The Elimination of Lymphatic Filariasis: A Strategy for Poverty Alleviation and Sustainable Development - Perspectives from the Philippines

BACKGROUND: Within the Philippines areas endemic for lymphatic filariasis are in regions with the highest incidence of poverty. Out of a total of 79 provinces, 39 have a higher poverty incidence than the national average and 30 of these 39 provinces are endemic for lymphatic filariasis. DISCUSSION: Recognizing that provinces endemic for lymphatic filariasis (LF) are also the poorest provinces, the elimination of lymphatic filariasis in these areas presents significant opportunities to reduce poverty and inequalities in health. The implementation of an effective national programme for the elimination of lymphatic filariasis will provide means for sustainable development at national, local and community levels. SUMMARY: The elimination of lymphatic filariasis as a public health problem is a 20-year strategic plan for the world community, with the vision of all endemic communities free of transmission of lymphatic filariasis by 2020 and with the commitment to ensure the delivery of quality technologies and human services to eliminate lymphatic filariasis worldwide through a multi-stakeholder global alliance of all endemic countries. This global goal of elimination of lymphatic filariasis is a significant opportunity for partnerships - a world with less poverty through sustainable development and free from the scourge of lymphatic filariasis.     

Progress towards eliminating lymphatic filariasis in Zanzibar: a model programme

Programmes to eliminate lymphatic filariasis are underway in ten countries of sub-Saharan Africa, and in several programmes outside Africa five rounds of mass drug administration (MDA) are being completed. In Africa, Egypt and Zanzibar have completed five rounds of MDA. Zanzibar was the first country to complete five rounds of treatment using a combination of albendazole and ivermectin, reducing both the prevalence and intensity of Wuchereria bancrofti. Characteristics of the Zanzibar programme serve as a model for other countries: factors crucial to its success include high-level political commitment, the development of appropriate social mobilization strategies, the involvement of communities in drug distribution, and the introduction of morbidity management for individuals with lymphoedema.     

The economic burden of lymphatic filariasis in India

Lymphatic filariasis affects 119 million people living in 73 countries, with India accounting for 40% of the global prevalence of infection. Despite its debilitating effects, lymphatic filariasis is given very low control priority. One of the reasons for this is paucity of information on the economic burden of the disease. Recent studies in rural areas of south India have shown that the treatment costs and loss of work time due to the disease are considerable. Based on the results of these studies, Kapa Ramaiah et al. here estimate the annual economic loss because of lymphatic filariasis for India and discuss the implications of their findings.     

Towards elimination of lymphatic filariasis in India

The global initiatives to eliminate lymphatic filariasis as a public health problem by the year 2020 have generated a great deal of debate in India, the largest endemic country. This has led to a shift in the focus from control to elimination of the disease. Although the campaign to eliminate filariasis has begun, much more needs to be done. Several recent research studies have provided an insight into various operational issues and prospects of elimination of lymphatic filariasis. In this article, the current scenario, recent research results, logistics and the prospects of eliminating lymphatic filariasis in India will be discussed.     

Lymphatic Filariasis (Elephantiasis) Elimination: A public health success and development opportunity

BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis, launched following World Health Assembly Resolution 50.29 (WHA 50.29), has been facilitated in its progress by new research findings, drug donations, the availability of diagnostic tools, disability management strategies to help those already suffering and the development of partnerships. The strategy recommended by the World Health Organization of annual treatment with a two-drug combination has proved safe. DISCUSSION: Using different approaches in several countries the elimination of lymphatic filariasis (LF) has been demonstrated to be feasible during earlier decades. These successes have been largely overlooked. However, the programme progress since 2000 has been remarkable - upscaling rapidly from 2 million treatments in 2000 to approximately 60 million in 2002. Around 34 countries had active programmes at the end of 2002. It is anticipated that there will be further expansion - but this will be dependent on additional resources becoming available. The programme also provides significant opportunities for other disease control programmes to deliver public health benefits on a large scale. Few public health programmes have upscaled so rapidly and so cost-effectively (<$0.03/treatment in some Asian settings) - one country treating 9-10 million people in a day (Sri Lanka). The LF programme is arguably the most effective pro-poor public health programme currently operating which is based on country commitment and partnerships supported by a global programme and alliance. Tables are provided to summarize programme characteristics, the benefits of LF elimination, opportunities for integration with other programmes and relevance to the Millennium Development Goals. SUMMARY: Lymphatic filariasis elimination is an "easy-to-do" inexpensive health intervention that provides considerable "beyond filariasis" benefits, exemplifies partnership and is easily evaluated. The success in global health action documented in this paper requires and deserves further support to bring to fruition elimination of lymphatic filariasis as a public health problem and health benefits to poor people. A future free of lymphatic filariasis will reduce poverty and bring better health to poor people, prevent disability, strengthen health systems and build partnerships.     

