Lymphatic filaria

Prof. Dr. Md. Akram Hossain March 2009 Introduction

fi Lymphatic filariasis is caused by the filarial worm Wuchereria bancrofti, Brugia malyai, and Brugia timori those live in the lymphatic vessels and lymph nodes. fi More than 120 million people of 83 countries are infected with lymphatic filarial parasites, 90 % of these infections are caused by W. bancrofti and most of the remainders by B. malyai. fi Lymphatic filariasis is a major cause of debilatating and disfiguring chronic disease manifestations (specially lymphoedema, elephantiasis and hydrocele) in endemic areas.

1/7/2014 Prof. Muhammad Akram, Filariasis 2 Epidemiology

fi A minimum of 120 million people in 83 countries worldwide are estimated to be infected with filarial parasites. According to WHO, it is second leading cause of permanent and long term disability.

fi Geographical distribution : The most widespread parasite is W. bancrofti , which affects about 106 million people in the tropical areas of Africa, India, South East Asia, the Pacific Islands, and South and Central America. Of these, India has by far the largest number of cases. Bangladesh is an endemic home of lymphatic filariasis. However, it is specially prevalent in the northern districts of Bangladesh. The closely related Brugia malayi and Brugia timori parasites, which are found only in South-east Asia, affect some 12.5 million people.

fi Economic and social impact : Lymphatic filariasis is primarily a disease of the poor.

1/7/2014 Prof. Muhammad Akram, Filariasis 3 Taxonomy

fiKingdom - Animalia, – Phylum - Nemathelminthes, • Class - Secernentea, • Order - Spirurida, • Super Family - Filarioidea, • Genera with species – – Wuchereria bancrofti, Brugia malyai, Brugia timori

1/7/2014 Prof. Muhammad Akram, Filariasis 4 Morphology

There are both free-living and parasite type of S. stercoralis. fi Morphology of free-living type : The adult fusiform male is 0.7 to 1 mm long by 40 to 50µm. The posterior end is pointed and curved ventrally. The female of this worm is 1.0 to 1.7 mm long by 40 to 50 µm, and has two-horned uterus. The rhabditoid larvae is about 380 by 20 µm and can be identified, based on the shape of esophagus, which has a club-shaped anterior part, with constriction in the middle and posterior bulbus . fi Microfilaria : The average microfilaria measures 240-300 µm in length. A thin and delicate sheath surrounds the organism. Numerous nuclei are contained in the body. The head is blunt and round and the tail is pointed. – The tail tip is free of nuclei, which are the primary characteristics that helps to distinguish it from other sheathed microfilaria. – Passing through the lymph node, these embryos find their ways by the main lymphatic trunks into circulating blood. They are very active in their habits and can move both with and against the blood circulation. Life span of microfilaria in the human body is 70 days. 1/7/2014 Prof. Muhammad Akram, Filariasis 5 Periodicity

fi Some species show periodicity either nocturnal or diurnal. W. bancrofti, B. malyai and B. timori exhibits a nocturnal while Loa loa exhibits diurnal periodicity. fi The exact mechanism of periodicity is not fully understood . It is determined by species and is influenced by sleeping and waking pattern and bodily activities of the host. fi Periodicity can be altered if the life style of the host changes e.g. the nocturnal periodicity of W. bancrofti can be altered to daytime periodicity if the person infected becomes a night worker.

1/7/2014 Prof. Muhammad Akram, Filariasis 6 Life cycle

1/7/2014 Prof. Muhammad Akram, Filariasis 7 Life cycle at a glance

• Life cycle at a glance • Life cycle stages : Adult, larva • Host : Two hosts, man (definitive) and mosquito (Intermediate) • Infective form : 3rd stage larva – microfilaria • Pathogenic form : Adults & larva • Route of infection : Penetration through skin by the bite of mosquito • Site of localization : Lymph nodes and lymph vessels • Time required for completion of life cycle in human : 5-18 months • Time required for completion of life cycle in mosquito : 2 weeks • No. of molting : 3 times

