226.1 🎓 醫孞生版

226.1.0.1 📌 䞀頁重點

226.1.0.1.1 4 Categories of Parasites
Category Examples
Protozoa (single-cell) Plasmodium, Trypanosoma, Leishmania, Entamoeba, Giardia, Toxoplasma, Babesia, Naegleria
Trematodes (flukes) Schistosoma, Fasciola, Clonorchis, Paragonimus
Cestodes (tapeworms) Taenia, Echinococcus, Hymenolepis
Nematodes (roundworms) Ascaris, Hookworm, Strongyloides, Trichuris, Filariae, Onchocerca, Toxocara
226.1.0.1.2 When to Suspect Parasitic Infection
  • Travel to endemic region
  • Immigration from endemic country
  • Immunocompromise (HIV, transplant) — opportunistic
  • Eosinophilia (especially helminth)
  • Chronic GI symptoms + weight loss + diarrhea
  • Hepatic / splenic enlargement + fever
  • Skin lesions (cutaneous Leishmaniasis, larva migrans)
  • CNS (cysticercosis, Toxo, malaria)
  • Pulmonary (Paragonimus, Strongyloides, Ascaris)
226.1.0.1.3 Diagnostic Approach
  • Travel + occupational + dietary history essential
  • Eosinophilia workup
  • Stool ova + parasite (multiple specimens different days)
  • Blood smear (malaria, Babesia, microfilaria)
  • Serology (Toxoplasma, Strongyloides, Schistosoma, etc.)
  • PCR + multiplex panels increasingly available
  • Tissue biopsy for specific (Leishmania, cysticercosis)
  • Imaging (echinococcal cysts, cysticerci)
226.1.0.1.4 Antiparasitic Agents Overview
226.1.0.1.4.1 Anti-Malarials
  • Artemisinin combination therapy (ACT) — first-line uncomplicated P. falciparum
    • Artemether-lumefantrine (Coartem)
    • Artesunate-amodiaquine
    • Dihydroartemisinin-piperaquine
  • Artesunate IV — severe malaria
  • Chloroquine — P. vivax + P. ovale (chloroquine-sensitive areas)
  • Primaquine, Tafenoquine — radical cure for P. vivax/ovale (hypnozoite) — G6PD test required
  • Mefloquine, Doxycycline, Atovaquone-proguanil (Malarone) — prophylaxis
226.1.0.1.4.2 Antiprotozoals (Non-Malaria)
  • Metronidazole, Tinidazole — Entamoeba, Giardia, Trichomonas, anaerobes
  • Nitazoxanide — Cryptosporidium, Giardia, broad
  • Pentamidine, Suramin, Eflornithine, Nifurtimox, Fexinidazole, Acoziborole — African Trypanosomiasis
  • Benznidazole, Nifurtimox — Chagas disease (American Trypanosomiasis)
  • Pentavalent antimonials (Glucantime, Pentostam), Liposomal amphotericin B, Miltefosine, Paromomycin — Leishmaniasis
  • Trimethoprim-Sulfamethoxazole, Pyrimethamine-Sulfadiazine, Atovaquone, Clindamycin — Toxoplasmosis, PJP
226.1.0.1.4.3 Anti-Helminthics
  • Albendazole — broad spectrum: nematodes, Echinococcus, neurocysticercosis, microsporidiosis
  • Mebendazole — pinworm, hookworm, Ascaris, Trichuris
  • Ivermectin — Strongyloides, Onchocerca, scabies, lice, intestinal helminths; broad spectrum
  • Praziquantel — Schistosoma + most trematodes + Taenia adult tapeworms
  • Niclosamide — adult tapeworms (Taenia)
  • Triclabendazole — Fasciola, Paragonimus
  • Diethylcarbamazine (DEC) — Filariasis (Loa loa, lymphatic filariasis, with caution)
  • Pyrantel pamoate — pinworm, hookworm
226.1.0.1.5 Key 2024 Drug Updates
  • Tafenoquine (Krintafel for P. vivax radical cure, Arakoda for prophylaxis) — single dose alternative to primaquine; requires G6PD testing
  • Fexinidazole (oral) — African Trypanosomiasis (now first-line for stage 1 + 2)
  • Acoziborole (single-dose oral) — African Trypanosomiasis Phase 3 success
  • Tipifarnib + ACT — antimalarial resistance research

