40% (90% (500 BC)

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Gloria Ford
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1 MALARIA causative agent = Plasmodium species 40% of world s population lives in endemic areas million clinical cases per year 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 Pf Pv/Po Pm Prepatent Period 6-9 d 8-12d 15-18d Incubation Period 6-25 d 8-27d 16d-8w

4 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

5 cold stage feeling of intense cold vigorous shivering, rigor lasts 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

9 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

10 Karunaweera et al (1992) PNAS 89:3200 rigor sweating TNF = tumor necrosis factor-α (!) proinflammatory cytokine (produced in response to malarial antigens?)

11 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

12 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

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

14 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

15 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-

16 Roper et al (1996) AJTMH 54:325 Date % Incidence Tested (smear/pcr)* Sep 93 13% (2/8) } Jan 94 19% (4/11) Apr 94 24% (8/11) } Jun 94 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/µl (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,

17 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)

18 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

Anti-Malaria Chemotherapy

Anti-Malaria Chemotherapy Causal Prophylaxis prevent infection (ie, liver stage) Suppressive Prophylaxis prevent clinical disease (ie, blood stages) Treatment Therapy (or clinical cure) relieve symptoms