malaria
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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
• 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)
•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
Malaria Transmission
Pf Pv/Po PmPrepatent Period 6-9 d 8-12d 15-18dIncubation Period 6-25 d 8-27d 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• intense heat• dry burning skin• throbbing headache• lasts 2-6 hours
sweating stage• profuse sweating• declining temperature• exhausted, weak sleep• lasts 2-4 hours
• paroxysms associated with synchrony of merozoite release
• temperature is normal and patient feels well between paroxysms
• falciparum may not exhi-bit classic paroxysms• continuous fever• 24 hr periodicity
Malaria Paroxysm
tertian malariaquartan malaria
Karunaweera et al (1992) PNAS 89:3200
• TNF = tumor necrosis factor- ()• proinflammatory cytokine (produced
in response to malarial antigens?)
rigor
sweating
•may be accompanied by spleno-megaly, hepatomegaly (slight jaundice), hemolytic anemia
•P. falciparum can be lethal in non-immune (eg., children, expatriates)
•paroxysms become less severe and irregular as infection progresses
•semi-immune may exhibit little (1-2 days fever) or no symptoms
Other Features of the Paroxysms
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 exo-
antigens 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
P. vivaxmost widespread, found in most endemic areas including some temperate zones
P. falciparumprimarily tropics and subtropics
P. malariaesimilar range as P. falciparum, but less common and patchy distribution
P. ovaleoccurs primarily in tropical west Africa
Distribution of Malarial Parasites
Stable or Endemic Malaria
• ~constant incidence over several years• includes seasonal transmission
• immunity and disease tolerance correlates with level of endemicity (especially adults)
Unstable or Epidemic Malaria
• periodic sharp increase in malaria• little immunity• high morbidity and mortality
Malaria Epidemiology
EndemicityLevels:• holo-• hyper-• meso-• hypo-
DateTested
% Incidence(smear/PCR)*
Sep 93 13% (2/8)Jan 94 19% (4/11) } 33% reported
symptomsApr 94 24% (8/11)Jun 94 19% (0/14) } no symptomatic
cases*Number of individuals testing positive by blood smearand PCR. PCR assay detects ~2.5 parasites/l (4-10Xmore sensitive than thick smears).
Roper et al (1996) AJTMH 54:325
• 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)
• susceptibility of anopheline species
• feeding habits• density• longevity• climatic factors
• temperature, humidity, rainfall, wind, etc
Mosquito Transmission
Anopheles
"Everything about malaria is so moulded by local conditions that it becomes a thousand epidemiological puzzles."
Hackett (1937)
Malaria ControlReduce 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
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