|Year : 2005 | Volume
| Issue : 1 | Page : 5-8
Basic science of lymphatic filariasis
Catherine R deVries
International Volunteers in Urology, University of Utah, USA
Catherine R deVries
International Volunteers in Urology, University of Utah
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Filarial disease, transmitted from person-to-person by mosquitoes, principally affects people in tropical and sub-tropical areas. One hundred and twenty million people in at least 80 nations of the world have lymphatic filariasis. One billion people are at risk of getting infected. Ninety percent of these infections are caused by Wuchereria bancrofti , and most of the remainder by Brugia malayi. For W. bancrofti , humans are the exclusive host. The major vectors for W. bancrofti are culicine mosquitoes in most urban and semiurban areas, anophelines in the more rural areas. Larvae in the blood of human hosts are ingested when the insect vectors feed. Within the vector, the microfilarias migrate to specific sites and develop from first-stage larvae into infective third-stage larvae. The vector transmits the infective larvae into a human host when feeding. Mosquitoes deposit the larvae on the host skin adjacent to the puncture site and the third stage larval (L3) parasites migrate through the venous system and lungs to eventually take up residence in the lymphatics. There they form nests occupied by male and female worms, and produce the first stage larvae or microfilariae by viviparous reproduction These larvae migrate from the lymphatics to the peripheral blood where mosquitoes ingest them. The filarial disease has protean manifestaions in the form of chronic, acute and 'asymptomatic' presentations as well as a number of syndromes associated with these infections that may or may or not be caused by the parasites.
Keywords: Filariasis, Life cycle, Biology, History, Epidemiology
|How to cite this article:|
deVries CR. Basic science of lymphatic filariasis. Indian J Urol 2005;21:5-8
| Introduction|| |
Lymphatic filariasis (LF) is one of the oldest and most debilitating diseases in the world. Centuries-old art and texts from Egypt, Japan, Africa, Persia and India depict the disease. ,, LF is one of the leading causes of permanent and long-term disability in the world. WHO estimates there are a billion people at risk in about 80 countries. Over 120 million have already been affected by it, and over 40 million of these 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 the rest are in South Asia, the Western Pacific and parts of Central and South America. The disease, transmitted from person-to-person by mosquitoes, principally affects people in tropical and sub-tropical areas of Asia, Africa and Latin America. Infection can lead to elephantiasis or lymphoedema, of arms and legs, breasts or genitals, as well as a thickening of the skin, hydrocele, chyluria or a number of other signs and symptoms. ,
| Brief history of filariasis|| |
Patrick Manson, known internationally as "the father of tropical medicine", while working in the remote Chinese port city of Amoy in 1877, first identified that mosquitoes were responsible for the transmission of lymphatic filariasis. Following the introduction in 1947 of the drug diethylcarbamazine (DEC) for the treatment of the disease, a number of countries (Japan, China, Malaysia, Korea and some islands in the Pacific) made significant improvement in treatment of lymphatic filariasis. ,, In 1993, an independent International Task Force for Disease Eradication identified LF as one of only six eliminable infectious diseases. LF was selected because of advances in treatment methods, both for controlling transmission and for managing the disease.  The World Health Assembly (1997) adopted a resolution calling for the elimination of LF as a public health problem worldwide. The principal strategy for interrupting transmission of infection is to identify areas in which LF is endemic and then implement community-wide programmes to treat the entire at-risk
population. The goal of such treatment is to break the cycle of transmission between mosquitoes and humans.
| Biology and life cycle|| |
There are six pathogenic nematodes (round worm) belonging to superfamily filariodea which develop to adult stage in humans [Table - 1]. The adult female W. bancrofti is a pale, threadlike nematode measuring 6-10 cm in length and 0.2 mm in width [Figure - 1]A. The male is smaller, at 4-6 cm in length and 0.1 mm width. Larvae (microfilarias) in the blood of human hosts are ingested when the insect vectors feed [Figure - 1]B. Within the vector, the microfilarias migrate to specific sites and develop from first-stage larvae into infective third-stage larvae. The vector transmits the infective larvae into a human host when feeding. Mosquitoes deposit the larvae on the host skin adjacent to the puncture site and the third stage larval (L3) parasites migrate through the venous system and lungs to eventually reside in the lymphatics [Figure - 2]. In adolescent and adult men, there is a preference for the lymphatics of the spermatic cord. There they form nests occupied by male and female worms, and produce the first stage larvae or microfilariae by viviparous reproduction These larvae migrate from the lymphatics to the peripheral blood where mosquitoes ingest them. The developing microfilariae become third stage larva, L3, within the mosquito. Their lifespan of 5-10 years renders adult worms are more resistant to anti-infective agents than are microfilariae. Microfilariae may live up to several months. The diurnal periodicity of microfilaria distribution in the blood stream is not related to discharge from the mature female, but instead relies on a circadian rhythm related to mosquito feeding patterns, which is not well understood.
