Filariasis in human is a group of diseases caused by tissue nematodes known as filarial worms. Man is the definitive host for the parasite and the adult worms are found either in the lymphatic system, subcutaneous tissue or in body cavities. They require an insect vector for development and transmission. They do not undergo multiplication in the vector. Adults are thread like. The female worms lay embryos and they are known as microfilariae (mff).Some filarial worms are responsible for human diseases that are major public health problems globally.
1. Wuchereria bancrofti
2. Brugian malayi
3. Loa loa
4. Onchocera volvulus
5. Dirofilariae
6. Mansonell spp.
GENERALIZED LIFE CYCLE OF A FILARIAL WORM
When a vector (mosquito/fly) sucks blood from an infected individual, microfilariae in the blood or subcutaneous tissue will enter into the vector. Then the microfilariae will undergo development (site of the development depends on the filarial type) and they will become larvae. This larva is the infective stage of the filarial life cycle. This larva migrates to the proboscis of the mosquito. When an infected mosquito takes blood meal, this larva enters the human body through the insect bite wound. Then this larva undergoes series of development and become adults. Adults will give rise to microfilariae and life cycle will continue.
PERIODICITY OF MICROFILARIAE
In those filarial infections where the microfilariae are found in the blood, variation in the numbers of microfilariae in the peripheral blood occurs in rhythmic pattern, repeated during each 24 hours. Periodicity is a physiological adaptation to suit the peak biting habits of the vector to ensure optimum transmission. The filarial infections are grouped based on the periodicity as follows:
A) Non-periodic: variation in microfilariae counts seen no rhythmic pattern.
periodic
a) Nocturnally periodic: peak microfilariae counts seen during nighttime(Wuchereria bancrofti and Brugian malayi infections).
b) Diurnally periodic: peak microfilariae counts seen during daytime (Loa loa infection).
B) Sub periodic: microfilariae present in peripheral blood all the time but consistent peak during 24-hour period.
a) Nocturnally sub periodic: peak microfilariae counts during nighttime( Brugia infection in Malaysia)
b) Diurnally subperiodic: peak microfilariae counts during daytime (Wuchereria bancrofti in south pacific islands).
A). LYMPHATIC FILARIASIS
Lymphatic Filariasis is caused by W. bancrofti, B. malayi, or B. timori. The threadlike adult parasites reside in lymphatic channels or lymphnodes, where they may remain viable for more than two decades.
1.Bancroftian Filariasis
Geographical distribution
W. bancrofti, the most widely distributed human filarial parasite, affects an estimated 115 million people and is found throughout the tropics and subtropics, including Asia and the Pacific Islands, Africa, areas of South America, and the Caribbean basin. Humans are the only definitive host for the parasite. Generally, the subperiodic form is found only in the Pacific Islands.
This is the major filarial infection in Sri Lanka. It is mainly confined to the western, Northwestern and Southern provinces costal belt extending from Puttalam to Hambantota.
Characteristics and life cycle
This is mainly a nocturnally periodic infection most part of the world. Adults are mostly found in the lymphatics of the groin, lower limb, and the genitalia. Female is 80-100 mm in length. Microfilariae are in the blood and show the peak prevalence between 10 pm to 2 am. During the day time they lie in the capillaries of the lung.
The microfilariae live for around 3-6 months and need to be taken up by the vector for further development. If ingested by the vector, Culex quinquefasciatus the microfilariae migrate to the thoracic muscles where they mould and develop into L3 larvae. This takes around 10-12 days. The L3 larvae migrate to the proboscis and escape from the mouthparts onto the skin of the host with the mosquito bite. They actively enter the host through the bite wound. In humans the larvae migrate to the lymphatics and grow into L4 larvae and then to adult. The adults have a long life span of 7-10 years. The incubation period is around one year.
Pathogenicty and Clinical presentation.
A wide spectrum of clinical presentation is attributed to the Bancroftian Filariasis. These range from asymptomatic infection to acute lymphangitis, lymphadenitis and to chronic lymph edema, while well defined extra-lymphatic features are also associated with the infection.
The pathological mechanisms underlying these presentations are yet to be clearly understood. The numbers of adult worm harboured, their location, the host immune response as well as secondary bacterial and fungal infection are some factors determining these varied clinical presentations. In endemic areas majority of residents show minimal clinical effects while short term visitors react differently to infection. Non-immune persons show lymphangitis and lymphadenitis very early on in the infection and this is probably due to host reaction to the developing worms. In endemic areas however, recent studies, using ultrasonography, therapeutic trials, surgery and histopathology, show that lymphatic disease is based on lymphangiectasis caused by non obstructive mechanisms due to toxin/products of the live worms.
Lymphangiectasis without inflammatory response is associated with live adult worms and is responsible for non-inflammatory, subclinical lymphatic deformity/dilatation. However, death of a worm leads to a host inflammatory response. In many persons this causes granulomatous nodules that are subclinical and do not cause any overt disease. In others this could present as episodes of acute lymphangitis due to temporary clogging of lymphatics. However, if the obstruction is extensive and collateral flow is not established this result in lymphatic dysfunction leading to lymphoedema. High protein lymphoedema predisposes to subcutaneous fibrosis and progressive sclerosis of the skin leading to elephantiasis. Due to the habitat of the adults clinical presentations associated with genitalia and lower limb is common in Bancroftian Filariasis. Rupture of dilated lymphatics results in extravasations of lymph leading to chyluria, chyloceles and lymph scrotum.
