Sulfadoxine-pyrimethamine remains efficacious against uncomplicated,<i>Plasmodium falciparum</i>malaria in north-eastern Afghanistan

Ezard, Nadine; Nellepalli, P.; Asha, A. W

doi:10.1179/000349804225003019

Cited by 11 publications

(12 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SP monotherapy was effective in the study population, with treatment failure rates remaining in the 5–10% range, similar to that seen in other studies in the region [5], [8], [45]. Molecular studies in the region show that genetic markers for SP resistance are still at low levels in the parasite population [46], [47].…”

Section: Discussionsupporting

confidence: 85%

“…In such areas of low seasonal transmission the operational effectiveness of SP before resistance arises appears to be short [7]. Whilst current effectiveness remains comparatively good in the region low level in vivo resistance to SP has been demonstrated [5], [8], [9]. Wide-scale adoption of effective SP based combinations, rather than SP monotherapy, which was being considered as an option to replace chloroquine at the time of the study, could delay the selection of resistance and prolong the useful life of SP across the subcontinent.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Defining Plasmodium falciparum Treatment in South West Asia: A Randomized Trial Comparing Artesunate or Primaquine Combined with Chloroquine or SP

Kolaczinski

Leslie

Ali³

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

IntroductionAntimalarial resistance has led to a global policy of artemisinin-based combination therapy. Despite growing resistance chloroquine (CQ) remained until recently the official first-line treatment for falciparum malaria in Pakistan, with sulfadoxine-pyrimethamine (SP) second-line. Co-treatment with the gametocytocidal primaquine (PQ) is recommended for transmission control in South Asia. The relative effect of artesunate (AS) or primaquine, as partner drugs, on clinical outcomes and gametocyte carriage in this setting were unknown.MethodsA single-blinded, randomized trial among Afghan refugees in Pakistan compared six treatment arms: CQ; CQ+(single-dose)PQ; CQ+(3 d)AS; SP; SP+(single-dose)PQ, and SP+(3 d)AS. The objectives were to compare treatment failure rates and effect on gametocyte carriage, of CQ or SP monotherapy against the respective combinations (PQ or AS). Outcomes included trophozoite and gametocyte clearance (read by light microscopy), and clinical and parasitological failure.FindingsA total of 308 (87%) patients completed the trial. Failure rates by day 28 were: CQ 55/68 (81%); CQ+AS 19/67 (28%), SP 4/41 (9.8%), SP+AS 1/41 (2.4%). The addition of PQ to CQ or SP did not affect failure rates (CQ+PQ 49/67 (73%) failed; SP+PQ 5/33 (16%) failed). AS was superior to PQ at clearing gametocytes; gametocytes were seen on d7 in 85% of CQ, 40% of CQ+PQ, 21% of CQ+AS, 91% of SP, 76% of SP+PQ and 23% of SP+AS treated patients. PQ was more effective at clearing older gametocyte infections whereas AS was more effective at preventing emergence of mature gametocytes, except in cases that recrudesced.ConclusionsCQ is no longer appropriate by itself or in combination. These findings influenced the replacement of CQ with SP+AS for first-line treatment of uncomplicated falciparum malaria in the WHO Eastern Mediterranean Region. The threat of SP resistance remains as SP monotherapy is still common. Three day AS was superior to single-dose PQ for reducing gametocyte carriage.Trial Registration ClinicalTrials.gov bold>

show abstract

Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Defining Plasmodium falciparum Treatment in South West Asia: A Randomized Trial Comparing Artesunate or Primaquine Combined with Chloroquine or SP

Kolaczinski

Leslie

Ali³

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…While follow-up and numbers of SP patients were too few in this trial to determine significance, the 12% SP failure rate raises questions about SP's long-term efficacy. While SP has a role as combination partner in Pakistan and Afghanistan, if administered without artesunate, resistance to SP may select rapidly [36,37]. …”

Section: Discussionmentioning

confidence: 99%

Clinical trial of extended-dose chloroquine for treatment of resistant falciparum malaria among Afghan refugees in Pakistan

