Malarial parasites malariae

Malaria. Malaria infection occurs in over 30% of the world s population and almost exclusively in developing countries. Approximately 150 X 10 cases occur each year, with one million deaths occurring in African children (87). The majority of the disease in humans is caused by four different species of the malarial parasite. Vaccine development is problematic for several reasons. First, the parasites have a complex life cycle. They are spread by insect vectors and go through different stages and forms (intercellular and extracellular sexual and asexual) as they grow in the blood and tissues (primarily fiver) of their human hosts. In addition, malaria is difficult to grow in large quantities outside the natural host (88). Despite these difficulties, vaccine development has been pursued for many years. An overview of the state of the art is available (89). 

Hemozoin, also known as malaria pigment, is, in teims of its chemical composition, identical to (3-hematin. Hemozoin is formed as a crystallization product of heme under the acidic conditions present in the food vacuole of malarial parasites. In the crystal, the heme molecules are linked into dimers through reciprocal iron-carboxylate bonds to one of the propionate side chains of each porphyrin. The dimers form chains linked by hydrogen bonds. 

One reason for the rapid growth in the use of pesticides worldwide has been the "Green Revolution" (5), Although there have been some benefits from pesticide use in agriculture, they also cause significant environmental and public health problems. The same is true in public health where Insecticides have been used to control malaria. However, today Increased resistance to insecticides in mosquitoes and Increased resistance to drugs by the malarial parasite are resulting in an explosive increase of malaria worldwide (5). 

Most cases of malaria in the United States result from individuals who have contracted the disease before they entered this country. It is also possible to contract malaria during a blood transfusion if the transfused blood has been taken from a malaria-infected individual. Additionally, hypodermic needles previously contaminated by blood containing malarial parasites can be the source of an infection this has occurred when needles are shared among drug addicts. 

The malarial parasite is a single-cell protozoan (plas-modium). Although more than 100 species of plasmodia have been identified, only four are capable of infecting humans Plasmodium malariae, P. ovale, P. vivax, and P. falciparum) the rest attack a variety of animal hosts. P. falciparum and P. vivax malaria are the two most common forms. 

Primaquine is an important antimalarial because it is essentially the only drug effective against the liver (exoerythrocytic) forms of the malarial parasite. The drug also kills the gametocytes in all four species of human malaria. Primaquine is relatively ineffective against the asexual erythrocyte forms. Primaquine finds its greatest... 

Following the development of synthetic antimalarial agents, such as chloroquine and mefloquine, the use of Cinchona alkaloid quinine declined. However, with the emergence of chloroquine-resistant and multiple-drug-resistant strains of malarial parasites, its use has become firmly reestablished. Quinine is the drug of choice for severe chloroquine-resistant malaria due to Plasmodium falciparum. In the U.S., the related alkaloid quinidine is recommended because of its wide availability and use as an antiarrhythmic agent. In many clinics in the tropics, quinine is the only effective treatment for severe malaria unfortunately, decreasing sensitivity of P. falciparum to quinine has already been reported from Southeast Asia. 

A disorder related to sickle cell anemia is the HbC disease, which is also found mostly among persons of African ancestry. Its symptoms, however, are less severe than those with the HbS disorder. HbC is a hemoglobin with a /36Glu—>Lys substitution. It is believed that HbS and HbC arose as a means of combating malaria, because red cells containing HbS and HbC are more resistant to the invasion of the malarial parasite than are normal red cells. 

A number of studies have noted that, in areas where malaria is endemic, riboflavin-deficient subjects are relatively resistant and have a lower parasite burden than adequately nourished subjects. Dietary deficiency of riboflavin, hypothyroidism, which induces functional riboflavin deficiency by lowering the synthesis of flavokinase (Section 7.2.4), or the administration of chlor-promazine, which inhibits flavokinase and can cause functional riboflavin deficiency (Section 7.4.4), all inhibit the growth of malarial parasites in experimental animals. However, although parasitemia is less in riboflavin deficiency, the course of the disease may be more severe (Dutta et al., 1985 Dutta, 1991 Akompong et al., 2000a, 2000b Shankar, 2000). 

Alphonse Laveran, a French Army physician working in North Africa in the 1880s, was the first to observe malarial parasites in human blood. Their mode of transmission was not understood, however, until Ronald Ross, a British medical officer in India, found the organisms within the bodies of Anopheles mosquitoes. Malaria is caused by four species of parasitic protozoa Plasmodium vivax, P. ovale, P. malariae, satid P. falciparum. These organisms have complex life cycles involving several different developmental stages in both human and mos-... 

Pyrimethamine and proguanil are used as oral antimalarials.and inhibit the utilization of folate by the malarial parasite, so are valuable in chemoprophylaxis and in preventing the transmission of malaria. (See ANTIMALARIALS.) Trimethoprim is a useful antibacterial, and as an antiprotozoal in antimalarial therapy. The selectivity of these agents derives, in part, from the fact that whereas mammals can obtain folic acid from the diet, bacteria and the asexual forms of the malarial parasite must synthesize it. Also, the dihydrofolate reductase enzyme in humans is less sensitive to these drugs than that of the parasites. 

The Scientific American (www.sciam.com, 2001) reported a study at the National Institute of Allergy and Infectious Disease (United States) in which two mouse strains were genetically engineered to produce large quantities of a malarial parasite surface protein from Plasmodium falciparum. The malaria vaccine secreted in their milk was able to contain the disease in monkeys vaccinated with the same. This study has now been extrapolated to target livestock as the source animals. GTC is currently... 

Mefloquine is a long-acting blood schizontocide with high efficacy against malarial parasites resistant to quinine, chloroquine and sulphonamide-pyrimethamine combinations [124-129], A single oral dose of the drug of 15 mg/kg (with a maximum of 750-1000 mg/adult) produces cure rates above 90%, Detailed clinical trials carried out in Zimbabwe, Thailand, Burma, Brazil and Europe have established mefloquine as an effective drug both for prophylaxis and treatment of vi-vax and falciparum malaria [125-130],... 

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