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
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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
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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
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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
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History1990 - 2004
• Major comeback– DDT resistance– Chloroquine
resistance• 300-500 million NEW
cases each year– Majority in children
of Sub-Saharan Africa
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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
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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
Life Cycle - HumanGetting in the erythrocyte
• 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
Life Cycle - HumanGetting in the erythrocyte
• The surface develops “bumps” (excresences)
• Allows for attachment to capillaries• Maximal “sticking” in 12-36 hours
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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.
Life Cycle - Mosquito
• 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
Plasmodium development in the mosquito
Ghosh et al. (2003) Trends in Parasitology 19:94-101.
Life Cycle - Mosquito
• 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
Plasmodium development in the mosquito
Ghosh et al. (2003) Trends in Parasitology 19:94-101.
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
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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