Prevalence of dihydropteroate synthase mutants in HIV-infected South African children with Pneumocystis jiroveci pneumonia.
BACKGROUND
Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia (PCP) is a major cause of mortality in human immunodeficiency virus (HIV)-infected infants in Africa, but the prevalence of mutations in the gene encoding dihydropteroate synthase (DHPS) in isolates from Africa has not been reported.


METHODS
This study investigated the prevalence of DHPS mutations in P. jiroveci isolates from South African HIV-infected children with PCP by amplifying DNA using 2 different polymerase chain reactions.


RESULTS
P. jiroveci DNA from 30 respiratory specimens was amplified; 26 specimens (86.7%) contained wild-type DHPS alleles. Of the 4 samples (13.3%) with DHPS mutations, 2 contained a homogenous population with single DHPS mutations, 1 contained a homogenous population with 2 DHPS mutations, and the fourth contained a heterogenous population of organisms with both wild-type and single-mutant DHPS genotypes. Only 1 child was receiving trimethoprim-sulphamethoxazole (TMP-SMZ) prophylaxis; this patient was infected with wild-type P. jiroveci. The mortality rate (overall, 20 [66.7%] of 30 children) was not significantly different between children infected with wild-type P. jiroveci (17 [65.4%] of 26) and those infected with mutant strains (3 [75%] of 4; P=.8).


CONCLUSIONS
DHPS mutations are uncommon in P. jiroveci isolates from South Africa. However, increasing use of TMP-SMZ prophylaxis may result in widespread development of mutations.
School of Child and Adolescent Health, Red Cross Childrens Hospital, University of Cape Town, Rondebosch, South Africa. hzars@ich.uct.ac.za
H J
HJ
Zar
M J
MJ
Alvarez-Martinez
A
A
Harrison
S R
SR
Meshnick
D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000382:microbiology; D004094:Dihydropteroate Synthase / Q000235:genetics*; D015658:HIV Infections / Q000150:complications* / Q000401:mortality; D006801:Humans; D009154:Mutation; D045363:Pneumocystis carinii / Q000201:enzymology* / Q000235:genetics*; D011020:Pneumonia, Pneumocystis / Q000150:complications* / Q000382:microbiology*; D011446:Prospective Studies; D013019:South Africa; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use
D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D004094:Dihydropteroate Synthase