Malarial parasite

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). 

Glycophorin A appears to serve a variety of functions on the red-cell membrane, and has been implicated in several red-cell disorders. Because it extends from the external environment of the cell into the cell cytoplasm, it is considered to constitute a receptor for malarial parasites,"" influenza viruses, lectins, and Portuguese man-of-war toxin. Many of these receptor functions are attributable to the carbohydrate composition of these... 

Quinine hydrochloride [Fig. 22(c)], an antimalarial agent, acts primarily as a schizonto-cide, affecting sporozoites or preerythrocytic forms of malarial parasites [43]. Figure 23(c) shows potential oscillation with ImM quinine hydrochloride [21]. Fb.sds became very... 

Horuk R, Chitnis CE, Darbonne WC, et al. A receptor for the malarial parasite Plasmodium vivax the erythrocyte chemokine receptor. Science 1993 261 1182-1184. 

The /.gtl 1 system is a more sophisticated bacteriophage version of the plasmid system described above and has been used to isolate many different antigens from various stages in the life cycle of the human malarial parasite using human immune sera as well as antigens from pathogens. 

A simple assay for the detection of the malarial parasite Plasmodium falciparum involves saponin lysis of blood sample and membrane filtration followed by amplification of the consensus sequence of eight 21-bp repeats. This procedure has been successfully used in the field (F2). A PCR assay targeting kinetoplast DNA sequences of Leishmania species was also successfully tested in the field (F2). Molecular methods for the detection of toxoplasma gondii and several other parasites have been reviewed (F2). 

Wendel WB. (1946) Influence of naphthoquinones on the respiratory and carbohydrate metabolism of malarial parasites. Fed Proc 5 406 07. 

All of these compounds are inhibitors of dihydrofolate reductase in bacteria, plasmodia, and humans. Fortunately, they have a significantly high affinity for bacterial and protozoan dihydrofolate reductases. Pyrimethamine, for example, inhibits parasite dihydrofolate reductase at levels several hundred times lower than required to inhibit dihydrofolate reductase in humans. This is the basis of their selective toxicity. The selective toxicity can be increased upon supplying additional folic acid to the host organism, which the parasite cannot use. In fact, diaminopyrimidines (trimetoprim, pyrimethamine) were initially suggested as medicinal and preventative drugs against malarial infections. It was shown that all powerful inhibitors of dihydrofolate reductase can remove the malarial parasite with relatively minor consequences in the host. 

So far this class of carbazole alkaloids contains only two natural products, calothrixin A and its N-deoxy-derivative calothrixin B. These two pentacyclic metabolites with a quinolino[4,3- 7]carbazole-l,4-quinone framework displayed potent inhibitory effects on the in vitro growth of both human malarial parasites and human cancer cells and inhibition of RNA polymerase activity. Owing to this pharmaceutical potential, these natural products have attracted the synthetic interest of various research groups (8). 

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. 

Once the presence of malarial parasites has been confirmed, it is vital to identify the particular plas-modial strain involved, since appropriate use of chemotherapy depends on the particular species responsible for the acute attack. Unfortunately, mixed infections, that is, simultaneous infections with more than one species of plasmodia, are often observed. If more than a single species is involved, treatment appropriate for the elimination of all strains must be instituted to avoid delayed attacks or misinterpretations. 

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... 

It probably influences haemoglobin degradation by parasitic lysosomes by raising intravesicular pH in malarial parasite cells. It also interferes with synthesis of nucleoproteins by the parasite. 

It is a highly effective erythrocytic schizonticide especially against mature trophozoite and schizont forms of malarial parasite. 

Krungkrai SR, Learngaramkul P, Kudan S, Prapunwattana P, Krungkrai JP (1999) Mitochondrial heterogeneity in human malarial parasite Plasmodium falciparum. Science Asia 25 77-83... 

A 16-year old girl was treated empirically with chloroquine (total 450 mg of chloroquine base) for fever, had no malarial parasites in the peripheral blood smear, but had severe hypoglycemia of 1.5 mmol/1 (27 mg/dl) (49). 

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