The superiority of the nested PCR employing H 1-d primers over culture or single-dilution Widal (4) should be reevaluated for isolates from unusual sites and from among those coinfected with human immunodeficiency virus (HIV)/AIDS. Numerous extraintestinal complications are known with Salmonella enterica serovar Typhi infection. For example, the involvement of the central nervous system might occur in 3 to 35% of cases, that of the cardiovascular system in 1 to 5% of cases, that of the pulmonary system in 1 to 86% of cases, that of bones and joints in ≤1% of cases, that of the hepatobiliary system in 1 to 26% of cases, and that of the genitourinary system in <1% of cases in other extraintestinal sites (2).
The recommendation to use a single-dilution Widal titer toward confirmation of a specific typhoid diagnosis needs to be reviewed among recipients of different typhoid vaccines. The background serologic response to inactivated vaccine might reduce the utility of a single-dilution Widal test in clinical practice. Furthermore, the serologic response might have been meager among those infected with HIV/AIDS. In India itself, there are estimated to be 5.1 million people infected with HIV, with an overall estimated adult prevalence of below 1%. Both HIV serotype 1 and HIV serotype 2 exist in India, and HIV-1 C is the commonest subtype reported (1).
With increased global travel, the previous receipt of a live typhoid vaccine from abroad by a febrile patient undergoing investigations to exclude typhoid might impede the utility of nested typhoid PCR (4). Clinicians in areas where typhoid is endemic might come across several HIV-positive patients who have been vaccinated with live typhoid vaccine prior to travel to these areas (3).
- Copyright © 2005 American Society for Microbiology
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Authors' Reply
Although the suggestions made by Arya and Agarwal seem to be somewhat inapplicable, it would be interesting to have a separate study looking into extraintestinal complications of Salmonella enterica serovar Typhi infections, as the H1-d gene is conserved even in nonflagellated variants (3). Our study was aimed at the detection of the S. enterica serovar Typhi flagellin gene-specific Hi-d sequence in blood samples from febrile children suspected of suffering from typhoid fever. The purpose of this PCR-based detection was to have a method more sensitive than blood culture, so that the single-tube Widal test can be evaluated in terms of its useful cutoff titer and utility in areas where typhoid fever is endemic. It is worth mentioning here that the prevalence of HIV in the adult population of this eastern part of northern India is <0.3% (1). Moreover, this was a study of febrile children for whom the prevalence of HIV might be still lower and vaccination against typhoid is rarely practiced. Further, none of our subjects had a history of vaccination for typhoid. Therefore, the observations made in our study remain fully relevant in the diagnosis of typhoid fever.
At present, the phenomenon of global travelers who receive live oral vaccines and undergo investigations to exclude typhoid fever affecting the utility of nested PCR seems to be imaginary. After live oral vaccination, occurrence of bacteremia is very unlikely (2); therefore, detection of the vaccine strain of S. enterica serovar Typhi (Ty 21 a) in blood does not seem to be logical. However, if the number of vaccinees increases, we will definitely be forced to revise the interpretation of the single-tube Widal test.