226.1.0.2 1⃣ Approach to Suspected Parasitic Disease

226.1.0.2.1 History
  • Travel hx detailed (countries, duration, activities, rural vs urban, freshwater exposure)
  • Immigration + country of origin
  • Occupational (farm, water, abattoir, jungle)
  • Pets + animals + insects
  • Dietary:
    • Raw / undercooked meat (Toxo, Trichinella, Taenia)
    • Raw fish (Anisakis, Diphyllobothrium, Clonorchis)
    • Raw vegetables / water (Giardia, Cryptosporidium, Cyclospora, Entamoeba)
    • Raw crustaceans (Paragonimus, Gnathostoma)
  • Mosquito / tick / fly exposure
  • Freshwater swimming (Schistosoma, Naegleria)
226.1.0.2.2 Clinical Features Suggesting Parasitic
  • Eosinophilia (especially helminth — tissue invasion)
  • Chronic diarrhea + malabsorption (Giardia, Cryptosporidium, Strongyloides)
  • Hepatosplenomegaly + fever (Leishmania, Schistosoma, malaria, amebic liver abscess)
  • Skin lesions (cutaneous Leishmania, larva migrans, scabies)
  • Lymphadenopathy (Trypanosoma, Toxoplasma, Filariasis)
  • CNS (cysticercosis, Toxo, malaria, Naegleria PAM)
  • Pulmonary:
    • Eosinophilia + Loeffler syndrome (Ascaris migration)
    • Strongyloides hyperinfection
    • Paragonimus
  • Ocular (Toxocara, Onchocerca, Toxoplasma, Acanthamoeba)
  • GU (Schistosoma haematobium, Trichomonas)
226.1.0.2.3 Diagnostic Tests
226.1.0.2.3.1 Stool
  • Stool ova + parasite (O+P) × 3 days
  • Trophozoite preservation (special media)
  • Wet mount + concentration + permanent stain
  • Stool antigen tests (Giardia, Entamoeba, Cryptosporidium) — high sensitivity
  • PCR-based panels (BioFire GI) — multi-pathogen, fast
226.1.0.2.3.2 Blood
  • Thick + thin blood smears:
    • Malaria (q12-24h × 3 if first negative)
    • Babesia (similar)
    • Microfilariae (timed for periodicity — nocturnal for Wuchereria bancrofti, daytime for Loa loa)
  • Buffy coat for trypomastigotes
  • PCR (malaria, Babesia, Trypanosoma)
  • Rapid antigen tests (malaria — PfHRP-2, LDH; useful for endemic + emergent)
226.1.0.2.3.3 Serology
  • IgM + IgG for many:
    • Toxoplasma
    • Strongyloides
    • Schistosoma
    • Cysticercosis
    • Echinococcus
    • Trypanosoma
    • Leishmania
  • Cross-reactivity considerations
  • Confirmatory tests (Western blot, etc.)
226.1.0.2.3.4 Tissue
  • Biopsy: lymph node, bone marrow, skin, liver
  • Histology + special stains (Giemsa, etc.)
  • IHC
  • Tissue PCR
226.1.0.2.3.5 Imaging
  • US (liver, spleen, biliary)
  • CT/MRI (CNS, lung, liver, kidney)
  • X-ray (Loeffler, cysts)
226.1.0.2.3.6 Eosinophil Count
  • Eosinophilia > 500/µL suggests tissue parasite or helminth
  • Other causes: drug rxn, allergy, asthma, lymphoma, certain other infections
  • “MIASMA” mnemonic: Microscopic colitis, Idiopathic, Allergic, Strongyloides, Malignancy, Adrenal insufficiency
  • Strongyloides especially — chronic asymptomatic
  • Filariae, Schistosoma, Echinococcus all cause eosinophilia

