Genetic polymorphisms associated with treatment failure and mortality in pediatric Pneumocystosis

Yogita Singh1, Bijay Ranjan Mirdha2, Randeep Guleria3

  • 1All India Institute of Medical Sciences, Department of Microbiology, New Delhi, 110029, India.

Scientific Reports
|February 6, 2019
PubMed

Insights

New data reveals specific Pneumocystis jirovecii genotypes in Indian children are linked to severe Pneumocystis pneumonia (PCP), treatment failure, and high mortality, highlighting the need for genotype-focused research.

Area of Science:

  • Medical Microbiology
  • Infectious Diseases
  • Pediatric Pulmonology

Background:

  • Limited data exists on Pneumocystis jirovecii genetic diversity in children, especially from the Indian subcontinent.
  • Understanding genotype-clinical characteristic associations is crucial for managing Pneumocystis pneumonia (PCP).

Purpose of the Study:

  • To investigate the genetic diversity of Pneumocystis jirovecii in pediatric PCP cases from the Indian subcontinent.
  • To determine associations between Pneumocystis jirovecii genotypes and clinical outcomes, including severity and treatment response.

Main Methods:

  • Genotyping of Pneumocystis jirovecii using mitochondrial large subunit ribosomal RNA (mtLSUrRNA), dihydropteroate synthase (DHPS), and dihydrofolate reductase (DHFR) genes.
  • Diagnosis of Pneumocystis pneumonia (PCP) via microscopy and nested PCR.
  • Phylogenetic analysis to identify sequence types (STs) and their clinical correlations.

Main Results:

  • mtLSUrRNA genotype 3 and novel mutations in DHFR (401T>C) and DHPS (96/98) were frequently observed.
  • Specific sequence types (STs), including 3-DHFR 401T>C-DHPS 96/98 - PJ1 and 3-DHFR 401T>C-DHPS 96 - PJ3, were significantly associated with treatment failure and high mortality.
  • The study identified 13 unique sequence types among the 37 pediatric cases.

Conclusions:

  • The findings suggest the emergence of virulent Pneumocystis jirovecii strains or genetic polymorphisms contributing to treatment failure and mortality in pediatric PCP.
  • This study is the first from the Indian subcontinent to report on the genetic diversity of Pneumocystis jirovecii in children and its clinical impact.
  • Further research focusing on Pneumocystis jirovecii genotypes is essential for understanding PCP epidemiology and improving patient outcomes.

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