Blood N Tissue Protozoa 3c4819

m

m

Organism

Vector

Y and Y Y

Tse-tse fly



Sand flies



Mosquitoes



Ticks

Y

-

Triatomine bugs

r x  rican trypanosomes



x sleeping sickness

x Y x agas¶ disease x S. and entral merica



KT = mitoc ondrial DN

x ’ species x leis maniasis x ocal distribution worldwide

Comparison of African Trypanosomes tse-tse vector ecology transmission cycle non-human reservoir epidemiology disease progression parasitemia asymptomatic carriers ë

Y

Y

dry bush or woodland

rainforest, riverine, lakes animal-fly-human, human-fly-human

ungulate-fly-human wild animals

domestic animals

high

endemic, some epidemics slow (~1 yr) acute c chronic low

rare

common

sporadic, safaris rapid, often fatal

r x invasion o blood c aracterized by irregular ever and eadac e (acute stage) x Y can be sel limiting or progressing to a more serious disease (c ronic) x includes invasion o lymp atics and NS

x parasites crossing bloodbrain barrier result in NS involvement and nervous impairment x x x x

described as meningoencep alitis increased apat y and atigue con usion and somnolence motor c anges including tics, slurred speec , incoordination x convulsions, coma, deat

r

linical Features x travel or residence in endemic area x irregular ever and enlarged lymp nodes x be avioral c anges/mental symptoms

Laboratory Diagnosis x serological tests x demonstration o trypanosomes in blood, lymp node aspirates, cerebral spinal luid

Early Stage No NS involvement

Late Stage NS involvement

x suramin x pentamidine x excellent prognosis

x melarsoprol x e lornit ine (resurrection drug)

Š Š

Š

Š

Š

Y





x cute P ase - active in ection (1 mont s) - most are asymptomatic (c ildren most likely to be symptomatic)

x Indeterminate P ase - 100 years o latency - seropositive wit no detectable parasitemia

x ronic P ase - 100% o in ected ex ibit cardiomyopat y - arr yt mias and conduction de ects - congestive eart ailure - t romboembolic p enomenon

’ x ocal distribution t roug out world, especially tropics and subtropics x new world: sout ern Texas to nort ern rgentina x old world: sia,  rica, middle east, Mediterranean

x transmitted by sand lies x new world: ’ x old world: ›

x parasite replicates wit in macrop ages o vertebrate ost x a variety o disease mani estations

’ utaneous Leis maniasis (L) most common form, relatively benign self-healing skin lesions (aka, localized or simple CL)

Mucocutaneous Leis maniasis (ML) simple skin lesions that metastasize to mucosae (especially nose and mouth region)

Visceral Leis maniasis (VL) generalized infection of the reticuloendothelial system, high mortality

m ’ m



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’ ’ m ë

r x geograp ical presence o parasite x demonstration o parasite in skin lesion or bone marrow x delayed ypersensitivity skin test (cutaneous orms) x serological tests (visceral disease)



x pentavalent antimonials x amp otericin B (less toxic, expensive) x milte osine (p ase IV, no ospitalization)

MLI x causative agent = › species x uman › species

x 0% o t e world¶s population lives in endemic areas x primarily tropical and subtropical

x 00 million clinical cases per year x 1..7 million deat s (90%  rica) x increasing problem (reemerging disease) › x resurgence in some areas x drug resistance ( mortality) › › ›

Li e ycle x

 x x

x x ! " x › ›

Li e ycle x #$ x x %!&

Li e ycle x x x

x

x x

linical Features x due to t e blood stage o t e in ection x no symptoms during liver stage (~ incubation period)

x c aracterized by acute ebrile attacks (malaria paroxysms) x periodic episodes o ever alternating wit symptom ree periods

x mani estations and severity depend on species and ost status x x x x

acquired immunity general ealt nutritional state genetics

Malaria Paroxysm x x '()* x " x +! x

x x x

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Falciparum omplications x ›! x x " "

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x

x x x

x x & !0 1

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Severe alciparum malaria x potentially ig parasitemias x sequestration x complex (and not ully understood) ostparasite interactions

m r x symptoms: ever, c ills, eadac e, malaise, etc. x istory o being in endemic area x splenomegaly and anemia as disease progresses x microscopic demonstration o parasite in blood smear (distinguis species) x t ick ilm: more sensitive x t in ilm: species identi ication easier

x repeat smears every 1 ours or ours i negative x antigen detection µdipstick¶ x ParaSig tF, OptiMal, etc

4 !m Drug lass

Examples

wast-acting blood schizontocide

choloroquine (+ other 4-a inoquinolines), quinine, quinidine, efloquine, antifolates (pyri etha ine, proquanil, sulfadoxine, dapsone), arte isinin derivatives (quinhaosu)

Slow-acting blood schizontocide Blood + ild tissue schizontocide Anti-relapsing Ga etocidal Co binations ë

doxycycline (other tetracycline antibiotics) proquanil, pyri etha ine, tetracyclines pri aquine pri aquine, 4-a inoquinolines (li ited?) wansidar (pyri etha ine + sulfadoxine), alopri (pyri etha ine + dapsone), alarone (atovaquone + proquanil)

c loroquine sensitive (all species) x c loroquine x + primaquine (vivax/ovale) c loroquine resistance (or unknown) x Fansidar, me loquine, quinine, artemisinin derivatives severe malaria x i.v. in usion o quinine or quinidine (or , i sensitive) x i.v. artemisinin derivatives (i available)