• Infected person with circulating microfilariae is the chief source and reservoirs of infection.
• Person to Person transmission occurs by the bite of infected mosquitos.

Pathogenesis:

• Though L3 larva are infective larva they do not have any pathogenic effect.
• Similarly, circulating microfilariae are also not pathogenic.
• The pathogenic effects are due to the fourth stage larva, moulting stage from L3 and adult worms whether living or dead present in the lymphatic vessels.
• The following stage occur sequentially during the pathogenesis or lymphatic filariasis.
• i. Dilation of lymph vessels:
  • The developing larva and metabolic products released during the moulting of the larva, unsheathing of microfilariae during moulting and the presence of the adult worms induces inflammatory reactions.
  • The intense inflammation of lymph vessels leads to dilation of lymph vessels during the early stage of infection.
  • Besides inflammation, immune reaction of host against the worms and toxic effects of the worms also results in dilation of lymphatic vessels.
  • Dilation of lymphatic causes an increased secretion of proteinaceous material from lymphatics into the surrounding tissue leading to the information of conspicuous lymphedema and thickening of the endothelium.
• ii. Infection of lymphatic vessels (lymphangitis):
  • Progression of infection develops with lymphangitis.
  •  It is characterized by presence of dilated, inflamed and thickened lymphatic vessels associated with erythema, edema and tender painful areas.
  • The main causes of lymphangitis are:
    • Irritation caused by the movement of the adult worm inside the lymphatic system.
    • Release of metabolic wastes by larva
    • Absorption of toxic wastes liberated from dead worms by host cells.
    • Secondary bacterial infection streptococci.
• iii. Obstructions of the lymph node:
  • The lymphangitis is followed by necrosis, sclerosis and obstruction of lymphatic vessels proximal to the lymph nodes.
  • Flow of lymph is obstructed due to-
    • Presence of worm in the lymph vessels
    • Thickening to lymphatic vessels as well as focal necrosis.
    • Giant cell formation, fibrosis as well as cellular changes result in obstruction of lymphatic vessels
    • The obstruction of the lymph flow results in elephantiasis which is the classical feature.
• The course of the events in the pathogenesis of the lymphatic filariasis are variable and depend upon interaction of a variety of host and parasitic factors.

Clinical manifestation: Lymphatic filariasis

• It is caused by the juvenile and adult worms of W. bancrofti.
• The clinical manifestation of the condition depend on stages of the disease as follows:

i. Endemic normal: No overt clinical symptoms

ii. Asymptomatic stage:

• Person in this stage have microfilariae in their blood but do not show any clinical manifestation of filariasis.
• They may remain asymptomatic for years or even after life.

iii. Acute filariasis:

• Acute filariasis or inflammatory phase is caused by antigens released from female adult worms.
• The condition is characterized by Filarial fever (usually low grade but occasionally severe), accompanied by chills, general malaise, headache and pain are other symptoms.
• Lymphedema
• Lymphadenitis
• Adeno-lymphangitis (ADL)

iv. Chronic filariasis:

• It is the obstructive phase usually takes 10-15 years to develop.
• Typical manifestation includes:
• Lymph varices: Caused by the obstruction of lymph flow and accumulation of lymph in the ducts leading to dilation of the ducts.
• Hydrocele: Caused by obstruction of the lymph vessels of the spermatic cord and exudation from the inflamed test and epididymis.
• Elephantiasis: It is the result of wuchererial infection and usually follows years of continual infections.
• It is caused by fibrotic construction of all the afferent lymphatics draining the past.
• Hypertrophy and hyperplasia seen are the result of excessive protein, in the lymph exudates stimulating the connective tissue to excessive growth.
• Elephantiasis in the scrotum, legs and arms of male and legs and arms of female is the feature of chronic elephantiasis.
• The affected part becomes enormously enlarged producing a tumor like solidity.
• The surface of the skin becomes rough, and even papillomatous.
• The hairs become rough and sparse.
• On section the skin cuts like an unripe pear, it is thickened, dense and fibrous.
• The subcutaneous tissue shows a blubbery appearance in which the dilated and thickened lymphatics and veins can be seen.
• The underlying muscles and bones do not usually show any alteration.
• Granuloma of breast: Characterized by the presence of film solitary mass in the breast.
• Chyluria: Urine shows chyle mixed with blood and occasionally microfilariae.
• Caused by escape of chyle through the urine due to the rupture of varicose chyle vessels through the mucous membrane of the urinary tract.

v. Occult filariasis:

• It denotes a condition of hypersensitivity reaction of the host to micro-filarial antigens characteristically microfilariae are not found in the peripheral blood and the classic features of lymphatic filariasis are absent.
• Tropical pulmonary eosinophilia (TPE) is the most important manifestation.
• Arthritis, tenosynovitis, dermatoses etc. in the endemic areas are the less frequent manifestation of occult filariasis.
• TPE is distinct clinical syndrome characterized by chronic pulmonary infiltration in chest X-ray, hypereosinophilia of the peripheral blood and respiratory symptoms like low grade fever, cough, chest pain and asthmatic attacks especially at night.

vi. Less frequent lesions:

• These includes granuloma of the spleen and other organs and the presence of adult W. bancrofti in the anterior chamber of the eye.

