Filariasis

Causative Organisms

Key difference: Brugian filariasis rarely involves the genitalia, unlike Bancroftian filariasis. - Park's Textbook of Preventive and Social Medicine

Life Cycle

1. An infected mosquito releases infective L3 larvae into the skin during a blood meal.
2. Larvae migrate into lymphatic channels and develop into adult worms (male and female) over several months (incubation 2-18 months).
3. Adult worms mate within lymphatics or lymph nodes and release sheathed microfilariae (Mf) into the bloodstream.
4. Mosquitoes ingest Mf during a blood meal; Mf develop into infective larvae within the mosquito over several days.
5. The cycle repeats.

Pathogenesis

Worm-mediated immune evasion

• Elastases and trypsin-like proteases - facilitate tissue invasion
• Surface glycoproteins with antioxidant function - protect against reactive oxygen species
• Cystatin homologues (cysteine protease inhibitors) - impair MHC class II antigen processing
• Serpins (serine protease inhibitors) - inhibit neutrophil proteases
• TGF-β and macrophage migration inhibition factor homologues - dampen host immune responses

Wolbachia endosymbionts

Lymphatic damage

• Acute phase: Presence of molting adolescent worms and dying adults causes lymphatic dilation, endothelial hyperplasia, infiltration by lymphocytes, plasma cells and eosinophils, and thrombus formation (acute lymphangitis), followed by granuloma formation and fibrosis.
• Chronic phase: Repeated infections lead to massive lymphatic blockade. Skin and subcutaneous tissues become edematous, thickened, and fibrotic. Dilated lymphatics may rupture, spilling lymph into tissues or body cavities.
• Bacterial and fungal superinfections frequently supervene and worsen tissue damage.

T-cell immunology

• Th1 responses drive granuloma formation around adult worms - major driver of lymphatic damage in chronic disease.
• Th2 responses (IL-4, IL-5) stimulate IgE and eosinophilia - associated with tropical pulmonary eosinophilia.

Clinical Spectrum

Stage 1 - Asymptomatic amicrofilaraemia

Stage 2 - Asymptomatic microfilaraemia

Stage 3 - Acute manifestations (filarial fever)

• Filarial fever - typically low-grade; occasionally up to 40°C with chills and myalgia
• Lymphadenitis - classically begins in the femoral region as a red, tender, enlarged lymph node, then spreads centrifugally down the lymphatic channels of the leg
• Lymphangitis - lymphatic vessels become enlarged and tender; overlying skin is warm, red, and edematous
• Urticaria and eosinophilia - elevated IgE levels
• In Bancroftian filariasis: lymphatics of the testicle, epididymis, and spermatic cord are frequently involved, causing painful orchitis, epididymitis, and funiculitis; inflamed retroperitoneal vessels may simulate an acute abdomen
• Acute episodes last a few days, resolve spontaneously, and recur periodically over weeks to months

Stage 4 - Chronic obstructive lesions (10-15 years after first acute attack)

• Lymphedema - affects legs (most common), arms, scrotum, penis, vulva, breasts (in that order of decreasing frequency)
• Elephantiasis - tough subcutaneous fibrosis with epithelial hyperkeratosis; skin shows dilated dermal lymphatics, widespread lymphocytic infiltrates, and focal cholesterol deposits; epidermis thickened and hyperkeratotic
• Hydrocele - fluid contains cholesterol crystals, red cells, and hemosiderin; causes thickening and calcification of the tunica vaginalis
• Chyluria - rupture of dilated lymphatics into the urinary tract, producing milky/white urine; usually intermittent and may spontaneously remit

Occult filariasis - Tropical Pulmonary Eosinophilia (TPE)

• Paroxysmal nocturnal cough and wheeze
• Marked peripheral eosinophilia (>3000/µL)
• Elevated IgE
• Histology: dead microfilariae surrounded by stellate eosinophilic precipitates within small epithelioid granulomas (Meyers-Kouwenaar bodies)
• Responds well to DEC

Clinical Image

Diagnosis

Blood smear (gold standard)

• Thick and thin blood smears stained with Giemsa or Wright stain
• Must be collected at the correct time - for W. bancrofti (nocturnal periodicity), collect blood between 10 PM and 2 AM
• If parasitemia is below detection threshold, concentrate the sample (Knott's concentration technique, membrane filtration)
• DEC provocation test: DEC stimulates migration of Mf from pulmonary to systemic circulation, increasing detection yield

Antigen detection

• Circulating filarial antigen (CFA) test - detects W. bancrofti antigen (Og4C3 ELISA or immunochromatographic card test); present in most microfilaraemic patients and some non-microfilaraemic infected individuals - useful for active infection
• Brugia Rapid test - antibody-based, for Brugian filariasis

Serology

• IgG4 ELISA - most specific serologic test; cross-reactivity with other tissue parasites is well described; limited value in endemic populations (prior exposure confounds results)

Ultrasound

• "Filarial dance sign" - characteristic movement of adult worms visible on scrotal ultrasound (W. bancrofti commonly found in intrascrotal lymphatic vessels)
• Filarial lymphadenopathy detectable in children (inguinal, crural, axillary nodes)

Eosinophilia

• Present during acute inflammatory episodes
• Marked eosinophilia (>3000/µL) in TPE

Treatment

Diethylcarbamazine (DEC) - Drug of choice

• Both microfilaricidal AND active against adult worms
• Results in long-term suppression or parasitologic cure in some cases
• Dying microfilariae trigger an allergic (Mazzotti-like) reaction - may require antihistamines and corticosteroids
• Important: Must exclude onchocerciasis before giving DEC in endemic areas - coinfection causes severe skin and eye reactions
• Used in mass drug administration (MDA) programs; sometimes added to cooking salt in highly endemic areas

Ivermectin

• Kills microfilariae only, NOT adult worms
• Single dose temporarily clears microfilaraemia
• Used in combination regimens (DEC + albendazole, or ivermectin + albendazole in areas co-endemic with onchocerciasis)

Albendazole

• Has beneficial effects on both microfilariae and adult worms
• Used in combination with DEC or ivermectin for MDA programs

Doxycycline (anti-Wolbachia strategy)

• Kills endosymbiotic Wolbachia bacteria
• With prolonged administration (4-6 weeks), impairs nematode survival and fertility
• Can ultimately kill adult worms
• May be used alone or in combination with albendazole

Management of complications

• Lymphedema: pressure bandages, elevation, limb hygiene (soap, water, proper footwear), pneumatic compression
• Bacterial/fungal superinfection: antibiotics/antifungals - essential to prevent progression
• Hydrocele: surgical excision with eversion of the sac ± excision of redundant scrotal skin
• Elephantiasis: tissue changes are often irreversible; surgical debulking is rarely performed due to poor success rates
• Chyluria: conservative management (dietary fat restriction, high fluid intake); endoscopic instillation of sclerosants; surgical - renal pedicle lymphatic disconnection (Gerota's fasciectomy) for intractable cases

Prevention and Control (WHO Global Programme)

1. Mass Drug Administration (MDA) - Annual single-dose treatment of entire at-risk populations with DEC + albendazole (or ivermectin + albendazole where onchocerciasis is co-endemic). Mass drug administration programs have greatly reduced cases in many nations.
2. Vector control - Mosquito control (insecticide spraying, bed nets, larval control)
3. Morbidity Management and Disability Prevention (MMDP) - Lymphedema management, hydrocele surgery
4. Disease mapping - Identifying endemic areas using CFA card tests
5. Surveillance - Post-MDA monitoring to verify elimination

Key Distinctions: Bancroftian vs. Brugian Filariasis