Clinical characteristics of enteric fever and performance of TUBEX TF IgM test in Indonesian hospitals

by Syndi Nurmawati, Anggraini Alam, Hofiya Djauhari, Tuti P. Merati, Pratiwi Sudarmono, Vivi Setiawaty, Dona Arlinda, Retna Indah Sugiyono, Mansyur Arief, Usman Hadi, Abu Tholib Aman, Dewi Lokida, M. Hussein Gasem, Emiliana Tjitra, C. Jason Liang, Aaron Neal, Herman Kosasih, Muhammad Karyana, Chuen-Yen Lau, Bachti Alisjahbana

Background

Accurate diagnosis of enteric fever is challenging, particularly in low- and middle-income countries, due to the overlap of clinical and laboratory features with other pathogens. To better understand the difficulties in enteric fever diagnosis, we evaluated the characteristics of patients clinically diagnosed with enteric fever and the real-world performance of TUBEX TF, one of the most used tests in Indonesia.

Methodology/Principal findings

Patients were recruited through the AFIRE (Etiology of Acute Febrile Illness Requiring Hospitalization) study at eight Indonesian hospitals. Blood culture was performed for all patients, and TUBEX TF was performed for suspected enteric cases. Salmonella PCR and ELISA tests were performed at a reference lab. Sensitivity and specificity of TUBEX TF and IgM and IgG anti-S. Typhi ELISA were determined. Of 301 patients clinically diagnosed with enteric fever, 50 (16.6%) were confirmed by blood culture and/or PCR. Confirmed cases were mostly school-aged children presenting with fever, anorexia, dizziness and/or abdominal pain with normal leukocyte count or leukopenia. TUBEX TF demonstrated a sensitivity of 97.6% to 70.7% and specificity of 38.3% to 67.2% at cutoffs of 4 and 6, respectively. Acute IgG demonstrated the best sensitivity and specificity, at 90.7% and 82.7%, respectively, and the best ROC characteristics.

Conclusions/Significance

A substantial proportion of enteric fever was misdiagnosed at all study hospitals, likely due to the overlap of clinical characteristics and lab parameters with those of other common pathogens. The TUBEX TF rapid serological assay demonstrated suboptimal performance in our setting and tended to over-diagnose enteric fever. The role of IgG from acute specimens for identification of enteric fever cases merits additional consideration.