|Year : 2005 | Volume
| Issue : 1 | Page : 12-17
Global elimination of lymphatic filariasis: origins, progress and challenges
Division of Parasitic Diseases, National Centre for Infectious Diseases, Centres for Disease Control and Prevention, Atlanta, GA, USA
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Lymphatic filariasis is a leading cause of chronic disability worldwide; an estimated 120 million persons are infected with the filarial parasites that cause the disease and an estimated 40 million persons suffer from chronic clinical manifestations, primarily lymphedema and hydrocele. Following a flurry of scientific advances during the late 1980s and early 1990s, the World Health Organization announced a Global Programme to Eliminate Lymphatic Filariasis (GPELF) in 1998. Unlike most other disease eradication or elimination programmes, the goals of the GPELF are twofold: to interrupt transmission of the filarial parasite and to alleviate the suffering of those with filariasis-related disease. Embracing the challenge of morbidity control or disability alleviation has both challenged and enriched the GPELF. The paper reviews the scientific developments and decisions that led to the creation of the GPELF, highlights progress towards achieving programme goals and discusses the remaining challenges.
Keywords: Elimination, Filariasis, Hydrocele, Lymphedema, Morbidity
|How to cite this article:|
Addiss D G. Global elimination of lymphatic filariasis: origins, progress and challenges. Indian J Urol 2005;21:12-7
| Introduction|| |
Lymphatic filariasis, an ancient parasitic disease, is responsible for untold human suffering. In 1995, the World Health Organization ranked lymphatic filariasis as the second leading cause of long-term chronic disability worldwide; approximately 14 million persons have lymphedema and 25 million suffer from urogenital manifestations. An estimated 120 million persons are infected by the parasitic roundworms that cause the disease. These species include Wuchereria bancrofti , responsible for about 90% of infections throughout the world, Brugia malayi , responsible for about 10% and limited to south Asia and the Pacific, and Brugia timori , affecting perhaps several thousand.
The adult worms are 1-10 cm in length depending on species and sex, and live inside human lymphatic vessels, where they lead to lymphatic vessel dilatation and dysfunction. The female worms produce millions of microscopic microfilariae, which are released into the blood and are taken up by specific mosquito vectors. Within the mosquito, microfilariae develop into third-stage larvae that are capable of infecting humans during a subsequent blood meal. This obligatory life cycle suggests several possible strategies for controlling lymphatic filariasis, including reducing human-mosquito contact (vector control) and use of antifilarial drugs to either kill the adult worm or to suppress the density of microfilariae in the blood below the level required to sustain transmission.
The geographic distribution of lymphatic filariasis, in the tropics and subtropics, is strongly associated with poverty. Indeed, economic development and improved sanitation alone are credited with interrupting transmission of the parasite in some countries, such as the United States. In the Solomon Islands, mosquito control for malaria was apparently sufficient to interrupt W. bancrofti transmission. A strategy of widespread blood examination (mass screening) and treatment of those who tested positive (selective treatment) was successfully used in Japan. China has achieved 'basic elimination' of lymphatic filariasis using a combined strategy of selective treatment with DEC tablets and mass treatment with DEC-medicated salt. Relatively few countries have successfully eliminated lymphatic filariasis without some measure of improvement in the predisposing conditions of poverty and poor sanitation. Indeed, in certain areas, the distribution of lymphatic filariasis is thought to be expanding as a result of environmental degradation and expanding urban slums. ,,
| Origins of the global programme to eliminate lymphatic filariasis|| |
In 1998, the World Health Organization announced the Global Programme to Eliminate Lymphatic Filariasis (GPELF). What were the factors that led to new optimism that global elimination of this disease was possible? First, diagnostic tests for W. bancrofti infection had been developed that obviated the need for blood collection at night. Knowledge about the geographic distribution of filarial infection had long been limited by a phenomenon known as periodicity, whereby the concentration of microfilariae in the peripheral blood fluctuates dramatically with time of day, being greatest during the peak feeding time of the mosquito vector and frequently undetectable when the mosquito is not active. Throughout much of the world, including India, Culex quinquefasciatus , a night-feeding mosquito, is the major vector of W. bancrofti , and peak microfilarial density occurs around midnight. Thus, nighttime blood collection was required, which was both inconvenient for research staff and often unacceptable for those being tested. A rapid card test that detects circulating antigen from adult worms is now available that is sensitive and specific for W. bancrofti infection; the antigen levels exhibit no periodicity. This field-ready assay has been used to rapidly 'map' the distribution of W. bancrofti in many filariasis-endemic countries., More recently, an antibody test for B. malayi has become available and can be used for the same purpose in areas where brugian filariasis is endemic.
