by both electrophoresis of agarose gel stained with ethidium bromide (EtBr) and by test strips. PCR based on EtBr and test strip methods identified 43 (54.4%) and 45 (56.9%) houses, respectively, as being filaria positive. The minimum mosquito infection rate, assuming one infected female/pool was 6.85% by the PCR test strips. Mosquito infection rate calculated by the PoolScreen2 algorithm software amounted to 8.1% [95% confidence interval 5.85, 10.47]. Because it is faster and safer, the PCR test strip is a practical tool, especially when combined with the PoolScreen algorithm method, for xenomonitoring the success of elimination programmes.