Drug resistance in Plasmodium falciparum from the Chittagong Hill Tracts, Bangladesh

Authors

  • Ingrid V. F. Van Den Broek,

    1. 1 Médecins sans Frontières-Holland, Dhaka, Bangladesh
      2 Shoklo Malaria Research Unit, Mae Sot, Thailand
      3 Southwest Foundation for Biomedical Research, San Antonio, TX, USA
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  • 1 Sophia Van Der Wardt,

    1. 1 Médecins sans Frontières-Holland, Dhaka, Bangladesh
      2 Shoklo Malaria Research Unit, Mae Sot, Thailand
      3 Southwest Foundation for Biomedical Research, San Antonio, TX, USA
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  • 1 Lenin Talukder,

    1. 1 Médecins sans Frontières-Holland, Dhaka, Bangladesh
      2 Shoklo Malaria Research Unit, Mae Sot, Thailand
      3 Southwest Foundation for Biomedical Research, San Antonio, TX, USA
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  • 1 Swarupa Chakma,

    1. 1 Médecins sans Frontières-Holland, Dhaka, Bangladesh
      2 Shoklo Malaria Research Unit, Mae Sot, Thailand
      3 Southwest Foundation for Biomedical Research, San Antonio, TX, USA
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  • 1 Alan Brockman,

    1. 1 Médecins sans Frontières-Holland, Dhaka, Bangladesh
      2 Shoklo Malaria Research Unit, Mae Sot, Thailand
      3 Southwest Foundation for Biomedical Research, San Antonio, TX, USA
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  • 2 Shalini Nair,

    1. 1 Médecins sans Frontières-Holland, Dhaka, Bangladesh
      2 Shoklo Malaria Research Unit, Mae Sot, Thailand
      3 Southwest Foundation for Biomedical Research, San Antonio, TX, USA
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  • and 3 Tim C. Anderson 3

    1. 1 Médecins sans Frontières-Holland, Dhaka, Bangladesh
      2 Shoklo Malaria Research Unit, Mae Sot, Thailand
      3 Southwest Foundation for Biomedical Research, San Antonio, TX, USA
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Authors
Ingrid V. F. van den Broek (corresponding author), Sophia van der Wardt, Lenin Talukder and Swarupa Chakma, Médecins sans Frontières-Holland, 42B, Road 41, Gulshan 2, Dhaka, Bangladesh. E-mail: ingrid.van.den.braek@london.msf.org, msfh-bangladesh@amsterdam.msf.org
Alan Brockman, Shoklo Malaria Research Unit, P.O. Box 46, Mae Sot, Tak Province, Thailand. E-mail: shoklo@cscoms.com
Shalini Nair and Tim C. Anderson, Southwest Foundation for Biomedical Research, P.O. Box 760 549, San Antonio, TX, USA. E-mail: tanderso@darwin.sfbr.org

Summary

Objective  To assess the efficacy of antimalarial treatment and molecular markers of Plasmodium falciparum resistance in the Chittagong Hill Tracts of Bangladesh.

Methods  A total of 203 patients infected with P. falciparum were treated with quinine 3 days plus sulphadoxine/pyrimethamine (SP) combination therapy, and followed up during a 4-week period. Blood samples collected before treatment were genotyped for parasite mutations related to chloroquine (pfcrt and pfmdr1 genes) or SP resistance (dhfr and dhps).

Results  Of 186 patients who completed follow-up, 32 patients (17.2%) failed to clear parasitaemia or became positive again within 28 days after treatment. Recurring parasitaemia was related to age (χ2 = 4.8, P < 0.05) and parasite rates on admission (t = 3.1, P < 0.01). PCR analysis showed that some of these cases were novel infections. The adjusted recrudescence rate was 12.9% (95% CI 8.1–17.7) overall, and 16.6% (95% CI 3.5–29.7), 15.5% (95% CI 8.3–22.7) and 6.9% (95% CI 0.4–13.4) in three age groups (<5 years, 5–14, ≥15). The majority of infections carried mutations associated with chloroquine resistance: 94% at pfcrt and 70% at pfmdr. Sp-resistant genotypes were also frequent: 99% and 73% of parasites carried two or more mutations at dhfr and dhps, respectively. The frequency of alleles at dhfr, dhps and pfmdr was similar in cases that were successfully treated and those that recrudesced.

Conclusions  The clinical trial showed that quinine 3-days combined to SP is still relatively effective in the Chittagong Hill Tracts. However, if this regimen is continued to be widely used, further development of SP resistance and reduced quinine sensitivity are to be expected. The genotyping results suggest that neither chloroquine nor SP can be considered a reliable treatment for P. falciparum malaria any longer in this area of Bangladesh.

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