Although subclinical lymphatic damage is common, chronic lymphatic disease is comparatively rare. Thus other cofactors precipitate chronic lymphatic pathology. Bacterial and fungal infections are now established as vital factors that aggravate pre-existing lymphatic pathology.
Extra lymphatic syndromes
1. tropical pulmonary eosinophilia (TPE)
Tropical pulmonary eosinophilia (TPE) is a distinct syndrome that develops in some individuals infected with lymphatic filarial species. This syndrome affects males and females in a ratio of 4:1, often during the third decade of life. The majority of cases have been reported from India, Pakistan, Sri Lanka, Brazil, Guyana, and Southeast Asia.
Some individuals are sensitive to the microfilaria causing a massive destruction in the lungs producing this syndrome.
Urticaria, monoarthritis and filarial fevers are other clinical presentations of Bancroftian Filariasis.
Laboratory Diagnosis
1.Direct methods ( detection of microfilariae/adults worms)
I.Microfilariae in stained thick blood films of night blood.
II. Knott’s concentration method; 1ml of venous blood is lysed in 10ml of 2% formalin centrifuged or allowed to stand for 12-24 hours and deposit is examined for microfilariae.
III. Membrane filtration method; when blood is forced through a membrane of pore size 5 micrometer using a syringe the microfilariae are retained on the membrane.
IV. Adults in biopsy specimens
2.Indirect methods ( Immunodiagnosis)
I. Antibody detection; IFA/ELISA
II. Antigen detection; Immunochromatographic card test (detects specific circulating W. bancrofti antigens in serum or blood using monoclonal antibodies.)
Management
The main goals of therapy are to prevent the development of irreversible lesions and to alleviate symptoms. Surgical excision is recommended when nodules are located on the head
Chemotherapy is the mainstay of management. Diethylcarbamazine (DEC) is the drug of choice. It is very effective microfilaricidal but the adulticidal effect is inconclusive. DEC is used at a dosage of 4 to 6 mg/kg of body weight per day for 14 days. Symptoms usually resolve within 3 to 7 days after the initiation of therapy. Relapse occurs in12 to 25% of cases (sometimes after an interval of years), requires re-treatment.
Ivermectin, a semisynthetic macrocyclic lactone active against microfilariae, is also very effective against the microfilariae while albendazole is shown to kill the adult worms.
2. Brugian Filariasis
Brugian Filariasis due to B. malayi occurs primarily in China, India, Indonesia, Korea, Japan, Malaysia, and the Philippines. B. malayi also has two forms distinguished by the periodicity of microfilaremia. The more common nocturnal form is transmitted in areas of coastal rice fields, while the subperiodic form is found in forests. B. malayi naturally infects cats as well as humans. B. timori exists only on islands of the Indonesian archipelago. B. pahangi is a neutral parasite of cats that can develop in human in experimental conditions.
B). SUBCUTANEOUS FILARIASIS
1.Onchocerciasis ( River blindness)
This condition is widely distributed in tropical Africa and Central America. Both adult worm and microfilaria are present in the subcutaneous tissue. Vector is Simulium fly (Black fly) which breeds in the fast flowing rivers. Eye lesions causing blindness is due to the microfilariae. Adult worms cause subcutaneous nodules and loss of skin elasticity while microfilariae in the subcutaneous tissue cause severe pruritus and rash.
2.Loasis ( Eye worm infection; Calabar swelling)
This is caused by the Loa loa worm. This infection is widely distributed throughout the tropical Africa. Adults are found in the subcutaneous tissue while microfilariae are found in the blood. Microfilaria shows diurnal periodicity and the vector is a day biting Tabanid fly. Adults cause migratory swellings. Worm is often detected when crossing the conjunctiva.
3. Dirofilariasis
This is a zoonotic filarial infection that affects primarily dogs, cats, and raccoons occasionally infect humans incidentally, as do Brugia and Onchocerca parasites that affect small mammals. Because humans are an abnormal host, the parasites never develop fully. Pulmonary dirofilarial infection caused by the canine heartworm Dirofilaria immitis generally presents in humans as a solitary pulmonary nodule. Chest pain, hemoptysis, and cough are uncommon. Infections with D. repen (from dogs) or D. tenuis (from raccoons) can cause local subcutaneous nodules in humans. Several mosquitoes such as Aedes, Armigeres and Mansonia are the vectors of this infection.
C). FILARIAL PARASITES OF BODY CAVITIES.
1. Mansonella perstans/Mansonella ozzardi
This infection is distributed in tropical Africa, South America and Central America. Vectors are Culicoides spp. (biting midges). Adults are in body cavities and associated tissues with microfilariae are in the blood. This is not known to cause serious disease in humans but microfilaria needs to be differentiated from those of major Filariasis.
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