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

Christian S Marchello,Megan Birkhold,John A Crump

doi:10.1016/j.jinf.2020.10.030

Christian S Marchello, Megan Birkhold + Show 1 more

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https://doi.org/10.1016/j.jinf.2020.10.030

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Abstract

Updated estimates of the prevalence of complications and case fatality ratio (CFR) among typhoid fever patients are needed to understand disease burden. Articles published in PubMed and Web of Science from 1 January 1980 through 29 January 2020 were systematically reviewed for hospital or community-based non-surgical studies that used cultures of normally sterile sites, and hospital surgical studies of typhoid intestinal perforation (TIP) with intra- or post-operative findings suggestive of typhoid. Prevalence of 21 pre-selected recognized complications of typhoid fever, crude and median (interquartile range) CFR, and pooled CFR estimates using a random effects meta-analysis were calculated. Of 113 study sites, 106 (93.8%) were located in Asia and Africa, and 84 (74.3%) were non-surgical. Among non-surgical studies, 70 (83.3%) were hospital-based. Of 10,355 confirmed typhoid patients, 2,719 (26.3%) had complications. The pooled CFR estimate among non-surgical patients was 0.9% for the Asia region and 5.4% for the Africa region. Delay in care was significantly correlated with increased CFR in Asia (r = 0.84; p<0.01). Among surgical studies, the median CFR of TIP was 15.5% (6.7-24.1%) per study. Our findings identify considerable typhoid-associated illness and death that could be averted with prevention measures, including typhoid conjugate vaccine introduction.

Highlights

Typhoid fever is caused by the organism Salmonella enterica subspecies enterica serovar Typhi (Salmonella Typhi); a systematic infection transmitted predominantly through water or food contaminated by human feces.1–3 Typhoid fever presents clinically across a spectrum of severity with a range of symptoms and signs including fever, abdominal pain, nausea, and vomiting, that make differentiating it from other febrile and gastrointestinal illnesses challenging.2 The ‘gold standard’ diagnostic method for typhoid fever is the culture of blood, bone marrow, or another normally sterile site
Our systematic review of published literature from 1980 through 2020 of predominantly hospitalized typhoid fever patients demonstrates a substantial prevalence of typhoid complications and death
Among hospital-based non-surgical studies, the case fatality ratio (CFR) of typhoid fever was significantly higher in Africa compared to Asia

Summary

Introduction

Typhoid fever is caused by the organism Salmonella enterica subspecies enterica serovar Typhi (Salmonella Typhi); a systematic infection transmitted predominantly through water or food contaminated by human feces. Typhoid fever presents clinically across a spectrum of severity with a range of symptoms and signs including fever, abdominal pain, nausea, and vomiting, that make differentiating it from other febrile and gastrointestinal illnesses challenging. The ‘gold standard’ diagnostic method for typhoid fever is the culture of blood, bone marrow, or another normally sterile site. Typhoid fever presents clinically across a spectrum of severity with a range of symptoms and signs including fever, abdominal pain, nausea, and vomiting, that make differentiating it from other febrile and gastrointestinal illnesses challenging.. The ‘gold standard’ diagnostic method for typhoid fever is the culture of blood, bone marrow, or another normally sterile site. Clinical microbiology services are not widely available in endemic areas and culture-based diagnosis has incomplete sensitivity.. And accurate diagnosis and treatment of typhoid fever in the community is needed to avert complications requiring hospitalization, and death.. Typhoid complications include typhoid intestinal perforation (TIP), gastrointestinal hemorrhage, hepatitis, cholecystitis, myocarditis, shock, encephalopathy, pneumonia, and anemia.. TIP and gastrointestinal hemorrhage are serious complications that are often fatal, even if managed surgically. And accurate diagnosis and treatment of typhoid fever in the community is needed to avert complications requiring hospitalization, and death. Typhoid complications include typhoid intestinal perforation (TIP), gastrointestinal hemorrhage, hepatitis, cholecystitis, myocarditis, shock, encephalopathy, pneumonia, and anemia. TIP and gastrointestinal hemorrhage are serious complications that are often fatal, even if managed surgically.

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