Case Series of Enteric Fever–Associated Hemophagocytic Lymphohistiocytosis

Background: Enteric fever caused by Salmonella typhi ( S. typhi ) was the most dreaded infection in developing countries. Improved living conditions, vaccination, and the introduction of antibiotics led to marked decline in typhoid fever–related morbidity and mortality in industrialized nations. But recently, morbidity and mortality have shown a surge because of growing antimicrobial resistance, and a new complication observed—secondary hemophagocytic lymphohistiocytosis (HLH). We present 5 pediatric cases of enteric fever complicated by HLH, along with the antibiotic sensitivity patterns of S. typhi isolates observed in our hospital over 1 year. Methods: We retrospectively reviewed the clinical records of 5 pediatric patients admitted to our tertiary care hospital between October 2024 and September 2025 with blood culture–proven Salmonella typhi infection complicated by HLH. Antimicrobial sensitivity patterns were analyzed. HLH was diagnosed on the basis of the H score. Results: Although all our cultures were sensitive (microbiologically) to ceftriaxone, some needed higher antibiotics and steroids. For XDR (ceftriaxone-resistant) strains, the antibiotics are limited to azithromycin (oral), carbapenems, and tigecycline (parenteral). Our observations underscore that Salmonella typhi has reemerged as a double-edged sword—not only due to rising antimicrobial resistance but also because of its association with severe complications such as HLH. All 5 patients fulfilled the criteria for HLH based on the H score, though none met the full HLH-2004 criteria due to limited testing. The onset of HLH ranged from day 6 to day 13 of illness. Only 2 patients received corticosteroids—case 1 (encephalitis) and case 5 (shock). Conclusions: HLH remains an important differential diagnosis in prolonged or severe typhoid fever. Evaluation of H score provides a tool for extra vigilant approach as management requires a balanced approach between antimicrobial escalation and selective immunosuppression.