Howard

Durrani²,

Sanda

et al. 2011

Malar J

View full text Add to dashboard Cite

BackgroundFalciparum malaria is a significant problem for Afghan refugees in Pakistan. Refugee treatment guidelines recommended standard three-day chloroquine treatment (25 mg/kg) for first episodes and extended five-day treatment (40 mg/kg) for recrudescent infections, based on the assumption that a five-day course would more likely achieve a cure. An in-vivo randomized controlled trial was conducted among refugees with uncomplicated falciparum malaria to determine whether five-day treatment (CQ40) was more effective than standard treatment (CQ25).Methods142 falciparum patients were recruited into CQ25 or CQ40 treatment arms and followed up to 60 days with regular blood smears. The primary outcome was parasitological cure without recrudescence. Treatment failures were retreated with CQ40. PCR genotyping of 270 samples, from the same and nearby sites, was used to support interpretation of outcomes.Results84% of CQ25 versus 51% of CQ40 patients experienced parasite recrudescence during follow-up (adjusted odds ratio 0.17, 95%CI 0.08-0.38). Cure rates were significantly improved with CQ40, particularly among adults. Fever clearance time, parasite clearance time, and proportions gametocytaemic post-treatment were similar between treatment groups. Second-line CQ40 treatment resulted in higher failure rates than first-line CQ40 treatment. CQ-resistance marker pfcrt 76T was found in all isolates analysed, while pfmdr1 86Y and 184Y were found in 18% and 37% of isolates respectively.ConclusionsCQ is not suitable for first-line falciparum treatment in Afghan refugee communities. The extended-dose CQ regimen can overcome 39% of resistant infections that would recrudesce under the standard regimen, but the high failure rate after directly observed treatment demonstrates its use is inappropriate.

show abstract

“…Resistance of P. falciparum to chloroquine in Afghanistan was first apparent in the late 1980s [4], and by 2002 the clinical efficacy of chloroquine and amodiaquine in eastern Afghanistan was extremely low [5]; neither did the addition of artesunate to amodiaquine provide sufficient efficacy, being associated with an adequate clinical and parasitological response rate of only 72% [5]. During this period the efficacy of sulphadoxine-pyrimethamine (SP) was relatively preserved, with cure rates of 77-92% reported in eastern [5] and northern Afghanistan [6] as well as adjacent areas of Pakistan [7] (only the last study was able to correct for re-infection by PCR). Comparable success rates with SP were also noted in south-east Iran, although here there was also evidence of clinical resistance in a small number of parasites, associated with target mutations in dihydrofolate reductase ( dhfr ) and dihydropteroate synthase ( dhps ) [8].…”

Section: Introductionmentioning

confidence: 99%

Prevalence of antifolate resistance mutations in Plasmodium falciparum isolates in Afghanistan

Awab

Pukrittayakamee

Jamornthanyawat

et al. 2013

Malar J

View full text Add to dashboard Cite

BackgroundArtesunate plus sulphadoxine-pyrimethamine (AS+SP) is now first-line treatment for Plasmodium falciparum infection in several south Asian countries, including Afghanistan. Molecular studies provide a sensitive means to investigate the current state of drug susceptibility to the SP component, and can also provide information on the likely efficacy of other potential forms of artemisinin-combination therapy.MethodsDuring the years 2007 to 2010, 120 blood spots from patients with P. falciparum malaria were obtained in four provinces of Afghanistan. PCR-based methods were used to detect drug-resistance mutations in dhfr, dhps, pfcrt and pfmdr1, as well as to determine copy number of pfmdr1.ResultsThe majority (95.5%) of infections had a double mutation in the dhfr gene (C59R, S108N); no mutations at dhfr positions 16, 51 or 164 were seen. Most isolates were wild type across the dhps gene, but five isolates from the provinces of Kunar and Nangarhar in eastern Afghanistan had the triple mutation A437G / K540E / A581G; all five cases were successfully treated with three receiving AS+SP and two receiving dihydroartemisinin-piperaquine. All isolates showed the pfcrt SVNMT chloroquine resistance haplotype. Five of 79 isolates had the pfmdr1 N86Y mutation, while 52 had pfmdr1 Y184F; positions 1034, 1042 and 1246 were wild type in all isolates. The pfmdr1 gene was not amplified in any sample.ConclusionsThis study indicates that shortly after the adoption of AS+SP as first-line treatment in Afghanistan, most parasites had a double mutation haplotype in dhfr, and a small number of isolates from eastern Afghanistan harboured a triple mutation haplotype in dhps. The impact of these mutations on the efficacy of AS+SP remains to be assessed in significant numbers of patients, but these results are clearly concerning since they suggest a higher degree of SP resistance than previously detected. Further focused molecular and clinical studies in this region are urgently required.

show abstract

Sulfadoxine-pyrimethamine remains efficacious against uncomplicated,Plasmodium falciparummalaria in north-eastern Afghanistan

Cited by 11 publications

References 9 publications

Defining Plasmodium falciparum Treatment in South West Asia: A Randomized Trial Comparing Artesunate or Primaquine Combined with Chloroquine or SP

Defining Plasmodium falciparum Treatment in South West Asia: A Randomized Trial Comparing Artesunate or Primaquine Combined with Chloroquine or SP

Clinical trial of extended-dose chloroquine for treatment of resistant falciparum malaria among Afghan refugees in Pakistan

Prevalence of antifolate resistance mutations in Plasmodium falciparum isolates in Afghanistan

Contact Info

Product

Resources

About