Vector for lymphatic filariasis
Ninety percent of these infections are caused by Wuchereria bancrofti, and most of the remainder by Brugia malayi. For W. bancrofti , humans are the exclusive host, and even though certain strains of B. malayi can also infect some felines and monkeys, the life-cycles in humans and in these other animals generally remain epidemiologically distinct so that little overlap exists. The major vectors for W. bancrofti are culicine mosquitoes in most urban and semiurban areas, anophelines in the more rural areas of Africa and elsewhere, and Aedes species in many of the endemic Pacific islands. For the brugian parasites, Mansonia species serve as the major vector, but in some areas anopheline mosquitoes are responsible for transmitting the infection. Brugian parasites are confined to areas of eastern and southern Asia especially India, Malaysia, Indonesia, the Philippines and China. ,,
| Pathogenesis and pathology|| |
The pathology associated with lymphatic filariasis results from a complex interplay of the pathogenic potential of the parasite, the immune response of the host, and external ('complicating') bacterial and fungal infections. Immune-mediated pathology in lymphatic filariasis most commonly derives from the lymphatic obstructive consequences of the responses to dead or dying worms in the lymphatics. While genital damage (particularly hydrocoeles) and lymphoedema / elephantiasis are the most recognizable clinical entities associated with lymphatic filarial infections, there are much earlier stages of lymphatic pathology and dysfunction. Histologically, dilatation and proliferation of lymphatic endothelium can be identified, and the abnormal lymphatic function associated with these changes can be readily documented by lymphoscintigraphy. What the immune system is doing during the development of this 'non-inflammatory pathology' is to keep itself 'down-regulated' through the production of contra-inflammatory immune molecules; specifically, the characteristic mediators of Th2-type T-cell responses (IL-4, IL-5, IL-10) and antibodies of the IgG4 (non-complement-fixing) subclass that serve as "blocking antibodies".
In addition to this 'non-inflammatory pathway' to lymphatic pathology, there is another pathological process that is mediated by host inflammatory responses. These responses can be initiated by immune reactivity (clinically expressed as the characteristic adenitis and retrograde lymphangitis earlier described as 'filarial fevers') or by bacterial and fungal superinfections of tissues with compromised lymphatic function originating from filarial infection. Recognition of the importance of these secondary infections in causing much of the progression and physical destruction associated with elephantiasis has had a major impact on improving the care, management and prospects for affected patients.,
| Clinical features|| |
There are chronic, acute and 'asymptomatic' presentations of lymphatic filarial disease, as well as a number of syndromes associated with these infections that may or may or not be caused by the parasites.
Hydrocoele, even though found only with W. bancrofti infections (i.e., not Brugia infections) is the most common clinical manifestation of lymphatic filariasis. It is uncommon in childhood but is seen more frequently post-puberty and with a progressive increase in prevalence with age. In many endemic communities 40-60% of all adult males have hydrocoele. It often develops in the absence of overt inflammatory reactions, and, indeed, many patients with hydrocoele also have microfilariae circulating in the blood. Lymphoedema, too, can develop in the absence of overt inflammatory reactions and in the early stages be associated with microfilaraemia, the development of elephantiasis (either of the limbs or the genitals) is most frequently associated with a history of recurrent inflammatory episodes. In such individuals the early pitting oedema gives rise to a later brawny oedema with hardening of the tissues. Still later, hyper-pigmentation and hyper-keratosis develop, often with wart-like protuberances which, on histological section, reveal dilated loops of lymphatic vessels within the nodular lesions. Patients with chronic lymphoedema or elephantiasis rarely are microfilaraemic. Chyluria is another form of the chronic filarial syndromes, is caused by the intermittent discharge of intestinal lymph (chyle) into the renal pelvis and subsequently into the urine.
There are 4 distinct acute manifestations of lymphatic filariasis, each with a different set of causal mechanisms and pathogenic implications. Most important are the acute inflammatory episodes of the limbs or scrotum that are related to bacterial or fungal superinfection of tissues with already-compromised lymphatic function. In the past these were termed 'filarial fevers' and more recently 'adenolymphangitis' (ADL); it has been suggested, however, that a better description would be 'DLA' (dermatolymphangioadenitis) to indicate that they start peripherally, have features of cellulitis and drain centrally towards lymph nodes. Confused with this picture in the past was another (second) type of 'filarial fever' in which the inflammation was initiated in the lymph node (commonly the inquinal node) with 'retrograde' extension down the lymphatic tract and an accompanying 'cold' oedema. Here the inflammation appears to be immune-mediated in response to an adult worm dying or being killed in the lymphatic tract. Such immune-mediated reactions are now recognized to be much less frequent (10-20%) than the episodes of inflammation initiated by dermal infection. A third acute filarial syndrome is tropical pulmonary eosinophilia, caused by an immunologic hyper-responsiveness to filarial infection. The fourth (and least commonly recognized) form of acute inflammatory reaction caused by filarial infection is that seen early after infection particularly in expatriates exposed to, and acquiring, the infection for the first time, as when military missions have been sent to filariasis-endemic areas.
