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Cited by 71Pneumocystis jirovecii pneumonia detection and treatmentPneumonia and Respiratory InfectionsHIV/AIDS drug development and treatment

Association between a Specific Pneumocystis jiroveci Dihydropteroate Synthase Mutation and Failure of Pyrimethamine/Sulfadoxine Prophylaxis in Human Immunodeficiency Virus–Positive and –Negative Patients

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Nahimana, Aimable, Rabodonirina, Meja, Zanetti, Giorgio, Meneau, Isabelle, Francioli, Patrick, Bille, Jacques, Hauser, Philippe M.·2003·The Journal of Infectious Diseases
DOI 10.1086/378239
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Abstract

To investigate the possible association between different prophylactic sulfa drugs and the genotype of the Pneumocystis jiroveci dihydropteroate synthase (DHPS) gene, we examined DHPS polymorphisms in clinical specimens from 158 immunosuppressed patients (38 HIV-negative and 120 HIV-positive), using polymerase chain reaction-single-strand conformation polymorphism. Fifty-seven (36.1%) of 158 patients were infected with a mutant DHPS genotype. All patients who developed P. jiroveci pneumonia (PcP) while receiving pyrimethamine/sulfadoxine (PM/SD) prophylaxis (n=14) had a strain harboring DHPS with an amino acid change at position 57 (Pro-->Ser). This mutation was only present in 20 (14%) of 144 patients not receiving prophylaxis (P<.001). Hospitalization in a specific hospital was an independent risk factor for having P. jiroveci harboring the same DHPS mutation, which indirectly supports that interhuman transmission may affect the dissemination of the mutant strains.

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  • Seven of the nine studies found that most HIV-infected patients with a diagnosis of PCP who had been prescribed TMP-SMX or dapsone for PCP prophylaxis had Pneumocystis that contained DHPS mutations (range 19%-80%).

    “Nevertheless, seven of the nine studies found that most HIV-infected patients with a diagnosis of PCP who had been prescribed TMP-SMX or dapsone for PCP prophylaxis had Pneumocystis that contained DHPS mutations (range 19%–80%, Table 2) (19–24,30).”

    From Dihydropteroate Synthase Gene Mutations in<i>Pneumocystis</i>and Sulfa Resistance (2004) · cites this paper as [30]

    The Predictors section reports DHPS mutations in 16 of 20 patients (80%) who developed PCP despite sulfa prophylaxis. But 14 of those patients received pyrimethamine/sulfadoxine and all 14 had mutations; the paper does not establish that most HIV-infected patients prescribed TMP-SMX or dapsone had mutations. It also does not establish the cited sentence’s count of seven of nine studies. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Several studies have consistently demonstrated a significant association between the use of TMP-SMX or dapsone for PCP prophylaxis in HIV-infected persons and the presence of DHPS gene mutations.

    “Several studies have consistently demonstrated a significant association between the use of TMP-SMX or dapsone for PCP prophylaxis in HIV-infected persons and the presence of DHPS gene mutations (Table 2) (19–25,30).”

    From Dihydropteroate Synthase Gene Mutations in<i>Pneumocystis</i>and Sulfa Resistance (2004) · cites this paper as [30]

  • One study extended these findings to the use of pyrimethamine plus sulfadoxine for PCP prophylaxis.

    “One study extended these findings to the use of pyrimethamine plus sulfadoxine for PCP prophylaxis (30).”

    From Dihydropteroate Synthase Gene Mutations in<i>Pneumocystis</i>and Sulfa Resistance (2004) · cites this paper as [30]

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1 of the 35 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. Fishman JA. Prevention of infection caused by Pneumocystis carinii in transplant recipients. Clin Infect Dis 2001; 33:1397-405.
  2. Goesch TR, Gotz G, Stellbrinck KH, Albrecht H, Weh HJ, Hossfeld DK. Transfer of Pneumocystis carinii between immunodeficient pa- tients. Lancet 1990; 336:627.

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Authors
Nahimana, A., Rabodonirina, M., Zanetti, G., Meneau, I., Francioli, P., Bille, J., & Hauser, P. M.
Affiliations
Centre Hospitalier Universitaire Vaudois (CH)
ORCID
Venue
The Journal of Infectious Diseases
Publisher
Oxford University Press (OUP)
Published
2003-10
Volume
188
Issue
7
Pages
1017-1023
ISSN
  • 0022-1899 (ISSN-L)
  • 1537-6613
DOI
10.1086/378239
OpenAlex
W2116758955
Cited by
71
References
35
Citations by year
2025: 1 · 2024: 1 · 2021: 3 · 2018: 2 · 2017: 2 · 2016: 3 · 2015: 2 · 2014: 8 · 2013: 4 · 2012: 5
FWCI
5.61
Type
journal article
Language
en
Open access
Locations
  • The Journal of Infectious Diseases (publishedVersion)
  • PubMed (publishedVersion)
  • reroDoc Digital Library (submittedVersion)
  • IRIS (submittedVersion)
  • SERVAL (Université de Lausanne) (submittedVersion, other-oa)
Funders
  • European Commission
  • Université de Lausanne
  • Hospices Civils de Lyon
Topics
  • Health Sciences › Medicine › Epidemiology › Pneumocystis jirovecii pneumonia detection and treatment
  • Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
Keywords
Pneumocystis jirovecii, dihydropteroate synthase, sulfadoxine-pyrimethamine, Pneumocystis carinii pneumonia, prophylaxis failure, HIV infection, immunocompromised patients, drug resistance, interhuman transmission, nosocomial infections
MeSH terms
Adolescent, Adult, Aged, Alleles, Anti-Bacterial Agents, Bronchoalveolar Lavage Fluid, Child, Child, Preschool, Dihydropteroate Synthase, Drug Combinations, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Pneumocystis, Pyrimethamine, Sulfadoxine, HIV-1, HIV Infections, Polymerase Chain Reaction, Pneumocystis Infections, Immunocompromised Host, Point Mutation, Polymorphism, Single-Stranded Conformational, Antibiotic Prophylaxis

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