Protozoal Infections

 

• Background

  • Protozoa are unicellular, eukaryotic, parasites.
  • Many primarily affect the GI tract – giardiasis, amebiasis, cryptosporidiosis, and cyclosporiasis – while others can cause systemic disease – trypanosomiasis, toxoplasmosis, leishmaniasis, and babesiosis.
  • Globally, the biggest protozoal disease burden comes from malaria, covered separately.

• Giardiasis

  Pathogen and epidemiology

  • Small bowel infection with the flagellated protozoa Giardia lamblia.
  • Faecal-oral transmission, 1-14 days incubation.
  • Occurs worldwide. Commonest cause of gastroenteritis in returning travellers to UK, but most UK cases are acquired domestically.
  • Commonest age <5.

  Presentation

  • Diarrhoea, often leading to weight loss.
  • Abdominal pain and bloating.
  • Eggy burps.
  • Can run chronic and/or relapsing course.
  • Post-infectious lactase deficiency.

  Diagnosis

  Stool studies: cysts on microscopy (↓sensitivity), ELISA, PCR.

  Management

  Metronidazole PO 5 days or tinidazole PO single-dose.

• Cryptosporidiosis

  Pathogen and epidemiology

  • Small bowel infection with the coccidian protozoa Cryptosporidium parvum or C. hominis.
  • Faecal-oral transmission. Often due to faecal contamination of drinking or recreational water, leading to large outbreaks.
  • Humans and animals are reservoirs.
  • 2-10 days incubation.
  • Occurs worldwide.

  Presentation

  • Watery diarrhoea and abdominal cramping, lasting 1-2 weeks.
  • Chronic, severe diarrhoea in HIV patients.

  Diagnosis

  Stool studies: microscopy with acid-fast staining (for oocytes), ELISA, PCR.

  Management

  • Self-limiting illness for most.
  • Nitazoxanide PO is licensed in some countries and shortens symptom duration.
  • Ensure HIV patients or on ART. Limited evidence for nitazoxanide in this group.

• Cyclosporiasis

  Pathogen and epidemiology

  • Small bowel infection with the coccidian protozoa Cyclospora cayetanensis.
  • Faecal-oral transmission, 2-10 days incubation.
  • Mainly tropical and sub-tropical areas, but outbreaks can occur in other countries from imported fruits and salads.

  Presentation

  • Watery diarrhoea and abdominal cramping.
  • May last several weeks, or even longer, especially if immunosuppressed.

  Diagnosis

  Stool studies: microscopy with acid-fast staining for oocytes, or PCR.

  Management

  Co-trimoxazole PO.

• Amoebiasis

  Pathogen and epidemiology

  • Infection with the protozoa Entamoeba histolytica.
  • Faecal-oral transmission.
  • Incubation 2-6 months, sometimes longer.
  • Found worldwide, but commonest in developing countries.

  Presentations

  • GI infection: from mild diarrhoea to amoebic dysentery (bloody diarrhoea).
  • Amoebic liver abscess: fever, jaundice, RUQ pain, hepatomegaly.

  Investigations

  • Bloods: ↑neutrophils, ↑CRP, deranged LFTs (esp. ↑alk phos).
  • Imaging: abdo US can usually visualise liver abscesses. CXR may show raised right hemidiaphragm.
  • Serology for antibodies after 5 days.
  • Stool studies: microscopy for trophozoites, ELISA, or PCR.

  Management

  Metronidazole PO.

• African trypanosomiasis

  Aka sleeping sickness.

  Pathogen and epidemiology

  • Infection with the flagellated protozoa Trypanosoma brucei.
  • Transmitted by the tsetse fly, which bites during daylight hours.
  • Humans are the main reservoir, but it is also found in animals.
  • T. brucei gambiense is found mainly in central Africa and parts of West Africa, while T. brucei rhodesiense is found in East and Southeast Africa.

  Presentation

  Early stage (haemolymphatic):

  • Flu-like: fever, myalgia, headache, lymphadenopathy.
  • May have itchy rash or large chancre at bite site.
  • T. b. rhodesiense is rapid: 1-2 week incubation, then progression to second stage within weeks.
  • T. b. gambiense: incubation can be several months, and progression to second stage takes 1-2 years.

