Drug resistance in Plasmodium falciparum from the Chittagong Hill Tracts, Bangladesh.
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 (chi(2) = 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, > or =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.
van den Broek
Ingrid V F
IV
Médecins sans Frontières-Holland, Gulshan, Dhaka, Bangladesh. ingrid.van.den.braek@london.msf.org
van der Wardt
Sophia
S
Talukder
Lenin
L
Chakma
Swarupa
S
Brockman
Alan
A
Nair
Shalini
S
Anderson
Tim C
TC
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D001459:Bangladesh / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000627:therapeutic use*; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D009154:Mutation / Q000235:genetics; D018512:Parasitemia / Q000188:drug therapy / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D015800:Protozoan Proteins / Q000235:genetics; D011739:Pyrimethamine / Q000627:therapeutic use*; D011803:Quinine / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000627:therapeutic use*; D016896:Treatment Outcome
D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; D004338:Drug Combinations; D005819:Genetic Markers; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; C059987:mdr gene protein, Plasmodium; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D011803:Quinine; D011739:Pyrimethamine