LYMPHATIC FILARIASIS

LYMPHATIC FILARIASIS

Lymphatic filariasis are parasitic diseases caused by the nematode worms living in lymphatic vessels and spaces whom more or less obstructed and producing early acute and chronic late manifestations which constitute lymphatic filariasis.

Lymphatic filariasis affects approximately 120 million people,WHO estimates, being a major public health problem in some tropical and subtropical countries.

ETIOLOGY

Human lymphatic filariasis are caused by three species of lymphatic filariae: Wuchereria bancrofti, which has a pacific variety in Oceania; Brugia malayi and Brugia timori. These filariae belong on Nematoda class, Onchocercidae or Filariinae family, Wuchereria and Brugia genera.

Morphology. Adult parasites or macrofilariae are long and filiform, 333d321d cylindrical-shape, white worms which are transmitted by the hematophagous arthropodes.

Wuchereria bancrofti filaria is a human specific parasite. Adult filaria is a threadlike nematod (cylindrical-shaped worm) of transparent yellow-white color, with sharp extremities but light rounded anterior (cephalic) extremity. The macrofilariae body of both sexes is covered by a smooth chitinous cuticle.

The male's dimensions are 40 mm long and 0.1 mm wide. The posterior extremity is curved, progressively attenuates ended with a corkscrew-shape tail.

The female is bigger, being of 6.5 to 10 cm long and 0.2-0.3 mm wide. The posterior extremity is narrow and sudden rounded. The uterus, which divides in two uterine tubes, occupied the largest part of the body; the uterine tubes contains eggs in different stages of growing.

Adult filariae of both sexes have a great longevity (10-15 years or even more) and cohabits, mainly in big lymphatic vessels from aortic region and pelvis, and also in lymphatic nodes.

The eggs have oval shape and measure 40/25 microns; they embryonates in uterus. Viviparous females release embryones (microfilariae) which permanently circulate through lymph and periodically through peripheric blood.

The microfilariae measure 250-300 microns in height and 7-9 microns in diameter; they are covered by a hyaline membranous sheath. On Giemsa colored smear the microfilariae body seem to be formed by a column of small, round and intense colored nuclei, arranged in a pattern that allows differentiation by another species microfilariae.

W. bancrofti has a variety named vauceli, outspread on west coast of Madagascar, and a variety named pacifica, outspread on center and south Pacific Ocean islands. The difference between the two varieties are regarding adult filaria or microfilariae.

The microfilariae are passing by peripheral capillaries with difficulty. W. bancrofti and those vauceli are less active daytime when they are retreating from peripheral circulation, hiding in pulmonary, heart and muscles vessels, also in large thoracic arteries (aorta, carotid) and veins. They are present in peripheral circulation during night, between 20-22 o'clock and 2 o'clock, having nocturnal periodicity. Pacifica microfilariae are present in peripheral blood daytime as well as night-time, so they are aperiodic.

The microfilariae does not suffer any transformation in human body where they survive approximately 70 days. Their future development take place in vector's body which is also a compulsory intermediate host.

Brugia malayi filaria. The adult parasites are morphologic identical with those of W. bancrofti but having smaller dimensions. The male has a length of 22-24 mm and a width of 88-90 microns meanwhile the female dimensions are 55 mm / 160 microns.

Brugia timori filaria, Brugia genus, is a human specific parasite; its vector is unknown. Its microfilariae are morphologic identical with those of B. malayi and have a nocturnal periodicity.

Life cycle. The adult females discharge microfilariae in lymphatic vessels from which they migrate to blood circulation, traversing in 24 hours the path from profound to peripheral vessels.

Peripheric blood circulating microfilariae are ingested during feeding by vectors represented by different species of mosquitoes from Anopheles, Aedes, Culex and Mansonia genera which are compulsory intermediate host. The ingested microfilariae develop in these culicide body and further transforming, in 12-24 days, in infected forms for the new definitive host.

The microfilariae reach the mosquito stomach where, in about one hour, lose their sheath. The embryones reach the gut, pass through the intestinal wall and the general cavity, and invades the muscles of the thorax as intracelular parasite of muscular cells.

In 10-14 days the embryones are transforming in stage II larvae then in stage III larvae which are infestant for a new host.

The development of B. malayi microfilariae into the vector's body is taking place in a short time (6-8.5 days).

The larvae leave thoracic muscles, enter again in general cavity of mosquito and then migrate through cephalic extremity of the insect and clump in proboscis sheath (labium). When mosquito sting a healthy person for feeding, the larvae actively enter in cutaneous tissue through the wound created by mosquito's bite.

In the human body, from cutaneous enter gate, the microfilariae are going to the regional lymphatic nodes, then migrate in lymphatic circulation. They become mature in peripheral lymphatic vessels where, after two molts, rich the stage of adult worm, sexually mature in approximately 3-18 months (6-12 months on average). After this period of "biologic incubation", fertilization is taking place and females discharge the new generations of microfilariae (stage I microfilariae). These pass the thoracic lymphatic channel, reach the venous circulatory system, then profound capillaries (especially pulmonary) and then peripheral circulation from where the life cycle restart.

EPIDEMIOLOGY

Lymphatic filariasis are transmisible, transcutaneous biohelmithiasis.

In rural areas, infection's transmission is provided by species of Anopheles, Aedes and Mansonia, endemic regions are those with favorable ecological conditions for vectors' survival: annual average temperature between 23-27 C and rain season long enough for permanently maintaining larvae nests. In urban or in crowded rural areas infection foci are maintaining by Culex mosquitoes which have favorable developing conditions in stagnant waters from undercrofts, different recipients, and so on.

