Correspondence

A Salmonella typhi Vi Conjugate Vaccine

N Engl J Med 2001; 345:545-546August 16, 2001

Article

To the Editor:

In their article on the polysaccharide conjugate typhoid vaccine Vi-rEPA, Lin et al. (April 26 issue)1 report an efficacy of 91.5 percent in the prevention of typhoid fever due to the development of IgG Vi antibodies, and they presume that the vaccination can help in the prevention of typhoid fever and in limiting the spread of multidrug-resistant enteric fever.

There were five cases of typhoid fever in the vaccine group, even though the serum levels of IgG Vi antibodies increased by a factor of at least 10 in 100 percent of the children. The levels of IgG Vi antibodies in the three serum samples collected from the five children with typhoid fever were 4.76, 14.6, and 40.3 enzyme-linked immunosorbent assay (ELISA) units. Two of these were clearly higher than the proposed protective level of 7 ELISA units. Among various phage types of Salmonella typhi, disease is caused by E1, UVS1, and Vi-negative phage types.2,3 Since the vaccine acts by effecting an antibody response against the Vi antigen of S. typhi, we are concerned about the efficacy of the vaccine in the prevention of disease due to Vi-negative phage types. Even though the number of patients with typhoid fever in the vaccinated group is small, it would be important to know the phage types of the S. typhi strains obtained from them in order to substantiate the effectiveness of the vaccine against various phage types, including the Vi-negative strains.

Parvaiz A. Koul, M.D.
Sheri-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, India
parvaizk@rediffmail.com

3 References

1. 1

   Lin FYC, Ho VA, Khiem HB, et al. The efficacy of a Salmonella typhi Vi conjugate vaccine in two-to-five-year-old children. N Engl J Med 2001;344:1263-1269
   Full Text | Web of Science | Medline

2. 2

   Koul PA, Quadri MI, Wani JI, Wahid A, Shaban M. Haemostatic abnormalities in multidrug-resistant enteric fever. Acta Haematol 1995;93:13-19
   CrossRef | Web of Science | Medline

3. 3

   Koul PA, Wani JI, Wahid A. Ciprofloxacin for multiresistant enteric fever in pregnancy. Lancet 1995;346:307-308
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: As mentioned in our article, bacteria that grew in blood culture were assayed for their biochemical traits and serotypes: all strains, including those from recipients of Vi-rEPA, were Vi-positive; all were resistant to ampicillin, chloramphenicol, tetracycline, and trimethoprim–sulfamethoxazole; and six were also resistant to ciprofloxacin.

Vi phages are defined by their adsorption to the Vi antigen of S. typhi, including those identified as Vi-degraded and E1 phages.1,2 Strains of S. typhi that are Vi-negative are referred to as W form. We have not documented and know of no Vi-negative S. typhi freshly isolated from blood. S. typhi may lose their Vi antigen after several passages in the laboratory or after prolonged storage. Another source of error is that some commercial antiserum used for typing may be unreliable.

The estimate of 7 ELISA units of IgG Vi antibodies proposed to prevent typhoid fever was derived from serum taken at random from healthy participants. In contrast, blood for culture and serologic tests was taken from all patients after three or more days of fever. The comparatively high levels of IgG Vi antibodies in the patients injected with Vi-rEPA were probably due to this stimulation in sensitized hosts.

Finally, we do not “presume that the vaccination can help in the prevention of typhoid fever.” We believe that our data show that it does.

Feng Ying C. Lin, M.D., M.P.H.
Shousun C. Szu, Ph.D.
National Institutes of Health, Bethesda, MD 20892

Phan Van Bay, M.D.
Dong Thap Provincial Hospital, Cao Lânh, Vietnam

2 References

1. 1

   Craigie J, Felix A. Typing of typhoid bacilli with Vi bacteriophage: suggestions for its standardisation. Lancet 1947;1:823-827
   CrossRef | Medline

2. 2

   Hickman-Brenner FW, Farmer JJ III. Bacteriophage types of Salmonella typhi in the United States from 1974 through 1981. J Clin Microbiol 1983;17:172-174
   Web of Science | Medline