Lymphatic Filariasis is the leading type of lymphedema worldwide, affecting an estimated 120 million people. It is an endemic conditions located in the tropical regions of the world. These areas include SE Asia, the Indian sub-continent, Africa, and areas of South America.
Infestation or infection by a microscopic threat like parasitic worm. The three main worms include Wuchereria bancrofti , Brugia malayi , and B. timori. The infections is spread through mosquito bites. However, there are five other species that may be involved, these include The other five species are Loa loa, Mansonella perstans, M. streptocerca, M. ozzardi, and Brugia timori.
The worm larvae (microfilaria) may be injected by an infected mosquito directly into the blood. The microfilaria then reproduce and spread throughout the bloodstream, eventually traveling to the lymph system where they grow into adults. What makes this condition frustrating difficult to diagnosis and treat early is that the symptoms of infection may not show up for years.
The symptom of infection swelling of an arm, leg or genital areas.
It is not the actual infection that can be life threatening, but the complications that occur as a result of the lymphedema. The most serious complication is massive infection (cellulitis, lymphangitis). Other complications include fibrosis (hardening) of the affected tissue, severe pain, gross disfigurement, sexual dysfunction. Long term fibrosis or tissue hardening can also cause venous thrombosis (blood clot).
Suspicion of lymphatic filiarisis of course, may be made upon the appearance of the lymphedema. However, to prevent this it is imperative to diagnosis filariare infection before it gets to this stage. This is usually done through microscopic examination of blood samples. However, there are other diagnostic tools available. These include antigen detection, molecular diagnosis (polymerase chain reaction), identification of adult worms through tissue samples, and antibody detection.
Treatment generally has a dual focus. First, you must eliminate the infection that caused the lymphedema and then you must subsequently treat the lymphedema itself.
Treatment for the parasitic infection include the administration of drugs such as diethylcarbamazine (DEC), albendazole and ivermectin.
Treatment for the lymphedema includes decongestive therapy on the affected limbs, surgical procedures on genital lymphedema and treatment of the numerous complications.
The real goal goal however, is in the prevention of this condition. A massive global alliance including the World Health Organization, medical professional and pharmacy companies (SmithKline Beecham and Merck and Co.) is seeking to eliminate this disease through preventative therapy.
Through studies being conducted in the affected regions, it has been found that preventative doses of the above medicines can actually prevent the initial infection. Other modalities include extensive community education, and intensive improvement in local hygiene.
Lymphatic Filariasis, known as Elephantiasis, puts at risk more than a billion people in more than 80 countries. Over 120 million have already been affected by it, over 40 million of them are seriously incapacitated and disfigured by the disease. One-third of the people infected with the disease live in India, one third are in Africa and most of the remainder are in South Asia, the Pacific and the Americas. In tropical and subtropical areas where lymphatic filariasis is well-established, the prevalence of infection is continuing to increase. A primary cause of this increase is the rapid and unplanned growth of cities, which creates numerous breeding sites for the mosquitoes that transmit the disease.In its most obvious manifestations, lymphatic filariasis causes enlargement of the entire leg or arm, the genitals, vulva and breasts. In endemic communities, 10-50% of men and up to 10% of women can be affected. The psychological and social stigma associated with these aspects of the disease are immense. In addition, even more common than the overt abnormalities is hidden, internal damage to the kidneys and lymphatic system caused by the filariae.
The thread-like, parasitic filarial worms Wuchereria bancrofti and Brugia malayi that cause lymphatic filariasis live almost exclusively in humans. These worms lodge in the lymphatic system, the network of nodes and vessels that maintain the delicate fluid balance between the tissues and blood and are an essential component for the body's immune defence system. They live for 4-6 years, producing millions of immature microfilariae (minute larvae) that circulate in the blood.
The disease is transmitted by mosquitoes that bite infected humans and pick up the microfilariae that develop, inside the mosquito, into the infective stage in a process that usually takes 7-21 days. The larvae then migrate to the mosquitoes' biting mouth-parts, ready to enter the punctured skin following the mosquito bite, thus completing the cycle.
The development of the disease itself in humans is still something of an enigma to scientists. Though the infection is generally acquired early in childhood, the disease may take years to manifest itself.Indeed, many people never acquire outward clinical manifestations of their infections. Even though there may be no clinical symptoms, studies have now disclosed that such victims, outwardly healthy, actually have hidden lymphatic pathology and kidney damage as well. The asymptomatic form of infection is most often characterized by the presence in the blood of thousands or millions of larval parasites (microfilariae) and adult worms located in the lymphatic system. The worst symptoms of the chronic disease generally appear in adults, and in men more often than in women.
