Rapid diagnostic tests for typhoid and paratyphoid (enteric) fever

Abstract

Background Differentiating both typhoid ( Salmonella Typhi) and paratyphoid ( Salmonella Paratyphi A) infection from other causes of fever in endemic areas is a diagnostic challenge. Although commercial point‐of‐care rapid diagnostic tests (RDTs) for enteric fever are available as alternatives to the current reference standard test of blood or bone marrow culture, or to the widely used Widal Test, their diagnostic accuracy is unclear. If accurate, they could potentially replace blood culture as the World Health Organization (WHO)‐recommended main diagnostic test for enteric fever. Objectives To assess the diagnostic accuracy of commercially available rapid diagnostic tests (RDTs) and prototypes for detecting Salmonella Typhi or Paratyphi A infection in symptomatic persons living in endemic areas. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, IndMED, African Index Medicus, LILACS, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) up to 4 March 2016. We manually searched WHO reports, and papers from international conferences on Salmonella infections. We also contacted test manufacturers to identify studies. Selection criteria We included diagnostic accuracy studies of enteric fever RDTs in patients with fever or with symptoms suggestive of enteric fever living in endemic areas. We classified the reference standard used as either Grade 1 (result from a blood culture and a bone marrow culture) or Grade 2 (result from blood culture and blood polymerase chain reaction, or from blood culture alone). Data collection and analysis Two review authors independently extracted the test result data. We used a modified QUADAS‐2 extraction form to assess methodological quality. We performed a meta‐analysis when there were sufficient studies for the test and heterogeneity was reasonable. Main results Thirty‐seven studies met the inclusion criteria and included a total of 5080 participants (range 50 to 1732). Enteric fever prevalence rates in the study populations ranged from 1% to 75% (median prevalence 24%, interquartile range (IQR) 11% to 46%). The included studies evaluated 16 different RDTs, and 16 studies compared two or more different RDTs. Only three studies used the Grade 1 reference standard, and only 11 studies recruited unselected febrile patients. Most included studies were from Asia, with five studies from sub‐Saharan Africa. All of the RDTs were designed to detect S. Typhi infection only. Most studies evaluated three RDTs and their variants: TUBEX in 14 studies; Typhidot (Typhidot, Typhidot‐M, and TyphiRapid‐Tr02) in 22 studies; and the Test‐It Typ...

Persistent Infection and Long-Term Carriage of Typhoidal and Nontyphoidal Salmonellae

“…Other currently commercially available enteric fever point-of-care diagnostic tests include Typhidot and Typhidot-M, which test IgM and/or IgG antibodies against a 50-kDa outer membrane protein antigen in a dot blot enzyme-linked immunosorbent assay (ELISA) format, and Tubex, which measures antibodies against S. Typhi LPS antigen by quantifying interference of binding between O9 monoclonal antibodies and LPS-coupled magnetic particles (115,116). Several other enteric fever rapid diagnostic tests were recently reviewed (117) and are not discussed further. Overall, the diagnostic accuracy for enteric fever using the currently available enteric fever rapid diagnostic tests was evaluated by a meta-analysis to have only moderate sensitivity (69 to 85%) and specificity (79 to 90%), and the authors of that study concluded that the moderate sensitivity and specificity of these tests do not justify their replacement of blood culture for enteric fever diagnosis and that there is an urgent need to develop rapid diagnostic tests for typhoid fever with better performance (116,117).…”

“…Several other enteric fever rapid diagnostic tests were recently reviewed (117) and are not discussed further. Overall, the diagnostic accuracy for enteric fever using the currently available enteric fever rapid diagnostic tests was evaluated by a meta-analysis to have only moderate sensitivity (69 to 85%) and specificity (79 to 90%), and the authors of that study concluded that the moderate sensitivity and specificity of these tests do not justify their replacement of blood culture for enteric fever diagnosis and that there is an urgent need to develop rapid diagnostic tests for typhoid fever with better performance (116,117). Thus, laboratory diagnosis of typhoid fever is still dependent mostly on the detection of bacteria in the blood by PCR (see below) or culture, despite its limited sensitivity.…”

A Comparative Study of the Typhidot (Dot-EIA) versus Widal Test in Diagnosis of Typhoid Fever among Egyptian Patients

“…It is a rapid, easy to perform, more reliable test for typhoid fever as compared to Widal. However, culture isolation of Salmonella remains essential, especially for antibiotic susceptibility testing and these serological tests should be used in conjunction with culture for the early diagnosis of enteric fever [14] [19].…”

“…Reports from different geographic regions showed that a commercially available typhidot is an inexpensive and reliable serodiagnostic test for diagnosis of typhoid fever with higher sensitivity and specificity [14] and that is why we compared typhidot with Widal test for early and accurate diagnosis of typhoid fever among Egyptian patients. In this study, typhidot showed better figures of sensitivity, specificity, positive and negative predictive values and overall diagnostic accuracy than that of Widal test in the diagnosis of typhoid against a reference of positive blood cultures and this would help early diagnosis and also early institution of therapy.…”

Screening for Salmonella typhi Serum Antibodies and Stool Antigen among Undergraduate Students of Babcock University, Ilishan-Remo, Ogun State, Nigeria

“…With regard to the symptomatology of S. typhi infection among the study participants, percentage of students without symptoms (18.0%) were non-significantly (P>0.05) higher than those with symptoms (16%). Report by Mallett et al [25], revealed that most typhoid fever cases diagnosed with RDT kits are mostly asymptomatic and may go undiagnosed. In this study, we defined symptomatic S. typhi infection as the presence of one or more of the immunological marker (anti-S. typhi IgM Ab, IgG Ab or stool Ag) in the presence of one or more signs and symptoms of typhoid fever in the participants.…”