Prevalence of dihydropteroate synthase mutants in HIV-infected South African children with Pneumocystis jiroveci pneumonia

Clin Infect Dis. 2004 Oct 1;39(7):1047-51. doi: 10.1086/424010. Epub 2004 Sep 7.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS-Related Opportunistic Infections / complications
  • AIDS-Related Opportunistic Infections / microbiology
  • Dihydropteroate Synthase / genetics*
  • HIV Infections / complications*
  • HIV Infections / mortality
  • Humans
  • Mutation
  • Pneumocystis carinii / enzymology*
  • Pneumocystis carinii / genetics*
  • Pneumonia, Pneumocystis / complications*
  • Pneumonia, Pneumocystis / microbiology*
  • Prospective Studies
  • South Africa
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use

Substances

  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Dihydropteroate Synthase