In endemic communities, some 10-50% of men suffer from genital damage, especially hydrocoele (fluid-filled balloon-like enlargement of the sacs around the testes) and elephantiasis of the penis and scrotum. Elephantiasis of the entire leg, the entire arm, the vulva, or the breast - swelling up to several times normal size - can affect up to 10% of men and women in these communities. Acute episodes of local inflammation involving skin, lymph nodes and lymphatic vessels often accompany the chronic lymphoedema or elephantiasis. Some of these are caused by the body's immune response to the parasite, but most are the result of bacterial infection of skin where normal defences have been partially lost due to underlying lymphatic damage.
Careful cleansing can be extremely helpful in healing the infected surface areas and in both slowing and, even more remarkably, reversing much of the overt damage that has occurred already.
In endemic areas, chronic and acute manifestations of filariasis tend to develop more often and sooner in refugees or newcomers than in local populations continually exposed to infection. Lymphoedema may develop within six months and elephantiasis as quickly as a year after arrival.
Until very recently, diagnosing lymphatic filariasis had been extremely difficult, since parasites had to be detected microscopically in the blood, and in most parts of the world, the parasites have a “nocturnal periodicity” that restricts their appearance in the blood to only the hours around midnight. The new development of a very sensitive, very specific simple “card test” to detect circulating parasite antigens without the need for laboratory facilities and using only finger-prick blood droplets taken anytime of the day has completely transformed the approach to diagnosis. With this and other new diagnostic tools, it will now be possible both to improve our understanding of where the infection actually occurs and to monitor more easily the effectiveness of treatment and control programmes.
The primary goal of treating the affected community is to eliminate microfilariae from the blood of infected individuals so that transmission of the infection by the mosquito can be interrupted. Recent studies have shown that single doses of diethylcarbamazine (DEC) have the same long-term (1-year) effect in decreasing microfilaraemia as the formerly-recommended 12-day regimens of DEC and, even more importantly, that the use of single doses of 2 drugs administered concurrently (optimally albendazole with DEC or ivermectin) is 99% effective in removing microfilariae from the blood for a full year after treatment. It is this level of treatment effectiveness that has made feasible the new efforts to eliminate lymphatic filariasis.
Both albendazole and DEC have been shown to be effective in killing the adult-stage filarial parasites (necessary for complete cure of infection), but ideal treatment regimens still need to be defined. It is clear that this anti-parasite treatment can result in improvement of patients' elephantiasis and hydrocoele (especially in the early stages of disease), but the most significant treatment advance to alleviate the suffering of those with elephantiasis has come from recognizing that much of the progression in pathology results from bacterial and fungal “superinfection” of tissues with compromised lymphatic function caused by earlier filarial infection. Thus, rigorous hygiene to the affected limbs, with accompanying adjunctive measures to minimize infection and promote lymph flow, results both in a dramatic reduction in frequency of acute episodes of inflammation (“filarial fevers”) and in an astonishing degree of improvement of the elephantiasis itself.
The strategy of the Global Programme to Eliminate Lymphatic Filariasis has two components: firstly, to stop the spread of infection (i.e. interrupt transmission), and secondly, to alleviate the suffering of affected individuals (i.e. morbidity control).
To interrupt transmission, districts in which lymphatic filariasis is endemic must be identified, and then community-wide (“mass treatment”) programmes implemented to treat the entire at-risk population. In most countries, the programme will be based on once-yearly administration of single doses of two drugs given together: albendazole plus either diethylcarbamazine (DEC) or ivermectin, the latter in areas where either onchocerciasis or loiasis may also be endemic; this yearly, single-dose treatment must be carried out for 4-6 years. An alternative community-wide regimen with equal effectiveness is the use of common table/ cooking salt fortified with DEC in the endemic region for a period of one year.
To alleviate the suffering caused by the disease, it will be necessary to implement community education programmes to raise awareness in affected patients. This would promote the benefits of intensive local hygiene and the possible improvement, both in the damage that has already occurred, and in preventing the debilitating and painful, acute episodes of inflammation.
The generous pledge in 1998 by the global healthcare company SmithKline Beecham to collaborate with the World Health Organization in its elimination efforts included the donation of numerous resources (but especially albendazole, one of the mainstay drugs in the elimination strategy), free of charge, for as long as necessary to ensure success of the elimination programme. This donation, coupled with the recent decision by Merck and Co., Inc., to expand its ongoing Mectizan® (ivermectin) Donation Programme to include treatment of lymphatic filariasis where appropriate, and the creation of additional partnerships with other private, public and international organizations, including the World Bank, have all further strengthened the prospects for success of these elimination efforts.
