Zoonotic Brugia pahangi filariasis in a suburbia of Kuala Lumpur City, Malaysia

Five local Malaysian patients with clinical manifestations consistent with lymphatic filariasis were referred to our medical centre between 2003 and 2006. Although no microfilariae (mf) were detected in their nocturnal blood samples, all were diagnosed to have lymphatic filariasis on the basis of clinical findings and positive serology results. PCR on their blood samples revealed that two of the patients were infected with Brugia pahangi, an animal filarial worm hitherto not known to cause human disease in the natural environment. All the patients were successfully treated with anti-filarial drugs: four patients were treated with a combination of diethylcarbamazine (DEC) and albendazole, and one with doxycycline. Four of them were residents of Petaling Jaya, a residential suburbia located 10 km southwest of Kuala Lumpur city, Malaysia. The fifth patient was a frequent visitor of the suburbia. This suburbia has no history or record of B. malayi infection. The most likely vector of the worm was Armigeres subalbatus as extensive entomological surveys within the suburbia revealed only adult females of this mosquito species were infected with B. pahangi larvae. Wild monkeys caught in the suburbia were free from B. pahangi mf, but domestic cats were mf positive. This suggests that infected cats might be the source of the zoonotic infection in the suburbia.     

Lymphatic filariasis: what mice can tell us

Human lymphatic filariasis is a major tropical disease in which clinical manifestations range from asymptomatic microfilaraemia to chronic pathology. Investigative immunological research into this disease is hampered by the fact that mice are refractory to the full developmental cycle of this parasitic nematode. However, studies using either single-stage infections or immunocompromised mice have greatly added to our knowledge of the filarial-induced immune pathways leading to protective immunity, pathology and immunological tolerance. In this review, Rachel Lawrence discusses the recent advances in our understanding of the immunology of lymphatic filariasis using the mouse model.     

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.     

Cytodiagnosis of filarial infections from an endemic area

OBJECTIVE: To throw light on cytologic findings as a possible mode of diagnosis of lymphatic filariasis. STUDY DESIGN: Filariasis has worldwide distribution, but lymphatic filariasis predominantly affects tropical and subtropical regions. Demonstration of microfilaremia, the specific test for diagnosis of lymphatic filariasis, often shows false negative results in endemic areas. The present study, done in an endemic area, showed the presence of microfilariae or adult worms of Wuchereria bancrofti in fine needle aspirates collected from amicrofilariaemic cases. In a few cases the discovery was incidental. A total 4,534 cases undergoing cytologic evaluation were carefully screened for the presence of adult worms or larvae, irrespective of clinical diagnosis. Microfilariae were demonstrated in both clinically suspected cases of filariasis and asymptomatic cases. RESULTS: A total of 1 positive cases were found; in 4 cases the clinical diagnosis was lymphatic filariasis, and 7 cases were asymptomatic. All 11 cases were amicrofilariaemic. CONCLUSION: Various sophisticated investigations are used for diagnosis of lymphatic filariasis without microfilaremia. Fine needle aspiration cytology, being a cheap, simple and easy procedure, may have some role in this field, but further detailed studies are needed before any final claim.     

Pathogenesis of lymphatic disease in bancroftian filariasis: a clinical perspective

The pathogenesis of lymphatic filariasis has been a matter of debate for many decades. Here, Gerusa Dreyer and colleagues propose a dynamic model of bancroftian filariasis, integrating clinical, parasitological, surgical, therapeutic, ultrasonographic and histopathological data. This model has profound implications for filariasis control programs and the management of the individual patient.     

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.     

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.     

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.     

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.     

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

BACKGROUND: Hygiene and skin care are effective and important interventions in the management of lymphoedema secondary to lymphatic filariasis. We analyzed the impact on the quality of life that education and introduction of a designated nurse had on lymphoedema patients in a community that was endemic for lymphatic filariasis. METHODS: Patients' life quality was assessed using a Dermatology Life Quality Index (DLQI) questionnaire. At the same time they received education on appropriate hygiene, skin care techniques and simple exercises that encourage lymph drainage. A designated nurse was provided with educational materials and treatments. The DLQI life quality measure was repeated one year later. RESULTS: The DLQI improved for all patients and reported acute attacks were reduced. A paired t-test showed the improvement in DLQI to be highly significant (P = < 0.0001). CONCLUSIONS: A nurse-led service combined with patient education in communities endemic for lymphatic filariasis is an effective intervention in improving the quality of life of patients with lymphoedema.     