Complications:

• Secondary bacterial infections of the overlying skin of elephantiasis of the leg or arm.

Laboratory diagnosis:

Parasitic diagnosis:

• Specimen: Peripheral blood is the specimen of choice.

Methods of examination includes:

i. Microscopy:

• The standard method for diagnosing active infection is the identification of microfilariae in blood smear by microscopic examination.
• Blood collection should be done at night to coincide with the appearance of the microfilariae.
• It can be determined by following method:
• Direct wet mount:
  • 2-3 drops of blood are collected on a clean glass slide and examined microscopically after placing cover slip on it.
  • -ive microfilariae are identified by their characteristic serpentine movement in the blood plasma.
• Stained thick blood film smears:
  • Thick and smear stained with Giemsa or Leishman is the most commonly used method.
  • The presence of sheath but the absence of nuclei in the tail end of microfilaria is diagnostic of W. bancrofti microfilaria.
• Concentration of blood:
  • Increase of low number of microfilariae in blood, their recovery can be increased by various concentration methods like knot’s method of concentration by sedimentation, membrane filtration concentration methods using Nucleopore or Millipore membrane filters.
• DEC provocation test:
  • In this test (Diethylcarbamazine) is given orally at a dose of 2-8 mg/kg. after 30 min the capillary blood is collected by finger prick for demonstration of microfilariae by direct wet amount or staining the smear.
  • DEC stimulates nocturnal periodic microfilariae to circulate in the peripheral blood during the day time.
• QBC:
  • This method can frequently demonstrate the circulating microfilariae in the blood.
• Urine microscopy:
  • Microfilariae can be demonstrated in the chylous urine.
  • 10 ml-20 ml of the first early morning urine is collected for examination and demonstration of microfilariae by microscopy.
  • Microscopy of hydrocele fluid and lymph node aspirations.
  • Microfilariae can also be demonstrated in hydrocele fluid and also in lymph node aspiration. Either is used hydrocele fluid to dissolve fat globules.

II. Immune diagnosis:

 Serological tests:

i. Demonstration of circulating antibodies:

• IHA, IFA, ELISA, RLA, luminescence immune analyses are used to demonstrate the circulating antibodies in the serum
• Disadvantage of these test are that they show cross reactivity with sera from other filarial and helminthic infections and they are unable discriminate between past and current infections.

ii. Demonstration of circulating antigens:

• The circulating antigens are present in serum only during recent or current infections.
• ELISA employing monoclonal antibody AD12 detects a 200 Kda of adult W. bancrofti in the serum.
• The other ELISA using monoclonal antibiotic Og4c3 detects adult worm as well as microfilariae antigen in the serum.

Molecular methods:

• PCR methods have been developed however they are not much sensitivity PCR is positive only when circulating microfilariae are found in the peripheral blood.

Imaging methods:

• X-ray: Chest x-ray shows diffuse pulmonary infiltrates in patients with TPE.
• Ultrasound: Only non-invasive method for detection of adult worms in the affected lymph nodes.
• The live adult worms are identified by a distinctive pattern of their movement known as filarial dance sign.

Other tests:

• Biopsy of lymph node that has been enlarged show cross sections of adult worms
• Eosinophilia can be seen in complete blood cell count

Treatment:

• Diethylcarbamazine (DEC), drug of choice.
• Dose: oral, 3mg to 6 mg/kg daily in divided doses for 3 weeks
• Others: Ivermectin, Levamisole, Mebendazole and Centprazine.

Prevention and control:

• Clinical control of mosquito by spraying DDT, malathion etc.
• Biological control by using of B. sphaericus, B. thuringienesis, Poecilid reticulate molliensis.
• Effective drainage and sewage system to eliminate breeding of mosquito
• Treatment of cases
• Use of bed nets, house screens
• Interrupting transmission of infection.

Lymphatic filariasis (W. bancrofti): transmission, Pathogenesis, clinical manifestation and treatment

The post Lymphatic filariasis (W. bancrofti): transmission, Pathogenesis, clinical manifestation and treatment appeared first on Online Biology Notes.

Habitat

• Adult worms are found in the lymphatic vessel, especially the lymph nodes.
• The microfilariae are found in the peripheral blood, occasionally they are also found in chylous urine or in hydrocele fluid.

