Malaria Harrisons 18th

Question 1

Etiology and pathogenesis

Answer 1

5 species cause nearly all malaria in humans: P. falciparum, P. vivax, P. ovale, P. malariae, P knowlesi (monkey malaria, South East Asia)

1. Female anopheline inoculates sporozoites from salivary glands
2. Sporozoites carried via blood to hepatocytes: asexual reproduction – each sporozoite may produce 10k – 30k merozoites
3. Merozoites discharged into blood – invade RBCs and multiply as trophozoites (sx begin when +- 100 mill parasites in blood; ring forms visible under LM, then differentiate into species specific characteristics)
4. @ end of intraerthrocytic life cycle, parasite is a shizont – it ruptures releasing 6 – 30 merozoites which can each invade RBCs
5. some parasites develop into gametocytes – from zygote in mosquito gut, then sporozoites which migrate to salivary glands
   Disease caused by RBC invasion and destruction; and host’s reaction

Question 2

Epidemiology

Answer 2

Occurs throughout most tropical regions of the world
Occurs in epidemic and endemic forms
Stable transmission (SSA) Unstable transmission
Mortality in children Symptomatic malaria @ all ages
Adults can have immunity (low grade parasitemia) Little protective immunity
Transmission all year round Erratic/seasonal/low-grade transmission

Question 3

Erythrocyte changes in malaria

Answer 3

Parasite consumes intracellular proteins, principally haemoglobin
RBC membrane is altered – it becomes more irregular, more antigenic, less deformable
P Falciparum:
Membrane protuberances appear that mediate attachment to endothelium (= cytoadherence), other infected RBCs (= agglutination) and uninfected RBCs (=forms rosettes)
Consequence is sequestration of infected RBCs in vital organs (particularly brain) – they interfere with microcirculatory flow; develop out of reach of splenic processing/haemofiltratin; parasitaemia may be underestimated

Question 4

Clinical features

Answer 4

Initially non-specific ie like a minor viral illness (malaise, headache, mm aches, abdo discomfort)
Classic paroxysms of regular fevers, chills, rigors uncommon suggest P. vivax/ovale)
Anaemia, splenomegaly, jaundice

Question 5

Severe malaria

Answer 5

Vital-organ dysfunction or >2% of RBCs infected = marked increase in mortality
Features: Cerebral malaria; hypoglycaemia (failed gluconeogenesis, quinine induced hyperinsulinaemia); acidosis (hyperlactataemia, renal failure); noncardiogenic pulmonary oedema; renal impairment (ATN); haematologic abnormalities (anaemia, slight coagulation dysfunction, mild thrombocytopenia); liver dysfunction

Question 6

Diagnosis

Answer 6

Demonstration of parasite: thin and thick stains done; level of parasitaemia determined
Antibody-based rapid diagnostic tests replacing microscopy (expensive, don’t quantify parisitaemia)

Question 7

Treatment

Answer 7

Severe malaria = parenteral treatment
Choice of drug depends on likely sensitivity of infecting parasites
Non-falciparum malaria: chloroquine (except in Indonesia and Papua New Guinea) + primaquine (treats hypnzoites; exclude G6PD deficiency* first)
Falciparum: artemisinin combination treatment (artesunate, artemether, dihydroartemisinin PLUS additional anti-malarial)
*G6PD deficiency: common, X-linked; may protect against P vivax; primaquine can cause severe haemolysis