  Late stage (CNS invasion):

  • Daytime somnolence, disturbed nocturnal sleep, personality changes, confusion.
  • Progression to coma and death, within months (T. b. rhodesiense) or years (T. b. gambiense).

  Diagnosis

  • Microscopy showing trypanosomes: blood film for T. b. rhodesiense, aspirate of cervical lymph node (if present) for T. b. gambiense.
  • CSF microscopy for all to assess for CNS invasion.

  Management

  Antitrypanosomal IV:

  • T. b. gambiense: pentamidine if early, eflornithine plus nifurtimox if late. Fexinidazole is a new PO alternative if late.
  • T. b. rhodesiense: suramin if early, melarsoprol if late.

• American trypanosomiasis

  Aka Chagas disease.

  Pathogen and epidemiology

  • Infection with the flagellated protozoa Trypanosoma cruzi.
  • Transmitted by the haematophagous insect triatomine ('kissing bug'), which emerges at night, tends to bite the face, then defecates. Protozoa in the faeces then enter through broken skin or mucous membranes. Vertical transmission also possible.
  • Humans and domestic and wild mammals are reservoirs.
  • Found throughout Latin America.

  Presentation

  Acute phase:

  • Usually asymptomatic, or a non-specific, mild febrile illness.
  • 1-2 weeks incubation, 1-3 months duration.
  • Rare: swelling at bite site, 'chagoma', which is known as Romaña's sign if on eyelid.
  • Very rare: myocarditis, meningoencephalitis.

  Chronic phase:

  • Indeterminate (latent) form: asymptomatic but +ve serology. Only 25% of these progress, after many years, to a definitive clinical form.
  • Chronic chagas cardiomyopathy (CCC): biventricular heart failure or, less commonly, symptomatic arrhythmias (anything from palpitations to sudden cardiac death) or stroke (due to mural thrombi).
  • GI disease (less common): dilation of oesophagus or colon, causing dysphagia and constipation.

  Investigations

  Acute phase:

  • Blood film: T. cruzi trypomastigotes.
  • In myocarditis, ST-T changes or conduction defects on ECG, pericardial effusion on echo.

  Indeterminate phase:

  • Serology (IgG).
  • ECG with 30s rhythm strip to screen for cardiac problems.
  • Consider echo: may have clinically silent changes (e.g. apical aneurysm) but no LVSD.

  Chronic disease:

  • Serology (IgG).
  • ECG: conduction defects (commonly RBBB or LAFB), ST-T changes, almost any atrial or ventricular arrhythmia.
  • Echo: dilated cardiomyopathy, mitral and tricuspid regurg, systolic dysfunction.
  • GI: dilation on barium studies, including achalasia, megaoesophagus, or megacolon.

  Management

  Antitrypanosomal PO:

  • Benznidazole (2 months) or nifurtimox (3 months).
  • Indicated in acute phase, indeterminate phase (if age <50), but no benefit in established cardiac or GI disease (though some centres use it in early stages).

  Chronic disease:

  • CCC: usual HF treatment, including transplant, PPM, or ICD in some.
  • GI: nifedipine for oesophageal disease, laxatives for colonic disease. Surgical repair (e.g. Heller's myotomy for achalasia) or resection may be needed in severe cases.

• Leishmaniasis

  Pathogen and epidemiology

  • Infection with protozoa of the genus Leishmania.
  • Transmitted by sandflies, usually nocturnal. Bite may be painful or painless. Rodents and dogs are common reservoirs.
  • Old World leishmaniasis (Asia, Middle East, Mediterranean, Africa) species include L. donovani, L. infantum, L. tropica, L. major, and L. aethiopica.
  • New World leishmaniasis (Latin America) species include L. mexicana and the L. Viannia subgenus.