1/7/2014 Prof. Muhammad Akram, Filariasis 8 Pathogenesis

fi The pathology varies greatly from one individual to another, and the exact mechanisms are not completely understood fi The pathology associated with lymphatic filariasis results from pathogenic potential of the parasite, the immune response of the host and complicating bacterial and fungal infections fi The pathogenic effect in lymphatic filariasis are produced by the adult worm, living or dead. Living Mf circulating in the blood are not directly toxic to the host except in occult filariasis. fi At the site of localization adult worm stimulate the proliferation of lymphatic endothelium and secrets some factors that causing lymphatic dilation, lymphoedema and elephantiasis. Th1 mediated immune response stimulates the formation of granuloma around the dead worm fi The host reaction to the parasite plays important role

1/7/2014 Prof. Muhammad Akram, Filariasis 9 Clinical Features

fi Developing worm and adult worm causes classical filariasis and microfilaria causes occult filariasis respectively. fi Symptoms of infection varies from one endemic area to another. fi Infections can be – Asymptomatic- – acute -In the acute form there are recurrent attacks of fever (filarial fever), with painful inflammation of the lymph node, (lymphadenitis), and lymphatic vessels (lymphangitis). – Chronic-This is characterized by hydrocele lymph edema and elephantiasis.

1/7/2014 Prof. Muhammad Akram, Filariasis 10 Pathogenic lesion in classical filariasis

fi 1. Inflammation – periodic attacks of fever with lymphadenitis and lymphangitis which are not necessary due to the presence of parasites but may be the result of sensitization to the metabolites of the worm located elsewhere. fi 2. Dilatation of the lymphatics - lymphangiovarix. fi 3. Rupture of lymphnagiovarix – fi a. lymphorrhgia – Lymphscrotum, lymphocoele, Lymphuria fi b. Chylurrhagia – chylocoele, chyluria, chylorrhgia or hematochyluria, chylus diarrhoea, chylus ascitis and chylothorax (obstruction in the chyle bearing vessels, thoracic duct) fi 4. Hyperplasia of skin and connective tissues- elephantiasis (solid edema) of various parts. fi 5. Secondary bacterial infections (with Streptococcus pyogenes or Staphylococcus aureus) – septic lymphangitis, abscess and septicemia.

1/7/2014 Prof. Muhammad Akram, Filariasis 11 Occult filariasis : (Meyers – kowenar syndrome)

fi This is a condition in which there is massive eosinophilia (30-80%, absolute count >3000/cumm), generalized lymph node enlargement, hepatosplenomegaly, pulmonary symptoms and absence of microfilariemia. fi The adult worm produces the microfilaria continuously but they do not reach the peripheral blood because they are destroyed in the tissues by the antibody dependent cell mediated cytotoxicity (ADCC).

1/7/2014 Prof. Muhammad Akram, Filariasis 12 Tropical pulmonary eosinophilia (TPE) Eosinophilic lung, Weingartens syndrome)

fi Tropical pulmonary eosinophilia is a syndrome of immunological hyper responsiveness to Mf in the lung. It is particularly found in filariasis endemic areas. There is a marked eosinophilia, raised ESR and high levels of filarial antibody including high titers of IgE. Eosinophils often appear vacuolated . fi Male are more commonly affected than females. TPE is classical example of occult filariasis and is characterized by low fever, loss of weight, paroxysmal cough with scanty sputum, dyspnoea and splenomegaly. Chest radiography shows increased bronchovascular markings or diffuse milliary mottling in the lung fields. MF may be demonstrated in tissues obtained by lung biopsy, although it is difficult to identify the species in tissue section.

1/7/2014 Prof. Muhammad Akram, Filariasis 13 Laboratory Diagnosis

fi Identification of microfilariae by microscopic examination is the most practical diagnostic procedure . fi Antigen detection using an immunoassay for circulating filarial antigens constitutes a useful diagnostic approach. Molecular diagnosis using polymerase chain reaction (PCR) is available for Wuchereria bancrofti, Brugia malayi . fi Antibody detection is of limited value. Substantial antigenic cross reactivity exists between filaria and other helminths, and a positive serologic test does not distinguish between past and current infection.

1/7/2014 Prof. Muhammad Akram, Filariasis 14 Treatment

fi Individual : – 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. fi Communities where filariasis is endemic : – 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 1/7/2014 for a full year afterProf. treatment. Muhammad Akram, Filariasis 15 Prevention

fi The strategy of the Global Program 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). fi To interrupt transmission, districts in which lymphatic filariasis is endemic must be identified, and then community -wide ("mass treatment") programs implemented to treat the entire at-risk population. fi In most countries, the program 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. fi 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. 1/7/2014 Prof. Muhammad Akram, Filariasis 16