Impact on the quality of life of lymphoedema patients following introduction of a hygiene and skin care regimen in a Guyanese community endemic for lymphatic filariasis: A preliminary clinical intervention study

BACKGROUND: Hygiene and skin care are effective and important interventions in the management of lymphoedema secondary to lymphatic filariasis. We analyzed the impact on the quality of life that education and introduction of a designated nurse had on lymphoedema patients in a community that was endemic for lymphatic filariasis. METHODS: Patients' life quality was assessed using a Dermatology Life Quality Index (DLQI) questionnaire. At the same time they received education on appropriate hygiene, skin care techniques and simple exercises that encourage lymph drainage. A designated nurse was provided with educational materials and treatments. The DLQI life quality measure was repeated one year later. RESULTS: The DLQI improved for all patients and reported acute attacks were reduced. A paired t-test showed the improvement in DLQI to be highly significant (P = < 0.0001). CONCLUSIONS: A nurse-led service combined with patient education in communities endemic for lymphatic filariasis is an effective intervention in improving the quality of life of patients with lymphoedema.     

Elimination and Eradication of Neglected Tropical Diseases with Mass Drug Administrations: A Survey of Experts

Background

Lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths, and trachoma are the five most prevalent neglected tropical diseases in the world, and each is frequently treated with mass drug administrations. We performed a survey of neglected tropical diseases experts to elicit their opinions on the role of mass drug administrations for the elimination of these infections.

Methodology/Principal Findings

We sent an online survey to corresponding authors who had published an article about a neglected tropical disease from 2007 to 2011. Of 825 unique authors who were invited to complete the survey, 365 (44.2%) responded, including 234 (28.4%) who answered questions regarding one of the five most prevalent neglected tropical diseases. Respondents had varying opinions about the goals of programmatic activities for their chosen neglected tropical disease, with elimination or eradication identified as the most important goal by 87% of lymphatic filariasis respondents, 66% of onchocerciasis respondents, 55% of trachoma respondents, 24% of schistosomiasis respondents, and 21% of soil-transmitted helminth respondents. Mass drug administrations, other non-medication health measures, and education were generally thought to be more important for elimination than vector control, development of a new tool, or the presence of a secular trend. Drug resistance was thought to be a major limitation of mass drug administrations for all five neglected tropical diseases. Over half of respondents for lymphatic filariasis and trachoma thought that repeated mass drug administrations could eliminate infection within ten years of the initiation of mass treatments.

Conclusions/Significance

Respondents for lymphatic filariasis, onchocerciasis, and trachoma were more enthusiastic about the prospects of elimination and eradication than were respondents for schistosomiasis or soil-transmitted helminths. Mass drug administrations were generally believed to be among the most important factors for the success of elimination efforts for each of the five neglected tropical diseases, highlighting the opportunity for integrating drug distributions.     

A possible case of spontaneous Loa loa encephalopathy associated with a glomerulopathy

Background

There is a danger that mass drug administration campaigns may fail to maintain adequate treatment coverage to achieve lymphatic filariasis elimination. Hence, additional measures to suppress transmission might be needed to ensure the success of the Global Program for the Elimination of Lymphatic Filariasis.

Discussion

Vector control successfully eliminated lymphatic filariasis when implemented alone or with mass drug administration. Challenges to lymphatic filariasis elimination include uncertainty of the exact level and duration of microfilarial suppression required for elimination, the mobility of infected individuals, consistent non-participation of some infected individuals with mass drug administration, the possible development of anti-filarial drug resistance and treatment strategies in areas co-endemic with loasis. Integration of vector control with mass drug administration can address some of these challenges. The potential benefits of vector control would include: (1) the ability to suppress filariasis transmission without the need to identify all individual 'foci of infection'; (2) minimizing the risk of reestablishment of transmission from imported microfilaria positive individuals; and (3) decreasing the risk of dengue or malaria transmission where, respectively, Aedes or Anopheles are lymphatic filariasis vectors.

Summary

With adequate sustained treatment coverage, mass drug administration should meet the criteria for elimination of lymphatic filariasis. However, it may be difficult to sustain sufficiently high mass drug administration coverage to achieve lymphatic filariasis elimination in some areas, particularly, where Aedes species are the vectors. Since vector control was effective in controlling and even eliminating lymphatic filariasis transmission, integration of vector control with mass drug administration will ensure the sustainability of transmission suppression and thereby better ensure the success of national filariasis elimination programs. Although trials of some vector control interventions are needed, proven vector control strategies are ready for immediate integration with mass drug administration for many important vectors. Vector control is the only presently available additional lymphatic filariasis control measure with the potential for immediate implementation.     