Lymphatic filariasis in children: clinical features, infection burdens and future prospects for elimination

Lymphatic filariasis (LF), a common parasitic infection in tropical countries, causes lymphoedema of limbs, hydrocele and acute attacks of dermato-lymphangio-adenitis. Recent advances in diagnosis have helped to recognize that LF infection is often acquired in childhood. Newly available diagnostic techniques like sensitive antigen and antibody assays, Doppler ultrasonography and lymphoscintigraphy have helped to understand the subclinical pathology caused by this infection, which was hitherto generally believed to be irreversible. Recent studies indicate that drugs used in the mass drug administration (MDA) programme under GPELF are capable of reversing the sub-clinical lymphatic damage in children and provide benefits other than interruption of transmission. Albendazole and ivermectin used in MDA are effective against soil-transmitted helminthic infections common in children in LF endemic areas. Thus MDA had other 'beyond LF' benefits in treated children including increased appetite, weight gain, greater learning ability and concentration, better school attendance and prevention of anaemia. MDA should no longer be viewed as a measure for interrupting transmission alone. Recent findings of reversibility of early lymphatic pathology in treated children indicate that both MDA and 'foot-hygiene' measures are effective strategies in preventing and managing morbidity. Programme managers should effectively utilize this information to strengthen their advocacy efforts to achieve high and sustainable coverage in MDA.     

Maternal Infection Is a Risk Factor for Early Childhood Infection in Filariasis

Background

Global Program to Eliminate Lymphatic Filariasis (GPELF) launched by WHO aims to eliminate the disease by 2020. To achieve the goal annual mass drug administration (MDA) with diethylcarbamazine (DEC) plus albendazole (ABZ) has been introduced in all endemic countries. The current policy however excludes pregnant mothers and children below two years of age from MDA. Since pregnancy and early childhood are critical periods in determining the disease outcome in older age, the present study was undertaken to find out the influence of maternal filarial infection at the time of pregnancy on the susceptibility outcome of children born in a community after implementation of MDA for the first time.

Methodology and Principal Findings

The participants in this cohort consists of pregnant mothers and their subsequently born children living in eight adjacent villages endemic for filarial infections, in Khurda District, Odisha, India, where MDA has reduced microfilariae (Mf) rate from 12% to 0.34%. Infection status of mother and their children were assessed by detection of Mf as well as circulating filarial antigen (CFA) assay. The present study reveals a high rate of acquiring filarial infection by the children born to infected mother than uninfected mothers even though Mf rate has come down to < 1% after implementation of ten rounds of MDA.

Significance

To attain the target of eliminating lymphatic filariasis the current MDA programme should give emphasis on covering the women of child bearing age. Our study recommends incorporating supervised MDA to Adolescent Reproductive and Sexual Health Programme (ARSH) to make the adolescent girls free from infection by the time of pregnancy so as to achieve the goal.     

National mass drug administration costs for lymphatic filariasis elimination

Background

Because lymphatic filariasis (LF) elimination efforts are hampered by a dearth of economic information about the cost of mass drug administration (MDA) programs (using either albendazole with diethylcarbamazine [DEC] or albendazole with ivermectin), a multicenter study was undertaken to determine the costs of MDA programs to interrupt transmission of infection with LF. Such results are particularly important because LF programs have the necessary diagnostic and treatment tools to eliminate the disease as a public health problem globally, and already by 2006, the Global Programme to Eliminate LF had initiated treatment programs covering over 400 million of the 1.3 billion people at risk.

Methodology/Principal Findings

To obtain annual costs to carry out the MDA strategy, researchers from seven countries developed and followed a common cost analysis protocol designed to estimate 1) the total annual cost of the LF program, 2) the average cost per person treated, and 3) the relative contributions of the endemic countries and the external partners. Costs per person treated ranged from $0.06 to $2.23. Principal reasons for the variation were 1) the age (newness) of the MDA program, 2) the use of volunteers, and 3) the size of the population treated. Substantial contributions by governments were documented – generally 60%–90% of program operation costs, excluding costs of donated medications.

Conclusions/Significance

MDA for LF elimination is comparatively inexpensive in relation to most other public health programs. Governments and communities make the predominant financial contributions to actual MDA implementation, not counting the cost of the drugs themselves. The results highlight the impact of the use of volunteers on program costs and provide specific cost data for 7 different countries that can be used as a basis both for modifying current programs and for developing new ones.     

