Beruflich Dokumente
Kultur Dokumente
Wiser
Department of Tropical Medicine
School of Public Health
Organism Vector
Trypanosoma gambiense Tse-tse fly
and T. rhodesiense
Trypansosma cruzi Triatomine bugs
Leishmania Sand flies
Plasmodium Mosquitoes
Babesia Ticks
Toxoplasma gondii -
Disease Causing Kinetoplastids
• African trypanosomes
• sleeping sickness
Kinetoplast • Trypanosoma cruzi
• Chagas’ disease
• S. and Central America
• Leishmania species
Nucleus • leishmaniasis
• focal distribution worldwide
KT = mitochondrial DNA
Comparison of African Trypanosomes
T. rhodesiense T. gambiense
tse-tse vector Glossina morsitans Glossina palpalis
dry bush or rainforest, riverine,
ecology
woodland lakes
transmission animal-fly-human,
ungulate-fly-human
cycle human-fly-human
non-human
wild animals domestic animals
reservoir
endemic, some
epidemiology sporadic, safaris
epidemics
disease slow (~1 yr) acute
rapid, often fatal
progression chronic
parasitemia high low
asymptomatic
rare common
carriers
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 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
Treatment
• pentavalent antimonials
• amphotericin B (less toxic, expensive)
• miltefosine (phase IV, no hospitalization)
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 P. falciparum
• drug resistance ( mortality) P. vivax
P. ovale
P. 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
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
Disease Severity
Pv Po Pm Pf
Paroxysm moderate mild to
mild severe
Severity to severe moderate
Average 50,000-
20,000 9,000 6,000
(per mm3) 500,000
Maximum
50,000 30,000 20,000 2,500,000
(per mm3)
Anemia ++ + ++ ++++
Duration
Disease 3-8 w 2-3 w 3-24 w 2-3 w
Infection 5-8 y* 12-20 m* >20 y 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.
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%
Possible
Pathophysiology
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
Selected Anti-Malarials
Drug Class Examples
choloroquine (+ other 4-aminoquinolines),
quinine, quinidine, mefloquine, antifolates
Fast-acting blood
(pyrimethamine, proquanil, sulfadoxine,
schizontocide dapsone), artemisinin derivatives
(quinhaosu)
Slow-acting blood
doxycycline (other tetracycline antibiotics)
schizontocide
Blood + mild tissue
proquanil, pyrimethamine, tetracyclines
schizontocide
Anti-relapsing primaquine
Gametocidal primaquine, 4-aminoquinolines (limited?)
Fansidar (pyrimethamine + sulfadoxine),
Combinations Maloprim (pyrimethamine + dapsone),
Malarone (atovaquone + proquanil)
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)