A second factor was the development of more effective antifilarial drugs and drug combinations and more convenient dosing regimens. For many years, the treatment of choice for W. bancrofti or B. malayi infection has been a 12-14 days course of diethylcarbamazine (DEC), a regimen ill-suited for mass treatment. During the 1990s, multi-centre trials demonstrated that a single 200-400 mg/kg dose of ivermectin results in rapid clearance and sustained suppression of microfilaraemia. An unexpected finding of these and other studies was the high degree to which a single 6 mg/kg dose of DEC also cleared microfilaraemia when measured 1 year after treatment, comparable to that observed 1 year after a 2-week course of treatment. Subsequent studies have indicated that a single 6 mg/kg dose of DEC is as effective as a 12-day course in killing the adult worms., Further studies have shown that combinations of antifilarial drugs (e.g., DEC and ivermectin; DEC and albendazole: or ivermectin and albendazole) are even more effective in suppressing microfilaraemia than single-drug regimens., These developments paved the way for the GPELF strategy adopted by WHO: selective screening to identify at-risk populations, followed by annual mass treatment with single-dose drug combinations. WHO recommends co-administration of DEC and albendazole, except in sub-Saharan African countries with co-endemic onchocerciasis, where ivermectin and albendazole are recommended.
A third factor that provided impetus for the creation of GPELF was a greater understanding of filarial morbidity. Pioneering studies in India had highlighted the important role of secondary bacterial infections, referred to as acute dermatolymphangioadenitis (ADLA), adenolymphangitis (ADL), erysipelas, or sometimes, simply 'acute attacks'. ,,, Recurrent episodes of ADLA result in progression of lymphedema to its advanced form, elephantiasis. This new understanding suggested that simple measures, such as hygiene and skin care, could prevent these acute episodes and halt progression of disease; thus programme managers and clinicians could intervene clinically to alter the course of filariasis-related lymphedema. ,,
Scientific progress, although necessary, was, by itself, insufficient to trigger public health action. Several important events and decisions catalyzed this process at the global level. In 1994, the International Task Force for Disease Eradication, after carefully reviewing a list of candidate diseases, declared that lymphatic filariasis was 'one of six diseases that could potentially be eradicated'. This Task Force declaration energized health officials and filariasis researchers. Just 3 years later, in May 1997, the World Health Assembly passed a resolution calling for the 'global elimination of lymphatic filariasis as a public health problem'. The imprecise wording of this resolution ('elimination as a public health problem' was not defined) provided a general framework that was acceptable to a wide variety of partners with differing interpretations of the final endpoint, ranging from enhanced disease control to global extinction of the parasite. The resolution also provided an institutional mandate for WHO to launch the global programme and a solid platform for coordinated action among all partners.
Another catalyst that proved critical for the launching of the GPELF came in January 1998, when the pharmaceutical company SmithKline Beecham announced its donation to WHO of billions of doses of albendazole for the elimination of lymphatic filariasis - the largest drug donation in history. This donation was followed a few months later by the extension of Merck and Co.'s donation of Mectizan® (ivermectin) for onchocerciasis to include lymphatic filariasis in countries where these two diseases are co-endemic. These two generous drug donations galvanized the GPELF and provided eligible national filariasis elimination programs with access to these drugs, free of charge. Although DEC is not currently donated, it is inexpensive.
Soon after the GPELF was announced, the Global Alliance to Eliminate Lymphatic Filariasis was created, a free and open public-private partnership of organizations and institutions that support the GPELF. As described in a recent review by Molyneux and Zagaria, the Global Alliance is characterized by a light governance structure that facilitates flexibility in addressing specific needs at the regional and national levels.
A final major catalyst to the programme came in 2000, in the form of a grant from the Bill & Melinda Gates Foundation to the Global Alliance. These funds have covered many of the 'start-up' costs for the global programme and have supported several national programmes as well. They have been supplemented by considerable resources from the governments of filariasis-endemic countries, by the Department for International Development (DFID) of the UK, and by contributions from other partners in the Global Alliance.
| GPELF - an unconventional disease elimination program|| |
In August 1998, 3 months after the World Health Assembly passed its resolution on filariasis elimination, a group of researchers, policy makers, health officials and representatives from nongovernmental organizations and the private sector met at Magnetic Island, near Townsville Australia, to further define the goals and activities required for 'global elimination of lymphatic filariasis as a public health problem'. A consensus emerged that filariasis elimination required both interrupting transmission of the filarial parasites and providing care to the estimated 40 million persons who currently suffer from filariasis-related disease. This twofold (or 'two pillar') approach was later endorsed by the GPELF in its 1999 strategic plan.
The rationale for including 'morbidity control' as an integral part of the GPELF was based on several considerations. First was the observation that treatment with antifilarial drugs did not usually reverse long-standing or advanced manifestations of lymphatic filariasis.,,, Thus, one could interrupt transmission but have little short-term impact on the public health problem of filariasis-related disease. Second was an ethical issue: how could the filariasis programme limit itself only to mass drug administration when millions of persons with chronic lymphedema and hydrocele could expect to receive little clinical benefit, and when safe and effective clinical interventions already existed that could address these conditions? Third, it has been a common experience that mobilizing communities to accept mass drug treatment is facilitated when access to care is provided for those with chronic filarial disease. Finally, it was thought that humanitarian and religious donors, who may have no inherent interest in elimination of a parasite per se , might be motivated to assist in relieving the suffering of affected individuals.
