239.1 🎓 醫學生版

239.1.0.1 📌 一頁重點

239.1.0.1.1 3 Main Filarial Diseases

Disease	Pathogen	Vector	Geography	Disease
Lymphatic Filariasis	Wuchereria bancrofti (worldwide), Brugia malayi/timori (Asia)	Mosquito	Africa, Asia, Pacific, Americas	Lymphedema, hydrocele, elephantiasis
Onchocerciasis	Onchocerca volvulus	Black fly (Simulium)	Sub-Saharan Africa + parts S America	“River blindness”, skin nodules
Loiasis	Loa loa	Deer fly (Chrysops)	West + Central Africa	Eye worm + Calabar swellings
Other (lesser)	Mansonella, Dirofilaria	Various	Tropics	Rare

239.1.0.1.2 Lymphatic Filariasis (LF)

• WHO Global Program to Eliminate LF (GPELF) 2030 goal
• Mass drug administration (MDA) = albendazole + ivermectin OR diethylcarbamazine
• 60M+ infected, 36M with disease (many resolved with MDA)

239.1.0.1.2.1 Pathogenesis

• Microfilariae circulate in blood (often nocturnal periodicity for W. bancrofti)
• Adult worms in lymphatic vessels → damage + lymphedema
• Damage progresses over years even after parasite cleared

239.1.0.1.2.2 Clinical

• Asymptomatic microfilaremia (most infected)
• Acute adenolymphangitis (ALA): episodic fever + lymphedema flares
• Chronic lymphedema: arm + leg (especially distal)
• Elephantiasis: severe disfiguring chronic
• Hydrocele (W. bancrofti scrotal involvement)
• Tropical pulmonary eosinophilia (TPE): hyperreactive form (S Asia); cough + wheeze + nocturnal + eosinophilia + IgE elevated

239.1.0.1.2.3 Diagnosis

• Blood microfilariae: thick smear, often nocturnal collection (10 PM - 2 AM)
• Circulating filarial antigen (CFA): ICT card test for W. bancrofti
• Antibody tests
• TPE: clinical + IgE elevated + IgG-filarial antibody + eosinophilia + response to DEC

239.1.0.1.2.4 Treatment

• Diethylcarbamazine (DEC) 6 mg/kg × 12 days OR
• Single dose: DEC + albendazole + ivermectin (modern MDA)
• Treatment for established lymphedema + elephantiasis: limb elevation + hygiene + decongestive therapy + sometimes surgery (severe hydrocele)
• Wolbachia endosymbiont — doxycycline targets it + reduces worms

239.1.0.1.3 Onchocerciasis

• Adult worms in subcutaneous nodules
• Microfilariae migrate through skin + eye
• “River blindness”: eye disease from microfilarial migration
• Sub-Saharan Africa primarily (40% global pop at-risk)
• Mectizan (ivermectin) Donation Program (Merck) since 1987 → > 1 billion treatments

239.1.0.1.3.1 Vector

• Black fly (Simulium damnosum complex) — breeds in fast-flowing rivers (hence “river blindness”)

239.1.0.1.3.2 Pathogenesis

• Adult worms in skin nodules
• Females release microfilariae into surrounding tissue
• Microfilariae migrate through skin + lymphatics
• Cause inflammation + tissue damage
• Eye involvement: progressive visual loss + blindness

239.1.0.1.3.3 Clinical

• Onchocerciasis Skin Disease (OSD):
  • Pruritus (severe; “onchodermatitis”)
  • “Hanging groin” (skin laxity)
  • “Leopard skin” (focal depigmentation)
  • Sowda (chronic papular dermatitis)
• Eye Disease:
  • Punctate keratitis → sclerosing keratitis → blindness
  • Iridocyclitis
  • Sub-conjunctival hemorrhages with visible microfilariae
  • Posterior segment: optic neuritis, chorioretinitis
• Subcutaneous nodules (“onchocercomas”) containing adult worms
• Onchocerciasis-Associated Epilepsy (newly recognized; African children)

239.1.0.1.3.4 Diagnosis

• Skin snip (excised piece of subcutaneous tissue, incubated in saline → microfilariae emerge → microscopy)
• Slit-lamp exam for ocular microfilariae
• PCR of skin snip
• Serology