Because of its prevalence often in remote rural areas, on the one hand, and in disfavoured periurban and urban areas, on the other, lymphatic filariasis is primarily a disease of the poor. In recent years, lymphatic filariasis has steadily increased because of the expansion of slum areas and poverty, especially in Africa and the Indian sub-continent. As many filariasis patients are physically incapacitated, it is also a disease that prevents patients from having a normal working life. The fight to eliminate lymphatic filariasis is also a fight against poverty.Lymphatic filariasis exerts a heavy social burden that is especially severe because of the specific attributes of the disease, particularly since chronic complications are often hidden and are considered shameful. For men, genital damage is a severe handicap leading to physical limitations and social stigmatization. For women, shame and taboos are also associated with the disease. When affected by lymphoedema, they are considered undesirable and when their lower limbs and genital parts are enlarged they are severely stigmatized; marriage, in many situations an essential source of security, is often impossible.
The proportions of the total, global burden posed by lymphatic filariasis that occur in the areas covered by the World Health Organization's regional offices for the Americas (AMRO), Eastern Mediterranean (EMRO), Africa (AFRO), South-east Asia (SEARO) and the Western Pacific (WPRO). Burden was estimated as the number of disability-adjusted life-years (DALY) lost and is shown split, in the pie chart for each region, according to the type of mosquito responsible for transmitting the causative parasite. Reprinted with permission from Annals of Tropical Medicine and Parasitology, Vol. 96, Supplement No. 2, S3–S13 (2002).
Lymphatic filariasis is caused by adult worms (filariae) that live in the lymphatic vessels. The female worms release microfilariae that circulate in the peripheral blood and are ingested by mosquitoes; thus, infected mosquitoes transmit the infection from person to person. The two major species of filariae that cause lymphatic disease in humans are Wuchereria bancrofti and Brugia malayi.
Lymphatic filariasis affects an estimated 120 million persons in tropical areas of the world, including sub-Saharan Africa, Egypt, southern Asia, the western Pacific islands, the northeastern coast of Brazil, Guyana, and the Caribbean island of Hispaniola (1). Because most infections are asymptomatic, many go unrecognized. On average, 16 cases are diagnosed, reported to CDC, and treated annually in the United States.
Short-term travelers to endemic areas are at low risk for this infection. Travelers who visit endemic areas for extended periods of time and who are intensively exposed to infected mosquitoes can become infected. Most infections seen in the United States are in immigrants from endemic countries.
Most infections are asymptomatic, but the living adult worm causes progressive lymphatic vessel dilation and dysfunction (2). Lymphatic dysfunction may lead to lymphedema of the leg, scrotum, penis, arm, or breast, which can increase in severity as a result of recurrent secondary bacterial infections (3,4). Tropical pulmonary eosinophilia is a potentially serious progressive lung disease with nocturnal cough, wheezing, and fever, resulting from immune hyperresponsiveness to microfilariae in the pulmonary capillaries.
No vaccine is available, nor has the effectiveness of chemoprophylaxis been well documented. Protective measures include avoidance of mosquito bites through the use of personal protection measures (see Chapter 2).
The drug of choice for treatment of travelers with W. bancrofti or B. malayi infections is diethylcarbamazine (DEC). DEC, which is available to U.S.-licensed physicians for this purpose, can be obtained from the CDC Parasitic Diseases Drug Service at 404-639-3670 under an Investigational New Drug protocol. (See http://www.cdc.gov/ncidod/srp/drugs/drug-service.html.) DEC kills circulating microfilariae and is partially effective against the adult worms and tropical pulmonary eosinophilia (5). Ivermectin does not kill the adult worms (6). Two potential alternative drugs being investigated are albendazole (7) and doxycycline (8). Many patients with lymphedema are no longer infected with the filarial parasite and do not benefit from antifilarial drug treatment. For chronic manifestations of lymphatic filariasis, such as lymphedema and hydrocele, specific lymphedema treatment (including hygiene, skin care, physiotherapy, and in some cases, antibiotics) and surgical repair, respectively, are recommended (9). To ensure correct diagnosis (10) and treatment, travelers should be advised to consult an infectious disease or tropical medicine specialist.
A Cohort Study of Lymphatic Filariasis on Socio Economic Conditions in Andhra Pradesh, India. 2012
Upadhyayula SM, Mutheneni SR, Kadiri MR, Kumaraswamy S, Nagalla B.
Bioinformatics Group, Biology Division, Indian Institute of Chemical Technology (CSIR), Hyderabad, Andhra Pradesh, India.
