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

Abstract

BackgroundComplications 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.MethodsA 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.ResultsThe 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.ConclusionsThis 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.

Complications and mortality of typhoid fever: A global systematic review and meta-analysis

“…Others have linked duration of illness prior to hospitalization with increased prevalence of typhoid complications. 19 Intestinal perforation was a common complication and an important contributor to typhoid mortality, especially in African studies where one in five patients with TIP died. A lack of access to surgical services and resources for post-operative management and intensive care, if needed, likely contribute to the high CFR seen among TIP patients.…”

“…Furthermore, some past reviews were restricted by location, population, or age. 10 , 16 , 17 , 18 , 19 In order to support country-level decisions on typhoid control, including TCV introduction, and to provide contemporary estimates of morbidity and mortality, we performed a systematic review and meta-analysis of the prevalence of complications and case fatality ratio (CFR) among patients with typhoid fever.…”

Primary Spontaneous Pneumothorax in Typhoid

“…Extra-intestinal complication of typhoid disease is a known clinical phenomenon. A recent systematic review showed a higher pooled prevalence of typhoid fever complications from studies including children 27% (95% CI, 19%-35%) than from studies including adults 17% (95% CI, 9%-25%), although with a very high heterogeneity for both groups [ 7 ]. Among extra-intestinal complications, pulmonary complications are relatively common.…”

The Severe Typhoid Fever in Africa Program Highlights the Need for Broad Deployment of Typhoid Conjugate Vaccines

“…Both articles demonstrate the high spatiotemporal variability of typhoid disease, which has significant implications for vaccination strategies and other control measures. The third meta-analysis showed that 25% of hospitalized typhoid fever patients had complications, and a 36% higher prevalence of complications among those patients reporting having symptoms for ≥10 days at time of hospitalization [23] All three studies are limited by lack of standardized, comparable surveillance data and systems.…”