239.1.0.1.3.5 Treatment

• Ivermectin 150 µg/kg PO single dose, repeated annually (kills microfilariae but not adult worms)
• Doxycycline 100 mg PO bid × 6 weeks targets Wolbachia → reduces adult worms + microfilariae (microfilaricidal effect)
• Combination ivermectin + doxycycline for individual treatment
• Mectizan Donation Program (Merck) — ivermectin free for endemic Africa
• WHO Mass Drug Administration annual

239.1.0.1.4 Loiasis

239.1.0.1.4.1 Vector

• Deer fly (Chrysops) — Central + W Africa rainforest

239.1.0.1.4.2 Pathogenesis

• Adult worms migrate through subcutaneous tissue
• Microfilariae circulate in blood (daytime periodicity — Chrysops is daytime biter)

239.1.0.1.4.3 Clinical

• Visible eye worm: pathognomonic — adult worm crossing conjunctiva (transient minutes-hours)
• Calabar swellings: transient pruritic / painful swellings (subcutaneous angioedema from worm migration)
• Eosinophilia
• Often asymptomatic for years

239.1.0.1.4.4 Diagnosis

• Blood microfilariae (thick smear, daytime collection)
• Visible eye worm on ophthalmology
• Serology
• PCR

239.1.0.1.4.5 Treatment + Caveat

• Diethylcarbamazine (DEC) for microfilariae + adult worms
• CAUTION: High microfilariae load (> 8000/mL) + DEC = severe encephalopathy risk (Mazzotti reaction)
• Pre-treatment microfilariae count + staged treatment
• Alternative: ivermectin (also caution in high MF load)
• Pretreatment apheresis + albendazole to reduce MF load before ivermectin
• Ivermectin contraindicated in high Loa loa load for onchocerciasis MDA — pre-screening required

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239.1.0.2 1️⃣ Lymphatic Filariasis (LF)

239.1.0.2.1 Pathogens

239.1.0.2.1.1 Wuchereria bancrofti

• Worldwide: tropical Africa, Asia, Latin America, Pacific
• Most cases of LF globally
• Vector: Anopheles + Culex + Aedes mosquitoes
• Nocturnal microfilarial periodicity (peak 10 PM - 2 AM)

239.1.0.2.1.2 Brugia malayi

• SE Asia + India
• Vector: Mansonia mosquitoes
• Nocturnal or subperiodic

239.1.0.2.1.3 Brugia timori

• Indonesian Eastern islands
• Vector: Anopheles barbirostris
• Nocturnal

239.1.0.2.2 Life Cycle

1. Mosquito takes blood meal containing microfilariae
2. Microfilariae mature to infective L3 larvae in mosquito (10-14 days)
3. Mosquito bites human → L3 larvae enter skin
4. Migrate to lymphatic vessels
5. Mature to adult worms (3-12 months)
6. Adults live for years; produce microfilariae
7. Microfilariae circulate in blood (periodic)

239.1.0.2.3 Pathogenesis

• Adult worms in lymphatics → mechanical + inflammatory damage
• Recurrent secondary bacterial infections (cellulitis) accelerate damage
• Eventually fibrotic + irreversible lymphatic obstruction
• Microfilariae usually don’t cause LF symptoms directly
• Tropical pulmonary eosinophilia: hyperreactive form with marked eosinophilia + IgE

239.1.0.2.4 Clinical

239.1.0.2.4.1 Asymptomatic Microfilaremia

• Many infected
• No symptoms despite circulating microfilariae

239.1.0.2.4.2 Acute Adenolymphangitis (ALA)

• Episodic fever + painful lymphadenitis + lymphangitis
• Flares last days-weeks
• Often triggered by secondary bacterial infection

239.1.0.2.4.3 Chronic Lymphedema

• Years-decades to develop
• Distal extremities most common (legs, arms)
• Progressive thickening + edema
• Recurrent secondary bacterial cellulitis exacerbates

239.1.0.2.4.4 Elephantiasis

• Severe chronic disfiguring lymphedema
• Limbs become massively swollen + hardened
• Functional impairment
• Quality of life severely impacted

