H J Zar1, M J Alvarez-Martinez, A Harrison, S R Meshnick. 1. School of Child and Adolescent Health, Red Cross Childrens Hospital, University of Cape Town, Rondebosch, South Africa. hzars@ich.uct.ac.za
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.
BACKGROUND:Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia (PCP) is a major cause of mortality in human immunodeficiency virus (HIV)-infectedinfants 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-infectedchildren 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.
Authors: Steve M Taylor; Steven R Meshnick; William Worodria; Alfred Andama; Adithya Cattamanchi; J Lucian Davis; Samuel D Yoo; Patrick Byanyima; Sylvia Kaswabuli; Carol D Goodman; Laurence Huang Journal: PLoS One Date: 2012-11-16 Impact factor: 3.240
Authors: Melanie T Cushion; A George Smulian; Bradley E Slaven; Tom Sesterhenn; Jonathan Arnold; Chuck Staben; Aleksey Porollo; Rafal Adamczak; Jarek Meller Journal: PLoS One Date: 2007-05-09 Impact factor: 3.240