INITIATIVE FOR VECTOR AND INSECT SCIENCE AT BOSTON COLLEGE

MALARIA

By John P. Roche

WHAT IS MALARIA?
Malaria is a disease caused by infection with a protozoan parasite of the genus Plasmodium. There are over 150 known species of Plasmodium, and four of these species infect humans: P. falciparum, P. vivax, P. ovale, and P. malariae.  All of these malaria species are transmitted to humans by bites from mosquitoes of the genus Anopheles (60 of the 380 known species of Anopheles carry malaria). People with malaria usually suffer from fever, headache, aches and pains, and vomiting.  They may sometimes experience convulsions, coma, kidney failure, and severe anemia.  Plasmodium falciparum is the most dangerous malaria species, causing the most human fatalities, and these fatalities are most common in young children. [Huge advances have been made in reducing malaria mortality worldwide, but it remains one of the world's most devastating communicable disease, and in 2015, it caused over 400,000 deaths.]

HOW DO PEOPLE CONTRACT MALARIA?
When an infected Anopheles mosquito bites a human, a form of the parasite called sporozoites are injected into the human's bloodstream from the salivary glands of the mosquito. The sporozoites travel to the person's liver, where they enter liver cells called hepatocytes. In the hepatocytes, the sporozoites multiply (in a process called exoerythrocytic schizogony). Then the sporozoites are released from the liver cells and enter the bloodstream again, where they enter red blood cells. Within the red blood cells, they produce either merozoites, or microgametocytes and macrogametocytes  (in a process called erythrocytic schizogony).  The asexual merozoites, which are released into the bloodstream and reinvade other red blood cells, are usually produced for some period before the sexual-stage gametocytes are produced.

When a suitable species of Anopheles mosquito takes a blood meal from a human with gametocytes in her blood, the gametocytes enter the mosquito. Once in the mosquito, the microgametocytes release flagellate cells, which fertilize the female macrogametocytes.  The resulting fertilized ookinetes enter cells and pass through the wall of the mosquito midgut, then develop into oocysts. The oocysts produce sporozoites in a process called sporogony. The oocysts then rupture, and sporozoites travel to the mosquito's salivary gland, ready to enter another person, beginning the parasite’s life cycle again.

Fever occurs in humans when erythrocytes rupture in unison at the end of an erythrocytic schizogony cycle, and these fevers often recur cyclically as the parasite goes through successive cycles of schizogony. The schizogony cycle is 48 hours long for P. ovale, P. vivax, and P. falciparum  and 72 hours long for P. malariae. As a result, the periods of cyclic fevers vary depending on the species of Plasmodium with which a person is infected.

WHAT IS THE GEOGRAPHIC DISTRIBUTION OF MALARIA?
More than 90% of malaria cases occur in sub-Saharan Africa. The majority of the remaining cases occur in the Mideast, the Indian subcontinent, Southeast Asia, South America, and Central America. The range of malaria in some parts of the world was reduced dramatically during the mid-twentieth century through concerted malaria-eradication efforts.  The range of the disease is beginning to expand again, however. For example, malaria has recently reappeared in Korea, Tajikistan, Azerbaijan, and some regions of southern Europe.  Malaria has also recently been observed to move higher in elevation in some areas, including Ethopia, Rwanda, Tanzania, Uganda, Zimbabwe, and Papua New Guinea. The expansion in the range of malaria could be the result of a variety of factors, including:

--Appearance of drug-resistant strains of Plasmodium

--Land use practices, including deforestation

--Reduction in malaria eradication efforts in some regions, due in part to funding constraints

--Climate change

Malaria had been largely eliminated from the continental United States by the mid-twentieth century.  Since 1990, however, cases have appeared in Georgia, Florida, Michigan, New Jersey, New York, Ontario, and Texas. Climate change and the prevalence of intercontinental travel may contribute to an increased incidence of malaria in the United States in the future. Anopheles mosquitoes capable of transmitting malaria live in North America, and the Plasmodium parasite is only an airliner-flight away from most American cities.

