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MALARIA

causative agent = Plasmodium species


40% of worlds population lives in
endemic areas
3-500 million clinical cases per year
1.5-2.7 million deaths (90% Africa)
known since antiquity

early medical writings from India and China


Hippocrates usually credited (500 BC)
Laveran identified parasite (1880)
Ross demonstrated mosquito transmission
(1898)
Garnham described liver stage (1940s)

Clinical Features
characterized by acute febrile attacks
(malaria paroxysms)
periodic episodes of fever alternating with
symptom-free periods

manifestations and severity depend on


parasite species and host status
immunity, general health, nutritional state,
genetics

recrudescences or relapses can occur


over months or years
can develop severe complications
(especially P. falciparum)

Malaria Transmission
natural (sporozoites/Anopheles)
blood transfusions
shorter incubation period
fatality risk (P. falciparum)
no relapses possible (vivax/ovale)

syringe sharing
congenital
relatively rare although placenta is
heavily infected

Prodromal Symptoms
end of incubation period
2-3 days before 1st paroxysm
includes: malaise, fatigue, lassitude,
headache, muscle pain, nausea, anorexia
(i.e., flu-like symptoms)
can range from none to mild to severe

Febrile Attack (Malaria Paroxysm)


periodic febrile episodes alternating with
symptom-free periods
initially fever may be irregular before
developing periodicity
may be accompanied by splenomegaly,
hepatomegaly (slight jaundice), anemia

cold stage
feeling of intense cold
vigorous shivering, rigor
lasts 15-60 min

hot stage

intense heat
dry burning skin
throbbing headache
lasts 2-6 hours

sweating stage

profuse sweating
declining temperature
exhausted, weak sleep
lasts 2-4 hours

Malaria Paroxysm
paroxysms associated
with synchrony of
merozoite release
between paroxysms
temperature is normal
and patient feels well
falciparum may not exhibit classic paroxysms
continuous fever
24 hr periodicity
tertian malaria
quartan malaria

Karunaweera et al (1992) PNAS 89:3200

sweating
rigor

TNF = tumor necrosis factor- ( )


proinflammatory cytokine (produced
in response to malarial antigens?)

Other Features of the Paroxysms


may be accompanied by splenomegaly, hepatomegaly (slight
jaundice), hemolytic anemia
P. falciparum can be lethal in nonimmune (eg., children, expatriates)
paroxysms become less severe and
irregular as infection progresses
semi-immune may exhibit little (1-2
days fever) or no symptoms

Immunity
slow to develop
short lived
premunition
non-sterilizing
lower parasitemia
less symptoms

Anti-Parasite Immunity
immune response prevents
merozoite invasion, eliminates
infected erythrocytes, etc.
Anti-Disease Immunity
eg., neutralization of exoantigens or toxic effects

Distribution of Malaria

tropical and subtropical climates


formerly widespread in
temperate zones (ague)
40% of worlds population live in
endemic regions

Distribution of Malarial Parasites


P. vivax
most widespread, found in most endemic
areas including some temperate zones

P. falciparum
primarily tropics and subtropics

P. malariae
similar range as P. falciparum, but less
common and patchy distribution

P. ovale
occurs primarily in tropical west Africa

Malaria Epidemiology
Stable or Endemic Malaria
~constant incidence over several
years

Endemicity
Levels:
includes seasonal transmission
holo immunity and disease tolerance
hypercorrelates with level of endemicity
meso(especially adults)
hypo-

Unstable or Epidemic Malaria


periodic sharp increase in malaria
little immunity
high morbidity and mortality

Roper et al (1996) AJTMH 54:325


Date
Tested
Sep 93
Jan 94
Apr 94
Jun 94

% Incidence
(smear/PCR)*
13% (2/8)
19% (4/11)
24% (8/11)
19% (0/14)

} 33% reported
symptoms
} no symptomatic
cases

*Number of individuals testing positive by blood smear


and PCR. PCR assay detects ~2.5 parasites/ l (4-10X
more sensitive than thick smears).

eastern Sudan (mesoendemic, seasonal)


rainy season June-Sept.
peak symptomatic malaria Oct.-Nov.
followed cohort of 79 individuals using
thick films and PCR (P. falciparum)

Mosquito
Transmission
susceptibility of
anopheline species
feeding habits
density
longevity
climatic factors
temperature, humidity,
rainfall, wind, etc

Anopheles

"Everything about malaria is so


moulded by local conditions
that it becomes a thousand
epidemiological puzzles."
Hackett (1937)

Malaria Control
Reduce Human-Mosquito Contact
impregnated bed nets
repellants, protective clothing
screens, house spraying

Reduce Vector
environmental modification
larvacides/insecticides
biological control

Reduce Parasite Reservoir


diagnosis and treatment
chemoprophylaxis