Plasmodium falciparum infection treatment

MacArthur J, Stennies GM, Macheso A, Kolczak MS, Green MD, Ali D, Barat LM, Kazembe PN, Ruebush TK 2nd. Efficacy of mefloquine and sulfadoxine-pyrimethamine for the treatment of uncomplicated Plasmodium falciparum infection in Machinga District, Malawi, 1998. Am J Trop Med Hyg 2001 65(6) 679-84. 

Kain, K.C., Craig, A.A. and Ohrt, C. (1996) Single-strand conformational polymorphism analysis differentiates Plasmodium falciparum treatment failures from re-infections. Molecular and Biochemical Parasitology 79, 167—175. 

Scientists at the University of Michigan Medical School, in collaboration with those at the Indian Institute of Science in Bangalore, have carried out tests on curcumin that show it to inhibit the drug-resist-ant forms of malaria and reported their findings in the Journal of Biological Chemistry in December 2004. Mice infected with the related parasite, Plasmodium falciparum, which causes rodent malaria, were fed curcumin and this reduced the number of parasites in the blood by as much as 90%, and completely protected more than a quarter of mice to whom it was given. Whether it could be a treatment for human malarial infection remains to be seen. 

When the infecting organism is not known or infection is mixed, treatment should begin as for Plasmodium falciparum (below). 

Artemisinin derivatives (artesunate and artemether) for the treatment of multidrug-resistant Plasmodium falciparum malaria have been evaluated in 83 Karen pregnant women in Thailand 55 women were treated for recrudescent infection after quinine or mefloquine, 12 for uncomplicated hyperparasitemic episodes, and 16 had not declared their pregnancy when treated (32). 

McGready R, Cho T, Keo NK, Thwai KL, Villegas L, Looareesuwan S, White NJ, Nosten F. Artemisinin antimalarials in pregnancy a prospective treatment study of 539 episodes of multidrug-resistant Plasmodium falciparum. Clin Infect Dis 2001 33(12) 2009-16. 

Anabwani G, Canfield CJ, Hutchinson DB. Combination atovaquone and proguanil hydrochloride vs. halofantrine for treatment of acute Plasmodium falciparum malaria in children. Pediatr Infect Dis J 1999 18(5) 456-61. 

Mefloquine, a fluorinated derivative of 4-quinoline methanol, is a product of the US Army s antimalarial research program. It is active against chloroquine-resistant Plasmodium falciparum, and has an excellent schizonti-cidal effect in the blood in experimentally induced Plasmodium vivax infections in volunteers. It is not gametocidal. P. vivax infections can persist after successful treatment of the falciparum infection with other drugs the fact that mefloquine is effective against both organisms is thus of practical importance (SEDA-13, 808). 

Bustos DG, Canfield CJ, Canete-Miguel E, Hutchinson DB. Atovaquone-proguanil compared with chloroquine and chloroquine-sulfadoxine-pyrimethamine for treatment of acute Plasmodium falciparum malaria in the Philippines. J Infect Dis 1999 179(6) 1587-90. 

Certain forms of malaria, especially infection with Plasmodium falciparum, have shown resistance to synthetic drugs but not to quinine as a result over 2 million people die from malaria and several hundred million are infected each year. For many, the only effective treatment involves either Quinine or Artemisinin. 

Homoharringtonine has been investigated in the treatment of malaria (166). It was found to cause 50% growth inhibition in two strains of chloro-quine-resistant Plasmodium falciparum malaria in vitro. In mice infected with P. yoelii, homoharringtonine also inhibited parasite growth. In a similar study, in vitro antimalarial activity of cephalotaxine, homoharringtonine. 

Hydroxychloroquine sulfate is a 4-aminoquinoline compound that interferes with parasitic nucleoprotein (DNA/ RNA) synthesis and parasite growth or causes lysis of parasite or infected erythrocytes. In rheumatoid arthritis, it may suppress formation of antigens responsible for symptom-producing hypersensitivity reactions. It is indicated for prophylaxis and treatment of acute attacks of malaria caused by Plasmodium vivax, Plasmodium malariae, and Plasmodium ovale, and susceptible strains of Plasmodium falciparum. It is also used for treatment of chronic discoid and systemic lupus erythematosus (SLE) and acute or chronic rheumatoid arthritis in patients not responding to other therapies. 

The first monoterpene found to have anthelmintic activity was ascaridole (6) which, alone or as a component of plant extracts, has been used in the treatment of hookworm infection [37]. Ascaridole is also a potent in vitro inhibitor (LC 0.05 jiM) of the development of the malarial parasite Plasmodium falciparum [173]. Thymol also exhibits anthelmintic activity, but is too toxic to be considered for use in animals and humans [37]. Since many monoterpenes taken internally in high doses are known to cause problems (irritation, acute toxicity) [174], more attention has been paid to evaluating these compounds against phytoparasitic nematodes. 

Clinical malaria is characterised by periodic fever, which follows the lysis of infected erythrocytes, and caused mainly by the induction of cytokines interleukin-1 and tumour necrosis factor. P. falciparum infection can have serious effects, for example anaemia, cerebral complications (from coma to convulsions), hypoglycaemia and glomerulonephritis. The disease is most serious in the non-immune, including children, pregnant women and tourists. Humans in endemic areas, who have survived an attack of malaria, are semi-immune and disease can be characterised by headache and mild fever. Infection by the other species of Plasmodium is normally self-limiting although relapses may occur, particularly in P. vivax infections. The species of parasite and the age and immune status of the patient are important in considerations of treatment and interpretation of the effects of all medicines. 

Quinine-pyrimethamine-sulfadiazine (or sulfadoxine). In the treatment of choice for infections caused by chloroquine-resistant Plasmodium falciparum ... 

Amodiaquine is a congener of chloroquine and is employed for the treatment of overt malarial attacks and for suppression. Although it is more active than chloroquine both in vitro and m vivo against certain strains of Plasmodium falciparum with decreased sensitivity to chloroquine, amodiaquine is not recommended for routine use in the treatment of such infections (1). It appears that phenolic hydroi l is essential to the activity of amodiaquine since the removal of this group depresses, and its methylation completely destroys antibacterial activity (2). Amodiaquine has been synthesized and patented under the name of Camoquin by Parke, Davis and Company in 1949 (3). It is used medicinally in the form of its dihydrochloride. 

Praziquantel (40 mg/kg), mefloquine (25 mg/kg), artesunate (3 doses of 4 mg/kg), and mefioquine + artesunate (3 doses of artesunate 100 mg - - mefloquine 250mg) have been compared in a randomized open trial in 83 schoolchildren with Schistosoma haematobium infections [22 ]. The effects on Schistosoma mansoni, malaria parasitemia, soil-transmitted helminths, and intestinal protozoa were also determined. Cure rates were 88%, 21 %, 25 %, and 61 % respectively. Both mefloquine-I-artesunate and praziquantel resulted in greater than 95% egg reduction rates. There were significantly lower egg reduction rates with artesunate (85%) and mefloquine (74%). In children co-infected with S. mansoni, praziquantel and mefloquine+artesunate, but not mefloquine and artesunate alone, resulted in high cure rates and egg reduction rates. Mefloquine, artesunate, and mefloquine-I-artesunate completely cured infections due to Plasmodium falciparum. There were no effects against soil-transmitted helminths and intestinal protozoa. There were four cases of mild headache (two with mefloquine and two with praziquantel) and two cases of moderate coughing (one with artesunate and one with mefloquine) both symptoms were also reported before treatment. There were 48 mild and 70 moderate adverse events recorded at 24,48, and 72 hours after... 

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. 

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