Evaluation of the Diagnostic Accuracy of a Typhoid IgM Flow Assay for the Diagnosis of Typhoid Fever in Cambodian Children Using a Bayesian Latent Class Model Assuming an Imperfect Gold Standard

Abstract

Rapid diagnostic tests are needed for typhoid fever (TF) diagnosis in febrile children in endemic areas. Five hundred children admitted to the hospital in Cambodia between 2009 and 2010 with documented fever (≥ 38°C) were investigated using blood cultures (BCs), Salmonella Typhi/Paratyphi A real-time polymerase chain reactions (PCRs), and a Typhoid immunoglobulin M flow assay (IgMFA). Test performance was determined by conventional methods and Bayesian latent class modeling. There were 32 cases of TF (10 BC- and PCR-positive cases, 14 BC-positive and PCR-negative cases, and 8 BC-negative and PCR-positive cases). IgMFA sensitivity was 59.4% (95% confidence interval = 41–76), and specificity was 97.8% (95% confidence interval = 96–99). The model estimate sensitivity for BC was 81.0% (95% credible interval = 54–99). The model estimate sensitivity for PCR was 37.8% (95% credible interval = 26–55), with a specificity of 98.2% (95% credible interval = 97–99). The model estimate sensitivity for IgMFA (≥ 2+) was 77.9% (95% credible interval = 58–90), with a specificity of 97.5% (95% credible interval = 95–100). The model estimates of IgMFA sensitivity and specificity were comparable with BCs and better than estimates using conventional analysis.

Validity of Immunoglobulin M Anti Salmonella typhi Serologic Test in Childhood Typhoid Fever

“…5,8 Positivity rate of blood culture was considered low. In contrast to a previous study which stated that the best period for blood culture is day <7 of disease, [14][15][16] the highest rate was noted on day 7. Low positivity rates of blood culture, which was also reported in a previous study, may as well be results from prior antibiotic use.…”

“…High sensitivity and low specificity of the test were also reported in the childrenpopulated study performed by Narayanappa, et al 11 This retrospective study was a hospitalbased study where most patients had previously visited the primary health care. Children with 1-14 days of fever were included because the best period of blood culture are the first few days of disease [14][15][16] and the best period of IgM anti S. typhi serologic test is the second week of disease. 5,8 The facts that antibiotics were widely used prior to the admission of patients could make the number of study subjects even lower and impossible to conduct this study; thus, children with prior antibiotic use were not excluded.…”

Epidemiology, Clinical Presentation, Laboratory Diagnosis, Antimicrobial Resistance, and Antimicrobial Management of Invasive Salmonella Infections

“…The specificity among patients with other conditions has usually been 100%. Several studies have reported patients with clinically suspected typhoid who are PCR positive and blood culture negative (266,272). The absence of a perfect reference standard makes interpretation of these results challenging.…”

“…The sensitivity of PCR without enrichment in blood-culture positive cases has exceeded 90% in some studies (271,273,(278)(279)(280)(281)(282)(283)(284)(285)(286), although other studies have reported much lower sensitivities more consistent with the number of bacteria in the blood (266,272,287). Bone marrow aspirates were examined in one study, with 100% sensitivity (287), and positive results have also been found in urine samples (288).…”

“…A modification for paratyphoid diagnosis has recently been developed (264). The Royal Tropical Institute (KIT), Netherlands, has developed a test detecting IgM against LPS using a dipstick, latex agglutination, and, most recently, a lateral-flow format (LifeAssay, Cape Town, South Africa) (249,265,266). Studies using the lateral-flow test report sensitivities of 60% and specificities of 98%.…”