239.1.0.2.4.5 Hydrocele (W. bancrofti)

• Scrotal involvement
• Painless swelling
• Common in endemic men

239.1.0.2.4.6 Tropical Pulmonary Eosinophilia (TPE)

• Hyperreactive immune response to circulating microfilariae
• Cough + wheeze + nocturnal symptoms + eosinophilia + elevated IgE + interstitial pulmonary infiltrates
• Often misdiagnosed as asthma
• Responds to DEC
• South Asian origin most common

239.1.0.2.5 Diagnosis

239.1.0.2.5.1 Microfilariae in Blood

• Thick smear during periodic peak (W. bancrofti: nocturnal 10 PM - 2 AM)
• Concentrated samples (membrane filtration)
• Day-time microfilaremia in some (Pacific strains, subperiodic Brugia)

239.1.0.2.5.2 Circulating Filarial Antigen (CFA)

• ICT card test (rapid) for W. bancrofti adult worm antigen
• High sensitivity even without microfilaremia
• Standard for surveillance + diagnosis

239.1.0.2.5.3 Antibody Tests

• BmR1 + others
• Cross-reactivity with other filariae

239.1.0.2.5.4 Ultrasound

• “Filaria dance sign” — moving adult worms in scrotal lymphatics
• Diagnostic for W. bancrofti hydrocele

239.1.0.2.5.5 TPE Diagnosis

• Clinical + eosinophilia + elevated IgE + IgG anti-filarial Ab
• Response to DEC
• Microfilaremia may be absent

239.1.0.2.6 Treatment

239.1.0.2.6.1 Individual Treatment

• Diethylcarbamazine (DEC) 6 mg/kg × 12 days (kills both microfilariae + adult worms)
• Single dose: DEC 6 mg/kg + albendazole 400 mg (preferred in MDA)
• Ivermectin + albendazole in Africa (where DEC avoided due Loa loa risk)
• Doxycycline 200 mg/d × 4-6 weeks targets Wolbachia → kills adult worms
• TPE: DEC × 14 days highly effective

239.1.0.2.6.2 Mass Drug Administration (MDA)

• WHO Global Program to Eliminate Lymphatic Filariasis (GPELF) 1997+
• Annual treatment of all endemic communities × 5-6 years
• Combinations:
  • Albendazole + Ivermectin (where onchocerciasis co-endemic, Loa loa absent)
  • Albendazole + DEC (most of Asia, Pacific, Latin America)
  • Albendazole + Ivermectin + DEC (Triple therapy IDA) — Newer + more effective
• Goal: interrupt transmission + eliminate as public health problem

• 8 billion treatments distributed since 2000

239.1.0.2.6.3 Lymphedema + Elephantiasis Management

• Limb elevation
• Hygiene + skin care
• Decongestive therapy (compression bandages, pneumatic devices)
• Antibiotic prophylaxis for recurrent cellulitis
• Surgery rarely for severe hydrocele

239.1.0.2.7 Elimination Progress (WHO 2024)

• 17 countries certified eliminated LF as public health problem (2024)
• More near certification
• 2030 elimination goal worldwide
• Major public health success story

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239.1.0.3 2️⃣ Onchocerciasis (“River Blindness”)

239.1.0.3.1 Pathogen

• Onchocerca volvulus

239.1.0.3.2 Vector

• Black fly (Simulium damnosum complex)
• Breeds in fast-flowing rivers
• Endemic communities near rivers (hence “river blindness”)

239.1.0.3.3 Geography

• Sub-Saharan Africa (95%): especially West Africa, Central Africa
• Yemen (small foci)
• S America (small foci — Colombia, Ecuador, Venezuela; Mectizan Donation eliminated in some)
• ~ 40 million people at risk

239.1.0.3.4 Life Cycle

1. Black fly bites human → injects L3 larvae
2. Larvae mature to adult worms in subcutaneous tissue (forming nodules)
3. Adult female releases microfilariae into skin + connective tissue
4. Microfilariae migrate through skin + into eye
5. Female lives 10-14 years; produces millions of microfilariae

239.1.0.3.5 Pathogenesis

• Microfilariae in skin + eye cause disease (not adults)
• Wolbachia endosymbiont important in pathogenesis + microfilariae viability
• Inflammatory response → skin + eye damage

