1. MALARIA causative agent = Plasmodium species
40% of world’s population lives in endemic areas
3-500 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

4. Febrile Attack (Malaria Paroxysm)
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 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 exhi-bit classic paroxysms
continuous fever
24 hr periodicity
tertian malaria
quartan malaria

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

11. 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

12. Immunity Anti-Parasite 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

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 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)

17. 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

18. Malaria Control Reduce Human-Mosquito Contact Reduce Vector
impregnated bed nets
repellants, protective clothing
screens, house spraying
Reduce Vector
environmental modificaton
larvacides/insecticides
biological control
Reduce Parasite Reservoir
diagnosis and treatment
chemoprophylaxis