Transcript No Slide Title

MALARIA
• causative agent = Plasmodium species
• 40% of world’s population lives in
endemic areas
• 3-500 million clinical cases per year
• 1.5-2.7 million deaths (90% Africa)
• known since antiquity
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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 (1940’s)
Clinical Features
• 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
• 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
Prepatent Period
Incubation Period
Pf
Pv/Po
Pm
6-9 d
6-25 d
8-12d
8-27d
15-18d
16d-8w
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
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intense heat
dry burning skin
throbbing headache
lasts 2-6 hours
sweating stage
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profuse sweating
declining temperature
exhausted, weak  sleep
lasts 2-4 hours
Malaria Paroxysm
• paroxysms associated
with synchrony of
merozoite release
• temperature is normal
and patient feels well
between paroxysms
• 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-a ()
• 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
Current 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)
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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 modificaton
• larvacides/insecticides
• biological control
Reduce Parasite Reservoir
• diagnosis and treatment
• chemoprophylaxis