Occurrence of Typhoid Fever Complications and Their Relation to Duration of Illness Preceding Hospitalization: A Systematic Literature Review and Meta-analysis

Abstract

Background: Complications from typhoid fever disease have been estimated to occur in 10%-15% of hospitalized patients, with evidence of a higher risk in children and when delaying the implementation of effective antimicrobial treatment. We estimated the prevalence of complications in hospitalized patients with culture-confirmed typhoid fever and the effects of delaying the implementation of effective antimicrobial treatment and age on the prevalence and risk of complications.

Methods: A systematic review and meta-analysis were performed using studies in the PubMed database. We rated risk of bias and conducted random-effects meta-analyses. Days of disease at hospitalization (DDA) was used as a surrogate for delaying the implementation of effective antimicrobial treatment. Analyses were stratified by DDA (DDA <10 versus ≥10 mean/median days of disease) and by age (children versus adults). Differences in risk were assessed using odds ratios (ORs) and 95% confidence intervals (CIs). Heterogeneity and publication bias were evaluated with the I2 value and funnel plot analysis, respectively.

Results: The pooled prevalence of complications estimated among hospitalized typhoid fever patients was 27% (95% CI, 21%-32%; I2 = 90.9%, P < .0001). Patients with a DDA ≥ 10 days presented higher prevalence (36% [95% CI, 29%-43%]) and three times greater risk of severe disease (OR, 3.00 [95% CI, 2.14-4.17]; P < .0001) than patients arriving earlier (16% [95% CI, 13%- 18%]). Difference in prevalence and risk by age groups were not significant.

Conclusions: This meta-analysis identified a higher overall prevalence of complications than previously reported and a strong association between duration of symptoms prior to hospitalization and risk of serious complications.

Keywords: complications; meta-analysis; prevalence; risk factors; typhoid fever.

Figure 1.

Study selection flow diagram (1990–2018).

Figure 2.

Forest plots showing the overall and subgroup prevalence of typhoid fever complications among hospitalized patients (1990–2018), by illness duration at hospitalization (A) and age (B). Abbreviations: A adults; All, all ages; C, children; CI, confidence interval; Comp, complications; DDA, mean/median illness duration (days) at hospitalization; ES, estimated prevalence; ID, study ID, study identification-first author (year of publication); MDR, multidrug antimicrobial resistance reported in each study; NR, not reported.

Figure 3.

Frequency (pooled across the studies reporting the complications and illness duration at hospitalization) of typhoid fever complications (1990–2018). Abbreviation: DDA, mean/median illness duration at hospitalization.