Malaria: drug use and the immune response

Targett, G. A. T.

doi:10.1017/s0031182000075363

Cited by 19 publications

(14 citation statements)

References 47 publications

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“…Indeed, compared to artemether-treated or to chloroquine-treated mice, which died because of the recrudescent parasitaemia, most of the mice treated with dioncophylline B when schizonts were predominant survived the crisis inherent to the recrudescence. Similar protective immune responses, induced by other antimalarial drugs, have been reported before (Targett 1992). In all cases, total clearance of parasites depends on the choice of the target stage and the completeness of the curative drug dosage.…”

Section: Discussionsupporting

confidence: 77%

A comparison of the stage-specific efficacy of chloroquine, artemether and dioncophylline B against the rodent malaria parasite Plasmodium chabaudi chabaudi in vivo

Chimanuka

François

Timperman

et al. 2001

Parasitology Research

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Chloroquine, artemether and dioncophylline B efficacy against Plasmodium chabaudi was compared. One intraperitoneal injection (10 mg/kg body weight) was given daily over 3 consecutive days to OF1 mice when they were predominantly bearing ring, trophozoite and schizont forms. The parasitaemia was monitored every 2 h during two schizogonic cycles and daily thereafter until parasites were cleared. Chloroquine was more efficient at the trophozoite stage, while artemether was effective against all erythrocytic stages, with a marked efficacy against the trophozoite stage. Chloroquine-treated and artemether-treated parasites displayed a pigment-clumping morphology and lowered the parasitaemia faster than dioncophylline B. Dioncophylline B was effective at trophozoite and schizont stages, but completely ineffective at the ring stage. These results demonstrate that a better timing of drug administration increases the efficacy of common and new antimalarial drugs and provides a model for antimalarial-action monitoring. Drug-induced changes in infected erythrocyte morphology are presented.

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Section: Discussionsupporting

confidence: 77%

A comparison of the stage-specific efficacy of chloroquine, artemether and dioncophylline B against the rodent malaria parasite Plasmodium chabaudi chabaudi in vivo

Chimanuka

François

Timperman

et al. 2001

Parasitology Research

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“…These findings are not surprising, as antimalarial immunity increases with age, and as the effectiveness of antimalarial drugs is affected by the immune status of the host. 31,32 Previous studies of mefloquine treatment in Thailand 17,33 and chloroquine treatment in the Solomon Islands 16 and Tanzania 19 have also reported younger age as an independent predictor of treatment failure. Our results and others suggest that age-dependent guidelines for antimalarial drug use may be appropriate in parts of Africa.…”

Section: Discussionmentioning

confidence: 99%

Predictors of chloroquine treatment failure in children and adults with falciparum malaria in Kampala, Uganda.

Dorsey

Kamya²,

Ndeezi³

et al. 2000

The American Journal of Tropical Medicine and Hygiene

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Abstract. Chloroquine-resistant falciparum malaria is a serious problem in much of sub-Saharan Africa. However, it is desirable to continue to use chloroquine as first-line therapy for uncomplicated malaria where it remains clinically effective. To identify predictors of chloroquine treatment failure, a 14-day clinical study of chloroquine resistance in patients with uncomplicated falciparum malaria was performed in Kampala, Uganda. Among the 258 patients (88% follow-up), 47% were clinical failures (early or late treatment failure) and 70% had parasitological resistance (RI-RIII). Using multivariate analysis, an age less than five (odds ratio [OR] ϭ 3.4, 95% CI ϭ 1.8-6.3) and a presenting temperature over 38.0ЊC (OR ϭ 2.0, 95% CI ϭ 1.1-3.7) were independent predictors of treatment failure. In addition, patients who last took chloroquine 3 to 14 days prior to study entry were significantly more likely to be treatment failures compared to patients with very recent (less than 3 days) or no recent chloroquine use. In areas with significant chloroquine resistance, easily identifiable predictors of chloroquine treatment failure might be used to stratify patients into those for whom chloroquine use is acceptable and those for whom alternative treatment should be used.

