Dynamics of Typhoid Fever outbreaks during 2000-2022: a systematic review and meta-analysis with time-series data

Abstract

Background: Typhoid fever is a systemic infection caused by Salmonella enterica serovars Typhi. Typhoid remains a substantial global health concern, particularly in regions with inadequate water and sanitation infrastructure. The emergence of antimicrobial resistance (AMR) of typhoid fever further complicates the landscape, necessitating in-depth comprehension of the typhoid outbreak dynamics. This study explores typhoid fever outbreaks spanning the years 2000 to 2022 aiming to understand outbreak patterns and dynamics using the effective reproduction number (R(t)). Methods: A systematic review identified forty outbreaks, adhering to the Cochrane Handbook and PRISMA guidelines. PubMed, OVID-Medline, and OVID-Embase were meticulously searched to identify relevant studies reporting time-series data on typhoid outbreaks. Eligible studies included those with diagnostic confirmation via blood or bone marrow culture or Rapid Diagnostic Tests (RDT) or Widal test. Meta-analyses for attack rates, Case Fatality Rates (CFR), hospitalization, and complications rates were performed. Furthermore, the effective reproduction number (R(t)) was estimated for thirty-four outbreaks excluding uncalculatable six outbreaks. Additional subgroup analyses by World Health Organization regions, investigation settings, and AMR status were performed to investigate the dynamics of typhoid fever. Results: Among the 1,406 publications initially screened, thirty-six articles with forty distinct typhoid outbreaks met the inclusion criteria. These outbreaks exhibited geographical concentration, primarily afflicting the African and South-East Asian regions. The meta-analysis unveiled a pooled estimate; attack rate of 0.98%, CFR of 0.53%, hospitalization rate of 37.68%, and complication rate of 10.17%. Age-specific distributions emphasized vulnerability among children and adolescents. The effective reproduction number (R(t)) displayed significant variation across outbreaks and WHO regions, underscoring the complex nature of typhoid transmission dynamics. Conclusion: This research offers an in-depth understanding of the heterogeneous landscapes of typhoid fever outbreaks, highlighting geographical variances, age-related susceptibilities, and dynamic transmission patterns. The quantification of the effective reproduction number (R(t)) contributes significantly to the understanding of transmission dynamics, thereby informing future research and policy directions. Despite challenges in standardizing definitions and data variability, this research underscores the importance of targeted preventive measures and interdisciplinary approaches in mitigating typhoid outbreaks. Moving forward, a multidisciplinary global effort is warranted to address the multifaceted dimensions of this persistent threat of typhoid fever.