A comparative study of the efficacies of chloroquine and a pyrimethamine‐dapsone combination in clearing <i>Plasmodium falciparum</i> parasitaemia in school children in Tanzania

Mshinda, Hassan; Font, F.; Hirt, R.; Mashaka, M.; Ascaso, Carlos; Menéndez, Clara

doi:10.1111/j.1365-3156.1996.tb00113.x

Cited by 11 publications

References 13 publications

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Antimalarial Agents

Casteel¹

2003

Burger's Medicinal Chemistry and Drug Discovery

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Malaria continues to be a major global health problem and seems to be increasing in some parts of the world. By way of an introduction, relevant aspects of the disease, including incidence and resistance, and of the parasite and its biochemistry and genetics are presented. The chemotherapeutic agents now available to prevent and treat malaria are discussed individually. Some of these drugs have been in use for decades or even centuries, such as quinine, chloroquine, and primaquine. Other agents are of more recent origin including mefloquine, halofantrine, atovaquone, and the artemisinins. Chloroquine had been the drug of first resort for many years. It is inexpensive, well‐tolerated, and extremely effective where parasites remain sensitive. But the development of resistance to chloroquine has emphasized the need for new agents and strategies to treat malaria. New information on the genetic basis of chloroquine resistance and on the overall mechanism of action of chloroquine holds promise for advances in therapy. Another important tactic in dealing with infection by resistant parasites is the use of drug combinations. The combination of pyrimethamine and sulfadoxine has been very successful, but resistance is developing. Newer, highly effective combinations include atovaquone with proguanil, lumefantrine with artemether, and chlorproguanil with dapsone. The artemisinin group of compounds has made a powerful positive impact on malaria chemotherapy although their use in monotherapy is not recommended. Details of the mechanism of action of these drugs are becoming clearer. Knowledge about action should assist in addressing issues of possible toxicity. Great progress has been made in sequencing the genome of Plasmodium falciparum . New molecular targets have been identified as a result and efforts are underway to develop antimalarial agents based on these targets. Researchers around the world are also exploring natural products for yet another lead in antimalarial chemotherapy. “If we take as our standard of importance the greatest harm to the greatest number, then there is no question that malaria is the most important of all infectious diseases 1 .” “Ah, poor heart! he is so shaked of a burning quotidian tertian, that it is most lamentable to behold [2].”

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Antimalarial Agents

Casteel¹

2003

Burger's Medicinal Chemistry and Drug Discovery

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7. Dynamics of multiple Plasmodium falciparum infections in infants in a highly endemic area of Tanzania

Smith

Felger

Kitua

et al. 1999

Transactions of the Royal Society of Tropical Medicine and Hygi

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The force of infection and recovery rate for malaria in infants in a highly endemic area ofTanzania were analysed using polymerase chain reaction-restriction fragment length polymorphism genotyping of the Plasmodium falciparum msp2 locus in 99 paired blood samples. Overall, new genotypes were acquired at a rate of 0.064 per day, and the average duration of infections was estimated to be 23 d. The highest recovery rates were in children under 4 months of age. The higher susceptibility of infants to clinical malaria in comparison with older children, in areas of very high transmission, may be largely a consequence of the short duration of infections which precludes the establishment of concomitant immunity. The high turnover of infections also implies that infection prevalence and multiplicity approach an equilibrium even in very young children, and calls into question the use of infant conversion rates as a measure of transmission intensity.

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Efficacy and safety of CGP 56697 (artemether and benflumetol) compared with chloroquine to treat acute falciparum malaria in Tanzanian children aged 1–5 years

Hatz

Abdulla

Mull

et al. 1998

Tropical Med Int Health

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SummaryA randomized, open trial involving 260 Tanzanian children, aged 1᎐5 years, with acute Plasmodium falciparum malaria was conducted to evaluate the efficacy of the combination antimalarial CGP 56697 (artemether and benflumetol), and to compare it with chloroquine, the standard drug used for malaria treatment in the Kilombero area. Children who had received rescue medication within the first 48 h or had a negative slide at the same time were excluded. Seven-day parasitological cure rates were 94% (95% CI 88᎐97.5) for CGP 56697 and 35.4% (95% CI 25.9᎐45.8) for chloroquine. Using the same definition, the 14-day parasitological cure rates were 86.4% (95% CI 78.5᎐92.2) for CGP 56697 and 10.3% (95% CI 5.1᎐18.1) for chloroquine. Gametocytes were more effectively suppressed by CGP 56697 than by chloroquine. There were no major adverse events with either drug. CGP 56697 is highly efficacious against P. falciparum in this area of Tanzania. The study contributes to the discussion on treatment strategies, particularly whether chloroquine may still fulfil its role as first-line drug in an area of high malaria transmission and very high levels of chloroquine resistance.

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A comparative study of the efficacies of chloroquine and a pyrimethamine‐dapsone combination in clearing Plasmodium falciparum parasitaemia in school children in Tanzania

Cited by 11 publications

References 13 publications

Antimalarial Agents

Antimalarial Agents

7. Dynamics of multiple Plasmodium falciparum infections in infants in a highly endemic area of Tanzania

Efficacy and safety of CGP 56697 (artemether and benflumetol) compared with chloroquine to treat acute falciparum malaria in Tanzanian children aged 1–5 years

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