To assess the impact of socioeconomic variables on lymphatic filariasis in endemic villages of Karimnagar district, Andhra Pradesh, India.
METHODS: A pilot scale study was conducted in 30 villages of Karimnagar district from 2004 to 2007. These villages were selected based on previous reports from department of health, Government of Andhra Pradesh, epidemiology, entomology and socioeconomic survey was conducted as per protocol. Collected data were analysed statistically by Chi square test, Principal Component Analysis, Odds ratio, Bivariate, multivariate logistic regression analysis.
RESULTS: Total of 5,394 blood samples collected and screened for microfilaria, out of which 199 were found to be positive (3.7%). The socioeconomic data of these respondents/participants were correlated with MF prevalence. The socioeconomic variables like educational status (Odds Ratio (OR) = 2.6, 95% Confidence Interval (CI) = 1.1-6.5), house structure (hut OR = 1.9, 95% CI = 1.2-3.1; tiled OR = 1.3, 95% CI = 0.8-2) and participation in mass drug administration program (OR = 1.8, 95% CI = 1.3-2.6) were found to be highly associated with the occurrence of filarial disease. The socioeconomic index was categorized into low (3.6%; OR-1.1, 95% CI: 0.7-1.5) medium (4.9%; OR-1.5, 95% CI = 1-2.1) and high (3.3%) in relation to percentage of filarial parasite prevalence. A significant difference was observed among these three groups while comparing the number of cases of filaria with the type of socioeconomic conditions of the respondents (P = 0.067).
CONCLUSIONS: From this study it is inferred that age, education of family, type of house structure and awareness about the filarial disease directly influenced the disease prevalence. Beside annual mass drug administration program, such type of analysis should be undertaken by health officials to target a few socioeconomic factors to reduce the disease burden. Health education campaigns in the endemic villages and imparting of protection measures against mosquitoes using insecticide treated bed nets would substantially reduce the disease in these villages.
Lymphangiosarcoma arising after 33 years within a background of chronic filariasis: a case report with review of literature.
Krishnamoorthy N, Viswanathan S, Rekhi B, Jambhekar NA.
Department of Pathology, Tata Memorial Hospital, Mumbai, India.
Keywords: chronic lymphedema;cutaneous angiosarcoma;filariasis;lymphangiosarcoma
Cutaneous angiosarcoma or lymphangiosarcoma represents an uncommon aggressive tumor known to arise on a background of chronic lymphedema secondary to various etiologies, principally following surgery or irradiation. There have been rarely reported cases of angiosarcoma following infective conditions that eventuate with lymphatic stasis. We report a case of angiosarcoma arising after 33 years within a background of filariasis. Awareness of this association can lead to early diagnosis and appropriate treatment of this potentially fatal malignant tumor. Krishnamoorthy N, Viswanathan S, Rekhi B, Jambhekar NA. Lymphangiosarcoma arising after 33 years within a background of chronic filariasis: a case report with review of literature.
Future prospects and challenges of vaccines against filariasis.
Babayan SA, Allen JE, Taylor DW.
Source Institute of Infection, Immunology Research Division of Pathway Medicine, University of Edinburgh, Edinburgh EH9 3JT, UK.
Abstract Filarial infections remain a major public health and socio-economic problem across the tropics, despite considerable effort to reduce disease burden or regionally eliminate the infection with mass drug administration programs. The sustainability of these programs is now open to question due to a range of issues, not least of which is emerging evidence for drug resistance. Vaccination, if developed appropriately, remains the most cost-effective means of long term disease control. The rationale for the feasibility of vaccination against filarial parasites including onchocerciasis (river blindness, Onchocerca volvulus) and lymphatic filariasis (Wuchereria bancrofti or Brugia malayi) is founded on evidence both from humans and animal models for the development of protective immunity. Nonetheless, enormous challenges need to be faced in terms of overcoming parasite induced suppression without inducing pathology as well as the need to both recognise and tackle evolutionary and ecological obstacles to successful vaccine development. Nonetheless, new technological advances in addition to systems biology approaches offer hope that optimal immune responses can be induced that will prevent infection, disease and/or transmission.
Blackwell Publishing Ltd.
Wolbachia and its implications for the immunopathology of filariasis.
Genchi C, Kramer LH, Sassera D, Bandi C.
Dipartimento di Patologia Animale, Igiene e Sanità Pubblica Veterinaria, Università degli Studi di Milano, via Celoria 10, 20133, Milano. firstname.lastname@example.org.
