In vivoandin vitrosensitivity of Falciparum malaria to quinine in Thai children

Abstract

The study was carried out to assess the efficacy of quinine in children with Falciparum malaria in relation to in vitro sensitivity (measured in terms of minimum inhibitory concentration: MIC) and to trough serum levels of quinine during the course of treatment. Fifty children aged ten months to 12 years with Falciparum malaria were randomly divided into two groups. Group I: 24 children were treated with quinine 10 mg base per body weight every eight hours for 14 days. Group II: 26 children were treated with quinine at the dosage adjusted to the body surface area based on an adult dose of 500 mg base eight hourly for 14 days. There were three treatment failures, one RI and one RII in group I, and one RI in group II. The serum concentrations of quinine reached a peak level on day two and levelled off by the end of the first week. Concentrations in group II were higher than in group I. The mean minimal inhibitory concentration (MIC) of quinine in the two groups was 14.89 nmol per ml ranging from 8-26 nmol per ml. In cases with treatment failure, the trough serum quinine levels became lower than the corresponding MIC after day six (RI) and after day two (RII). The rise of MIC suggests that sensitivity of Falciparum malaria parasites to quinine may be decreasing in Thailand. Failures of treatment in standard dosage may occur in cases infected by parasites with high MIC, in which trough serum quinine levels cannot be maintained above the MIC longer than six days during the course of treatment. However in one cured case, the trough serum quinine levels were below the MIC throughout treatment. More research is needed on the real relationship between serum quinine concentrations, the MIC, and clinical and parasitological response to quinine.

Adverse Effect of Rifampin on Quinine Efficacy in Uncomplicated Falciparum Malaria

“…In order to provide a cure for malaria, therapeutic drug concentrations must be present in blood for at least four asexual cycles (i.e., 8 days) (20). Falciparum malaria treatment failures in children treated with Q have also been attributed to a decline in Q levels in plasma after the fourth day of treatment (2). These results indicate that rifampin should not be combined with Q.…”

Quinine Pharmacokinetic-Pharmacodynamic Relationships in Uncomplicated Falciparum Malaria

“…This probably explains why the concentrations in plasma in the first days of treatment in the present study were higher in those with a slower resolution of fever and a slower clearance of parasites. In children, in whom the therapeutic response may be worse than that in adults because of a lack of background immunity, this decline in the concentrations in blood in the second half of the treatment course may lead to treatment failure (2). This led to a suggestion 20 years ago that the dose of quinine in children should be increased by 50% in the second half of the treatment course (2).…”

“…As a result, concentrations in plasma fall. In areas with resistant strains of P. falciparum in order to achieve good therapeutic responses in children, the dose of quinine must be increased after the 3rd day of treatment to compensate for this decline in the concentration in plasma which occurs with recovery (2). These observations suggest that quinine concentrations must remain above levels which inhibit parasite multiplication throughout the course of treatment to eradicate the infection from the body (14).…”

“…To date there is no convincing evidence of high-grade quinine resistance in the treatment of severe malaria (9). The pharmacokinetic properties of and therapeutic responses to quinine vary with age, pregnancy, immunity, and disease severity (2,8,14). As patients recover from malaria, the total apparent volume of distribution of quinine expands and systemic clearance increases (13).…”

Activity of a combination of three cinchona bark alkaloids against Plasmodium falciparum in vitro

“…It is generally agreed, but not well established, that the emergence and spread of resistance has resulted from drug pressure. Among some of the major antimalarial drugs, most of them belonging to the quinoline group, cross resistance has been described, particularly between chloroquine and quinine (5). Cross resistance may also be responsible for the occurrence of parasites resistant to mefloquine, a quinoline methanol, which was recently observed in areas of the world where drug pressure by this new compound has never been exerted (3,4).…”