subject: Lymphatic filariasis pathology and pathogenasis [print this page] Lymphatic filariasis pathology and pathogenasis
Lymphatic filariasis is a group of filarial infections in whichadult worms, found in major abdominal lymphatic vessels,shed microfilariae which are carried to the bloodstream.In contrast to onchocerciasis, it is the adults that causethe pathological changes resulting in lymphoedema. Thisoccurs in a relatively small proportion of those infected.The three species involved are Wuchereria bancrofti,Brugia malayi and B. timori.
Aetiology and transmission W. bancrofti females measure 80-100 mm longby 0.3mm. The males are smaller, 40-50 mm long. Theadults live in lymphatic channels and the female shedsabout 50000 sheathed microfilariae per day; these arecarried to the bloodstream in lymph. They circulate in theblood and are taken up by mosquito vectors of the generaCulex, Anopheles and Aedes. The infective larvae moulttwice after they enter a human host when the insectbites. W. bancrofti exhibits periodicity of microfilaraemiathroughout most of its geographic distribution, releasingmicrofilariae during the night hours; maximal counts are atabout 1 am, in close relation to the nocturnal feeding habitsof the mosquito vectors. Subperiodic strains release microfilariaethroughout the 24-hour period.Brugia malayi and B. timori have similar adult morphologyand a similar lifecycle.
Distribution ana incidence Bancroftian filariasis has the widest geographical distribution,covering tropical Africa, Asia east of Pakistan as faras eastern China, Indonesia, the Philippines, Papua NewGuinea, the Caribbean and the northeastern regions ofSouth America (all periodic forms). Subperiodic forms arewidely distributed in southeast Asia and the Pacific.Current estimates indicate that about 905 million peoplelive in endemic areas, about 10% of whom are infected. Ofthese, 90% have W. bancrofti. Two-thirds of all thoseinfected live in China, India and Indonesia.
Pathology and pathogenesis Obstructive lymphoedema of the arms, breasts, genitaliaor legs is the main outcome of inflammatory changes in themain lymphatic channels elicited by the presence of adultworms. Adult worms may be found in lymphatics or lymphnodes. Distal to this obstruction the lymphatics are dilated.Inflammatory changes in the epididymis can be an earlymanifestation of the host response to W. bancrofti.Similar histological features occur in infection withBrugia species, but these most often affect the legs. Inestablished infections episodic non-bacterial lymphangitisand lymphadenitis occur, evoked by allergy to filarialantigens. Eosinophils, giant cells, dead adult wormsand fibroblasts are seen in the affected lymphatics andglands.Established lymphoedema predisposes to and is exacerbatedby bacterial cellulitis and lymphangitis. Minor cutsand abrasions and tinea pedis are routes for entry of streptococciand staphylococci. Bacterial infections add to theirreversible changes caused by the filarial obstruction oflymphatic channels. In the chronic phase lymphatic channelsare obstructed by fibrosis with distal lymphoedema.There is fibrosis in the lymphoedematous tissue.
Clinical features Many infected people have no symptoms related to thedisease. The earliest feature is often generalized painlessswelling of the leg. There is no rash, and inguinal glandsmay be normal. The swelling is worst in the evening anddeclines while the patient is recumbent overnight. Thisoccurs within months of infection, before microfilariae areshed, which indicates a response to adult worms. Withouttreatment this swelling may progress to the chroniclymphoedema of filariasis. Filarial lymphangitis is anotherpresentation of filariasis. Lymphatics are red and tender,and inguinal glands are swollen and painful. The lymphangitismay spread distally in a limb, which is the oppositeof spread in bacterial lymphangitis. Epididymitis,which may or may not relapse, is another manifestation ofthe same process.The end stage is non-pitting lymphoedema with thickened,lichenified skin.The penis, scrotum or labia maybe involved. The breast is sometimes involved. Infectionwith Brugia species tends only to affect the lower limbs.Filarial abscesses can develop along the line of lymphaticchannels, more often proximally in the limb. These ruptureand discharge, and the ulcerated area heals well.W. bancrofti infection may cause intermittent chyluria,in which anastomoses between intestinal and renal lymphaticchannels are open; these are due to more proximalobstruction in main lymphatics leading to the cisternachylae and thoracic duct.An uncommon presentation of filariasis is referred to astropical pulmonary eosinophilia (TPE). It occurs with bothbancroftian filariasis and with Brugia malayi infections.It takes 6 months before TPE develops with bancroftianinfections, but only 3 months with Brugia. The manifestationsof this condition are almost entirely pulmonary. Dyspnoeawith cough, predominantly nocturnal, is the majorsymptom. There may also be some night sweats. Wheeze isnot a usual feature.Chest X-rays may show a fibronodular pattern andperipheral blood eosinophil counts are markedly raised(6.0 x 109/L is not uncommon), with strongly positivefilarial serology. Day and night bloods are free of microfilariae.It is thought that this is a manifestation ofhypersensitivity on the part of the host's immune systemto the microfilariae, resulting in retention and destructionof the nocturnally released larvae within the pulmonaryvasculature.
Management Diethylcarbamazine (DEC) is used, as for onchocerciasis though 12 days' therapy is sufficient. Reactions dueto death of worms do occur. Lymphoedema is best controlledby elevation of the affected limbs at night andpressure bandaging. Albendazole and ivermectin are alsoeffective. Surgery to excise the lymphoedematous tissue isnot satisfactory and is only a final resort.Prophylactic penicillin V, 250 mg twice daily, is helpful inpatients who have had repeated attacks of bacterial lymphangitis.Meticulous care of the feet, and particularly theskin between the toes, is essential. Staphylococci andstreptococci are the common causes of bacterial infectionin the affected limbs. TPE responds to DEC in the same dosage regimen, though it may be necessary to give prednisoloneas well to inhibit exacerbations of pulmonary symptoms.
