protozoan infection of the lung

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PARASITIC LUNG DISEASES : PROTOZOANS By Dr. Mahmoud Alsalahy Assist prof of Chest Medicine Banha University, Egypt

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PROTOZOAL INFECTIONS: Amoebiasis Malaria Toxoplasmosis HELMINTHIC INFESTATION: Nematode Infections: Intestinal 1. Ascaris 2. Ankylostoma 3. Strongyloides Tissue-Dwelling Nematodes: 1. Lymphatic filariasis 2. Dirofilariasis 3. Trichinosis 4. Viceral larva migrans Cestodes : Echinococcosis Trematodes : 1- Paragonimiasis 2- Scistosomiasis

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AMOEBIASIS: Causative agent: Entamoeba histolytica 40 to 50 million cases of amoebiasis occur each year with 40,000 to 100,000 deaths Common in developing countries: 21% have cysts Cause dysentery and liver abscess Risk for infection: Poor hygiene Crowded population Mentally retarded Homosexuals Malnutrition Alcohol ↑ risk of liver abscess ASD ↑ risk of lung disease

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Transmission and life cycle: Is by fecal oral root: contaminated food or water Cockroaches act as reservoirs Cyst Trophozoite

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Pathogenesis: Trophozoite attach to mucosa by a lectin bond Induces mucosal cell apoptosis Ulcers develop with surrounding inflammation Organism pass through blood to the liver Adaptation occur within the liver, then lyses liver cells with development of liver abscess (need 5 months) Previous amebic liver disease give some protection

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Clinical pictures: Intestinal disease: In 10% of cyst carriers Very variable from mild diarrhea to severe dysentery Liver disease: In 3-9% of intestinal disease More in males Liver abscess: very bad general conditions, liver ++ & very tender Abscess may rupture (2-7%) in pleura, lung or pericardium Lung disease: 86%: direct extension from the liver, 14% hematogenous, rarely by aspiration In 40% of patients with liver disease Reactive pleurisy( sterile fluid), amebic empyema (49%) Hepatobronchial fistula (47%) Lung abscess (14%) : Rt. LL in 86% , Lt LL. (14%) Lung consolidation (10%)

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Diagnosis: Stool analysis: usually negative Serology: Entamoeba H Abs.: useful in non endemic areas Papanicolau smear from sputum or BAL Amoeba Antigen: > 95% sensitivity PCR : > 70% sensitivity Aspiration: sterile yellowish or anchovy sauce Radiology: Elevated Rt. copula Pleural thickening, pleural effusion Consolidation, lung abscess

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Pap smear showing EH Trophozoite EH light microscopy fresh smear (stool)

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Two liver amoebic abscesses Amoebic empyema with ++ liver

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Treatment: Medical: Active disease: by tissue aoebicides Metronidazole: 500-750mg tds oral or IV/10 days Tinidazole : 2gm/day oral/10 days Omidazole : 500mg tid /10 days Luminal cysts: Paromomycine : 25-35mg/kg divided tds /7 days Diloxanide : 500mg tds /day/10 days Surgical: Aspiration or removal if: Medical treatment fails Abscess is about to rupture Prevention: Sanitation, safe water & food, vaccine

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MALARIA: Causative agent: Plasmodium (vivax, falciparum, ovale, malariae) 200-500 million cases occur , with 1 million deaths each year Most common in Africa and Asia Pacific The 3 rd leading cause of death from infections after HIV &TB P. falciparum is the main cause in Africa while vivax in south America and SE of Asia Malaria is the most common cause of fever in travellers to endemic areas The parasite has a sexual life cycle in female Anopheles mosquito and an asexual one in human body P. vivax and ovale can transform to a hypnozoite in the liver

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releases Sexual stage Asexual stage

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Pathogenesis: P. falciparum is the most serious because: Parasitize large no. of red cells Make red cells sequestrable: - Surface knobs - Cell rigidity Tissue ischemia from micro vessel occlusion → micro infarcts Red cell destruction → release of p. antigen → cytokine release with tissue inflammation In the lung, p. cause severe interstitial edema, but the mechanism of this injury is not understood

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Low power microscopy High power microscopy Scarlet blue stain CD68 immunostaining

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Clinical picture: General: after 2 wks-1 month (up to 1yr) incubation Recurrent fever (tertian or quartan) Drenching sweats Anemia & splenomegaly Hemoglobinuria in severe disease Pulmonary: 99%: mild to moderate disease with cough, small airway disease, impaired diffusion, bronchiolitis obliterans (later) 1%: severe disease with ARDS: most common by falciparum followed by vivax