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“…Regardless of the objectives in these trials, the characterization of the limitations of an antimalarial regimen in important subgroups of patients at high risk of failure, who may also be disproportionately susceptible to adverse clinical outcomes, will provide critical information for setting policy recommendations. In areas of high malaria transmission, the value of an antimalarial drug depends largely on its performance in nonimmune populations at highest risk of P. falciparum malaria, i.e., young children and pregnant women in areas of high endemicity.The differential effects of parasite population size and host age on the risk of recrudescence have long been known (8,22,31,41). These associations were subsequently, though not universally (33), shown to operate in diverse transmission settings (11,18,32,35,39).…”

mentioning

confidence: 99%

“…The differential effects of parasite population size and host age on the risk of recrudescence have long been known (8,22,31,41). These associations were subsequently, though not universally (33), shown to operate in diverse transmission settings (11,18,32,35,39).…”

mentioning

confidence: 99%

Effects of Plasmodium falciparum Parasite Population Size and Patient Age on Early and Late Parasitological Outcomes of Antimalarial Treatment in Children

Borrmann

Matsiégui

Missinou

et al. 2008

Antimicrob Agents Chemother

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The design and interpretation of trials assessing the chemotherapeutic effects of antimalarial drugs depend on our understanding of how different selection criteria affect treatment outcomes. In this study, we analyzed the effects of baseline parameters on the initial parasite elimination rate and the risk of subsequent recrudescence as a marker for incompletely eliminated asexual blood-stage parasites in pediatric patients with uncomplicated Plasmodium falciparum infection treated with amodiaquine in a high-transmission area. We found that (i) parasite population size and patient age independently determine early and late parasitological treatment outcome measurements; (ii) the rate of recrudescence is higher in patients 1 to 3 years of age than in patients aged <1 or >3 years; (iii) patients aged >5 years with parasite densities between 2,000 and 10,000/l have a lower recrudescence rate (13%; 95% confidence interval [CI], 8% to 21%) than patients aged <5 years with parasite densities of >10,000/l (40%; 95% CI, 30% to 50%); and (iv) the sensitivity of detecting recrudescences outside this high-risk group, i.e., in patients of >5 years of age or with parasite densities of <10,000/l, is as low as 27% or 22%, respectively. In conclusion, these findings highlight the need to use adequate selection criteria and to report parasitological outcome results adjusted for the readily available determinants of chemotherapeutic failure, i.e., patient age and baseline parasitemia. The thresholds may vary by transmission intensity and drug regimen. A better understanding of the limitations of antimalarial regimens in high-risk subgroups of patients has important implications for setting policy recommendations.Antimalarial treatment trials provide the empirical evidence base for antimalarial treatment policies in countries where malaria is endemic (44). These trials use variable endpoints to address a range of public health questions. For instance, trials conducted to monitor the emergence or the spread of in vivo resistance or to determine the chemotherapeutic efficacy of a new regimen are designed to measure the ability of the treatment to completely eliminate asexual blood-stage parasites and, thus, to prevent recrudescent infections. On the other hand, the delay of reinfection caused by the effects of slowly eliminated drugs on the erythrocytic and, in some cases, hepatic stages of Plasmodium falciparum infection (14) can be an important additional clinical benefit of antimalarial treatment. This has been investigated in studies that use a combined measurement of the chemotherapeutic and the "posttreatment prophylactic" effects ("recurrence rate") or that simply determine the requirement for retreatment (12). Regardless of the objectives in these trials, the characterization of the limitations of an antimalarial regimen in important subgroups of patients at high risk of failure, who may also be disproportionately susceptible to adverse clinical outcomes, will provide critical information for setting policy recommendations. ...

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Malaria: drug use and the immune response

Cited by 19 publications

References 47 publications

A comparison of the stage-specific efficacy of chloroquine, artemether and dioncophylline B against the rodent malaria parasite Plasmodium chabaudi chabaudi in vivo

A comparison of the stage-specific efficacy of chloroquine, artemether and dioncophylline B against the rodent malaria parasite Plasmodium chabaudi chabaudi in vivo

Predictors of chloroquine treatment failure in children and adults with falciparum malaria in Kampala, Uganda.

Effects of Plasmodium falciparum Parasite Population Size and Patient Age on Early and Late Parasitological Outcomes of Antimalarial Treatment in Children

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