MALARIA causative agent Plasmodium species

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 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 1 st 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-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

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 • 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