Case Fatality Rate of Enteric Fever in Endemic Countries: A Systematic Review and Meta-analysis

Abstract

Enteric fever is a febrile illness, occurring mostly in Asia and Africa, which can present as a severe and possibly fatal disease. Currently, a case fatality rate (CFR) of 1% is assumed when evaluating the global burden of enteric fever. Until now, no meta-analysis has been conducted to summarize mortality from enteric fever. Therefore, we conducted a systematic review and meta-analysis to aggregate all available evidence. We estimated an overall CFR of 2.49% (95% confidence interval, 1.65%-3.75%; n = 44), and a CFR in hospitalized patients of 4.45% (2.85%-6.88%; n = 21 of 44). There was considerably heterogeneity in estimates of the CFR from individual studies. Neither age nor antimicrobial resistance were significant prognostic factors, but limited data were available for these analyses. The combined estimate of the CFR for enteric fever is higher than previously estimated, and the evaluation of prognostic factors, including antimicrobial resistance, urgently requires more data.

Figure 1.

Flow diagram of the study selection process.

Figure 2.

Forest plot for the case fatality rate (CFR) of enteric fever. The overall estimate was obtained from a random intercept logistic regression model. I² = 94.7%. The 95% confidence intervals (CIs) of the individual studies were Wilson score intervals, and the CI of the overall estimate was based on a t distribution. Abbreviations: n, number of cases; Y, number of deaths.

Figure 3.

Forest plot for the odds of dying of enteric fever in children (≤15 years of age) versus adults (>15 years of age). The overall estimate was obtained from a random intercept logistic regression model. I² = 76.3%. The 95% confidence intervals (CIs) of the individual studies were Wilson score intervals, and the 95% CI of the overall estimate was based on a t distribution. Abbreviations: n, number of cases; OR, odds ratio; Y, number of deaths.

Figure 4.

Forest plot for the odds of dying of enteric fever when infected with a resistant versus a sensitive strain. The overall estimate was obtained from a random intercept logistic regression model. I² = 0%. The 95% confidence intervals (CIs) of the individual studies were Wilson score intervals, and the 95% CI of the overall estimate was based on a t distribution. Abbreviations: AMR, antimicrobial resistance; AMS, antimicrobial sensitivity; n, number of cases; OR, odds ratio; Y, number of deaths.

Figure 5.

Risk of bias assessment. The proportion of all studies (n = 42) judged to have high (black), low (dark gray), or unclear (light gray) risk of bias is plotted for each of the 4 categories: measurement, attrition, surveillance, and population bias. Studies reporting a separate case fatality rate for typhoid and paratyphoid fever were included only once.