Most major disease elimination or eradication programs have eschewed involvement in providing clinical care to affected persons, and have focused entirely on interrupting transmission in order to prevent disease in future generations. The intentional decision of GPELF to attempt to address the needs of these persons has provided both challenges and opportunities. In this sense, the GPELF is similar to the Alliance for the Global Elimination of Blinding Trachoma. As with the GPELF, the strategies for elimination of blinding trachoma involve not only mass treatment with antibiotics (to reduce Chlamydia trachomatis transmission), but also a surgical intervention (for trichiasis) and promotion of hygiene (washing the face). Such programs are more complex and difficult to manage than single-focus programmes such as polio eradication. However, they are also less 'vertical', involve a broader array of partners, and are more attuned to the health systems of endemic countries. These characteristics are important in the emerging international health climate, in which the theme of programme integration is gaining momentum.,
For lymphatic filariasis programme managers, whose primary focus has been to scale up mass drug administration to cover all at-risk populations, providing lymphedema care at the same time has been challenging. Adding surgical care for urogenital disease to their list of duties has proved even more difficult, for a variety of reasons. Few programme managers are surgeons, and in most countries, collaborative networks between vectorborne disease control programmes and surgical societies have been nonexistent, or at best limited. In addition, for decades, filariasis research has been dominated by immunologists and epidemiologists, who had little direct experience with the various urogenital manifestations of the disease, and did not bother to discriminate among them in surveys or epidemiologic studies. Indeed, in areas endemic for bancroftian filariasis, the term 'hydrocele' has often been used to describe all urogenital swelling in men. This is in marked contrast to earlier detailed descriptions of urogenital filarial disease, particularly by clinical investigators in India.
| Current status of the GPELF|| |
In a recent paper that weighed the costs and benefits of filariasis elimination, Ramaiah and Das stated that 'elimination of lymphatic filariasis using annual mass drug administration is one of the cheapest and most beneficial disease control strategies in the annals of public health history'. Recognizing these tremendous public health benefits, the GPELF has set 2020 as the target date to achieve the elimination of lymphatic filariasis, and has moved quickly to scale up mass drug administration. Of 82 countries endemic for lymphatic filariasis, 42 have initiated annual mass distribution of antifilarial drugs (World Health Organization, unpublished data). In 2004, an estimated 250 million persons were treated. Several countries have already completed 5 years of mass drug administration and are beginning to assess whether the intervention can be withdrawn. At this point, the lack of precision inherent in the original World Health Assembly resolution is less helpful, as one's understanding of the ultimate goal of the programme influences both the decision of when to stop mass treatment and the intensity of surveillance established to detect any recrudescence of transmission.
Because most of the resources and attention of the GPELF have focused on interrupting transmission, morbidity control, also referred to as disability alleviation, has been less successful in scaling up. The basic principles of lymphedema management or 'foot care' are well accepted, and several studies have documented that these simple measures can dramatically reduce the incidence of ADLA, improve clinical outcome and enhance quality of life.,,,,, Recent work has also been done to incorporate ayurvedic principles and practices into lymphedema management. However, scaling up these activities to the state or national level remains a significant challenge. At the heart of this challenge lies the issue of how best to integrate this treatment into existing health services.
As with lymphedema management, urogenital filarial disease has been successfully addressed in several centres of excellence. But few filariasis-endemic countries have established access to medical and surgical care for all those who suffer from filariasis-related urogenital disease. Hydrocele surgery has been the mainstay of such programmes, and WHO has released preliminary guidelines for hydrocele surgery in filariasis-endemic areas. However, lymph scrotum, scrotal elephantiasis, chyluria and other manifestations, such as chylocele, have received much less attention from the GPELF. The research base that would provide the foundation for scaling up remains inadequate. Little is known for example, about the relative frequency of hydrocele, chylocele or hematochylocele in filariasis-endemic areas; about the incidence of postoperative infection or other complications; or about the incidence of hydrocele recurrence following hydrocelectomy using different surgical techniques.
| Conclusion|| |
Since it was created in 1998, the GPELF has been one of the most rapidly expanding global public health programmes in history. The main focus of the programme has been on interrupting transmission of the parasite. The GPELF has repeatedly emphasized its commitment not only to interrupt transmission, but also to provide access to care for those with filariasis-related disease. This commitment has both enriched the programme and made it more complex. To realize the full promise of this commitment, it will be necessary to expand morbidity control activities from centres of excellence and integrate them firmly within national health systems. To expand access to surgical care for persons with filariasis-related urogenital disease, increased collaboration will be required among public health officials, filariasis programme directors, funding agencies, surgeons, surgical societies, and surgical researchers. The public health benefits of such collaboration promise to be substantial.
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