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

Catrin E Moore, Wirichada Pan-Ngum, Lalith P M Wijedoru, Soeng Sona, Tran Vu Thieu Nga, Pham Thanh Duy, Phat Voong Vinh, Kheng Chheng, Varun Kumar, Kate Emary, Michael Carter, Lisa White, Stephen Baker, Nicholas P J Day, Christopher M Parry, Catrin E Moore, Wirichada Pan-Ngum, Lalith P M Wijedoru, Soeng Sona, Tran Vu Thieu Nga, Pham Thanh Duy, Phat Voong Vinh, Kheng Chheng, Varun Kumar, Kate Emary, Michael Carter, Lisa White, Stephen Baker, Nicholas P J Day, Christopher M Parry

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.

Figures

Figure 1.
Figure 1.
Flowchart showing enrolment of 500 children admitted to the study. BC = blood culture; pos = positive.
Figure 2.
Figure 2.
Duration of illness before admission to hospital in patients with a positive laboratory test (blood culture-, PCR-, or IgMFA-positive at two or higher). Each bar denotes the duration of illness ( 7 days).

References

    1. Karkey A, Aryjal A, Basnyat B, Baker S. Kathmandu, Nepal: still an enteric fever capital of the world. J Infect Dev Ctries. 2008;2:461–465.
    1. Crump JA, Luby SP, Mintz ED. The global burden of typhoid fever. Bull World Health Organ. 2004;82:346–353.
    1. Petit PL, Wamola IA. Typhoid fever: a review of its impact and diagnostic problems. East Afr Med J. 1994;71:183–188.
    1. Bhutta ZA. Current concepts in the diagnosis and treatment of typhoid fever. BMJ. 2006;333:78–82.
    1. Dance D, Richens JE, Ho M, Acharya G, Pokhrel B, Tuladhar NR. Blood and bone marrow cultures in enteric fever. J Clin Pathol. 1991;44:1038.
    1. Wain J, Diep TS, Ho VA, Walsh AM, Nguyen TT, Parry CM, White NJ. Quantitation of bacteria in blood of typhoid fever patients and relationship between counts and clinical features, transmissibility, and antibiotic resistance. J Clin Microbiol. 1998;36:1683–1687.
    1. Wain J, Pham VB, Ha V, Nguyen NM, To SD, Walsh AL, Parry CM, Hasserjian RP, HoHo VA, Tran TH, Farrar J, White NJ, Day NP. Quantitation of bacteria in bone marrow from patients with typhoid fever: relationship between counts and clinical features. J Clin Microbiol. 2001;39:1571–1576.
    1. Nga TV, Karkey A, Dongol S, Thuy HN, Dunstan S, Holt K, Tu le TP, Campbell JI, Chau TT, Chau NV, Arjyal A, Koirala S, Basnyat B, Dolecek C, Farrar J, Baker S. The sensitivity of real-time PCR amplification targeting invasive Salmonella serovars in biological specimens. BMC Infect Dis. 2010;10:125.
    1. Parry CM, Wijedoru L, Arjyal A, Baker S. The utility of diagnostic tests for enteric fever in endemic locations. Expert Rev Anti Infect Ther. 2011;9:711–725.
    1. Dutta S, Sur D, Manna B, Sen B, Deb AK, Deen JL, Wain J, Von Seidlein L, Ochiai L, Clemens JD, Kumar Bhattacharya S. Evaluation of new-generation serologic tests for the diagnosis of typhoid fever: data from a community-based surveillance in Calcutta, India. Diagn Microbiol Infect Dis. 2006;56:359–365.
    1. Keddy KH, Sooka A, Letsoalo ME, Hoyland G, Chaignat CL, Morrissey AB, Crump JA. Sensitivity and specificity of typhoid fever rapid antibody tests for laboratory diagnosis at two sub-Saharan African sites. Bull World Health Organ. 2011;89:640–647.
    1. Wijedoru LP, Kumar V, Chanpheaktra N, Chheng K, Smits HL, Pastoor R, Nga TV, Baker S, Wuthiekanun V, Peacock SJ, Putchhat H, Parry CM. Typhoid fever among hospitalized febrile children in Siem Reap, Cambodia. J Trop Pediatr. 2012;58:68–70.
    1. Pastoor R, Hatta M, Abdoel T, Smits H. Simple, rapid, and affordable point-of-care test for the serodiagnosis of typhoid fever. Diagn Microbiol Infect Dis. 2008;61:129–134.
    1. Kasper MR, Sokhal B, Blair PJ, Wierzba TF, Putnam SD. Emergence of multidrug-resistant Salmonella enterica serovar Typhi with reduced susceptibility to fluoroquinolones in Cambodia. Diagn Microbiol Infect Dis. 2010;66:207–209.
