Speakers - 2025

Biography

Working as a professor in the Department of Microbiology, AIIMS, New Delhi. Academic activity includes teaching UG (MBBS) and postgraduate medical (MD) and DM (infectious disease) students and guiding PhD students. Research activities include understanding host-pathogen relations and molecular epidemiology of Streptococcus pneumoniae, Haemophilus influenzae, and Meningococcal meningitidis. Interest also involves understanding HIV immunology. Had been involved in vaccine development of rotavirus vaccine for India which  led to the development, licensing and finally implementation of the rotavirus vaccine (Rotavac)  based on  AIIMS neonatal rotavirus 116E , currently a part of expanded program of immunization for children in  India
 

Abstract

Introduction: Typhoid fever, a systemic febrile illness caused by Salmonella Typhi (S. Typhi), has a complex history of ofongoing adaptation and progressive build-up of resistance to commonly used antibiotics. Since the XDR (resistant to chloramphenicol, trimethoprim-sulfamethoxazole, ampicillin, fluoroquinolones, and third-generation cephalosporins) typhoid fever outbreak in Sindh, Pakistan, cases from different parts of the world have been reported, but no XDR case has been reported from India until now. To better understand the seasonal dynamics in India to aid the evaluation of disease surveillance and control efforts, we analyze the typhoid data from 2017 to 2024. 

Overall, the data was divided into two groups: pre-COVID-19 (2017-2019) and post-COVID-19 (2020-2024), which also includes the isolation of one XDR Salmonella Typhi in 2023.

Methods:

All the culture-positive enteric fever cases during 2017–2024 presenting to our hospital were included in the study. Antimicrobial susceptibility was done against amoxicillin, chloramphenicol, cotrimoxazole, ciprofloxacin, levofloxacin, ofloxacin, pefloxacin, ceftriaxone, and azithromycin as per corresponding CLSI guidelines for each year.

Whole-genome sequencing (WGS): WGS was carried out outfor molecular characterization of the XDR isolate with paired-end 2 x 150 bp reads on Illumina MiSeq (Illumina, USA) employing v2 and v3 chemistry. 

Results: Total isolation of blood culture positive typhoidal Salmonella was 596 during the study period (2017-2024). Out of which Salmonella Paratyphi A was 117, followed by 479 Salmonella Typhi.

Pre-COVID-19, fluoroquinolones (CIP, LEV, OFL) show notable non-susceptibility, which is 14–20%, followed by 74–89% intermediate susceptibility and exhibiting only 2–6% susceptibility.

While ceftriaxone and cefixime showed complete susceptibility, azithromycin resistance was observed in 2% of isolates. Resistance to chloramphenicol, cotrimoxazole, and ampicillin (MDR) was recorded in 2-3% of isolates.

Post-COVID-19, fluoroquinolones (CIP, LEV, OFL) show an increase in non-susceptibility, which is 28–52%, followed by 69–44% intermediate susceptibility and exhibiting only 3–4% susceptibility.

In the case of ceftriaxone and cefixime, marginal resistance starts appearing with the isolation of XDR Salmonella Typhi, while azithromycin azithromycinresistance was observed in 2% of Salmonella Paratyphi A. In the case of Salmonella Typhi, though there was an increased MIC, it was completely sensitive. Resistance to chloramphenicol, cotrimoxazole, and ampicillin (MDR) was again observed in 2-3% of isolates.

WGS analysis-—genomic analysis revealed this isolate belongs to H58 lineage 1 (genotype 4.3.1.1). It carried mutations in gyrBS464F, aac6-Ib-cr, and qnrB genes responsible for resistance to ciprofloxacin and other fluoroquinolones; blaCTX-M-15_23; blaOXA-1; blaTEM-1D for ampicillin resistance; blaCTX-M-15_23 for cephalosporin resistance; catA1 for chloramphenicol resistance; dfrA1; dfrA7; sul1; and sul2 for trimethoprim-sulfamethoxazole resistance. The presence of IncR plasmid was also observed. The genomic analysis revealed a resistance pattern consistent with XDR, aligning with the outbreak reported in Pakistan. Interestingly, the strain displayed a new lineage, distinct from known XDR isolates in Pakistan.

Conclusion: These results support the fact that ceftriaxone resistance in India is evolving independently. Azithromycin remains the available treatment option for XDR S. Typhi since most isolates in India are currently susceptible to azithromycin, with only occasional reports indicating an increase in MIC.