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Diagnosis: Standard: Giemsa stain of a blood smear: show the parasite in RBCs Repeated/12 hrs for 48-72 hrs if negative Immunodiagnosis: Histidine-rich protein 2: specific to falciparum Plasmodium LDH: for falciparum and vivax Immunodiagnosis is highly sensitive and specific as well as rapid

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Trophozoites Gametocytes EM of trophozoite Ring forms

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Treatment: Vivax & ovale: Chloroquine Adults: 500-800mg/day/3days Children: 10 mg/kg/day/ 3days Followed by primaquine for 2 wks to eradicate parasite from the liver Falciparum: is chloroquine resistant Mefloquine : 750 mg followed by 500 mg 12 hrs later Quinine sulphate : 650 mg/day/3 days + tetracycline Atovaquone-proguanil : 4 tab /day/3days In very severe cases: iv Artesunate , 2.4 mg/kg in 4 doses: 1 st on admission, after 12, 24, 48 hrs Respiratory symptoms: Mild: symptomatic Severe: of ARDS

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Prophylaxis: Insect control measures: Insecticides, insecticide treated cloths, insecticide bed nets Chemoprophylaxis: Mefloquine : 750 mg single dose weekly starting 1 wk before travel and continued for 4 wks Atovaquone-proguanil : 1 tab /day 1-2 day before travel, continued till a wk after return Doxycycline: 100 mg/12 hrs 1 wk before, during travel and for a wk after return Malaria vaccine: Against: circumsporozoite antigen of P.F Still in phase II studies: reduced infection by about 4-60%

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TOXOPLASMOSIS: Causative agent: Toxoplasma gondii Obligate intracellular parasite Definitive host is cats, intermediate host is sheep, pigs, rats, birds Humans are incidental host Infection is very common: 50% of population Before HIV epidemics: Disease in humans was rare and limited to repeated abortions and congenital malformation Infection is by ingestion of cysts: Oocyts in unwashed vegetables & fruits Oocysts directly from cats Tissue cysts in poorly cooked meat Congenital (intra uterine)

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Toxoplasma tachyzoites

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Pathogenesis: Oocyst attach via surface receptors to body cells and eternalize by a parsitophorus vacuole (kinozoite) Induces a T cell reaction and can be killed Has the ability to down regulate this immune reaction and survive as tissue cysts ( Bradizoite ) All body cells can be invaded but nerve cells, muscles and lymph nodes are preferred In the lung , can cause necrotizing pneumonia, nodules, interstitial pneumonitis florid bronchitis and diffuse alveolar damage Disease severity parallels that of immune suppression

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Interstitial pneumonitis Multiple tissue cysts

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Clinical picture: General: Immunocompetent: Immunosuppressed: Cerebral disease: 98%, most common is necrotizing encephalitis Extra cerebral: 2%: ocular, cardiac, pulmonary, septic shock Pulmonary: Immunocompetent: Picture of pneumonia with prominent systemic symptoms Immunosuppressed: Severe pneumonia, can progress to ARDS Transplant from a seropositive donor can cause reactivation disease Asymptomatic Painless lymphadenopathy Mononucleosis like illness

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Diagnosis: Radiology: Non specific: consolidation, nodules, interstitial, effusion,.. Standard: Giemsa stain of sputum smear or BAL show the tachyzoites Eosin- hematoxyline or silver methen -amine stain for tissue biopsy show cysts Immunodiagnosis: Fluorescent Ab. Staining of samples +/- polar staining High blood LDH in a patient with pneumonia is suggestive but not specific PCR: still under evaluation

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IFA IFA with polar reaction

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Treatment: In Immunocompetent: Need no treatment In immunocompromized: Same as cerebral disease 1. Oral pyrimethamine 50 to 100 mg + folinic acid 10 to 25 mg daily, along with oral sulfadiazine , 1 to 1.5 gm every 6 hours 2. Pyrimethamine in the same dose + clindamycin 400-600mg/oral or 600-1200mg iv / 6hrs daily Life long suppressive chemotherapy: In immunocompromized patient Pyrimethamine 25 to 50 mg daily with leucovorin + sulfadiazine 500 to 1000 mg four times daily

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Prophylaxis: Infection control measures: Avoiding contact with infected cat feces Washing hands and kitchen utensils that come into contact with raw meat Washing fruits and vegetables well Cooking all meat thoroughly. Disease prophylaxis in immunosuppressed patients: Patients with CD4 count< 200 + positive serology Trimethoprim- sulfamethoxazole (TMP-SMX) Pyrimethamine or dapsone in supha allergic patients AIDS prevention: combating HIV

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وَلاَ تَقْتُلُواْ أَنفُسَكُمْ إِنَّ اللّهَ كَانَ بِكُمْ رَحِيماً} } ٢٩ : النساء