Filarial infections are characterized by immunopathological phenomena, that are responsible for the onset of often dramatic pathological outcomes, such as blindness (Onchocerca volvulus) and elephantiasis (W. bancrofti). In addition, the long-term survival (as long as 10 years) of these parasites in otherwise immunocompetent hosts indicates that these nematodes are capable of manipulating the host immune response. The ground-breaking discovery of the bacterial endosymbiont Wolbachia, which resides in most filarial nematodes causing disease, has led to increasing interest in the role it may play in immuno-modulation, pro-inflammatory pathology and other aspects of filarial infection. Indeed, Wolbachia has been shown to be responsible for exacerbating inflammation (as in river blindness), while at the same time blocking efficient elimination of parasites through the host immune response (Onchocerca ochengi). While studies aimed at identifying Wolbachia as a potential target for anti-filarial therapy are at the forefront of current research, understanding its role in the immunology of filarial infection is a fascinating field that has yet to uncover many secrets.
The emerging story of disability associated with lymphatic filariasis: a critical review.
Zeldenryk LM, Gray M, Speare R, Gordon S, Melrose W.
School of Public Health Tropical Medicine and Rehabilitation Sciences, James Cook University, Australia.
Globally, 40 million people live with the chronic effects of lymphatic filariasis (LF), making it the second leading cause of disability in the world. Despite this, there is limited research into the experiences of people living with the disease. This review summarises the research on the experiences of people living with LF disability. The review highlights the widespread social stigma and oppressive psychological issues that face most people living with LF-related disability. Physical manifestations of LF make daily activities and participation in community life difficult. The findings confirm the need for the Global Programme to Eliminate Lymphatic Filariasis (GPELF) to support morbidity management activities that address the complex biopsychosocial issues that people living with LF-related disability face.
Filarial and Wolbachia Genomics.
Scott AL, Ghedin E, Nutman TB, McReynolds LA, Poole CB, Slatko BE, Foster JM.
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe, Baltimore, MA 21205, USA Department of Computational & Systems Biology, Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892 New England Biolabs, 240 County Rd, Ipswich, MA 01938, USA.
Filarial nematode parasites, the causative agents of a spectrum of acute and chronic diseases including lymphatic filariasis and river blindness, threaten the wellbeing and livelihood of hundreds of millions of people in the developing regions of the world. The 2007 publication on a draft assembly of the 95 Mb genome of the human filarial parasite Brugia malayi - representing the first helminth parasite genome to be sequenced - has been followed in rapid succession by projects that have resulted in the genome sequencing of six additional filarial species, seven non-filarial nematode parasites of animals and nearly thirty plant parasitic and free-living species. Parallel to the genomic sequencing, transcriptomic and proteomic projects have facilitated genome annotation, expanded our understanding of stage-associated gene expression and provided a first look at the role of epigenetic regulation of filarial genomes through microRNAs. The expansion in filarial genomics will also provide a significant enrichment in our knowledge of the diversity and variability in the genomes of the endosymbiotic bacterium Wolbachia leading to a better understanding of the genetic principles that govern filarial-Wolbachia mutualism. The goal here is to provide an overview of the trends and advances in filarial and Wolbachia genomics.
Process for lymphatic filariasis elimination in Jiangsu Province, China.
[Article in Chinese] Xu XZ, Jin XL, Cao HJ, Qian YX, Shen MX, Jiang WC, Sun FH.
Source Jiangsu Institute of Parasitic Diseases, Wuxi 214064, China.
OBJECTIVE: To review the process of lymphatic filariasis elimination in Jiangsu Province, and summarize the control experience.
METHODS: The data of epidemic status, control and surveillance of lymphatic filariasis were collected and analyzed in Jiangsu Province from 1950s to 1990s.
RESULTS: Lymphatic filariasis was endemic in 71 counties (cities) among all 75 counties (cities) in Jiangsu Province. Filariasis bancrofti distributed widely in the province, and in some areas of the south of Jiangsu, there were filariasis bancrofti and Brug' s filariasis co-existing. Before 1971, the microfilaria rate (mfr) in some areas had ever reached 20. 15% , from 1979, large scale control programme was carried out and the mfr in all endemic villages decreased to below 1% , and in 1989, the rate dropped to 0.016%. By 2001, the whole regions of the province reached the criteria of filariasis elimination.
CONCLUSION: The elimination of lymphatic filariasis in Jiangsu Province provides valuable experience for lymphatic filariasis control in other areas.
Keywords: Lymphatic filariasis; Wuchereria bancrofti; Ethiopia; Onchocerciasis; Immunochromatographic Test (ICT); Antigenaemia