Chloroquine sensitivity

Halofantrine, a 9-phenanthrenemethanol derivative, is a blood schizonticide and is active against Plasmodium vivax and chloroquine sensitive as well as chloroquine resistant strains of Plasmodium falciparum. As no parenteral preparation is available it cannot be used for severely ill patients. Oral absorption is slow and incomplete and is increased by a fatty meal. 

In order to determine the significance of the 1,5-H shift and the secondary radical species for antimalarial activity, the trioxanes 22a—c were synthesized and tested18. The diastereomeric trioxanes 22a and 22b possessed very different antimalarial activity against both chloroquine-resistant and chloroquine-sensitive strains of the parasite the 4-/3 isomer was approximately twice as active as artemisinin while the 4-a isomer and the disubsti-tuted trioxane were more than sixty times less potent. The authors proposed that the (y-substitucnt prevented the suprafacial 1,5-H shift and therefore suppressed the activity of these compounds. 

Riscoe and coworkers synthesized X5 and confirmed its remarkable in vitro activity with both chloroquine sensitive and resistant strains of P. falciparum [66]. 

Type of Malaria Chloroquine-sensitive Primary Agent(s) Adjunctive/Alternative Agent(s) Chloroquine Primaquine ... 

II. Antiplasmodial Activity Against the 3D7 Chloroquine-sensitive Strain Antiplasmodial activity against the 3D7 chloroquine-sensitive strain of P. falciparum was determined using the method of Wright (1). Testing results are provided in Table 1. 

Mefloquine (t) 21 d) is similar in several respects to quinine although it does not intercalate with plasmodial DNA. It is used for malaria chemoprophylaxis, to treat uncomplicated Plasmodium falciparum (both chloroquine-sensitive and chloroquine resistant) and chloroquine-resistant Plasmodium vivax malaria. Mefloquine is rapidly absorbed from the gastrointestinal tract and its action is terminated by metabolism. When used for prophylaxis, 250 mg (base)/week should be taken, commencing 1-3 weeks before entering and continued for 4 weeks after leaving a malarious area. It should not be given to patients with hepatic or renal impairment. 

In the treatment of paludism, a series of newly synthesized phenothiazine compounds were found to inhibit the growth of both chloroquine-sensitive and chloroquine-resistent strains of Plasmodium falciparum. The antimalar-ial activity of these phenothiazines increased with the number of alkaline groups located in the alkylamino side chain. Also, phenothiazine, chloropro-mazine and other novel phenothiazine compounds inhibited the formation of (1-hematin, in a way similar to chloroquine [120]. 

Cimanga et al (17) assessed the anti-plasmodial (anti-malarial) activity of three different extracts and four alkaloids from the root back of C. sanguinolenta in vitro against P. falciparum D-6 (chloroquine-sensitive strain), K-1, and W-2 (chloroquine-resistant strains). 

Qinghao (Artemisia annua L.) is an important medicinal herb, which has h>een used in the Chinese traditional system of medicine for many centuries. In 1972, Chinese scientists isolated (+)-artemisinin (7, qinghaosu) from the above plant, which is indigenous to China [27-30]. Artemisinin is a sesquiterpene lactone peroxide, whose structure and synthesis have been worked out [27,28]. It has marked activity against both chloroquine-sensitive and resistant strains of Plasmodium falciparum and is particularly suitable for treating cerebral malaria as it is very fast acting [29-31]. 

Halofantrine is a potent blood schizontocidal agent with high activity against chloroquine-resistant and chloroquine-sensitive P, falciparum. The drug has been used at a dose of Ig/adult given daily for 3 days no phototoxicity or gastrointestinal problems were observed [138,139],... 

A previously described 4-day suppressive protocol was used to screen the extracts. The chloroquine-sensitive P. berghei strain ANKA was used to assess the intrinsic in vivo antimalarial activity. The parasite strain was maintained by serial passage of blood from an infected mouse to a naive mouse. Female Swiss mice (6-7 weeks old 20-22 g) were randomly infected by intraperitoneal (i.p.) inoculation of 107 erythrocytes parasitized with... 

Akoachere, M., Buchholz, K., Fischer, E., Burhenne, J., Haefeli, W. E., Schirmer, R. H., and Becker, K. (2005). In vitro assessment of methylene blue on chloroquine-sensitive and -resistant Plasmodium falciparum strains reveals synergistic action with artemisinins. Antimicrob. Agents Chemother. 49,4592-4597. 

Vander Jagt, D. L., Hunsaker, L. A., and Campos, N. M. (1987). Comparison of proteases from chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. Biochem. Pharmacol. 36, 3285-3291. 

Quinine (650 mg every 8 honrs for 5 to 7 days) is indicated for the treatment of chloroquine-resistant falciparum malaria, either alone, with pyrimethamine and a sulfonamide, or with a tetracycline. It is also considered as an alternative therapy for chloroquine-sensitive strains of P. falciparum, P. malariae, P. ovale, andP vivax. Mefloquine and clindamycin may also be nsed with quinine, depending on the geographical location in which the malaria was acquired. 

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