Malaria Plasmodium falciparum

The mechanism of action of chloroquine in Plasmodium falciparum malaria is elimination of... 

The Plasmodium falciparum malaria PD model successfully described the antimalarial effect of artemisinin, mefloquine, and a combination of the two drugs... 

It turns out female Anopheles mosquitoes, the most important vectors for Plasmodium falciparum malaria, possess odorant receptors for these molecules. This permits the mosquito to home in on humans, at least those that sweat. Malaria is responsible for more than a million deaths per year. This finding suggests novel ways of creating mosquito repellants and/or traps. ... 

Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI. (2005) The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature 434 214-217. 

Artemisinin, a tetracyclic 1,2,4-trioxane isolated from Artemisia annua L., is currently recommended as a first-line agent against Plasmodium falciparum malaria. Artemisinin and its synthetic derivatives have also been shown to be promising prototypes for the development of new antiproliferative agents. This chapter presents the recent advances on the analytic methods for extraction and quantification of artemisinin from A. annua plants as well as the biological properties of this natural product. 

T3. Targett, G. A. T., Antibody response to Plasmodium falciparum malaria comparisons of immunoglobulin concentrations. Antibody litres and the antigenicity of different asexual forms of the parasite. Clin. Exp. Immunol. 7, 501-517 (1970). 

Quinidine gluconate - Life-threatening Plasmodium falciparum malaria. 

Many pathogenic protozoa. Including Trypanosoma brucei (trypanosomiasis or African sleeping sickness), Plasmodium falciparum (malaria), Leishmania species (leishmaniasis), and the intestinal parasites Giardia lamblia and Entamoeba histolytica, depend on farnesylated proteins for growth... 

The pharmaceutical properties of artemisinin are far from optimal it is insoluble in water and only marginally soluble in oil. It has poor oral bioavailability and has been administered for the treatment of Plasmodium falciparum malaria in humans at total doses of about 1 g (over 3 days). Early studies by Chinese scientists in 1979 led to the discovery of dihydroartemisinin 3, artemether 4 (Artenam), and sodium artesunate 5, oil and water soluble derivatives, respectively (Figure 9.1 ).6-7 These drugs are currently in clinical use in Asia in a number of preparations such as suppositories, i.v. injectables, oil depos, to name only a few.8 Capsules containing 0.5 g of artemisinin for oral administration are available in Vietnam. 

The sulfones and sulfonamides synergize with the inhibitors of dihydrofolate reductase, and the combinations have been effective in controlling malaria, toxoplasmosis, and coccidiosis. Fansidar, a combination of sulfadoxine and pyrimethamine, has been successful in controlling some strains of chloroquine-resistant Plasmodium falciparum malaria (see Chapter 53 Antiprotozoal Drugs). However, reports of Fansidar resistance have increased in recent years. New inhibitors effective against the sulfonamide-resistant 7,8-dihydropteroate synthase are needed. 

Roth EF Jr, Calvin MC, Max-Audit I et al (1988) The enzymes of the glycolytic pathway in erythrocytes infected with Plasmodium falciparum malaria parasites. Blood 72(6) 1922-1925... 

Perch M, Kofoed P, Fischer TK, Co F, Rombo L, Aaby P, et al. Serum levels of soluble urokinase plasminogen activator receptor is associated with parasitemia in children with acute Plasmodium falciparum malaria infection. Parasite Immunol 2004 26(5) 207-211. 

There was a high frequency of amphetamine abuse and withdrawal among patients from the Thai-Myanmar border area admitted to hospital with Plasmodium falciparum malaria (90). This co-morbidity can cause diagnostic confusion, alter malaria pathophysiology, and lead to drug interactions. Considering the potential neuropsychiatric adverse effects of mefloquine, an important component of current antimalarial treatment in Southeast Asia, it should be avoided in patients who abuse amphetamines. 

The enolic thiofuranone derivatives 35 (e.g. R = n-propyl and R = n-decyl) and 36 are also inhibitors of fatty acid synthase and have served as drug leads against Plasmodium falciparum (malaria) and Trypanosoma (sleeping sickness) . Several tetronic acid derivatives exhibit significant inhibition toward bacterial peptidoglycan synthesis (K = 0.19 p.M for the derivative R = 2-naphthalene and (R, R ) = vinyl-1-naphthalene in equation 8 analogous to 39) . ... 

Kumar CA, Das UN. Lipid peroxides, nitric oxide and essential fatty acids in patients with Plasmodium falciparum malaria. Prostaglandins Leukot Essent Eatty Acids 1999 61 255-258. Xiao L, Patterson PS, Yang C, Lai AA. Role of eicosanoids in the pathogenesis of murine cerebral malaria. Am. J. Trop. Med. Hyg. 1999 60 668-673. 

Perkins DJ, Kremsner PG, Weinberg JB. Inverse relationship of plasma prostaglandin E2 and blood mononuclear cell cyclo-oxygenase-2 with disease severity in children with Plasmodium falciparum malaria. J. Infect. Dis. 2001 183 113-118. 

Qinghao (Sweet Wormwood) is the dried aerial parts of the herb Artemisia annua L. (Asteraceae family), which has been used in China for centuries to treat fever and malaria. Artemisinin (Nl) (Qing Hao Su) (128), the active principle, directly kills Plasmodium falciparum (malaria parasites) with little toxicity to animals and humans. Thus, it is a clinically effective, safe, and rapid antimalarial agent (129, 130). The novel endo-peroxide link is essential for the antimalarial activity. 

Avery MA, McLean G, Edwards G, Ager A. Structure-activity relationships of peroxide-based artemisinin antimalarials. In Biologically Active Natural Products Pharmaceuticals. Cutler SI, Cutler HG, eds. 2000. CRC Press, Boca Raton, EL, pp. 121-132. Pareek A, Nandy A, Kochar D, Patel KH, Mishra SK, Mathur PC. Efficacy and safety of f -arteether and a/f -arteether for treatment of acute Plasmodium falciparum malaria. Am. J. Trop. Med. 2006 75 139-142. http //mednet3.who.int/EMUb/. 

A number of histidine analogues, including 2-azido-L-histidine (201), have been evaluated by the NIH as part of a programme directed towards the development of new antimalarials for the prophylaxis and treatment of drug-resistant Plasmodium falciparum malaria [261]. Asexual P. falciparum parasites have a much higher histidine content than mammalian cells, and several histidine-rich proteins are thought to be functionally important in... 

Drugs used to treat Plasmodium falciparum malaria must always be selected with regard to the prevalence of local patterns of drug resistance. 

Pyrimethamine is combined with dapsone (Malo-prim) (see p. 271) for prophylaxis of Plasmodium falciparum malaria. 

Quinine (t) 9 h 18 h in severe malaria) is obtained from the bark of the South American Cinchona tree. It binds to plasmodial DNA to prevent protein synthesis but its exact mode of action remains uncertain. It is used to treat Plasmodium falciparum malaria in areas of multiple-drug resistance. Apart from its antiplasmodial effect, quinine is used for myotonia and muscle cramps because it prolongs the muscle refractory period. Quinine is included in dilute concentration in tonics and aperitifs for its desired bitter taste. 

Rezbach, R, Some, E., Taylor, W.R.J. Amodiaquine-artesunate versus amodiaquine for uncomplicated Plasmodium falciparum malaria in African children a randomized, multicentre trial. Lancet 2002 359 1365-1372... 

Gaudebout C, Pussard E, Clavier F, Gueret D, Le Bras J, Brandicourt O, Verdier F. Efficacy of intramuscular amopyroquin for treatment of Plasmodium falciparum malaria in the Gabon Republic. Antimicrob Agents Chemother 1993 37(5) 970-4. 

Artemisinin is an antimalarial constituent isolated from Qinghao. It is a sesquiterpene lactone with an endoper-oxide bridge, structurally distinct from other classes of antimalarial agents. Several derivatives of the original compound have proved effective in the treatment of Plasmodium falciparum malaria and are currently available in a variety of formulations artesunate (intravenous, rectal, oral), artelinate (oral), artemisinin (intravenous, rectal, oral), dihydroartemisinin (oral), artemether (intravenous, oral, rectal), and artemotil (intravenous). Artemisinic acid (qinghao acid), the precursor of artemisin, is present in the plant in a concentration up to 10 times that of artemisinin. Several semisjmthetic derivatives have been developed from dihydroartemisinin (1). 

In 25 patients with acute uncomplicated Plasmodium falciparum malaria treated with artemotU (3.2 mg/kg followed by either 1.6 mg/kg or 0.8 mg/kg), the most frequent adverse events were headache, dizziness, nausea, vomiting, and abdominal pain two patients complained of mild pain at the site of injection (8). 

The novel combination (Artekin ) of dihydroartemisinin and piperaquine has been assessed in 106 patients (76 children and 30 adults) with uncomplicated Plasmodium falciparum malaria in Cambodia (19). The respective doses of dihydroartemisinin and piperaquine, which were given at 0,8, 24, and 32 hours, were 9.1 mg/kg and 74 mg/kg in children and 6.6 and 53 mg/kg in adults. AH the patients became aparasitemic within 72 hours. Excluding the results in one child who died on day 4, there was a 97% 28-day cure rate (99% in children and 92% in adults). Patients who had recrudes-cent infections used low doses of Artekin. Adverse effects, most commonly gastrointestinal complaints, were reported by 22 patients (21%) but did not necessitate premature withdrawal. 

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). 

Looareesuwan S, Wilairatana P, Chokejindachai W, Chalermrut K, Wernsdorfer W, Gemperli B, Gathmann I, Royce C. A randomized, double-blind, comparative trial of a new oral combination of artemether and benflumetol (CGP 56697) with mefloquine in the treatment of acute Plasmodium falciparum malaria in Thailand Am J Trop Med Hyg 1999 60(2) 238 3. 

Van Vugt M, Angus BJ, Price RN, Mann C, Simpson JA, Poletto C, Htoo SE, Looareesuwan S, White NJ, Nosten F. A case-control auditory evaluation of patients treated with artemisinin derivatives for multidrug-resistant Plasmodium falciparum malaria. Am J Trop Med Hyg 2000 62(l) 65-9. 

Shanks GD, Gordon DM, Klotz FW, Aleman GM, Qloo AJ, Sadie D, Scott TR. Efficacy and safety of atovaquone/pro-guanil as suppressive prophylaxis for Plasmodium falciparum malaria. Clin Infect Dis 1998 27(3) 494-9. 

Convulsions were more common in hypoglycemic children. This commonly unrecognized comphcation contributes to morbidity and mortality in cerebral Plasmodium falciparum malaria. Hypoglycemia is amenable to treatment with intravenous dextrose or glucose, which may help to prevent brain damage (SEDA-13, 804). 

Sowunmi A, Ayede AI, Falade AG, Ndikum VN, Sowunmi CO, Adedeji AA, Falade CO, Happi TC, Oduola AM. Randomized comparison of chloroquine and amodiaquine in the treatment of acute, uncomplicated, Plasmodium falciparum malaria in children. Ann Trop Med Parasitol 2001 95(6) 549-58. 

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