239.1.0.3.6 Clinical

239.1.0.3.6.1 Onchocerciasis Skin Disease (OSD)

• Severe pruritus (“itch”)
• Onchodermatitis: papular rash
• Acute papular onchodermatitis (early)
• Chronic papular onchodermatitis
• Lichenified onchodermatitis (“Sowda” form — Yemen + parts Africa; severe pruritic localized)
• Atrophic dermatitis (advanced) — thin, scarred, hypopigmented
• “Leopard skin” — focal hypopigmentation
• “Hanging groin” — skin laxity from chronic damage

239.1.0.3.6.2 Subcutaneous Nodules (Onchocercomas)

• Firm, painless, mobile
• 0.5-3 cm
• Hip, shoulder, scalp common locations
• Contain adult worms

239.1.0.3.6.3 Eye Disease (“River Blindness”)

• Progressive (years-decades)
• Anterior segment:
  • Punctate keratitis → sclerosing keratitis
  • Iritis, iridocyclitis
  • Visible microfilariae in cornea + anterior chamber (slit-lamp diagnostic)
• Posterior segment:
  • Optic neuritis
  • Chorioretinitis
  • Macular involvement
• Blindness in 10-20% of heavily infected
• Major cause of blindness in endemic Africa (historically up to 50% in some villages near rivers)

239.1.0.3.6.4 Onchocerciasis-Associated Epilepsy (Newly Recognized)

• High onchocerciasis transmission → epilepsy in children
• Mechanism not fully understood
• Mass deworming may reduce incidence

239.1.0.3.7 Diagnosis

239.1.0.3.7.1 Skin Snip

• 2-4 mm skin biopsy (no anesthesia) over scapula / iliac crest / calf
• Incubated in saline 24 hr at RT
• Microscopic exam for emerging microfilariae
• Highly specific

239.1.0.3.7.2 Slit-Lamp Exam

• Visible microfilariae in cornea + anterior chamber
• Diagnostic

239.1.0.3.7.3 Nodulectomy

• Excise subcutaneous nodule → adult worms

239.1.0.3.7.4 Serology

• Anti-Onchocerca antibody
• Cross-reactivity with other filariae

239.1.0.3.7.5 PCR

• Skin snips or biopsy

239.1.0.3.8 Treatment

239.1.0.3.8.1 Ivermectin

• 150 µg/kg PO single dose annually (or biannually in heavy areas)
• Kills microfilariae (not adult worms)
• Adult worms continue producing microfilariae for years
• Repeated annual dosing for ~ 15 years (life span of adult worms) to clear infection
• WHO Mass Drug Administration program

239.1.0.3.8.2 Doxycycline

• 100 mg PO daily × 6 weeks targets Wolbachia endosymbiont
• Wolbachia killed → adult worms die over months
• Microfilaricidal effect develops over months
• More effective in individual treatment than MDA

239.1.0.3.8.3 Combination

• Ivermectin + doxycycline for individual treatment
• Higher cure rates

239.1.0.3.8.4 Mectizan Donation Program (Merck)

• Free ivermectin for onchocerciasis since 1987

• 1 billion treatments distributed

• WHO + Carter Center + other partners
• Major public health success
• Eliminated onchocerciasis in some countries (Colombia, Ecuador, Mexico, Guatemala)
• Africa: 40+ countries with MDA programs

239.1.0.3.8.5 Elimination Progress

• 4 Latin American countries eliminated
• Africa elimination targets being met in some (Uganda, Sudan, Ethiopia areas)
• WHO 2030 goals
• “Eliminate as public health problem” → “verification of elimination” pathway

239.1.0.3.8.6 Pre-Treatment Caution

• Loa loa screening in Central Africa endemic areas → high MF load + ivermectin = severe encephalopathy
• Pre-treatment with albendazole alone or apheresis for MF reduction
• WHO RAPLOA (Rapid Assessment Procedure for Loa loa) screening tool

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239.1.0.4 3️⃣ Loiasis (Loa loa)

239.1.0.4.1 Vector

• Deer fly (Chrysops) — Central + West African rainforest
• Daytime biter
• Forest workers + indigenous + travelers at risk

239.1.0.4.2 Life Cycle

1. Chrysops bites infected human → ingests microfilariae
2. Microfilariae mature to L3 in fly (7-10 days)
3. Chrysops bites uninfected human → injects L3
4. L3 mature to adult worms in subcutaneous tissue (1-3 years)
5. Adult worms migrate through subcutaneous tissue
6. Microfilariae circulate in blood (daytime periodicity)

