Clinical characteristics and prevalence of dihydropteroate synthase gene mutations in Pneumocystis jirovecii-infected AIDS patients from low endemic areas of China.

Pneumocystis pneumonia (PCP) is an opportunistic and potentially life-threatening infection of AIDS patients caused by the fungus Pneumocystis jirovecii (P. jirovecii). Trimethoprim-sulfamethoxazole (TMP-SMX) is the most commonly used drug combination in the treatment and prophylaxis of PCP. However...

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Main Authors: Mingli Zhu, Ning Ye, Jiru Xu
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2020-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0238184
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spelling doaj-bc1bf96753584844b33b228841fbb1c52021-03-03T22:04:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01159e023818410.1371/journal.pone.0238184Clinical characteristics and prevalence of dihydropteroate synthase gene mutations in Pneumocystis jirovecii-infected AIDS patients from low endemic areas of China.Mingli ZhuNing YeJiru XuPneumocystis pneumonia (PCP) is an opportunistic and potentially life-threatening infection of AIDS patients caused by the fungus Pneumocystis jirovecii (P. jirovecii). Trimethoprim-sulfamethoxazole (TMP-SMX) is the most commonly used drug combination in the treatment and prophylaxis of PCP. However, with long-term use of this combination, mutations in the dihydropteroate synthase (DHPS) gene of P. jirovecii bring about the development of resistance. Data on the prevalence of P. jirovecii and its DHPS mutants in China, especially in low endemic areas, are still limited. Thus, in the present study, we measured the P. jirovecii infection rate among HIV-positive and AIDS (HIV/AIDS) patients with suspected PCP and investigated the relationship between CD4+ T cell count and PCP occurrence. As well as the polymerase chain reaction (PCR) analysis and sequencing, the restriction fragment length polymorphism (RFLP) method was used to analyze DHPS point mutation in P. jirovecii strains. P. jirovecii was detected in 40.82% of cases. The clinical symptoms and signs of PCP were not typical; with decreasing CD4+ T cell counts, PCP infection in HIV/AIDS patients increased. In only one case (1.67%), the patients' DHPS gene could not be cut by the Acc I restriction enzyme. Furthermore, mutation at codon 171 was detected in 11 cases and no mutation was found at codon 57. Patients treated with sulfamethoxazole combined with Voriconazole or Caspofungin exhibited favorable results. After treatment, the symptoms of dyspnea were alleviated, and chest computed tomography findings showed the improvement of lung shadows. These indicated that the prevalence of DHPS mutations in P. jirovecii isolates in AIDS-PCP patients in the region was low. Thus, the contribution of gene mutations to treatment failure requires further research.https://doi.org/10.1371/journal.pone.0238184
collection DOAJ
language English
format Article
sources DOAJ
author Mingli Zhu
Ning Ye
Jiru Xu
spellingShingle Mingli Zhu
Ning Ye
Jiru Xu
Clinical characteristics and prevalence of dihydropteroate synthase gene mutations in Pneumocystis jirovecii-infected AIDS patients from low endemic areas of China.
PLoS ONE
author_facet Mingli Zhu
Ning Ye
Jiru Xu
author_sort Mingli Zhu
title Clinical characteristics and prevalence of dihydropteroate synthase gene mutations in Pneumocystis jirovecii-infected AIDS patients from low endemic areas of China.
title_short Clinical characteristics and prevalence of dihydropteroate synthase gene mutations in Pneumocystis jirovecii-infected AIDS patients from low endemic areas of China.
title_full Clinical characteristics and prevalence of dihydropteroate synthase gene mutations in Pneumocystis jirovecii-infected AIDS patients from low endemic areas of China.
title_fullStr Clinical characteristics and prevalence of dihydropteroate synthase gene mutations in Pneumocystis jirovecii-infected AIDS patients from low endemic areas of China.
title_full_unstemmed Clinical characteristics and prevalence of dihydropteroate synthase gene mutations in Pneumocystis jirovecii-infected AIDS patients from low endemic areas of China.
title_sort clinical characteristics and prevalence of dihydropteroate synthase gene mutations in pneumocystis jirovecii-infected aids patients from low endemic areas of china.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2020-01-01
description Pneumocystis pneumonia (PCP) is an opportunistic and potentially life-threatening infection of AIDS patients caused by the fungus Pneumocystis jirovecii (P. jirovecii). Trimethoprim-sulfamethoxazole (TMP-SMX) is the most commonly used drug combination in the treatment and prophylaxis of PCP. However, with long-term use of this combination, mutations in the dihydropteroate synthase (DHPS) gene of P. jirovecii bring about the development of resistance. Data on the prevalence of P. jirovecii and its DHPS mutants in China, especially in low endemic areas, are still limited. Thus, in the present study, we measured the P. jirovecii infection rate among HIV-positive and AIDS (HIV/AIDS) patients with suspected PCP and investigated the relationship between CD4+ T cell count and PCP occurrence. As well as the polymerase chain reaction (PCR) analysis and sequencing, the restriction fragment length polymorphism (RFLP) method was used to analyze DHPS point mutation in P. jirovecii strains. P. jirovecii was detected in 40.82% of cases. The clinical symptoms and signs of PCP were not typical; with decreasing CD4+ T cell counts, PCP infection in HIV/AIDS patients increased. In only one case (1.67%), the patients' DHPS gene could not be cut by the Acc I restriction enzyme. Furthermore, mutation at codon 171 was detected in 11 cases and no mutation was found at codon 57. Patients treated with sulfamethoxazole combined with Voriconazole or Caspofungin exhibited favorable results. After treatment, the symptoms of dyspnea were alleviated, and chest computed tomography findings showed the improvement of lung shadows. These indicated that the prevalence of DHPS mutations in P. jirovecii isolates in AIDS-PCP patients in the region was low. Thus, the contribution of gene mutations to treatment failure requires further research.
url https://doi.org/10.1371/journal.pone.0238184
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