Malaria Plasmodium malariae

Malaria is transmitted by the bite of an infected female Anopheles mosquito, one of the few species of the insect capable of carrying the human malaria parasite. The responsible protozoa ate from the genus P/asmodium of which only four of some 100 species can cause the disease in humans. The remaining species affect rodents, reptiles, monkeys, birds, and Hvestock. The species that infect humans are P/asmodium falciparum Plasmodium vivax Plasmodium malariae and Plasmodium ovale. Note that concomitant multiple malaria infections are commonly seen in endemic areas, a phenomenon that further compHcates choice of treatment. 

Plasmodium vivax, responsible for the most prevalent form of malaria (benign tertian), has an incubation period of 8—27 days (14 average). A variety seen in northern and northeastern Europe has an incubation period as long as 8—10 months. The disease can cause splenic mpture and anemia. Relapses (renewed manifestations of erythrocytic infection) can occur with this type of malaria. Overall, P. vivax is stiU susceptible to chloroquine however, resistant strains have been reported from Papua New Guinea and parts of Indonesia. Plasmodium malariae the cause of quartan malaria, has an incubation period of 15—30 days and its asexual cycle is 72 hours. This mildest form of malaria can cause nephritis in addition to the usual symptoms. It is a nonrelapsing type of malaria but the ted blood ceU infection can last for many years. No resistance to chloroquine by this plasmodium has been reported. Plasmodium ovale responsible for ovale tertian malaria, has an incubation period of 9—17 days (15 average). Relapses can occur in people infected with this plasmodium. No chloroquine resistance has been reported for this parasite. 

Four different protozoa of the genus Plasmodium -P. falciparum, P. vivax, P. ovale and P malariae - can cause malaria. P. falciparum is the most virulent, being responsible for virtually all fatal malaria cases. Humans are infected by a feeding female Anopheles mosquito (Fig. 2). The clinical symptoms of malaria are associated with the development of the parasite within human red blood cells, while the liver stages remain asymptomatic. The following dtugs (in alphabetical order) are currently in use for the treatment of malaria [5]. 

Malaria remains a major public health problem in many parts of the world, including Southeast Asia, sub-Saharan Africa and Latin America where an estimated 300-500 million people are infected. 1-3 million die of malaria every year. The etiologic agents of malaria are protozoan parasites of the genus Plasmodium. Of the four pathogens that can cause malaria in humans (Plasmodium falciparum, P. vivax, P. ovale,... 

Malaria is transmitted from person to person by a certain species of the Anopheles mosquito. The four different protozoans causing malaria are Plasmodium falciparum, P. malariae, P. ovale, and P. vivax. Drugp used to treat or prevent malaria are called anti malarial drags. Three antimalarial drugs are discussed in the chapter chloroquine, doxycycline, and quinine sulfate. Other examples of antimalarial drugs in use today are listed in the Summary Drug Table Antimalarial Drugs. 

The plasmodium causing malaria must enter the mosquito to develop, reproduce, and be transmitted. When the mosquito bites a person infected with malaria, it ingests the male and female forms (gametocy tes) of the plasmodium. The gametocytes mate in the mosquito s... 

Inhibitors for proteases plasmepsin I and II of the malaria parasite Plasmodium falciparum, with a good plasmepsin/human protease cathepsin D selectivity, have been identified via library construction involving rapid microwave-accelerated Suzuki reactions [57]. The phenyl ring of the biphenyl unit in the lead compound M-((lS)-l- [((lS,2S)-3- [(lS)-2-amino-l-(4-phenyl-benzyl)-2-oxoethyl]amino -2-hydroxy-l-phenoxypropyl)amino]carbonyl -2-methylpropyl)pyridine-2-carboxamide has been altered by performing Suzuki reactions on N-((lS)-l- [((lS,2S)-3- [(lS)-2-amino-l-(4-bromobenzyl)-2-oxoethyl]amino -2-hydroxy-l-phenoxypropyl)amino]carbonyl -2-methyl-propyl)pyridine-2-carboxamide (Scheme 37). In particular, a 2-benzofuryl moiety proved to be interesting since a Ki value of 13 nM for plasmepsin I and... 

Bfx and Fx derivatives have been evaluated against the parasites Trypanosoma cruzi (T. cruzi), which is responsible for American Trypanosomiasis and Plasmodium falciparum (P. falciparum) responsible for Malaria. 

Malaria is transmitted by the bites of the Anopheles mosquitoes which introduce into the bloodstream one of four species of sporozoites of the plasmodia (Plasmodium falciparum, P. ovale, P. vivax or P. malariae). Initial symptoms of malaria are nonspecific and may resemble influenza and include chills, headache, fatigue, muscle pain, rigors, and nausea. The onset of the symptoms is between 1 to 3 weeks following exposure. Fever may appear 2 to 3 days after initial symptoms and may follow a pattern and occur every 2 or 3 days (P. vivax, P. ovale and P. malariae). Fever with P. falciparum can be erratic and may not follow specific patterns. It is not unusual for patients to have concomitant infections with P. vivax and P. falciparum. Falciparum malaria must always be regarded as a life-threatening medical emergency. 

The primary goal in the management of malaria is the rapid identification of the Plasmodium species by blood smears (both thick and thin smears repeated every 12 hours for 3 days). Antimalarial therapy should be initiated promptly to eradicate... 

Detection by LDMS and structural elucidation of other secondary metabolite products, generated in the host during the onset of the parasite disease, is discussed. These molecules may serve as additional biomarkers for rapid malaria diagnosis by LDMS. For instance, choline phosphate (CP) is identified as the source of several low-mass ions observed in parasite-infected blood samples in addition to heme biomarker ions. The CP levels track the sample parasitemia levels. This biomarker can provide additional specificity and sensitivity when compared to malaria detection based on heme ion signals alone. Furthermore the observed elevated CP levels are discussed in the context of Plasmodium metabolism during its intra-erythrocytic life cycle. These data can... 

Carlton, J. M. et al. Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii. Nature 2002, 419,512-519. 

Francis, S. Sullivan, D. J. Goldberg, D. E. Hemoglobin metabolism in the malaria parasite Plasmodium falciparum. Annu. Rev. Microbiol. 1997, 51, 97-123. 

Pandey, A. Tekwani, B. Pandey, V. Characterization of hemozoin from liver and spleen of mice infected with Plasmodium yoelii, a rodent malaria parasite. Biomed. Res. 1995,16,115-120. 

Gardner M), Tettelin H, Carucci DJ et al. Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum. Science 1998 282[5391] 1126 1132. Hoffman SL, Rogers WO, Carucci DJ, Venter JC. From genomics to vaccines malaria as a model system. Nature Med 1998 4[12] 1351—1353. 

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