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Pneumocystis jirovecii Infection and the Associated Dihydropteroate Synthase (DHPS) and Dihydrofolate Reductase (DHFR) Mutations in HIV-Positive Individuals from Pune, India

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Abstract

The present study was undertaken to detect Pneumocystis jirovecii infection among HIV-positive patients presenting with symptoms of lower respiratory tract infection and analyze the associated dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) mutations. P. jirovecii infection was detected in 12.6 % cases. We did not find DHPS gene mutations at the commonest positions of codon 55 and 57; however, mutation at codon 171 was detected in two cases. No mutations in DHFR gene were detected. The results indicate low prevalence of DHPS and DHFR mutations in Indian P. jirovecii isolates, suggesting that the selective pressure of sulfa drugs on the local strains has probably not reached the levels found in developed nations.

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References

  1. Friaza V, Morilla R, Respaldiza N, et al. Pneumocystis jiroveci dihydropteroate synthase gene mutations among colonized individuals and Pneumocystis pneumonia patients from Spain. Postgrad Med. 2012;122:24–8.

    Article  Google Scholar 

  2. Tyagi AK, Mirdha BR, Luthra K, et al. Study of dihydropteroate synthase (DHPS) gene mutations among isolates of Pneumocystis jirovecii. Indian J Med Res. 2008;128:734–9.

    CAS  PubMed  Google Scholar 

  3. Alvarez-Martinez M, Moreno A, Miro JM, et al. Pneumocystis jirovecii pneumonia in Spanish HIV-infected patients in the combined antiretroviral era: prevalence of dihydropteroate synthase mutations and prognostic factors of mortality. Diagn Microbiol Infect Dis. 2008;62:34–43.

    Article  CAS  PubMed  Google Scholar 

  4. Valerio A, Tronconi E, Mazza F, et al. Genotyping of Pneumocystis jirovecii pneumonia in Italian AIDS patients. Clinical outcome is influenced by dihydropteroate synthase and not by internal transcribed spacer genotype. J Acquir Immune Defic Syndr. 2007;45:521–8.

    Article  PubMed  Google Scholar 

  5. Rabodonirina M, Vaillant L, Taffé P, et al. Pneumocystis jirovecii genotype associated with increased death rate of HIV-infected patients with pneumonia. Emerg Infect Dis. 2013;19:21–8.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Taylor SM, Meshnick SR, Worodria W, et al. Low prevalence of Pneumocystis pneumonia (PCP) but high prevalence of Pneumocystis dihydropteroate synthase (dhps) gene mutations in HIV-infected persons in Uganda. PLoS One. 2012;7:e9991. doi:10.1371/journal.pone.0049991.

    Google Scholar 

  7. Yoon C, Subramanian A, Chi A, et al. Dihydropteroate synthase mutations in Pneumocystis pneumonia: impact of applying different definitions of prophylaxis, mortality endpoints and mutant in a single cohort. Med Mycol. 2013;51:568–75.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Takahashi T, Endo T, Nakamura T, et al. Dihydrofolate reductase gene polymorphisms in Pneumocystis carinii f. sp. hominis in Japan. J Med Microbiol. 2002;51:510–5.

    CAS  PubMed  Google Scholar 

  9. Costa MC, Esteves F, Antunes F, Matos O. Genetic characterization of the dihydrofolate reductase gene of Pneumocystis jirovecii isolates from Portugal. J Antimicrob Chemother. 2006;58:1246–9.

    Article  CAS  PubMed  Google Scholar 

  10. Nahimana A, Rabodonirina M, Bille J, et al. Mutations of Pneumocystis jirovecii dihydrofolate reductase associated with failure of prophylaxis. Antimicrob Agents Chemother. 2004;48:4301–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Esteves F, Gaspar J, Marques T, et al. Identification of relevant single-nucleotide polymorphisms in Pneumocystis jirovecii: relationship with clinical data. Clin Microbiol Infect. 2010;16:878–84.

    Article  CAS  PubMed  Google Scholar 

  12. Queener SF, Cody V, Pace J, et al. Trimethoprim resistance of dihydrofolate reductase variants from clinical isolates of Pneumocystis jirovecii. Antimicrob Agents Chemother. 2013;574:990–8.

    Google Scholar 

  13. Tyagi AK, Mirdha BR, Luthra K, et al. Dihydropteroate synthase (DHPS) gene mutation study in HIV-Infected Indian patients with Pneumocystis jirovecii pneumonia. J Infect Dev Ctries. 2010;4:761–6.

    CAS  PubMed  Google Scholar 

  14. Wakefield AE, Pixley FJ, Banerji S, et al. Amplification of mitochondrial ribosomal RNA sequences from Pneumocystis carinii DNA of rat and human origin. Mol Biochem Parasitol. 1990;43:69–76.

    Article  CAS  PubMed  Google Scholar 

  15. NACO. Antiretroviral Therapy guidelines for HIV infected adults and adolescents including post exposure prophylaxis. Ministry of Health and Family Welfare, Govt. of India, New Delhi; 2007. http://naco.gov.in/upload/Policies%20&%20Guidelines/7Guidelines%20for%20Prevention%20and%20Management%20of%20common%20opportunistic%20infections.pdf.

  16. Vajpayee M, Kanswal S, Seth P, et al. Spectrum of opportunistic infections and profiles of CD4 cell counts among AIDS patients in Northern India. Infection. 2003;31:336–40.