Chyluria with proteinuria or filarial nephropathy? An enigma

Lymphatic filariasis is endemic in India. Out of 128 million infected individuals worldwide, India accounts for 48 million cases [Manson's Tropical Diseases, 21st Ed. p 1488]. Filariasis can have protean manifestations, but Tropical pulmonary eosinophilia and chyluria are unusual manifestations reported mainly from South Asian countries [Manson's Tropical Diseases, 21st Ed. p 1494]. Chyluria occurs only in 2% of filarial afflicted patients in the filarial belt [Diamond E, Schapira HE. Chyluria--a review of literature. Urology 1985;26(5): 427-31]. Lymphatic filariasis presenting as chyluria may be equally rare. Predominant chyluria with no overt lymphatic filariasis remains an enigma.     

The geographical distribution of lymphatic filariasis infection in Malawi

Background

Papua New Guinea is the only endemic country in the Western Pacific Region that has not yet introduced a countrywide programme to eliminate lymphatic filariasis. However, on Misima Island in Milne Bay Province, government and private sectors have collaborated to implement a pilot elimination programme. Although interim evaluation indicated that the programme has been parasitologically successful, an appreciation that sustainable health gains depend on understanding and accommodating local beliefs prompted this qualitative study.

Methods

We investigated Misima community members knowledge and attitudes about lymphatic filariasis and the elimination programme. A combination of focus groups and key informant interviews were used to explore participants perceptions of health; knowledge of the aetiology and symptoms of filariasis, elephantiasis and hydrocele; attitudes towards the disease and mass drug distribution; and the social structure and decision-making protocols within the villages.

Results

Focus group discussions proved inferior to key informant interviews for gathering rich data. Study participants did not consider lymphatic filariasis ("pom") a major health problem but were generally positive about mass drug administration campaigns. A variety of conditions were frequently and incorrectly attributed to filariasis. Participants expressed the belief that individuals infected with filariasis always had visible manifestations of disease. A common misconception was that taking drugs during campaigns provided long-term immunity against disease. The role of mosquito vectors in transmission was not generally appreciated and certain clinical presentations, particularly hydrocele, were associated with supernatural forces. Multiple adverse events were associated with mass drug administration campaigns and most study participants mentioned community members who did not participate in campaigns.

Conclusion

Important issues requiring educational intervention and elimination activity modification in the Misima region were identified during this study. Research outcomes should assist Papua New Guinea in developing and implementing a national elimination strategy and inform discussions regarding the appropriateness of current elimination strategies.     

How to (or Not to) Integrate Vertical Programmes for the Control of Major Neglected Tropical Diseases in Sub-Saharan Africa

Combining the delivery of multiple health interventions has the potential to minimize costs and expand intervention coverage. Integration of mass drug administration is therefore being encouraged for delivery of preventive chemotherapy (PCT) to control onchocerciasis, lymphatic filariasis, schistosomiasis, soil-transmitted helminthiasis, and trachoma in sub-Saharan Africa, as there is considerable geographical overlap of these neglected tropical diseases (NTDs). With only a handful of countries having embarked on integrated NTD control, experience on how to develop and implement an efficient integrated programme is limited. Historically, national and global programmes were focused on the control of only one disease, usually through a comprehensive approach that involved several interventions including PCT. Overcoming the resulting disease-specific structures and thinking, and ensuring that the integrated programme is embedded within the existing health structures, pose considerable challenges to policy makers and implementers wishing to embark on integrated NTD control. By sharing experiences from Uganda, Tanzania, Southern Sudan, and Mozambique, this symposium article aims to outlines key challenges and solutions to assist countries in establishing efficient integrated NTD programmes.     

A cost-benefit analysis of Chagas disease control.

Chagas disease transmission can be effectively interrupted by insecticidal control of its triatomine bug vectors. We present here a simple model comparing the costs and benefits of such a programme, designed to eliminate domestic populations of Triatoma infestans throughout its known area of distribution over the seven southernmost countries of Latin America. The model has been simplified to require only four financial estimates relating to the unit cost of housing spraying and benefits due to avoidance of premature death in the acute phase of the disease, avoidance of supportive treatment and care in the chronic phase of the disease, and avoidance of corrective digestive and cardiac surgery. Except for these direct medical costs, all other potential benefits have been ignored. Nevertheless, the model shows that the direct financial benefits of such a programme would far outweigh the costs, and the project would support a remarkably high internal rate of return under the least optimistic estimates.     