Brugia malayi Asparaginyl - tRNA Synthetase Stimulates Endothelial Cell Proliferation,Vasodilation and Angiogenesis

A hallmark of chronic infection with lymphatic filarial parasites is the development of lymphatic disease which often results in permanent vasodilation and lymphedema, but all of the mechanisms by which filarial parasites induce pathology are not known. Prior work showed that the asparaginyl-tRNA synthetase (BmAsnRS) of Brugia malayi, an etiological agent of lymphatic filariasis, acts as a physiocrine that binds specifically to interleukin-8 (IL-8) chemokine receptors. Endothelial cells are one of the many cell types that express IL-8 receptors. IL-8 also has been reported previously to induce angiogenesis and vasodilation, however, the effect of BmAsnRS on endothelial cells has not been reported. Therefore, we tested the hypothesis that BmAsnRS might produce physiological changes in endothelial by studying the in vitro effects of BmAsnRS using a human umbilical vein cell line EA.hy926 and six different endothelial cell assays. Our results demonstrated that BmAsnRS produces consistent and statistically significant effects on endothelial cells that are identical to the effects of VEGF, vascular endothelial growth factor. This study supports the idea that new drugs or immunotherapies that counteract the adverse effects of parasite-derived physiocrines may prevent or ameliorate the vascular pathology observed in patients with lymphatic filariasis.     

Mapping of lymphatic filariasis in Nepal

BACKGROUND: Human infection with Wuchereria bancrofti causes a disabling parasitic disease known as lymphatic filariasis, which is a major public health and socio-economic problem in many parts of the world. At the onset of the study, little was known of the distribution of filariasis and its current importance as a public health problem in Nepal. METHODS: Epidemiological mapping was undertaken to determine the prevalence of infection by Wuchereria bancrofti in 37 districts of Nepal between July to December 2001. The study population above 15 years of age was selected, and the immunochromatographic test (ICT Filariasis) was used to screen for circulating filarial antigen (CFA). RESULTS: The overall prevalence of lymphatic filariasis from a 4,488-sample population was 13% and 33/37 districts were found to be endemic. On the basis of geographical data, the highest number of cases was found at altitudes between 500-700 m; however, a substantial number of infected individuals were found in the highly populated Kathmandu valley, at altitudes between 900-1,500 metres where transmission appears to take place. Prevalence rates above 20% were found in 11 districts (with the highest rate of 40%), 6-19% were found in 15 districts, and 0.1-5% were in 7 districts.Information on people's knowledge, attitudes and behaviour towards filariasis was also collected by means of a structured questionnaire, which is presented and discussed in the study. CONCLUSIONS: This is the most extensive study of lymphatic filariasis undertaken to date in Nepal. The study indicates that the prevalence of infection is far greater that was previously reported and that lymphatic filariasis should be a much higher health priority than currently given.     

A Mechanism for Chronic Filarial Hydrocele with Implications for Its Surgical Repair

Background

Chronic hydrocele is the most common manifestation of bancroftian filariasis, an endemic disease in 80 countries. In a prospective study, we evaluated the occurrence of intrascrotal lymphangiectasia, gross appearance/consistency of the testis, and the efficacy of complete excision of hydrocele sac in patients living in a bancroftian filariasis endemic area who underwent hydrocelectomy at the Center for Teaching, Research and Tertiary Referral for Bancroftian Filariasis (NEPAF).

Methodology/Principal Findings

A total of 968 patients with uni- or bilateral filarial hydrocele (Group-1) and a Comparison Group (CG) of 218 patients from the same area who already had undergone hydrocele-sac-sparing hydrocelectomy elsewhere were enrolled at NEPAF. Twenty-eight patients from the Comparison Group with hydrocele recurrence were re-operated on at NEPAF and constitute Group-2. In Group-1 a total of 1,128 hydrocelectomies were performed (mean patient age of 30.3yr and mean follow-up of 8.6yr [range 5.3–12]). The hydrocele recurrence rates in Group-1 and in the Comparison Group (mean age of 31.5 yr) were 0.3%, and 19.3%, respectively (p<0,001). There was no hydrocele recurrence in Group-2 (mean patient age of 25.1yr and mean follow-up of 6yr [range 5–6.9]). Per surgically leaking or leak-prone dilated lymphatic vessels were seen in the inner or outer surface of the hydrocele sac wall or in surrounding tissue, particularly in the retrotesticular area, in 30.9% and in 46.3% of patients in Group-1 and Group-2, respectively (p = 0.081). The testicles were abnormal in shape, volume, and consistency in 203/1,128 (18%) and 10/28 (35.7%) of patients from Group-1 and Group-2, respectively (p = 0,025).