Morphology of W. bancrofti

1. Adult worms

• W. bancrofti exhibits considerable sexual dimorphism.
• These are minute, long hair like transparent (often creamy in color) nematodes.
• They are filiform in shape with both ends tapering.
• The head end terminating in a slightly round swelling, and surrounded by two rows of 10 sessile papillae. The posterior end contains anus at its terminal end.
• The male measures 2.5-4 cm in length with 0.1 mm in thickness. The tail end is curved ventrally and contains two spicules of unequal length.
• The females are longer than males measure 8-10 cm in length with 0.2-0.3 mm in thickness. Its tail end is narrow and abruptly pointed. The females are oviparous.
• The adults obtain their nourishment from the lymph of the lymphatic system.
• The life span of the adult worms is long, probably several years (5-10 year or even more).

2. Microfilariae (Embryos):

• The first stage of larva is called microfilariae.
• They are very active in their habits and can move both with and against the blood stream, when sustained, they appear as colorless and transparent bodies with blunt heads and pointed tails.
• The embryo measures about 290 mm in length by 6-7 mm in breadth.
• When dead and stained with Romanowsky’s stains, they show the following morphological features:
• Hyaline sheath:
  • It is a sac like envelope which is much longer (359 mm) than the larval body represents the chorionic envelop of the eggs.
  • It remains as investing membrane around the larva.
• Cuticle:
  • It is lined by subcuticular cells and is seen only with vital stains.
• Somatic cells or nuclei:
  • Nucleiappear as granules in the central axis of the body and extend from the head to the tail end, except the terminal 5% of the tip of the tail. This is the distinguishing feature of the parasite.
  • The space at the anterior end devoid of granules is seen called as cephalic space.
  • The granules are broken at definite places serving as the landmarks for identification of the species.
  • They include:
    (a) Nerve ring; an oblique space
    (b) anterior V-spot represents the rudimentary excretory system
    (c) the posterior V spot or tail spot represents the terminal part of the alimentary canal/anus or cloaca.

3. Third stage of larva (infective form):

• The L3 larva the infective form of the parasite is found only in mosquito.
• They are elongated, filariform, measures 1.4-2 cm in length and 18-23 cm in breadth.

Life cycle:

• W. bancrofti completes its life cycle in two hosts:
  • Definite host: Human
  • Intermediate host: mosquito, belonging to genus Culex, Aedes and Anopheles.
• Life cycle in Human: Entrance in the human and development into adult worms
  • Infection is acquired by the bite of infected mosquito during which L3 larva are deposited on the skin.
  • The L3 larva are not directly injected into the blood stream.
  • The L3 larva are deposited on the skin near the site of the puncture.
  • Later attracted by the warmth of the skin, the larva enters through the puncture wound or penetrates through the skin on their own.
  • The L3 larva after penetrating the skin, reaches the lymphatic channels, settles down at some spot (inguinal, scrotal or abdominal lymphatics), metamorphose and becomes sexually mature.
  • The male fertilizes the female and the gravid females discharge microfilariae which usually appear in the peripheral blood in 8-12 month of infection.
  • These micro filariae circulate in the blood for 6 months to 2 years and then die if not taken by mosquito.
• Life cycle in Mosquito: Stages in the development of micro filaria
  • Microfilaria ingested by the mosquito lose their sheath within 2 to 6 hours of their arrival in the stomach.
  • Then they penetrate the gut wall and migrate to the thoracic muscle, where they rest and begin to grow.
  • In the next 2 days, microfilaria become thick, short sausage shaped with a short spiky tail, measuring 124-200 mm in length 10-17 mm in breadth. This is the first stage larva L1.
  • The larvae possesses a rudimentary digestive tract.
  • During 3-7 days of time, the larva grows rapidly, moults once or twice and measures 225-330 mm in length by 15-30 mm in breadth. This is the second stage larva L2.
  • Metamorphosis completes by 10-11days with distinct features such as the tail atrophies to a mere stump and the digestive system, body cavity and genital organs are now fully developed. This is the third stage larva L3.
  • These L3 larva are the infective form which enters the proboscis sheath of the mosquito on or about the 14^th day.
  • When the mosquito bites a man during the blood meal, the L3 larva are released from the tip of proboscis of mosquito and the cycle is repeated.
  • Development in mosquito takes place within 10-20 days.

Epidemiology of Wuchereria bancrofti

• W. bancrofti is largely confined to tropics and subtropics. They are found in India, West-Indies, Puerto Rico, Southern China, Japan, Pacific Island, West and central Africa, South America.
• The disease is endemic in 83 countries with more than 1.2 billion at risk.
• It is estimated that more than 120 million people are infected.
• More than 25 million men suffer from genital symptoms and more than 15 million people suffer from lymphedema or elephantiasis of leg.

Periodicity:

• The microfilariae of oriental countries (India and China) show nocturnal periodicity.
• They are found periodically in peripheral blood at night especially between 10pm to 4 am.

Wuchereria bancrofti: Morphology, life cycle and Epidemiology

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