Blood and Tissue Protozoa

1. Blood and Tissue Protozoa Mark F. Wiser Department of Tropical Medicine School of Public Health

2. Protozoa of Blood and Tissues

3. Disease Causing Kinetoplastids • African trypanosomes • sleeping sickness • Trypanosoma cruzi • Chagas’ disease • S. and Central America • Leishmania species • leishmaniasis • focal distribution worldwide Kinetoplast Nucleus KT = mitochondrial DNA

5. Disease Course and Symptoms • invasion of blood characterized by irregular fever and headache (acute stage) • T. gambiense can be self-limiting or progressing to a more serious disease (chronic) • includes invasion of lymphatics and CNS • parasites crossing blood-brain barrier result in CNS involvement and nervous impairment • described as meningoencephalitis • increased apathy and fatigue • confusion and somnolence • motor changes including tics, slurred speech, incoordination • convulsions, coma, death

6. Diagnosis and Treatment • Clinical Features • travel or residence in endemic area • irregular fever and enlarged lymph nodes • behavioral changes/mental symptoms • Laboratory Diagnosis • serological tests • demonstration of trypanosomes in blood, lymph node aspirates, cerebral spinal fluid • Early Stage • No CNS involvement • suramin • pentamidine • excellent prognosis • Late Stage • CNS involvement • melarsoprol • eflornithine (resurrection drug)

7. Trypanosoma cruziand Chagas Disease • Transmitted by triatomine bugs • Inefficient transmission (parasite in feces of bug) • Associated with infestation of houses with triatomines (rural poverty) • Urban transmission associated with blood transfusions • Leading cause of cardiac disease in S. and central America

8. Clinical Course of Chagas • Acute Phase • active infection (1-4 months) • most are asymptomatic (children most likely to be symptomatic) • Indeterminate Phase • 10-30 years of latency • seropositive with no detectable parasitemia • Chronic Phase • 10-30% of infected exhibit cardiomyopathy • arrhythmias and conduction defects • congestive heart failure • thromboembolic phenomenon

9. Leishmaniasis • focal distribution throughout world, especially tropics and subtropics • new world: southern Texas to northern Argentina • old world: Asia, Africa, middle east, Mediterranean • transmitted by sand flies • new world: Lutzomyia • old world: Phlebotomus • parasite replicates within macrophages of vertebrate host • a variety of disease manifestations

10. Clinical Spectrum of Leishmaniasis • Cutaneous Leishmaniasis (CL) • most common form, relatively benign self-healing skin lesions (aka, localized or simple CL) • Mucocutaneous Leishmaniasis (MCL) • simple skin lesions that metastasize to mucosae (especially nose and mouth region) • Visceral Leishmaniasis (VL) • generalized infection of the reticuloendothelial system, high mortality

12. Diagnosis • geographical presence of parasite • demonstration of parasite in skin lesion or bone marrow • delayed hypersensitivity skin test (cutaneous forms) • serological tests (visceral disease) Treatment • pentavalent antimonials • amphotericin B (less toxic, expensive) • miltefosine (phase IV, no hospitalization)

13. MALARIA • causative agent = Plasmodium species • 4 human Plasmodium species • 40% of the world’s population lives in endemic areas • primarily tropical and sub-tropical • 3-500 million clinical cases per year • 1.5-2.7 million deaths (90% Africa) • increasing problem (re-emerging disease) • resurgence in some areas • drug resistance ( mortality) P. falciparum P. vivax P. ovale P. malariae

14. Life Cycle • transmitted by Anopheles mosquitoes • sporozoites injected with saliva • sporozoites invade liver cells • undergo an asexual replication • 1000-10,000 merozoites produced • hypnozoites and relapses in Pv and Po

15. Life Cycle • merozoites invade RBCs • repeated rounds of asexual replication • 6-30 merozoites formed

16. Life Cycle • some merozoites produce gametocytes • gametocytes infective for mosquito • fusion of gametes in gut • sporogony on outside of gut wall • asexual replication • sporozoites invade salivary glands

17. Clinical Features • due to the blood stage of the infection • no symptoms during liver stage (~ incubation period) • characterized by acute febrile attacks (malaria paroxysms) • periodic episodes of fever alternating with symptom-free periods • manifestations and severity depend on species and host status • acquired immunity • general health • nutritional state • genetics

18. Malaria Paroxysm • paroxysms associated with synchrony of merozoite release • 48 or 72 hr cycles • release of antigens, etc •  TNF- • temperature is normal and patient feels well between paroxysms • falciparum may not exhibit classic paroxysms • continuous fever • paroxysms become less severe and irregular as infection progresses

20. P. falciparum expresses ‘knobs’ on the surface of infected erythrocytes. Knobs mediate cytoadherence to endothelial cells.

21. Falciparum Complications • sequestration of Pf-infected erythrocytes • immune evasion • primarily in brain, heart, lungs, and gut • leads to complications • cerebral malaria • consciousness ranges from stupor to coma • convulsions frequently observed • onset can be gradual or sudden • mortality 30-50%

22. Possible Pathophysiology cytoadherence  cerebral ischemia  hypoxia, metabolic effects, cytokines (eg, TNF-)  coma  death

23. Severe falciparum malaria • potentially high parasitemias • sequestration • complex (and not fully understood) host-parasite interactions

24. Malaria Diagnosis • symptoms: fever, chills, headache, malaise, etc. • history of being in endemic area • splenomegaly and anemia as disease progresses • microscopic demonstration of parasite in blood smear (distinguish species) • thick film: more sensitive • thin film: species identification easier • repeat smears every 12 hours for 48 hours if negative • antigen detection ‘dipstick’ • ParaSight-F, OptiMal, etc

25. Selected Anti-Malarials

26. Treatment Strategies • chloroquine sensitive (all species) • chloroquine • CQ + primaquine (vivax/ovale) • chloroquine resistance (or unknown) • Fansidar, mefloquine, quinine, artemisinin derivatives • severe malaria • i.v. infusion of quinine or quinidine (or CQ, if sensitive) • i.v. artemisinin derivatives (if available)