239.1.0.4.3 Geography

• Central + West African rainforest: Cameroon, Republic of Congo, DRC, Gabon, Equatorial Guinea, Nigeria
• ~ 10 million infected

239.1.0.4.4 Clinical

239.1.0.4.4.1 Visible Eye Worm

• Pathognomonic: adult worm crossing conjunctiva
• Transient (minutes-hours)
• Patient may present with “worm in eye”
• Ophthalmology consult

239.1.0.4.4.2 Calabar Swellings

• Transient painful / pruritic subcutaneous angioedema
• Localized swellings 5-10 cm
• Often hands, forearms
• Last hours-days
• Migratory (worm in subcutaneous tissue)

239.1.0.4.4.3 Eosinophilia

• Common; intermittent

239.1.0.4.4.4 Asymptomatic Carriage

• Many infected without symptoms

239.1.0.4.4.5 Loiasis-Related Disease

• Cardiomyopathy
• Encephalopathy (rare without treatment)
• Renal disease (proteinuria + glomerulonephritis)
• Mass effect with worm in body cavity (rare)

239.1.0.4.5 Diagnosis

239.1.0.4.5.1 Microfilaremia

• Thick smear, daytime collection (10 AM - 2 PM)
• Concentrated samples
• Density variable

239.1.0.4.5.2 Visible Eye Worm

• Ophthalmology consultation
• Surgical removal possible if persistent

239.1.0.4.5.3 Serology + PCR

• Anti-Loa loa antibody
• PCR of blood, tissue

239.1.0.4.6 Treatment

239.1.0.4.6.1 Diethylcarbamazine (DEC) — Classical

• 6-9 mg/kg/day × 14-21 days
• Effective against microfilariae + adult worms
• Best efficacy
• Caution: high microfilariae load (> 8000/mL) → severe encephalopathy (“Mazzotti reaction”), encephalitis, coma, death
• Pre-treatment microfilariae count:
  • < 2000 MF/mL: standard DEC dosing
  • 2000-8000 MF/mL: gradual dose escalation + steroid + monitoring
  • > 8000 MF/mL: pre-treatment with albendazole or apheresis to reduce MF load before DEC
• ICU monitoring

239.1.0.4.6.2 Ivermectin

• Single dose 200 µg/kg
• Effective for microfilariae
• Same caution as DEC for high MF load
• Doesn’t kill adult worms

239.1.0.4.6.3 Albendazole

• Slowly kills adult worms (months)
• Used to reduce MF load before DEC (safer treatment)
• 200 mg PO bid × 21 days

239.1.0.4.6.4 Surgical

• Visible eye worm: ophthalmology may remove

239.1.0.4.7 Loa loa + Onchocerciasis MDA Caveat

• Loa loa endemic + onchocerciasis endemic regions overlap (Central Africa)
• Ivermectin MDA for onchocerciasis can cause Mazzotti encephalopathy in Loa loa-infected
• Pre-screening (RAPLOA, CFA) before MDA
• Affected individuals get pre-treatment albendazole + monitoring
• Major implementation challenge for MDA in Central Africa

239.1.0.4.8 Mazzotti Reaction

• Severe inflammatory response to dying microfilariae
• Headache, fever, hypotension, pruritus, edema
• Severe: encephalopathy + death
• Pre-medication: antihistamine + steroid

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239.1.0.5 4️⃣ Other Filarial Infections

239.1.0.5.1 Mansonella

• Various species (M. perstans, M. ozzardi, M. streptocerca)
• Vector: Culicoides midges or Simulium
• Africa + S America
• Usually mild; eosinophilia, papular rash, peritoneal/pericardial fluid
• Doxycycline targeting Wolbachia (M. perstans has Wolbachia)
• DEC + ivermectin variably effective

239.1.0.5.2 Dirofilaria

• Heartworm of dogs (D. immitis)
• Human accidental host
• Pulmonary nodules (“coin lesions”) on CXR
• Self-limited; surgical resection for diagnostic certainty
• Usually no treatment needed

239.1.0.5.3 Filaria in Returning Travelers

• Rare but recognized
• Workups: blood smears + serology + ophthalmology if eye sx

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