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MALARIA

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)

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MALARIA

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  1. 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)

  2. 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)

  3. 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

  4. 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

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

  6. hot stage • intense heat • dry burning skin • throbbing headache • lasts 2-6 hours

  7. sweating stage • profuse sweating • declining temperature • exhausted, weak  sleep • lasts 2-4 hours

  8. Malaria Paroxysm • 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 tertian malaria quartan malaria

  9. Karunaweera et al (1992) PNAS 89:3200 sweating rigor • TNF = tumor necrosis factor-a () • proinflammatory cytokine (produced in response to malarial antigens?)

  10. Other Features of the Paroxysms • 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

  11. Anti-Parasite Immunity • immune response prevents merozoite invasion, eliminates infected erythrocytes, etc. • Anti-Disease Immunity • eg., neutralization of exo-antigens or toxic effects • Immunity • slow to develop • short lived • ‘premunition’ • non-sterilizing • lower parasitemia • less symptoms

  12. Current Distribution of Malaria • tropical and subtropical climates • formerly widespread in temperate zones (ague) • 40% of worlds population live in endemic regions

  13. 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

  14. Malaria Epidemiology • 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 • Endemicity • Levels: • holo- • hyper- • meso- • hypo-

  15. 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)

  16. Mosquito Transmission • susceptibility of anopheline species • feeding habits • density • longevity • climatic factors • temperature, humidity, rainfall, wind, etc "Everything about malaria is so moulded by local conditions that it becomes a thousand epidemiological puzzles." Hackett (1937) Anopheles

  17. 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

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