226.1.0.3 2⃣ Antiparasitic Agents — Mechanism + Use

226.1.0.3.1 Antimalarials
226.1.0.3.1.1 Artemisinin Derivatives (Chinese Discovery, Nobel Prize Tu Youyou 2015)
  • Artesunate, artemether, dihydroartemisinin
  • Activate via heme → free radical generation → parasite killing
  • Rapid blood schizonticidal
  • Combination therapy (ACT) universally recommended (prevent resistance)
    • Artemether-lumefantrine
    • Dihydroartemisinin-piperaquine
    • Artesunate-amodiaquine
  • IV artesunate: drug of choice for severe malaria
  • Resistance emerging in SE Asia (kelch13 mutation)
226.1.0.3.1.2 Chloroquine
  • Weak base, accumulates in food vacuole → blocks heme detoxification
  • Active against: chloroquine-sensitive P. vivax, P. ovale, P. malariae, P. falciparum
  • P. falciparum widely resistant
  • Toxicity: retinal (long-term high dose — used in autoimmune diseases at lower dose)
  • Available for vivax/ovale + autoimmune (HCQ)
226.1.0.3.1.3 Mefloquine, Atovaquone-Proguanil, Doxycycline
  • Prophylaxis for travelers
  • Mefloquine: weekly; CNS side effects, contraindicated psych history
  • Atovaquone-proguanil (Malarone): daily + 7 days post-return; fewer side effects
  • Doxycycline: daily; photosensitivity, GI; cheap
226.1.0.3.1.4 Primaquine + Tafenoquine
  • 8-aminoquinolines — kill hypnozoites (latent liver stage) of P. vivax + P. ovale
  • Radical cure for vivax/ovale (prevents relapses)
  • Cause hemolysis in G6PD deficiency — REQUIRES G6PD testing before use
  • Tafenoquine: single dose alternative (300 mg PO × 1)
  • Primaquine: 14-day course
  • Prophylaxis use (off-label)
226.1.0.3.2 Antiprotozoal Agents
226.1.0.3.2.1 Metronidazole + Tinidazole
  • Reduced by anaerobic enzymes → DNA damage
  • Active: Giardia, Entamoeba, Trichomonas, anaerobic bacteria, Helicobacter pylori combo
  • Tinidazole: longer half-life, single dose options
  • Side effects: GI, metallic taste, disulfiram reaction with alcohol, peripheral neuropathy long-term
  • Pregnancy: 1st trimester avoid (theoretical); generally safe later
226.1.0.3.2.2 Nitazoxanide
  • Inhibits pyruvate-ferredoxin oxidoreductase
  • Broad spectrum: Cryptosporidium, Giardia, Entamoeba, helminths, viral antidiarrheal
  • Generally safe; GI side effects mild
  • 500 mg PO bid × 3d
226.1.0.3.2.3 Pentamidine
  • Cell membrane / mitochondrial damage
  • Active: African Trypanosomiasis (stage 1), Leishmaniasis, PJP
  • Toxic: nephro + arrhythmia + hyperglycemia / hypoglycemia + injection site
  • IV / IM / inhaled
226.1.0.3.2.4 Antimony Compounds (Pentavalent)
  • Sodium stibogluconate (Pentostam), meglumine antimoniate (Glucantime)
  • Active: Leishmaniasis
  • Mechanism unclear (inhibits parasite glycolysis + DNA synthesis)
  • Toxicity: cardiac (QTc, arrhythmia), pancreatitis, hepatic, hematologic
  • IV / IM × 28+ days
226.1.0.3.2.5 Amphotericin B (Liposomal)
  • Liposomal AmB: visceral Leishmaniasis (high efficacy)
  • Also cryptococcal meningitis, severe fungal
  • Renal toxicity (less with liposomal)
226.1.0.3.2.6 Miltefosine
  • Alkylphosphocholine
  • Visceral + cutaneous Leishmaniasis (oral)
  • Free-living amebae (Acanthamoeba, Balamuthia, Naegleria)
  • Teratogenic — pregnancy contraindicated
226.1.0.3.2.7 Paromomycin
  • Aminoglycoside, oral non-absorbed
  • Active: Cryptosporidium (mild), Entamoeba (luminal), tapeworms, visceral Leishmaniasis (IV)
  • Aminoglycoside side effects
226.1.0.3.2.8 TMP-SMX
  • Folate antagonist
  • Active: PJP, Toxoplasma (alternative), Cyclospora, Cystoisospora (Isospora)
226.1.0.3.2.9 Sulfadiazine + Pyrimethamine
  • Folate antagonist combination
  • Toxoplasmosis first-line
    • Leucovorin to prevent bone marrow toxicity
226.1.0.3.3 Anti-Helminthics
226.1.0.3.3.1 Albendazole + Mebendazole
  • Benzimidazoles
  • Inhibit tubulin polymerization → parasite microtubule failure
  • Active: nematodes (Ascaris, hookworm, Trichuris, Strongyloides), Echinococcus, neurocysticercosis
  • Albendazole > mebendazole (better absorption)
  • Side effects: GI, transaminitis, marrow suppression (long course)
  • Pregnancy 1st trimester avoid
226.1.0.3.3.2 Ivermectin
  • Glutamate-gated chloride channel opener in parasite → paralysis
  • Active: Strongyloides, Onchocerca, Filariasis, scabies, lice, broad
  • Doesn’t kill ova (need rescue therapy after 2 wk)
  • Used in mass drug administration (MDA) for filariasis + onchocerciasis
  • 200-400 µg/kg single dose; repeat in 2 wk for some
  • Safe but loa loa caution (encephalopathy in high microfilariae loads)
226.1.0.3.3.3 Praziquantel
  • Increases parasite membrane Ca++ permeability → muscle contraction + paralysis
  • Active: Schistosoma, most trematodes (Clonorchis, Fasciolopsis, Paragonimus), Taenia adult, cysticercosis
  • Single or short course
  • Safe; mild side effects (GI, headache)
226.1.0.3.3.4 Niclosamide
  • Inhibits parasite ATP production
  • Active: adult tapeworms (Taenia, Hymenolepis)
  • Single dose; not for tissue cysts
226.1.0.3.3.5 Triclabendazole
  • Active: Fasciola hepatica, Paragonimus
  • Single or short course
226.1.0.3.3.6 Diethylcarbamazine (DEC)
  • Active: Filariasis (Loa loa, Wuchereria, Brugia, Onchocerca)
  • Caution: severe reactions in high microfilariae load (especially Loa loa) — encephalopathy, eosinophilia
  • Pre-treatment screening
  • Albendazole + ivermectin combination for MDA
226.1.0.3.3.7 Pyrantel Pamoate
  • Neuromuscular block
  • Active: pinworm, hookworm, Ascaris
  • OTC in some
  • Single dose

