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




Defining Plasmodium falciparum Treatment in South West Asia: A Randomized Trial Comparing Artesunate or Primaquine Combined with Chloroquine or SP - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Introduction

Antimalarial 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.

Methods

A single-blinded, randomized trial among Afghan refugees in Pakistan compared six treatment arms: CQ; CQ+single-dosePQ; CQ+3 dAS; SP; SP+single-dosePQ, and SP+3 dAS. 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.

Findings

A 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.

Conclusions

CQ 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>



Autor: Kate Kolaczinski , Toby Leslie, Iftikhar Ali, Naeem Durrani, Sue Lee, Marion Barends, Khalid Beshir, Rosalynn Ord, Rachel Hallett

Fuente: http://plos.srce.hr/



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