Post on 15-Mar-2016
description
Blood and Tissue Protozoa
Mark F. WiserDepartment of Tropical Medicine
School of Public Health
Protozoa of Blood and TissuesOrganism Vector
Trypanosoma gambiense and T. rhodesiense
Tse-tse fly
Trypansosma cruzi Triatomine bugs
Leishmania Sand flies
Plasmodium Mosquitoes
Babesia Ticks
Toxoplasma gondii -
Disease Causing Kinetoplastids
Kinetoplast
Nucleus
•African trypanosomes• sleeping sickness
•Trypanosoma cruzi• Chagas’ disease• S. and Central America
•Leishmania species• leishmaniasis• focal distribution worldwide
KT = mitochondrial DNA
Comparison of African Trypanosomes T. rhodesiense T. gambiense tse-tse vector Glossina morsitans Glossina palpalis
ecology dry bush or woodland
rainforest, riverine, lakes
transmission cycle ungulate-fly-human animal-fly-human,
human-fly-human non-human reservoir wild animals domestic animals
epidemiology sporadic, safaris endemic, some epidemics
disease progression rapid, often fatal slow (~1 yr) acute
chronic parasitemia high low asymptomatic carriers rare common
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
Diagnosis and TreatmentClinical 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
Late StageCNS involvement• melarsoprol• eflornithine (resurrection
drug)
Early StageNo CNS involvement• suramin• pentamidine• excellent prognosis
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
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
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
Clinical Spectrum of LeishmaniasisCutaneous 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
Some Leishmania Species Infecting Humans New World Cutaneous, Mucocutaneous, and
Diffuse Leishmaniasis
Old World Cutaneous, Recidivans, and
Diffuse Leishmaniasis
Visceral
Leishmaniasis Mexicana Complex
L. mexicana L. amazonensis
Braziliensis Complex
L. braziliensis L. panamensis L. guyanensis
L. tropica
L. major
L. aethiopica
L. infantum*
L. donovani (old world)
L. infantum* (Mediterranea)
L. chagasi** (Americas)
*Both dermotrophic and viscerotrophic strains exist. **L. chagasi (Americas) may be the same as L. infantum (Mediteranean)
Diagnosis
• pentavalent antimonials• amphotericin B (less toxic, expensive) • miltefosine (phase IV, no hospitalization)
• geographical presence of parasite• demonstration of parasite in skin
lesion or bone marrow• delayed hypersensitivity skin test
(cutaneous forms)• serological tests (visceral disease)
Treatment
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. falciparumP. vivaxP. ovaleP. malariae
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
Life Cycle• merozoites invade RBCs• repeated rounds of
asexual replication• 6-30 merozoites formed
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
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
• 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
Malaria Paroxysm
Disease Severity Pv Po Pm Pf Paroxysm Severity
moderate to severe mild mild to
moderate severe
Average (per mm3) 20,000 9,000 6,000 50,000-
500,000 Maximum (per mm3) 50,000 30,000 20,000 2,500,000
Anemia ++ + ++ ++++ Duration
Disease Infection
3-8 w 5-8 y*
2-3 w 12-20 m*
3-24 w >20 y
2-3 w 6-17 m
Complications renal cerebral** *true relapses ( recrudescence) due to dormant hypnozoite stage in liver **plus many other organs
P. falciparum expresses ‘knobs’ on the surface of infected erythrocytes. Knobs mediate cytoadherence to endothelial cells.
• 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%
Falciparum Complications
PossiblePathophysiology
cytoadherence
cerebral ischemia
hypoxia, metabolic effects,
cytokines (eg, TNF-)
coma
death
Severe falciparum malaria• potentially high parasitemias• sequestration• complex (and not fully understood)
host-parasite interactions
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
Drug Class Examples
Fast-acting blood schizontocide
choloroquine (+ other 4-aminoquinolines), quinine, quinidine, mefloquine, antifolates (pyrimethamine, proquanil, sulfadoxine, dapsone), artemisinin derivatives (quinhaosu)
Slow-acting blood schizontocide doxycycline (other tetracycline antibiotics)
Blood + mild tissue schizontocide proquanil, pyrimethamine, tetracyclines
Anti-relapsing primaquine Gametocidal primaquine, 4-aminoquinolines (limited?)
Combinations Fansidar (pyrimethamine + sulfadoxine), Maloprim (pyrimethamine + dapsone), Malarone (atovaquone + proquanil)
Selected Anti-Malarials
Treatment Strategieschloroquine 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)