Therapeutic efficacy of sulphadoxine/pyrimethamine and susceptibility in vitro of P. falciparum isolates to sulphadoxine‐pyremethamine and other antimalarial drugs in Malawian children

Abstract

SummarySince 1993 sulphadoxine/pyrimethamine (SP) has been used as the ®rst-line drug for uncomplicated Plasmodium falciparum malaria in Malawi. To investigate the current ef®cacy of SP and other antimalarial drug resistance, we studied in vivo and in vitro responses to SP, chloroquine (CQ), me¯oquine (MF), quinine (QN), and halofantrine (HF) in Salima, central Malawi. In a follow-up of 14 days, nine (13.8%) of 65 children under ®ve showed RII/RIII parasitological resistance, and in in vitro microtests 18 (62.1%) of 29 isolates showed <90% inhibition of schizont maturation at pyrimethamine 75 nmol/l blood medium mixture, indicating resistance. The discrepancy between in vivo and in vitro results might be partially explained by acquired immunity in this holoendemic area. In vitro one (3.4%) of 29 isolates failed schizont inhibition at 1.6 lmol/l blood of CQ, indicating resistance. Compared with an in vitro study conducted in 1988 in another region of Malawi using the same cut-off point, the proportion of resistant isolates had decreased signi®cantly (P < 0.01). Although 31% of isolates were borderline, showing schizont maturation at 0.8 lmol/l blood but no schizonts at 1.6 lmol/l in our study, the results suggest possible recovery of CQ sensitivity after long-term absence of drug pressure. Resistance remains a major problem in malaria control. Monitoring resistance patterns in vitro provides early warning signs of impending loss of therapeutic ef®cacy of the standard treatment, and may detect changing patterns in alternative drug resistance.

Reemergence of Chloroquine‐SensitivePlasmodium falciparumMalaria after Cessation of Chloroquine Use in Malawi

“…Nine of 11 fresh P. falciparum isolates were sensitive to chloroquine in vitro, consistent with a recent report of a high prevalence of in vitro chloroquine-sensitive P. falciparum in central Malawi [24]. The finding that 2 infections yielded microtest values in the intermediate range is most likely explained by inaccuracies of the in vitro test, or by mixed resistant and sensitive parasites infections.…”

The effect of Point Mutations in Dihydrofolate reductase genes and Multidrug resistance gene 1-86 on treatment of falciparum malaria in Sudan

“…It is likely that the AQ component of the drug combination is responsible for treatment outcome or success. In support of this hypothesis prior to the introduction of AQ/AS as the first-line drug, CQ treatment failure rates were in excess of 30% [40], whereas the combination drug gave an adequate clinical response of 92%. Of the two combinations, AS + AQ is likely to have a prolonged therapeutic lifespan given global SP resistance trends [41].…”

“…3D7 and 7G8 were used as wild types while K1 and Dd2 as mutant types. In the primary PCR amplification, the reaction took place in a total volume of 20 µl containing 10 mM Tris-HCl pH 8 After the restriction digest, the restriction fragments that resulted were used to score the isolates based on the controls used. After radio probing, parasite clones and isolates were scored either as wild types or mutants compared to the specific probe used in a given blot or as indicated by the controls.…”

“…However, CQ was being used in Sudan for quite a long time as the second-line treatment for malaria, and SP as the first-line drug for malaria treatment owing to the increasing number of CQ treatment failures. Despite changing treatment policies in favour of SP, the development and rapid spread of SP resistant strains [7,8] has threatened its use and better treatment regimens are being sought to replace SP. Combination therapy (CT), especially Artemisinin based combination therapy (ACT), presently seems to be the best option.…”

P. falciparum Malaria Related with Travel: Four Cases

“…Sudan'daki sıtma olgularının %90'ında, Uganda'daki sıtma olgularının %85'inde P. falciparum'un etken olduğu bildirilmiştir (12). Sudan'da klorokin direnci nedeni ile SP tedavisi ilk planda önerilmekte iken SP'ye karşı direncin yaygınlaşması ile kullanımı kısıtlanmış ve bu tedavi yerini özellikle artemisin içeren kombinasyon preparatlarına bırakmıştır (13,14).…”