HOW CAN MALARIA BE TREATED AND CONTROLLED?
Protection from the Malaria Parasite: One approach to preventing malaria is to protect people from the parasite by the use of chemical prophylaxis. Antimalarial drugs include chloroquine, doxycycline, hyrdoxychloroquine sulfate, mefloquine, primaquine, quinine, sulfadoxine-pyrimethamine, and tetracycline.  Chloroquine is inexpensive and often effective, but chloroquine-resistant strains of Plasmodium have appeared in Africa, India, and South America, and are especially prevalent in Southeast Asia.  Where choloroquine resistant-strains of malaria are present, more expensive drugs such as mefloquine need to be used.  However, strains of Plasmodium with resistance to multiple antimalarial drugs are becoming an increasing problem in Southeast Asia.  When antimalarial drugs are used, it is essential for the right drugs to be taken for a long enough time; inappropriate or ineffective drug-treatment regimens cause increases in parasite drug resistance.

[This description of medicines is given for general information purposes only; contact your health care provider for details on specific treatment options.]

Vaccines: Potential vaccines for malaria are being investigated and developed by a number of organizations, including the National Institute of Allergy and Infectious Diseases at the National Institute of Health, the Centers for Disease Control, the Naval Medical Research Center, and the Walter Reed Army Institute of Research. Vaccine development is focusing on pre-erythrocytic stage, blood-stage, and transmission-blocking targets. For pre-erythrocytic-stage vaccines, immunization strategies under consideration include inducing antibodies that will prevent sporozoites from entering liver cells and inducing T-cell responses that will attack parasite-infected liver cells. Strategies for the creation of blood-stage vaccines include the induction of antibodies that will keep merozoites from entering red blood cells. Transmission-blocking vaccines would create antibodies that would disrupt Plasmodium in the mosquito during the gamete or ookinete stage.

Protection from Mosquito Vectors: Another approach for preventing malaria is to reduce the incidence of bites from Anopheles mosquitoes. This can be done by reducing Anopheles populations with chemical (e.g., DDT) or biological (e.g., the bacterium Bacillus thuringiensi or the fungus Lagenidium giganteum) agents. It can also be achieved by employing physical barriers, such as long sleeves, house screens, and insecticide-impregnated bednets. DDT was a huge success in reducing mosquito populations for many years, but its use has been limited in many countries because of concerns over environmental dangers of the insecticide (DDT is relatively safe for humans, but is dangerous to some wildlife species) and because of the development of DDT-resistance in some strains of Anopheles. However, because residential applications of DDT on the walls of homes pose a minimal threat to humans and the environment, and can greatly reduce the transmission of malaria, many health experts advocate the continued residential use of DDT  in malaria-endemic areas.  Insecticide-impregnated bed nets are used with success in many regions, and this approach is very low cost (nylon bed nets cost about four dollars; pyrethroid insecticide applications, which only need to be repeated every six months, cost twenty-five cents). Though the bed net approach helps reduce malaria infection considerably, it does not eliminate it entirely; a Johns Hopkins School of Public Health study in Tanzania found that bednets reduced malaria infection rates by 50%.

WHERE CAN YOU FIND OUT MORE ABOUT MALARIA?
Maurel, M. 1994. Malaria: A Layman’s Guide. Southern Book Publishers, South Africa.

Sherman, I. W. (Ed.). 1998. Malaria: Parasite Biology, Pathogenesis, and Protection. American Society of Microbiology Press.

Guerrant, R. L., Walker, D. H., and Weller, P. F. (Eds.) 2001. Essentials of Tropical Infectious Diseases. W. B. Saunders, Philadelphia.

Beaty, B. J., and Marquardt, W. C. (Eds.) 1996. The Biology of Disease Vectors. Univ. of Colorado Press, Niwot, Colorado.

Malaria information from the National Institute of Allergy and Infectious Diseases, National Institute of Health: www.niaid.nih.gov/publications/malaria.htm

The Centers for Disease Control, Division of Parasitic Diseases: http://www.cdc.gov/ncidod/dpd/parasites/malaria/default.htm

World Health Organization: www.who.int/health-topics/malaria.htm

UNDP-World Bank-WHO-Special Programme for Research and Training in Tropical Diseases: www.who.int/tdr/diseases/malaria/default.htm

Malaria Foundation International: www.malaria.org/

(Reprinted from the Initiative for Vector and Insect Science website)