    1. Emary K, Moore CE, Chanpheaktra N, An KP, Chheng K, Sona S, Duy PT, Nga TV, Wuthiekanun V, Amornchai P, Kumar V, Wijedoru L, Stoesser NE, Carter MJ, Baker S, Day NP, Parry CM. Enteric fever in Cambodian children is dominated by multidrug-resistant H58 Salmonella enterica serovar Typhi with intermediate susceptibility to ciprofloxacin. Trans R Soc Trop Med Hyg. 2012;106:718–724.
    1. Chheng K, Carter MJ, Emary K, Chanpheaktra N, Moore CE, Stoesser N, Putchhat H, Sona S, Reaksmey S, Kitsutani P, Sar B, van Doorn HR, Uyen NH, Van Tan L, Paris D, Blacksell SD, Amornchai P, Wuthiekanun V, Parry CM, Day NP, Kumar V. A prospective study of the causes of febrile illness requiring hospitalization in children in Cambodia. PLoS One. 2013;8:e60634.
    1. Vlieghe ER, Phe T, De Smet B, Veng HC, Kham C, Lim K, Koole O, Lynen L, Peetermans WE, Jacobs JA. Bloodstream infection among adults in Phnom Penh, Cambodia: key pathogens and resistance patterns. PLoS One. 2013;8:e59775.
    1. Limmathurotsakul D, Jamsen K, Arayawichanont A, Simpson JA, White LJ, Lee SJ, Wuthiekanun V, Chantratita N, Cheng A, Day NP, Verzilli C, Peacock SJ. Defining the true sensitivity of culture for the diagnosis of melioidosis using Bayesian latent class models. PLoS One. 2010;5:e12485.
    1. Limmathurotsakul D, Turner EL, Wuthiekanun V, Thaipadungpanit J, Suputtamongkol Y, Chierakul W, Smythe LD, Day NP, Cooper B, Peacock SJ. Fool's gold: why imperfect reference tests are undermining the evaluation of novel diagnostics: a reevaluation of 5 diagnostic tests for leptospirosis. Clin Infect Dis. 2012;55:322–331.
    1. Pan-ngum W, Blacksell SD, Lubell Y, Pukrittayakamee S, Bailey MS, de Silva HJ, Lalloo DG, Day NP, White LJ, Limmathurotsakul D. Estimating the true accuracy of diagnostic tests for dengue infection using bayesian latent class models. PLoS One. 2013;8:e50765.
    1. Royal Tropical Institute . Typhoid F IgM Flow Assay. Amsterdam, The Netherlands: Royal Tropical Institute Koninklijk Instituut voor de Tropen (KIT); 2007.
    1. Altman DG. Practical Statistics for Medical Research. London, UK: Chapman and Hall; 1991.
    1. Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Lijmer JG, Moher D, Rennie D, de Vet HC. Standards for Reporting of Diagnostic Accuracy Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD Initiative. Radiology. 2003;226:24–28.
    1. Dendukuri N, Joseph L. Bayesian approaches to modeling the conditional dependence between multiple diagnostic tests. Biometrics. 2001;57:158–167.
    1. Lunn D, Spiegelhalter D, Thomas A, Best N. The BUGS project: evolution, critique and future directions. Stat Med. 2009;28:3049–3067.
    1. Gasem MH, Dolmans WM, Isbandrio BB, Wahyono H, Keuter M, Djokomoeljanto R. Culture of Salmonella typhi and Salmonella paratyphi from blood and bone marrow in suspected typhoid fever. Trop Geogr Med. 1995;47:164–167.
    1. Akoh JA. Relative sensitivity of blood and bone marrow cultures in typhoid fever. Trop Doct. 1991;21:174–176.
    1. Farooqui BJ, Khurshid M, Ashfaq MK, Khan MA. Comparative yield of Salmonella typhi from blood and bone marrow cultures in patients with fever of unknown origin. J Clin Pathol. 1991;44:258–259.
    1. Gilman RH, Terminel M, Levine MM, Hernandez-Mendoza P, Hornick RB. Relative efficacy of blood, urine, rectal swab, bone-marrow, and rose-spot cultures for recovery of Salmonella typhi in typhoid fever. Lancet. 1975;1:1211–1213.
    1. Ross IN, Abraham T. Predicting enteric fever without bacteriological culture results. Trans R Soc Trop Med Hyg. 1987;81:374–377.
    1. Hosoglu S, Geyik MF, Akalin S, Ayaz C, Kokoglu OF, Loeb M. A simple validated prediction rule to diagnose typhoid fever in Turkey. Trans R Soc Trop Med Hyg. 2006;100:1068–1074.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren