Plasmodium falciparum infection chloroquine-resistant

Verdier, F., Le Bras, J., Clavier, F., Hatin, I., and Blayo, M. (1985) Chloroquine uptake by Plasmodium falciparum-infected human erythrocytes during in vitro culture and its relationship to chloroquine resistance. Antimicrob. Agents Chemother. 27(4), 561-564. 

Chloroquine is a rapidly acting blood schizonti-cide with some gametocytocidal activity. It is used with primaquine for Plasmodium vivax and Plasmodium ovale infections. It has been widely used prophylactically by traveler s to endemic areas. Its mechanism of action is unclear. It is believed to hinder the metabolism of hemoglobin in the parasite. Presumably chloroquine prevents the formation in the plasmodia of polymers out of free heme which then builds up and becomes toxic. Resistance occurs as a consequence of the expression of a membrane phospho-glycoprotein pump in the plasmodia which is able to expel chloroquine from the parasite. Plasmodium falciparum is the most likely to become resistant. 

Artemisia annua L. A. apiacea Hance ex Walpers Qing Guo (Stinking artemisia) (aerial part) Dihydroartemisinin, artesunate, artemisinin, chloroquine, flavonoids, sesquiterpene.33-269-476 This herb is mildly toxic. A schizonticidal agent, antimalarial, treat infections of multidrug-resistant strains of Plasmodium falciparum, the cause of human malignant cerebral malaria. 

Malaria remains one of the most important diseases of humanity with over half of the world population at risk of infection. It affects mainly those living in tropical and subtropical areas with an incidence of 500 million cases per year globally. The antimalarial activity of 4-(5-trifluoromethyl-17/-pyrazol-l-yl)chloroquine analogues 875 has been evaluated in vitro against a chloroquine-resistant Plasmodium falciparum clone <2006BML649>. 

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). 

Webster, H. K., Wiesmann, W. P., and Pavia, C. S. (1984b). Adenosine deaminase in malaria infection Effect of 2 -deoxycoformycin in vivo. Adv. Exp. Med. Biol. 165(Pt A), 225-229. Weidekamm, E., Wallach, D. F., Lin, P. S., and Hendricks, J. (1973). Erythrocyte membrane alterations due to infection with Plasmodium berghei. Biochim. Biophys. Acta 323,539-546. Wellems, T. E., Walker-Jonah, A., and Panton, L. J. (1991). Genetic mapping of the chloroquine-resistance locus on Plasmodium falciparum chromosome 7. Proc. Natl. Acad. Sci. USA 88,3382-3386. 

The antimalarial activity of ferroquine, as compared to that of chloroquine, has been studied in vitro on the chloroquine-sensitive Plasmodium falciparum strain, HB3 5CQS, and in this case ferroquine and chloroquine were shown to have a comparable level of activity. However, a different situation is observed when the activity of the two compounds is compared on chloroquine-resistant strains such as Dd2. In this case, ICso values of 22 nM for ferroquine as against 130 nM for chloroquine are obtained.This interesting effect is also observed on other isolates of Plasmodium falciparum, originating in Gabon and Senegal. In vivo, ferroquine administered to mice for 4 days at a dose of 8.4 mg kg protects them from fatal infection. ... 

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

Quinine (Fig. 9) is probably the oldest effective therapeutic agent for the prophylaxis and therapy of Plasmodium infections and, although now largely superseded for routine use, it is of considerable value in the treatment of chloroquine-resistant P. falciparum, for which it is used in combination with other antimalarials. The main side effects of quinine therapy comprise a syndrome of classical cinchonism, i.e., tinnitus, vision defects, nausea, headache and gastrointestinal effects, but im-munologically the much rarer complication, drug-induced thrombocytopenia is of more interest. 

Douglas and coworkers [171] have strongly recommended artemisinin-based combination therapies to eliminate malaria, which is used to treat P. falciparum malaria even when most blood-stage infections caused by Plasmodium vivax still respond to chloroquine treatment, a chloroquine-resistant P. vivax strain has been already detected, suggesting that artemisinin-based combination therapies should be used to treat both parasite strains. 

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