Geographic and Behavioral Determinants of Typhoid and Antimicrobial Resistance in Children Across Urban, Rural, and Nomadic Populations of Punjab, Pakistan

<b>Background/Objectives</b>: This study aimed to determine the antimicrobial susceptibility patterns of multidrug resistant (MDR) and extensively resistant (XDR) <i>Salmonella enterica serovar</i> Typhi (<i>S</i>. Typhi) strains among children, along with the associated behavioral and environmental risk factors across different population groups in multiple districts of Punjab, Pakistan. <b>Methods</b>: A cross-sectional study was conducted across 20 districts in Punjab, Pakistan. Structured questionnaires were used to assess sociodemographic and behavioral determinants. Blood cultures from febrile children were obtained for the isolation and identification of <i>S</i>. Typhi, followed by antimicrobial susceptibility testing and screening for the resistance genes. <b>Results</b>: A total of 900 blood samples were collected and 41.5% were positive for <i>S</i>. Typhi. The proportion of culture-positive cases were higher among children aged 6-12 years (34.8%). Sociodemographic and behavioral analysis revealed that children from low-income households (PKR < 20,000 showed significantly higher infection rate (67.1%, <i>p</i> < 0.001). Antimicrobial susceptibility testing revealed high resistance rates against several antibiotics: Ciprofloxacin (88.8%), Trimethoprim/sulfamethoxazole (83.7%), Ampicillin (73.8%) and Chloramphenicol (72.7%). However, all isolates remained susceptible to carbapenems and azithromycin. The prevalence of MDR and XDR <i>S.</i> Typhi in urban areas was 28.1% and 60.8%, respectively, while rural areas showed 22.6% MDR and 20.6% XDR. In contrast, nomadic populations exhibited a higher rate of MDR (49.3%) but a lower XDR prevalence of 18.6% with significant geographic variations in resistance patterns. Molecular analysis revealed a high prevalence of resistance genes, including <i>sul1</i> (83.7%), <i>sul2</i> (79.7%), followed by <i>dfrA7</i> (81.3%), <i>catA1</i> (64.9%) and <i>bla</i>_TEM (60.5%), <i>bla</i>_CTX-M-1 (12.5%), <i>bla</i>_CTX-M-15 (25.9%) and <i>qnrS</i> (88.8%), respectively. <b>Conclusions</b>: The study underscores a persistent typhoid burden and widespread antimicrobial resistance among children in Punjab. Targeted vaccination, antibiotic stewardship, public health education are urgently needed, especially among the nomadic population, where healthcare access and hygiene awareness are limited.