Conclusions/Significance

Lymph fluid from ruptured dilated lymphatic vessels is an important component of chronic filarial hydrocele fluid that threatens the integrity of the testis in an adult population living in bancroftian filariasis endemic areas. To avoid hydrocele recurrence the authors advise complete excision of hydrocele sac and when identified, leaking or leak-prone dilated lymphatic vessels should be sutured or excised.     

Global mapping of lymphatic filariasis

Disease maps are becoming increasingly important in infectious disease epidemiology and control. For lymphatic filariasis, the development of such maps has been hampered in the past by the lack of data on the geographical distribution of levels of infection or disease. Here, Edwin Michael and Don Bundy present an atlas for this parasitic disease derived from a recently compiled geographical database. Focusing on mapping and analysis of case prevalence data at the global and regional levels, the authors show how mapping the geographical distribution is integral not only to assessing spatial patterns in the infection and disease distribution but also to stratifying endemic areas by infection and/or disease rate.     

Profiling the cellular immune response to multiple Brugia pahangi infections in a susceptible host

Human lymphatic filariasis is caused primarily by Brugia malayi and Wuchereria bancroffi. Unraveling this disease is complex, as people living in endemic areas exhibit a vast array of clinical states and immune responses. The Mongolian gerbil (Meriones unguiculatus)-B. pahangi model of human lymphatic filariasis has provided much information on immune parameters associated with filarial infection. Prior investigations in our laboratory have shown that gerbils closely mimic a subset of patients classified as microfilaremic but asymptomatic, a group that comprises the majority of people living in endemic areas. Worm recovery data suggest that gerbils carrying current B. pahangi infections do not show any resistance to subsequent subcutaneous B. pahangi infections. The aim of the present studies was to investigate the T cell cytokine response in gerbils receiving multiple infections of B. pahangi as a means of mimicking the conditions experienced by people in endemic areas. The T cell cytokine profile generated by multiply infected gerbils was not different from that previously generated by gerbils infected only once with B. pahangi. Gerbils infected multiple times with B. pahangi showed a transient increase in IL-5, which corresponded to the increased eosinophil levels previously reported from multiply infected gerbils. Chronically infected gerbils showed elevated IL-4 mRNA levels, as has been reported from gerbils infected only once with B. pahangi. Chronic infections were also associated with a state of immune hyporesponsiveness, as determined by the characterization of lymphatic thrombi and lymphoproliferation of spleen and renal lymph node cells to worm antigen.     

Mass drug administration to eliminate lymphatic filariasis in India

Mass drug administration (MDA) to eliminate lymphatic filariasis is already in place in 32 out of 83 endemic countries. Expansion of the MDA programme to other countries and within large countries such as India is necessary to achieve the goal of lymphatic filariasis elimination. However, expansion and sustenance of the global campaign to eliminate lymphatic filariasis requires commitment and allocation of funds by governments and donor agencies. This could be achieved, at least to some extent, by highlighting the benefits of the programme in relation to costs. On the basis of various studies in south India, this article assesses the costs, effectiveness and economic and social benefits of the MDA programmes aimed at eliminating lymphatic filariasis.     

The role of albendazole in programmes to eliminate lymphatic filariasis.

Citing earlier advances in the treatment of lymphatic filariasis [particularly the effectiveness of single-dose diethylcarbamazine (DEC) in reducing microfilaraemia and its enhanced effectiveness when co-administered with single-dose ivermectin], Eric Ottesen, Mahroof Ismail and John Horton consider recent studies on the antifilarial activity of albendazole that have led to the current recommendations for its use in single-dose regimens in conjunction with either DEC or ivermectin for large-scale control/elimination programmes. Furthermore, the potential of albendazole as a macrofilaricide for treating individual patients with lymphatic filarial infections is emphasized as one of a number of important research questions that remain to be explored.