EJMS

Abstract

Malaria is an ancient disease and has been a major cause of human suffering for thousands of years. It occurs in over 90 countries worldwide. In many malarious areas of the world, especially sub-Saharan Africa, malaria is ranked among the most frequent causes of morbidity and mortality among children and is often the leading identifiable cause. The causative agents of human malaria are four species of Plasmodium. Plasmodium falciparum alone accounts for most of the morbidity and mortality because of its virulence and drug resistance. Clinical diagnosis offers the advantages of ease, speed, and low cost. Microscopic diagnosis of malaria is performed by staining thick and thin blood films to visualize the malaria parasite. Detection in patient samples of malaria parasite antigens such as histidine rich protein II or plasmodium lactate dehydrogenase can be performed by rapid, point of care tests based on immunochromatographic methods. Quantitative buffy coat is a method for identifying the malarial parasite in the peripheral blood. Techniques also exist for detecting anti-malaria antibodies in serum specimens. Detection of parasite genetic material through polymerase-chain reaction (PCR) techniques is becoming a more frequently used tool in the diagnosis and surveillance of drug resistance in malaria. In general, resistance appears to occur through spontaneous mutations that confer reduced sensitivity to a given drug or class of drugs. In Chloroquine resistance, an amino acid substitution at position 76 from lysine to threonine (K76T) in pfcrt confers resistance to CQ. The 76 T allele in the chloroquine resistance transporter gene (pfcrt) is predictive of chloroquine and amodiaquine treatment failure. The 86Y allele of the multidrug resistance gene 1 (pfmdr1) has been linked with chloroquine and amodiaquine resistance and increased chloroquine inhibitory concentrations in P. falciparum with pfcrt 76 T. Amplifications of pfmdr1 have been associated with mefloquine resistance, lumefantrine tolerance and reduced sensitivity to artesunate. Antifolate combination drugs act through sequential and synergistic blockade of 2 key enzymes involved with folate synthesis. Pyrimethamine and related compounds inhibit the step mediated by dihydrofolate reductase while sulfones and sulfonamides inhibit the step mediated by dihydropteroate synthase. In P. falciparum, resistance to antifolates is associated with point mutations in the dihydrofolate reductase (pfdhfr) and dihydropteroate synthetase (pfdhps) genes. The resistance can be detected via in vivo tests for monitoring of the parasitological and/or clinical response over time. The in vitro tests, can be performed on isolates, several drugs can be assessed simultaneously, and experimental drugs can be tested. Prevention strategies can be divided into the prevention of the malaria infection and the reduction of drug resistance. Improving the diagnosis of malaria, diagnostic test, such as microscopy or a rapid antigen test, would result in the greatest reduction of unnecessary malaria treatments and decrease the probability that parasites are exposed to sub-therapeutic blood levels of drug. The theory underlying combination drug treatment of tuberculosis, leprosy, and HIV infection is well known and is now generally accepted for malaria.