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

2. History ?? - 1800’s Mentioned in Egyptian hieroglyphs Etymology: comes from “bad air” in Italian First cure in 1600’s Quinine isolated in 1820

3. 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

4. History 1900-1950 William C. Gorgas applied early work in Panama 1905 fumigation car eradicating the mosquitoes

5. History 1900-1950 Therapeutic malaria 1930’s - 1940’s drug development DDT development Liver stage discovered in 1948

6. History1950’s DDT successfully used in –Venezuela –Italy –Greece –Guyana –Ceylon –USA Malaria exterminated from Carolinas in 1951

7. 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

8. History1990 - 2004 Major comeback –DDT resistance –Chloroquine resistance 300-500 million NEW cases each year –Majority in children of Sub-Saharan Africa

10. 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

11. 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

12. The Human Parasite Human malaria is caused by: –Plasmodium falciparum –P. vivax –P. malariae –P. ovale

13. 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)

15. 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

17. Life Cycle - Human Getting 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

18. Life Cycle - Human Getting 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

19. Life Cycle - Human Getting in the erythrocyte The surface develops “bumps” (excresences) Allows for attachment to capillaries Maximal “sticking” in 12-36 hours

20. 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

22. 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

23. Plasmodium development in the mosquito Ghosh et al. (2003) Trends in Parasitology 19:94-101.

24. 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

25. Plasmodium development in the mosquito Ghosh et al. (2003) Trends in Parasitology 19:94-101.

26. 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

27. Plasmodium development in the mosquito Ghosh et al. (2003) Trends in Parasitology 19:94-101.

28. 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

29. 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