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Published on: April 1, 2019
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.
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.
Abstract:
Data on the genetic diversity of Pneumocystis jirovecii causing Pneumocystis pneumonia (PCP) among children are still limited, and there are no available data from the Indian subcontinent, particularly associations between genotypes and clinical characteristics. A total of 37 children (62 days-12 years [median 5.5 years]) were included in this study. Pneumocystis was diagnosed by microscopy using Grocott-Gomori methenamine silver stain in 12 cases and by nested PCR using mtLSUrRNA in 25 cases. Genotyping was performed using three different genes, mitochondrial large subunit ribosomal RNA (mtLSUrRNA), dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR). mtLSUrRNA genotype 3 and novel mutations at the gene target DHFR (401 T > C) and DHPS 96/98 were frequently observed and clinically associated with severe PCP and treatment failure. Phylogenetic analyses revealed 13 unique sequence types (STs). Two STs (i) 3-DHFR 401 T > C-DHPS 96/98 - PJ1 and (ii) 3-DHFR 401 T > C-DHPS 96- PJ3 were significantly associated with treatment failure and high mortality among PCP-positive patients. In conclusion, the present study strongly suggests the emergence of virulent P. jirovecii strains or genetic polymorphisms, leading to treatment failure and high mortality. Our study is the first of its kind from the Indian subcontinent and has highlighted the genetic diversity of Pneumocystis jirovecii among children and their clinical outcomes. These findings emphasize the need to focus more on genotypes to better understand the epidemiology of Pneumocystis pneumonia.
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