9. malaria

How did the WHO hope to eradicate malaria? Why did that effort
fail?

DDT (dichlorodiphenyltrichloroethane) was used to control mosquito vector until they developed resistance to it

it was banned in the US for being toxic

How prevalent is malaria worldwide? What continent and age group is most affected?

250 million cases per year

95% of cases occur in Africa

80% of cases in children under 5 years old

What causes malaria?: P. falciparum

1 of 4 Plasmodium species

causes 98% of cases of malaria

malaria is transmitted by

Anopheles mosquito

Three stages of malaria

first flu like symptoms for weeks then:

1. Cold phase

2. Hot phase

3. Wet phase

CYCLE REPEATS

Three stages of malaria: Cold phase

abrupt onset of shaking chills, for 1 hour

Three stages of malaria: Hot phase

temperature rises to 104°F (40 °C), several hours

Three stages of malaria: Wet phase

temperature falls and get a drenching sweat

Fatigue for 24-48 hours, cycle repeats

What are the target cells of malaria infections?

liver cells

What are the infectious and replicative forms of the malaria parasite?

infectious = sporozoite + gametocytes

replicative = merozoites and trophozoites

Are there naturally resistant human populations who get a milder form of disease? If so, how?

Some people of African decent lack RBC receptor for P. vivax (Duffy blood
group antigen-negative)

People with sickle cell anemia (HbS) are partially resistant to infection

Some parasites are evolving to be able to grow in the presence of the HbS
sickle cell allele

pathogenesis of malaria

RBC adhere to each other and to walls of capillaries → vessels plug up → lack of oxygen to tissue → enlarged spleen

How is malaria treated or prevented?

weekly doses of chloroquine in malarial areas (also primaquine + artemisinin)

mosquito netting impregnated with insecticide

vaccines

chloroquine and mefloquine:

kill RBC parasites,

prevents detoxification of heme from RBCs

primaquine:

effective against more forms, including gametocytes, and liver-stage disease

artemisinin:

from sweet wormwood in China and Vietnam now being expressed in E. coli

used when Plasmodium strain is resistant to chloroquine

leads to oxygen free radicals that can damage parasite proteins

ACTs (artemisinin-based combined therapies) now often recommneded

Artemisinin resistance

Since 2019 reported in Rwanda, Eritrea, Uganda and Mekong Region

Malaria vaccine RTS,S (Mosquirix)

approved by WHo

Recombinant protein vaccine to prevent sporozoite infection of liver cells

How effective is the malaria vaccine? Mosquirix

30% effective at reducing hospitalizations from severe malaria cases

Could prevent 23,000 childhood deaths/year

Is 73% effective at reducing childhood deaths if doses timed with rainy seasons and provided along with monthly dose of anti-malarial medication

75% reduction in symptomatic cases

R21/Matrix-M

more recent vaccine

also recombinant protein vaccine, targets sporozoite

$2-$4/dose

USAID instrumental in development/administration of these vaccines

• recently this aid was cancelled