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Journal of Clinical Microbiology, September 2005, p. 4920, Vol. 43, No. 9
0095-1137/05/$08.00+0 doi:10.1128/JCM.43.9.4920.2005
Nested PCR for Diagnosis of Typhoid Fever

LETTER
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).

REFERENCES
1 - Godbole, S., and S. Mehendale. 2005. HIV/AIDS epidemic in India: risk factors, risk behaviour & strategies for prevention & control. Indian J. Med. Res. 121:356-368.[Medline]
2 - Huang, D. B., and H. L. DuPont. 2005. Problem pathogens: extra-intestinal complications of Salmonella enterica serotype Typhi infection. Lancet Infect. Dis. 5:341-348.[Medline]
3 - Panasiuk, A. 2004. Vaccination for HIV positive travelers. Przegl Epidemiol. 58(Suppl. 1):97-100. (In Polish.)
4 - Prakash, P., O. P. Mishra, A. K. Singh, A. K. Gulati, and G. Nath. 2005. Evaluation of nested PCR in diagnosis of typhoid fever. J. Clin. Microbiol. 43:431-432.[Abstract/Free Full Text]
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Subhash C. Arya*
Nirmala Agarwal
Sant Parmanand Hospital 18 Alipore Road Delhi-110054, India
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* E-mail: subhashji{at}hotmail.com |
Authors' Reply

LETTER
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.

REFERENCES
1 - Gulati, A. K., and G. Nath. 1999. HIV infection in Varanasi. J. Commun. Dis. 31:117-120.[Medline]
2 - Parker, M. T. 1990. Enteric infections: typhoid and paratyphoid, p. 424-446. In M. T. Parker and L. H. Collier (ed.), Topley & Wilson's principles of bacteriology, virology, and immunology, vol. 3, 8th ed. Arnold, London, United Kingdom.
3 - Woo, P. C. Y., A. M. Y. Fung, S. S. Y Wong, H. W. Tsoi, and K. Y. Yuen. 2001. Isolation and characterization of a Salmonella enterica serotype Typhi variant and its clinical and public health implications. J. Clin. Microbiol. 39:1190-1194.[Abstract/Free Full Text]
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Pradyot Prakash*
Anil Kumar Gulati
Gopal Nath
Department of Microbiology Institute of Medical Sciences Banaras Hindu University Varanasi-221 005, India
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* E-mail: pradyot_micro{at}yahoo.co.in |
Journal of Clinical Microbiology, September 2005, p. 4920, Vol. 43, No. 9
0095-1137/05/$08.00+0 doi:10.1128/JCM.43.9.4920.2005