Haldar Lab
Plasmodium falciparum

Introduction to Malaria

The term malaria comes from 'mal' 'aria', or bad air. The Romans noticed that they got sick when they took walks in the night air. Approximately 100 years ago, Dr. Ronald Ross, a British Medical Officer in Hyderabad, India discovered that mosquitoes transmitted malaria. He first recognized that the black pigment associated with human disease was also present in the gut of the mosquito and later showed that when infected mosquitoes bit chickens the disease was indeed transmitted. For his studies he received the 1902 Nobel Prize in Medicine.

Figure 1 (below) shows the distribution of malaria in the US in 1848. Malaria's prevalence today is shown in Figure 2 (below). A worldwide effort to control malaria was undertaken after the Second World War. However, due to the onset of drug resistance and the ban on DDT, there has been a resurgence of the disease. One of every five infant deaths in Africa is due to malaria, and 40% of the world's population lives at risk for infection.

Malaria USA 1882 Malaria World

The eradication of malaria in the Midwestern United States was achieved by (i) breeding fish that ate mosquito larvae and (ii) increasing the standard of living. The female Anopheline mosquito is highly prevalent in the Southern United States. Thus, the emergence of drug resistant parasites elsewhere and more frequent international travel increases the risk of malaria in the US. The CDCP predicts that the highest risk of entry is Florida, due to immigration from Haiti.

The blood stages of infection are responsible for all of the clinical symptoms and pathoglogies associated with malaria. These stages are our main focus of interest. The parasite has a complex life as shown in Figure 3 (below). When a mosquito bites a human host, sporozoites are released from the salivary glands of the mosquito into the bloodstream. These reach the liver and undergo a cycle of development in hepatocytes. The resulting merozoites lyse out of liver cells and subsequently infect erythrocytes to undergo asexual proliferation as shown in Figure 4 (below). Here a single merozoite gives rise to ~16 daugther cells, which then re-infected red cells and thereby maintain the asexual cycle. The length of the cycle determines the periodicity of the fevers and chills associated with malaria. In falciparum malaria, the parasite development in the red cell takes 48 hours. Fever occurs concomitant with release of merozoites into the blood stream, every two days.

Human and insect life cycle
 
Blood stage life cycle