| Diagnosis making|| |
Until recently, diagnosis of filarial infection depended on the direct demonstration of the parasite (almost always microfilariae) in blood or skin specimens using relatively cumbersome techniques which took into account the periodicity (nocturnal or diurnal) of microfilariae in blood. Now a days circulating filarial antigen (CFA) detection is regarded as the 'gold standard' for diagnosing Wuchereria bancrofti infections. The specificity of these assays is near complete, and the sensitivity is greater than that achievable by the earlier parasite-detection assays. Two commercial configurations of this assay are available, one based on ELISA methodology that yields semi-quantitative results, and the other based on a simple card (immunochromatographic) test, yielding only qualitative (positive/negative) answers. Prior to the development of the CFA assay, detection of microfilariae in blood was the standard approach to diagnosing lymphatic filarial infection (or loiasis), and it is the one still required today for both brugian filariasis and those situations where the antigen detection test is not available for bancroftian filariasis. For such assessments one must take into account the parasites' possible nocturnal periodicity in selecting the optimal blood drawing time (10 p.m.-2 a.m. for most brugian filariasis and bancroftian infections). ,,,,
| Preventive measures|| |
Filarial infection can be acquired only from vector-borne infective larvae. Therefore, prevention of infection can be achieved either by decreasing contact between humans and vectors or by decreasing the amount of infection the vector can acquire, by treating the human host. Efforts at filariasis control in populations through reducing the numbers of mosquito vectors have proven largely ineffective. Even when good mosquito control can be put into place, the long life-span of the parasite (4-8 years) means that the infection remains in the community for a long period of time, generally longer than intensive vector control efforts can be sustained., More recently, with the advent of extremely effective single-dose, once-yearly, 2-drug treatment regimens (selecting among albendazole and either ivermectin or diethylcarbamazine [DEC]), an alternative approach has been taken in an initiative being launched through the World Health Organization to utilize a strategy of yearly mass treatment to all "at risk" population to eliminate lymphatic filariasis as a public health problem by decreasing microfilariae in the population, thereby interrupting transmission and preventing infection. Contact with infected mosquitoes can be decreased through the use of personal repellents, bednets or insecticide-impregnated materials. Alternatively, suggestive evidence from animal models and some limited experience in human populations indicate that a prophylactic regimen of DEC (6 mg/kg per day x 2 days each month) could be effective in preventing the acquisition of infection.
| References|| |
|1.||Mc Mohan, Simonsen PE. In: J E Manson's tropical diseases. 12th edn. WB Saunders. London 1334-6. |
|2.||Subra R, Hebrard G. Ecology of Culex pipiens fatigans larvae in an area of high endemicity of Bancroftian filariasis. Tropenmed Parasitol 1975;26:48-59. [PUBMED] |
|3.||Jones CG, Heathcote OH, Magayuka SA. Epidemiological study of infections in the mosquito: selective trapping of unfed malaria-filariasis vectors seeking a blood meal in bedrooms. Trans R Soc Trop Med Hyg 1972;66:24. [PUBMED] |
|4.||Babu S, Blauvelt CP, Kumaraswami V, Nutman TB. Chemokine receptors of T cells and of B cells in lymphatic filarial infection: a role for CCR9 in pathogenesis. J Infect Dis 2005;191:1018-26. [PUBMED] [FULLTEXT]|
|5.||Miranda J, Maciel A, Souza RM, Furtado AF, Malagueno E. Proteic profile and antigenic recognition of extracts from Wuchereria bancrofti L3 infective larvae. Rev Soc Bras Med Trop 2005;38:27-32. |
|6.||Miranda J, Maciel A, Souza RM, Furtado AF, Malagueno E. Proteic profile and antigenic recognition of extracts from Wuchereria bancrofti L3 infective larvae. Rev Soc Bras Med Trop 2005;38:27-32. |
|7.||Pichon G. Limitation and facilitation in the vectors and other aspects of the dynamics of filarial transmission: the need for vector control against Anopheles-transmitted filariasis. Ann Trop Med Parasitol 2002;96:S143-52. [PUBMED] |
|8.||Ravindran B. Are inflammation and immunological hyperactivity needed for filarial parasite development? Trends Parasitol 2001;17:70-3. |
|9.|| Tisch DJ, Michael E, Kazura JW. Mass chemotherapy options to control lymphatic filariasis: a systematic review. Lancet 2005;5:514-23. |
|10.||Meyrowitsch DW, Simonsen PE. Long-term effect of mass diethyl carbamazine chemotherapy on bancroftian filariasis: results at four year after start of treatment. Trans R Soc Trop Med Hyg 1998;92:98-103. |
[Figure - 1], [Figure - 2]
[Table - 1]
|This article has been cited by|
||Chyluria in Pregnancy-A Decade of Experience in a Single Tertiary Care Hospital
| ||Khalid Mahmood,Ahsan Ahmad,Kaushal Kumar,mahendra singh,sangeeta pankaj,Kalpana singh |
| ||Nephro-Urology Monthly. 2015; 7(2) |
|[Pubmed] | [DOI]|