MALARIA A Family of nine, all with Malarial Symptoms. Photo: Darshan Sudarshi

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MALARIA

A Family of nine, all with Malarial Symptoms. Photo: Darshan Sudarshi

History ?? - 1800’s

• Mentioned in Egyptian hieroglyphs

• Etymology: comes from “bad air” in Italian

• First cure in 1600’s

• Quinine isolated in 1820





History 1800’s

• Alfonso Laveran first to describe (~1880)

• Sir Patrick Manson - mosquito = vector?

• Sir Ronald Ross proved mosquito to be vector for bird malaria (1898)

• Giovanni Grassi proved mosquito to be vector for humans (1901)– Only a certain kind of mosquito

History 1900-1950

• William C. Gorgas applied early work in Panama



1905 fumigation car eradicating the mosquitoes

History 1900-1950

• Therapeutic malaria

• 1930’s - 1940’s drug development

• DDT development

• Liver stage discovered in 1948

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History1950’s

• DDT successfully used in– Venezuela– Italy– Greece– Guyana– Ceylon– USA

• Malaria exterminated from Carolinas in 1951



History1990’s

• By 1997 WHO launches world campaign• Major success in:

– Europe

– North America

– Parts of Asia

– Former USSR

– Australia

• Not as great a success in tropical areas



History1990 - 2004

• Major comeback– DDT resistance– Chloroquine

resistance• 300-500 million NEW

cases each year– Majority in children

of Sub-Saharan Africa



Factors in Disease Emergence and Spread

• Societal events: Population growth and migration; economic impoverishment; war or civil conflict; lack of education & sanitation

• Environmental changes: Changes in water ecosystems; deforestation; flood/drought

• Public health infrastructure: Curtailment or reduction in prevention programs; inadequate communicable disease surveillance; lack of trained personnel; drug availability, distribution and cost; research priorities

• Microbial adaptation and change: Changes in virulence; development of drug resistance

Adapted from Dr. C. Sterling’s VSC 503 lecture notes

The Parasite

• Zoonotic - disease of animals that is transmissible to humans.

• Caused by a protozoa (one-celled, often microscopic, eukaryotic organism)

• In the genus Plasmodium• ~120 species

– All animal except four




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The Human Parasite

• Human malaria is caused by:– Plasmodium

falciparum– P. vivax– P. malariae– P. ovale



Life Cycle - Human

• Inoculated into vertebrate blood by mosquito

• Goes directly to hepatocytes (liver cells)• Non-symptomatic phase• Called the exoerythrocytic cycle• 1 sporozoite ---> 10,000 / 6 days

(falciparum)• 1 sporozoite ---> 1,000 / 8-9 days (vivax)

Life Cycle - Human

• Merozoites (what emerges from hepatocyte) need to infect erythrocytes (red blood cells)

• Asexual multiplicative cycle in erythrocytes• With falciparum, fever every 24 hours• With vivax, fever every 48 hours

Life Cycle - HumanGetting in the erythrocyte

• Erythrocytes are not phagocytic (bringing in particulate matter by invagination of its surface membrane and then pinching off the invaginated protion of a vacuole)

• Structures at the anterior end of the parasite enable it to move into the erythrocyte

• Once the invasion process is complete it ends up in a parasitoferous vacuole


• There are no proteins in the vacuole• Parasite secretes its own proteins

– Dictate what goes out and comes into the vacuole

• Multiply infected erythrocytes are often found

• Some proteins go to surface of erythrocyte


• The surface develops “bumps” (excresences)

• Allows for attachment to capillaries• Maximal “sticking” in 12-36 hours


Life Cycle - Human

• After a few erythrocytic cycles, some differentiate into gametocytes

• Mosquitoes need gametocytes to become successful vector

• Gametocytes physiologically pre-adapted to life in mosquito

Life Cycle - Mosquito

• Gametocytes undergo transformation within 10 minutes of entering the mosquito

• Formation of zygote– Only 2n stage of parasite life cycle

• Divides and becomes an öokinate• Moves to gut wall

Plasmodium development in the mosquito

Ghosh et al. (2003) Trends in Parasitology 19:94-101.


• Öokinate then traverses the gut wall• Asexual division takes place on the

hemolymph side of the gut wall now structure is called an öocyst

• 1 zygote ---> several THOUSAND sporozoites (what comes out of the öocyst)

• Development to here takes 10-15 days




• After the öocyst ruptures, sporozoites spill out into the hemolymph

• Adheres to salivary gland and is stored there

• Mosquito then bites another human and the cycle begins again



The Mosquito

• Adult, female, Anopheline mosquitoes are the only vector

• Live about 1 month• Males do not blood feed rather, they are

nectar feeders• Anophelines are crepuscular feeders

– Feeding at dawn and dusk



The Mosquito

• When an infected female Anopheles feeds, only a few hundred sporozoites are released at a time

• If interrupted, new host also gets a few hundred sporozoites

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MALARIA A Family of nine, all with Malarial Symptoms. Photo: Darshan Sudarshi