Blood and Tissue Protozoa

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Blood and Tissue Protozoa

• Mark F. Wiser
• Department of Tropical Medicine
• School of Public Health

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Protozoa of Blood and Tissues
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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
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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

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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)

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Trypanosoma cruzi and 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

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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

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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

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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
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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)

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MALARIA

• causative agent Plasmodium species
• 4 human Plasmodium species
• 40 of the worlds 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
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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

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Life Cycle

• merozoites invade RBCs
• repeated rounds of asexual replication
• 6-30 merozoites formed

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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

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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

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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

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

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Possible Pathophysiology
cytoadherence ? cerebral ischemia ? hypoxia,
metabolic effects, cytokines (eg,
TNF-?) ? coma ? death
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• Severe falciparum malaria
• potentially high parasitemias
• sequestration
• complex (and not fully understood) host-parasite
  interactions

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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

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Selected Anti-Malarials
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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)