A Review of Factors That Influence Individual Compliance with Mass Drug Administration for Elimination of Lymphatic Filariasis

Background

The success of programs to eliminate lymphatic filariasis (LF) depends in large part on their ability to achieve and sustain high levels of compliance with mass drug administration (MDA). This paper reports results from a comprehensive review of factors that affect compliance with MDA.

Methodology/Principal Findings

Papers published between 2000 and 2012 were considered, and 79 publications were included in the final dataset for analysis after two rounds of selection. While results varied in different settings, some common features were associated with successful programs and with compliance by individuals. Training and motivation of drug distributors is critically important, because these people directly interact with target populations, and their actions can affect MDA compliance decisions by families and individuals. Other important programmatic issues include thorough preparation of personnel, supplies, and logistics for implementation and preparation of the population for MDA. Demographic factors (age, sex, income level, and area of residence) are often associated with compliance by individuals, but compliance decisions are also affected by perceptions of the potential benefits of participation versus the risk of adverse events. Trust and information can sometimes offset fear of the unknown. While no single formula can ensure success MDA in all settings, five key ingredients were identified: engender trust, tailor programs to local conditions, take actions to minimize the impact of adverse events, promote the broader benefits of the MDA program, and directly address the issue of systematic non-compliance, which harms communities by prolonging their exposure to LF.

Conclusions/Significance

This review has identified factors that promote coverage and compliance with MDA for LF elimination across countries. This information may be helpful for explaining results that do not meet expectations and for developing remedies for ailing MDA programs. Our review has also identified gaps in understanding and suggested priority areas for further research.     

Pacific collaboration to eliminate lymphatic filariasis

A regional programme to combat lymphatic filariasis in the Pacific islands is showing great promise as it reaches its halfway point. The Pacific Programme to Eliminate Lymphatic Filariasis (PacELF), established in 1999, aims to eliminate the disease from the Pacific by 2010 - ten years ahead of the global target. Set up with support from Australia, and now funded primarily by Japan and underpinned by the Word Health Organization, PacELF is providing evidence that Pacific nations can work cooperatively to rid the region of one of its worst scourges, in addition to discovering techniques and new tools that should be of use in other regions.     

Impact of two rounds of mass drug administration using diethylcarbamazine combined with albendazole on the prevalence of Brugia timori and of intestinal helminths on Alor Island, Indonesia

Background

Annual mass drug administration (MDA) using diethylcarbamizine (DEC, 6 mg/kg) combined with albendazole (alb, 400 mg) is recommended by the Global Programme to Eliminate Lymphatic Filariasis (GPELF). This strategy has been shown to be efficient in the of control bancroftian filariasis, but data on brugian filariasis as well as on the positive side effects on intestinal helminths are lacking.

Methods

The effect of one selective treatment and two rounds of MDA using DEC and alb on the prevalence and intensity of Brugia timori infection were studied on Alor island using a cross-sectional and a cohort approach. Before the campaign and ten months after each treatment cycle microfilariae (mf) were assessed by filtration of night blood. Before and ten months after MDA, stool samples were collected and the prevalence of intestinal helminths were determined.

Results

In all, the mf-rate dropped from 26.8% before any treatment to 3.8% following the second MDA. Almost all mf-positive, treated individuals showed very low mf densities. The crude prevalence of hookworm dropped from 25.3% to 5.9%. The reduction of prevalence of Ascaris lumbricoides (32.3% to 27.6%) and Trichuris trichiura (9.4% to 8.9%) was less pronounced. Within a cohort of 226 individuals, which was examined annually, the prevalence of A. lumbricoides dropped from 43.8% to 26.5% and of T. trichiura from 12.8% to 6.6%. The results indicate that this MDA approach reduces not only the mf prevalence of B. timori but also the prevalence of hookworm and to a lesser extent also of A. lumbricoides and T. trichiura.

Conclusion

The MDA using DEC and alb as recommended by GPELF is extremely effective for areas with brugian filariasis. The beneficial effect of MDA on intestinal helminths may strengthen the national programme to eliminate lymphatic filariasis in Indonesia and may set resources free which are otherwise used for deworming campaigns of schoolchildren.     