226.1.0.4 3⃣ Mass Drug Administration (MDA) Programs

226.1.0.4.1 Lymphatic Filariasis
  • WHO Global Program to Eliminate LF
  • Albendazole + ivermectin OR diethylcarbamazine
  • Annual treatment of entire endemic communities
226.1.0.4.2 Onchocerciasis
  • Ivermectin annual (Mectizan Donation Program — Merck)
  • Africa primarily
226.1.0.4.3 Soil-Transmitted Helminths (STH)
  • Albendazole / mebendazole annual / biannual mass deworming
  • WHO targeted school-age children
  • 800 million pediatric doses/yr

226.1.0.4.4 Schistosomiasis
  • Praziquantel annual
  • School-age + at-risk adults

226.1.0.5 4⃣ Special Considerations

226.1.0.5.1 Pregnancy
  • Avoid most antiparasitics 1st trimester:
    • Albendazole, mebendazole (avoid)
    • Metronidazole (1st trim avoid; 2nd-3rd OK)
    • Praziquantel (safety reasonable)
    • Atovaquone-proguanil (limited data)
    • Chloroquine (safe)
    • Primaquine, tafenoquine (G6PD + pregnancy contraindicated)
  • Travel pregnancy: counseling + alternative options
226.1.0.5.2 Immunocompromise
  • More severe disease
  • Strongyloides hyperinfection — IDU/immunosuppressed at risk
  • Toxoplasma reactivation (HIV CD4 < 100)
  • Cryptosporidium chronic
  • Microsporidia chronic
  • Leishmaniasis VL severe + relapsing in HIV+
226.1.0.5.3 Pediatric
  • Weight-based dosing
  • Some restrictions (albendazole < 1 yr varies)
  • Mass deworming for school-age