TY - JOUR
T1 - Dihydrofolate reductase I164L mutations in Plasmodium falciparum isolates
T2 - clinical outcome of 14 Kenyan adults infected with parasites harbouring the I164L mutation
AU - Hamel, Mary J.
AU - Poe, Amanda
AU - Bloland, Peter
AU - McCollum, Andrea
AU - Zhou, Zhiyong
AU - Shi, Ya Ping
AU - Ouma, Peter
AU - Otieno, Kephas
AU - Vulule, John
AU - Escalante, Ananias
AU - Udhayakumar, Venkatachalam
AU - Slutsker, Laurence
N1 - Funding Information:
The Opportunistic Infections Working Group, Centers for Disease Control and Prevention and the Antimicrobial Resistance Working Group, Centers for Disease Control and Prevention. AA Escalante was supported by NIH grant R01 GM60740.
PY - 2008/4
Y1 - 2008/4
N2 - Recently, Plasmodium falciparum bearing dihydrofolate reductase (DHFR) I164L was isolated from Africa. Quadruple mutations containing I164L confer high-level resistance to antifolate antimalarials. We prospectively measured the effect of co-trimoxazole (CTX) prophylaxis on P. falciparum antifolate resistance development among HIV-infected persons. HIV-positive patients with CD4 cell count <350 cells/μl (n = 692) received CTX; HIV-positive patients with CD4 cell count ≥350 cells/μl (n = 336) and HIV-negative patients (n = 132) received multivitamins. Malaria microscopy-positive samples (n = 413) and selected microscopy-negative/PCR-positive samples (n = 76) were analysed for DHFR mutations at baseline and during six months follow up. We identified I164L in 14 patients. Seven were malaria microscopy-positive: two failed sulfadoxine-pyrimethamine (SP). Among seven microscopy-negative/PCR-positive patients, none developed patent infections with I164L. I164L was not associated with high-level SP resistance or poor outcome among adults living where malaria is highly endemic. Surveillance to monitor spread of I164L is critical, especially among children and pregnant women, who are potentially a source for I164L amplification.
AB - Recently, Plasmodium falciparum bearing dihydrofolate reductase (DHFR) I164L was isolated from Africa. Quadruple mutations containing I164L confer high-level resistance to antifolate antimalarials. We prospectively measured the effect of co-trimoxazole (CTX) prophylaxis on P. falciparum antifolate resistance development among HIV-infected persons. HIV-positive patients with CD4 cell count <350 cells/μl (n = 692) received CTX; HIV-positive patients with CD4 cell count ≥350 cells/μl (n = 336) and HIV-negative patients (n = 132) received multivitamins. Malaria microscopy-positive samples (n = 413) and selected microscopy-negative/PCR-positive samples (n = 76) were analysed for DHFR mutations at baseline and during six months follow up. We identified I164L in 14 patients. Seven were malaria microscopy-positive: two failed sulfadoxine-pyrimethamine (SP). Among seven microscopy-negative/PCR-positive patients, none developed patent infections with I164L. I164L was not associated with high-level SP resistance or poor outcome among adults living where malaria is highly endemic. Surveillance to monitor spread of I164L is critical, especially among children and pregnant women, who are potentially a source for I164L amplification.
KW - DHFR
KW - Drug resistance
KW - Malaria
KW - Mutation
KW - Plasmodium falciparum
KW - Sulfadoxine-pyrimethamine
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U2 - 10.1016/j.trstmh.2008.01.018
DO - 10.1016/j.trstmh.2008.01.018
M3 - Article
C2 - 18321547
AN - SCOPUS:40249118197
SN - 0035-9203
VL - 102
SP - 338
EP - 345
JO - Transactions of the Royal Society of Tropical Medicine and Hygiene
JF - Transactions of the Royal Society of Tropical Medicine and Hygiene
IS - 4
ER -