Global eradication of lymphatic filariasis: the value of chronic disease control in parasite elimination programmes

The ultimate goal of the global programme against lymphatic filariasis is eradication through irrevocable cessation of transmission using 4 to 6 years of annual single dose mass drug administration. The costs of eradication, managerial impediments to executing national control programmes, and scientific uncertainty about transmission endpoints, are challenges to the success of this effort, especially in areas of high endemicity where financial resources are limited. We used a combined analysis of empirical community data describing the association between infection and chronic disease prevalence, mathematical modelling, and economic analyses to identify and evaluate the feasibility of setting an infection target level at which the chronic pathology attributable to lymphatic filariasis--lymphoedema of the extremities and hydroceles--becomes negligible in the face of continuing transmission as a first stage option in achieving the elimination of this parasitic disease. The results show that microfilaria prevalences below a threshold of 3.55% at a blood sampling volume of 1 ml could constitute readily achievable and sustainable targets to control lymphatic filarial disease. They also show that as a result of the high marginal cost of curing the last few individuals to achieve elimination, maximal benefits can occur at this threshold. Indeed, a key finding from our coupled economic and epidemiological analysis is that when initial uncertainty regarding eradication occurs and prospects for resolving this uncertainty over time exist, it is economically beneficial to adopt a flexible, sequential, eradication strategy based on controlling chronic disease initially.     

Mass drug treatment for lymphatic filariasis and onchocerciasis

This review summarizes the progress towards control of lymphatic filariasis (LF) and onchocerciasis, focussing on the impact of mass drug administration (MDA) programmes, in particular those that have developed following the donation of ivermectin and albendazole. The contrasting strategies and objectives of the different programmes are compared, and the impact on transmission, clinical disease and public health assessed. The constraints on programme success are: (i) the absence of a macrofilaricide, which can be used in a public health context; (ii) the sustainability of high coverage of ivermectin over many years in onchocerciasis control; and (iii) the problem of treatment in areas where Loa loa (tropical eye worm) is co-endemic with onchocerciasis because of the rare severe adverse events. LF programmes are expanding rapidly in over 30 countries, where circa 60 million people received treatments in 2002. No serious adverse events have been associated with MDAs for LF elimination. Research on new approaches to treatment using antibiotics are showing promising results in pilot settings because doxycyline has been shown to have long-term embryostatic effects and sustained reductions of microfilaria loads in onchocerciasis and bancroftian filariasis.     

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.     

Epidemiological Assessment of Eight Rounds of Mass Drug Administration for Lymphatic Filariasis in India: Implications for Monitoring and Evaluation

Background

Monitoring and evaluation guidelines of the programme to eliminate lymphatic filariasis require impact assessments in at least one sentinel and one spot-check site in each implementation unit (IU). Transmission assessment surveys (TAS) that assess antigenaemia (Ag) in children in IUs that have completed at least five rounds of mass drug administration (MDA) each with >65% coverage and with microfilaria (Mf) levels <1% in the monitored sites form the basis for stopping the MDA. Despite its rigour, this multi-step process is likely to miss sites with transmission potential (‘hotspots’) and its statistical assumptions for sampling and threshold levels for decision-making have not been validated. We addressed these issues in a large-scale epidemiological study in two primary health centres in Thanjavur district, India, endemic for bancroftian filariasis that had undergone eight rounds of MDA.

Methodology/Principal Findings

The prevalence and intensity of Mf (per 60 µl blood) were 0.2% and 0.004 respectively in the survey that covered >70% of 50,363 population. The corresponding values for Ag were 2.3% and 17.3 Ag-units respectively. Ag-prevalence ranged from 0.7 to 0.9%, in children (2–10 years) and 2.7 to 3.0% in adults. Although the Mf-levels in the survey and the sentinel/spot check sites were <1% and Ag-level was <2% in children, we identified 7 “residual” (Mf-prevalence ≥1%, irrespective of Ag-status in children) and 17 “transmission” (at least one Ag-positive child born during the MDA period) hotspots. Antigenaemic persons were clustered both at household and site levels. We identified an Ag-prevalence of ∼1% in children (equivalent to 0.4% community Mf-prevalence) as a possible threshold value for stopping MDA.

Conclusions/Significance

Existence of ‘hotspots’ and spatial clustering of infections in the study area indicate the need for developing good surveillance strategies for detecting ‘hotspots’, adopting evidence-based sampling strategies and evaluation unit size for TAS.     

Mathematical models and lymphatic filariasis control: endpoints and optimal interventions

The current global initiative to eliminate lymphatic filariasis is a major renewed commitment to reduce or eliminate the burden of one of the major helminth infections from resource-poor communities of the world. Mathematical models of filariasis transmission can serve as an effective tool for guiding the scientific development and management of successful community-level intervention programmes by acting as analytical frameworks for integrating knowledge regarding parasite transmission dynamics with programmatic factors. However, the power of these tools for supporting control interventions will be realized fully only if researchers address the current uncertainties and gaps in data and knowledge of filarial population dynamics and the effectiveness of currently proposed filariasis intervention options.