Continued efficacy of sulfadoxine–pyrimethamine as second line treatment for malaria in children in Guinea-Bissau
Karolinska Institutet, Сольна, Stockholm, Sweden Acta Tropica
(Impact Factor: 2.27).
01/2007; 100(3):213-7. DOI: 10.1016/j.actatropica.2006.09.014
Sulfadoxine-pyrimethamine (S/P) is widely used for treatment of failures following the first line treatment for malaria in Africa. In Guinea-Bissau, it has been recommended as second line therapy by the National Malaria Programme since 1996. In order to monitor any change of the in vivo sensitivity, the efficacy of S/P was studied immediately before the introduction of the drug and 6-9 years later.
Children participating in clinical in vivo studies were given S/P if having late clinical treatment failure following the treatment with quinine, chloroquine, or amodiaquine. Parasitological and clinical failures were evaluated during a 35-day follow-up. During the first study period whole blood sulfadoxine concentrations were measured on day 7.
Altogether, 56 children failed the initial treatment and were included in 1995/1996 as well as 55 children in 2002/2004. The PCR-uncorrected adequate clinical and parasitological response rates on day 28 were 94% and 91%, and on day 35 they were 89% and 91%, respectively, in the two periods. No difference between median blood drug concentration in children with and without treatment failure was observed.
The efficacy of S/P as second line treatment for uncomplicated malaria has remained unchanged in spite of a relatively high level of genetic markers associated with Plasmodium falciparum resistance to S/P previously found in the area.
Available from: europepmc.org
- "PS is the second-line drug for controlling malaria. Some countries find its good efficacy to treat malaria (142–144). Some malaria resistance to PS is shown in other countries (145–148). "
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ABSTRACT: The children aged under 5 years from vast African areas badly suffer from falciparum malaria and many of them die of this disease. Therapeutic efficacy of anti-malaria drugs, especially pyrimethamine-sulfadoxine (PS) and chloroquine (CQ) to falciparum malaria is frequently evaluated and reported in recent 10 years. Unfortunately, to date, these widespread materials and researches have not been systematically collected and analyzed. In our study, two investigators were employed to widely and independently gather researches on efficacy of PS vs. CQ mono-therapy of falciparum malaria in children aged below 5 years in unpublished and published databases. Meta-analyses were conducted in categories of PS group and CQ group respectively. Pooled OR of PS vs. CQ was 0.11 (95%CI, 0.05-0.24). PS showed higher therapeutic efficacy to falciparum malaria in less-than-5-year children than CQ. Random model was chosen to analyze for the heterogeneity existence between different studies. Subgroup analyses were performed, but heterogeneity was still presented. Heterogeneity might be caused by different resistance of falciparum malaria to PS and CQ in different settings. Malaria type associated with parasite species, basic information of PS and CQ, and PS & CQ resistant malaria control measures were demonstrated and discussed respectively in detail in this article.
Available from: Weiwei Zhang
- "malaria (Mulenga et al. 1999; Van Dillen et al. 1999; Kofoed et al. 2006; Kolaczinski et al. 2007; Obonyo et al. 2007; Conteh et al. 2010; Aziken et al. 2011 "
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ABSTRACT: Given that the intensive application of sulfonamides in aquaculture, animal husbandry and malaria treatment has lead to an increase in sulfonamide discharge into the environment, there is an increasing need to find a way to remediate sulfonamide-contaminated sites. The bacterial strain DX7 was isolated from a marine environment and is capable of degrading sulfadoxine. DX7 was identified as a Pseudomonas sp. based on 16S rRNA gene sequencing. Approximately 30% of sulfadoxine was degraded after Pseudomonas sp. DX7 was inoculated into mineral salt plus tryptone media containing 10 mg l(-1) sulfadoxine for 2 days. The degradation efficiency under different environmental conditions was characterized using HPLC. The optimal temperature and pH for sulfadoxine biodegradation were around 30°C and 6.0, respectively. The optimal concentrations of sulfadoxine and tryptone for sulfadoxine biodegradation were determined to be approximately 30 mg l(-1) and between 2.0 and 8.0 g l(-1), respectively. Cytotoxicity analysis indicated that the metabolites of sulfadoxine generated by Pseudomonas sp. DX7 showed significantly reduced cytotoxicity to Hela cells. These results suggest that Pseudomonas sp. DX7 is a new bacterial resource for degrading sulfadoxine and indicate the potential of the isolated strain in the bioremediation of sulfadoxine-contaminated environments.
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ABSTRACT: We compared sulfadoxine-pyrimethamine (SP) with unsupervised artemether-lumefantrine (AL) and unsupervised amodiaquine-artesunate (ASAQ) fixed-dose formulation for the treatment of uncomplicated malaria in children in Benin.
This open-label, noninferiority comparative trial included children aged 6-60 months. The follow-up period was 6 weeks, and the primary objective was a comparison of polymerase chain reaction (PCR)-adjusted effectiveness rates at day 28.
The study included 240 children (48 received SP, and 96 each received AL and ASAQ). The intention-to-treat analysis showed effectiveness rates on day 28 of 20.8%, 78.1%, and 70.5% for SP, AL, and ASAQ, respectively. After adjustment for PCR results, these rates were 27.1%, 83.3%, and 87.4%, respectively. The per-protocol analysis (217 patients) showed effectiveness rates on day 28 of 21.7%, 88.0%, and 76.1% for SP, AL, and ASAQ, respectively. After adjustment for PCR results, these rates were 28.3%, 94.0%, and 93.2%, respectively. SP was less effective than the other drugs in the PCR-adjusted analysis, whereas AL and ASAQ were equally effective. The rate of new infection was higher among children treated with ASAQ than among those treated with AL.
This was the first trial, to our knowledge, to compare unsupervised AL with unsupervised ASAQ fixed-dose formulation; both treatments provided high PCR-adjusted day 28 effectiveness rates. Efficacy rates for SP were surprisingly low. Clinical trials registration. NCT00460369.
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