Geographic distribution. Lymphatic filariasis are distributed, in limited foci, in tropical and subtropical areas from all continents, between 41 northern and 30 southern parallels.

Bancroftian filariasis is largely dispersed in every tropical and subtropical regions of the world affecting approximately 79 millions of people. It is endemic in many regions of Africa, Central and South America, the Caribbean, Indian subcontinent, South-East Asia, West Pacific islands.

In intertropical Africa the bancroftian filariasis spreading is less omogene. Endemic foci are found in southern Sahara, from west to east coast and as far as Mozambic, in many islands of Indian Ocean: Madagascar, Comore, Mauritius, Reunion. There is also a small focus in Egypt.

In America this filariasis is limited at intertropical coasts from Central and South America, especially along the Atlantic coast (Brasilia, Guyana) and also in Caribbean Islands.

Brugia malayi infection is spread on South-East Asia, excusivelly in rural areas, where in some areals coexists with W. bancrofti. It is endemic in India, South-East Asia, some of the West Pacific Islands. Brugia malayi filariasis affects approximately 6 millions of people. The disease is endemic in some Indonesian islands; prevalence rate largely varies from one region to another (from 1% to 30 %).

Brugia timori infection exists only in small foci in Indonezia and especially in Flores, Celebes and Timor islands.

Infection reservoir. For W. bancrofti the only definitive host and source of infection is the man, so this parasite is human specific; the disease produced by this filaria is an anthropozoonosis.

The source of infection and definitive host for the periodic variety of Brugia malayi is the man; in this case, malayan filariosis is an anthropozoonosis. The aperiodic variety of Brugia malayi has also an animal reservoir. In this case, the sources of infection and the definitive hosts of this filaria are the wild and domestic cats, dogs, some monkeys species (Macaca and Presbytis) which can transmit the infection to humans. Thereby, malayan filariasis, produced by the aperiodic variety of B. malayi, is a zoonosis with natural foci.

No natural reservoires are found for B. timori. Thereby, this filaria is a human specific parasite and the associated disease is an anthroponosis.

All lymphatic filariae in adult worm stage infest the human lymphatic system.

Transmition routes. Lymphatic filariasis are transcutaneous transmitting by the vectors which have also the role of compulsory intermediate hosts. The night-time feeding vectors usually transmit nocturnal periodicity filariae, and the day-time feeding vectors especially transmit aperiodical lymphatic filariae.

The vectors for lymphatic filariae are represented by mosquito species from Culex, Aedes, Anopheles and Mansonia genera, different from one filaria to another. Because only the female of this culicids is hematophagous, it is the only responsible and capable for transmit the infection.

Susceptibility to infection is universal. There is no direct interhuman transmision. Lymphatic filariosis are very rare at children under 3 years. In endemic areas the infection is first discover at children of 5-10 years of age. The microfilariemia prevalence rises with the age and stabilised at young adults.

Immunity. The endemic areas population develops some degree of immunity by repetitive infections. This immunity does not provide a complete protection against the parasitic reinfections, but diminished the adult parasites number and microfilariemia. In this case, the disease is asymptomatic or has a mild course. It is possibly that a part of endemic areas population to develop a protective immunity which can provides a resistence against lymphatic filariae reinfection.

DIAGNOSIS

Positive diagnosis of lymphatic filariasis is based on clinical data (acute or chronic typically manifestations), on epidemiological date (illness symptoms occuring in endemic areas) and on laboratory data.

Laboratory exams allow diagnosis of lymphatic filariasis:

Adult parasite is exceptionally detected by a lymph node biopsy which however is not to be indicated because they are capable to determined repetitive lymphangitis and elephantiasis.

Microfilariae detecting in peripheric blood is not allways possible. For filariae with nocturnal periodicity, blood specimen needs to be obtained between 22 and 2 o'clock (the best moment is about 23 o'clock). For subperiodic filariae the blood specimen is to be taken in the afternoon, around 16 o'clock, and anytime for the aperiodic ones.

The blood is inspected by direct exam of the fresh specimen, in which can be observed mobile microfilariae, completed with a Giemsa colored blood smear and thick smear, for studying filariae distinct morphological characteristics.

Microfilariae can be observed in liquids of: hydrocele, testicle vaginal sheaths drain, lymphatic varicose or chylous urine, where embryos can only occasionally be seen.

v     Presumptive arguments

Peripheral hypereosinophilia is usually absent, except the acute inflamation episodes.

Immunodiagnosis

Serologic tests for specific antibodies detection have a limited value as long as cannot distinct neither between different forms of filariasis nor between a recent and a more anterior infection. There are used the following serologic tests: bentonite flocculation test, complement fixation, indirect hemagglutination, ELISA and indirect immunofluorescence.

PCR allow DNA-W. bancrofti sanguin identification.

Diagnosis procedures. Echography of the lymphatic vessels from spermatic cord may reveals mobile adult worms in dilated lymphatics. Lymphoangiography and lymphoscintigraphy show circulation disturbancies at the shanks.

Diethylcarbamazine provocative test (Mazzoti test). Administration of an "infraaccidentally" (1 mg/kg) dose of diethylcarbamazine releases foreign proteins resulting from microfilariae lysis, to which organism allergically react, with fever, allergic manifestations, rarely by lymphangitis but allways by peripheral hypereosinophilia.

Diferential diagnosis is made with many other diseases, depending on clinical picture of lymphatic filariasis: bacterial lymphangitis, bacterial or viral febrile diseases, adenopathies (in reticuloses, lymphoma, leukemia, tuberculous lymphadenitis), different orchitis, elephantisis with chronic lymphedema of bacterial or other parasitic diseases, familial lymphedema, carcinoma, and so on.