We read with interest the article on detection of immunoglobulin M and immunoglobulin G antibodies against Orientia tsutsugamushi for scrub typhus (ST) diagnosis by Gupte, et al. [1]. This study was done to estimate the regional cut-off of optical density (OD) values of serum IgM antibodies by ELISA for the diagnosis of ST. Authors had successfully determined regional cut off of OD value for IgM antibodies, which will be utilized in diagnosing ST in that area. This study has shed light into one of the most obvious pitfalls in diagnosing ST by serology (IgM ELISA) i.e., using an inaccurate, arbitrary OD value cut off for diagnosis. This has serious implications that are applicable beyond the study population.

We would like to raise two pertinent points based on the study conclusions. Most studies conducted in pediatric ST using serology by IgM ELISA used 0.5 OD as an arbitrary cut off in accordance with the definition of ‘probable case’ by the IAP guidelines on rickettsial diseases in children [2]. Since OD of 0.5 is much lower than most of the cut offs reported from Southeast Asia, where ST is endemic in many parts, all these studies with OD cut off of 0.5 might have actually over diagnosed ST and hence the results have to be cautiously interpreted [3-5]. Since the OD cut off is going to be influenced by geographical location and degree of endemicity, it is imperative to use location specific OD cut off to diagnose ST [4]. Conducting epidemiological studies to identify the OD cut off in the normal population would be challenging and not feasible. The Government run laboratories in the district and state headquarters can pitch in and publish district- or state-wise OD cut off based on the previous samples tested, which can be regularly updated with time.

Timely diagnosis is crucial in reducing morbidity and mortality of ST in children, and since ST PCR is not freely available everywhere, earliest laboratory confirmation is often done by serology by IgM ELSIA after 5-7 days of fever onset [2]. While IgM ELISA serology testing to diagnose ST is affordable, easy-to-use, with reasonable diagnostic accuracy for screening and diagnostic purposes, regional cut-offs should be identified and maintained by regional health authorities and should be validated from time to time in order to prevent misdiagnosis.

1. Gupte MD, Gupte M, Kamble S, et al. Detection of immunoglobulin M and immunoglobulin G antibodies against Orientia tsutsugamushi for scrub typhus diagnosis and serosurvey in endemic regions. Indian Pediatr. 2020; S097475591600242.

2. Rathi N, Kulkarni A, Yewale V; For Indian Academy of Pediatrics Guidelines on Rickettsial Diseases in Children Committee. IAP Guidelines on Rickettsial Diseases in Children. Indian Pediatr. 2017;54:223-29.

3. Gupta N, Chaudhry R, Thakur CK. Determination of cutoff of ELISA and immunofluorescence assay for scrub typhus. J Glob Infect Dis. 2016;8:97-99.

4. Rawat V, Singh RK, Kumar A, et al. Diagnostic validation of IgM and IgG ELISA and real-time PCR in detecting scrub typhus infection in endemic regions. J Vector Borne Dis. 2018;55:165-67.