    CAS  PubMed  Google Scholar 

  17. Udwadia ZF, Doshi AV, Bhaduri AS. Pneumocystis carinii pneumonia in HIV infected patients from Mumbai. JAPI. 2005;53:437–40.

    CAS  PubMed  Google Scholar 

  18. Chawla K, Martena S, Gurung B, et al. Role of PCR for diagnosing Pneumocystis jirovecii pneumonia in HIV-infected individuals in a tertiary care hospital in India. Indian J Pathol Microbiol. 2011;54:326–9.

    Article  PubMed  Google Scholar 

  19. Lowe DM, Rangaka MX, Gordon F, et al. Pneumocystis jirovecii pneumonia in tropical and low and middle income countries: a systematic review and meta-regression. PLoS One. 2013;8:e69969. doi:10.1371/journal.pone.0069969.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Fisk DT, Meshnick S, Kazanjian PH. Pneumocystis carinii pneumonia in patients in the developing world who have acquired immunodeficiency syndrome. Clin Infect Dis. 2003;36:70–8.

    Article  PubMed  Google Scholar 

  21. Wissmann G, Alvarez-Martinez M, Meshnick S, et al. Absence of dihydropteroate synthase mutations in Pneumocystis jirovecii from Brazilian AIDS patients. J Eukaryot Microbiol. 2006;53:305–7.

    Article  CAS  PubMed  Google Scholar 

  22. Beser J, Dini L, Botero-Kleiven S, et al. Absence of dihydropteroate synthase gene mutations in Pneumocystis jirovecii isolated from Swedish patients. Med Mycol. 2012;50:320–3.

    Article  CAS  PubMed  Google Scholar 

  23. Munoz C, Zuluaga A, Restrepo A, et al. Molecular diagnosis and detection of Pneumocystis jirovecii DHPS and DHFR genotypes in respiratory specimens from Colombian patients. Diagn Microbiol Infect Dis. 2012;72:204–13.

    Article  CAS  PubMed  Google Scholar 

  24. Robert-Gangneux F, Perrot M, Rouille A, et al. Absence of Pneumocystis dihydropteroate synthase mutants in Brittany, France. Diagn Microbiol Infect Dis. 2013;76:113–5.

    Article  PubMed  Google Scholar 

  25. Deng X, Zhuo L, Lan Y, et al. Mutational analysis of Pneumocystis jirovecii dihydropteroate synthase and dihydrofolate reductase genes in HIV-infected patients in China. J Clin Microbiol 2014; JCM.01848-14; published ahead of print 13 August 2014.

  26. Hauser PM, Nahimana A, Taffe P, et al. Interhuman transmission as a potential key parameter for geographical variation in the prevalence of Pneumocystis jirovecii dihydropteroate synthase mutations. Clin Infect Dis. 2010;51:28–33.

    Article  Google Scholar 

  27. Ma L, Borio L, Masur H, et al. Pneumocystis carinii dihydropteroate synthase but not dihydrofolate reductase gene mutations correlate with prior trimethoprim-sulfamethoxazole or dapsone use. J Infect Dis. 1999;180:1969–78.

    Article  CAS  PubMed  Google Scholar 

  28. Riebold D, Fritzsche C, Lademann M, et al. Pneumocystis jiroveci dihydropteroate synthase gene mutations at codon 171 but not at codons 55 or 57 detected in germany. Clin Infect Dis. 2006;42:582–3.

    Article  PubMed  Google Scholar 

  29. Siripattanapipong S, Leelayoova S, Mungthin M, et al. Study of DHPS and DHFR genes of Pneumocystis jirovecii in Thai HIV-infected patients. Med Mycol. 2008;46:389–92.

    Article  CAS  PubMed  Google Scholar 

  30. Matos O, Esteves F. Epidemiology and clinical relevance of Pneumocystis jirovecii Frenkel, 1976 dihydropteroate synthase gene mutations. Parasite. 2010;17:219–32.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors thank the support of all staff for collection of samples at the Department of Chest TB, Sassoon General Hospital and the NARI-VIA Clinic.

Conflict of interest

None.

Ethical standard

The study protocol was approved by the institutional ethical review boards of the National AIDS Research Institute, Pune, India and BJ Medical College and Sassoon General Hospitals, Pune, India.

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Authors and Affiliations

  1. National AIDS Research Institute, 73 ‘G’ Block, MIDC Bhosari, Pune, 411026, Maharashtra, India

    Arati Mane, Jipsi Chandra & Arun Risbud

  2. Department of Chest and TB, Sassoon General Hospitals, Pune, 411001, Maharashtra, India

    Pankaj Gujar, Rahul Lokhande, Tilak Dhamgaye & Shivhari Ghorpade

Authors
  1. Arati Mane
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  2. Pankaj Gujar
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  3. Jipsi Chandra
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  4. Rahul Lokhande
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  5. Tilak Dhamgaye
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  6. Shivhari Ghorpade
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  7. Arun Risbud
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Corresponding author

Correspondence to Arati Mane.

Additional information

The GenBank accession numbers for the dihydropteroate synthase (DHPS) gene sequences of the two mutant Pneumocystis jirovecii isolates are JX101868 and JX101869.

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Mane, A., Gujar, P., Chandra, J. et al. Pneumocystis jirovecii Infection and the Associated Dihydropteroate Synthase (DHPS) and Dihydrofolate Reductase (DHFR) Mutations in HIV-Positive Individuals from Pune, India. Mycopathologia 179, 141–145 (2015). https://doi.org/10.1007/s11046-014-9818-5

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  • DOI: https://doi.org/10.1007/s11046-014-9818-5

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