  Presentation

  Cutaneous leishmaniasis (CL):

  • Commonest form.
  • Skin lesion appears weeks or months post exposure, and can persist for years, followed by atrophic scar.
  • Initially papule, then plaque, then ulcer with elevated border and central depression. Painful or painless.
  • Individuals may acquire ≥1 primary lesion, as well as satellite lesions, lymphadenopathy, and nodular lymphangitis (subcutaneous nodules).

  Mucosal leishmaniasis (ML):

  • Complication of L. Viannia CL, due to spread from skin to naso-oropharyngeal mucosa.
  • May cause nasal symptoms (e.g. epistaxis) or, if untreated, septal perforation.

  Visceral leishmaniasis (VL), aka kala-azar:

  • Insidious onset fever, weight loss, splenomegaly (± hepatomegaly), and pancytopaenia (from bone marrow invasion).
  • Usually fatal if untreated.
  • Incubation typically months but can be years.
  • Usually due to L. donovani or L. infantum.

  Investigations

  • Diagnosis: microscopy and PCR of skin scraping/biopsy or bone marrow biopsy. Serology can support VL diagnosis.
  • Bloods in VL: pancytopaenia, ↑protein, ↓albumin, hypergammaglobulinemia.

  Management

  • Miltefosine PO, liposomal amphotericin B IV (esp. for VL), or pentavalent antimony IV (sodium stibogluconate or meglumine antimoniate).
  • Uncomplicated CL (1-2 small lesions, no ML risk) can be managed conservatively or with local therapy (intralesional pentavelent antimony and/or cryotherapy).

• Toxoplasmosis

  Pathogen and epidemiology

  • Infection with the protozoa Toxoplasma gondii.
  • T. gondii lifecycle takes place in cats, with oocytes shed in faeces. Human infection results from ingestion of oocytes (e.g. soil or water contaminated with cat faeces), ingestion of tissue cysts in undercooked meat, or vertically.
  • Occurs worldwide. >10% of UK population, and perhaps much more, infected at some point.

  Presentation

  Asymptomatic in most, otherwise:

  • Acute mononucleosis/flu-like illness: non-tender cervical lymphadenopathy (commonest sign), fever, myalgia, sore throat, rash, hepatosplenomegaly. Occurs 5-20 days post-exposure.
  • Ocular disease: chorioretinitis (a posterior uveitis) causing floaters or visual loss.
  • Encephalitis can occur in the immunosuppressed e.g. HIV.
  • Congenital infection is usually asymptomatic, but can cause chorioretinitis, CNS disease (hydrocephalus, calcifications), and mononucleosis-like symptoms.

  Diagnosis

  • Serology: IgM +ve in 1 week, IgG +ve in 2 weeks.
  • Ocular disease: ophthalmoscopy showing iritis, vitritis, and chorioretinitis (white retinal lesions).
  • Encephalitis: ring-enhancing lesions on MRI. CSF PCR sensitivity is variable, so +ve serology is sufficient.

  Management

  • Acute infection usually does not require treatment.
  • Ocular or CNS disease: pyrimethamine plus sulfadiazine, plus leucovorin to prevent sulfadiazine bone marrow toxicity, all PO for 6 weeks.

• Babesiosis

  Pathogen and epidemiology

  • Infection with protozoa of the genus Babesia, which – like malaria – invade RBCs ('intraerythrocytic').
  • Transmitted by ticks of the genus Ixodes from various mammalian reservoirs.
  • Northeast US: B. microti (from mice), via I. scapularis (which usually live on uninfected deer).
  • Europe: B. divergens or B. bovis (from cows or small mammals), via I. ricinus. Rare and limited to the immunosuppressed, esp. asplenic.

  Presentation

  Usually asymptomatic, otherwise:

  • Flu-like: malaise, lethargy, fevers and chills (co-incident with ↑parasitaemia), myalgia.
  • Complications include severe intravascular haemolysis (with haemoglobinuria and jaundice), AKI, shock, splenic rupture, and death.
  • Incubation weeks to months, with bite rarely recalled.

  Investigations

  • FBC: ↓Hb (haemolytic anaemia), ↓PLT.
  • Diagnosis: blood film.

  Management

  2 options:

  • Atovaquone plus azithromycin.
  • Clindamycin plus quinine. 1st line if severely ill.