Paratyphoid Fever in India: An Emerging Problem.

To the Editor: Enteric fever is a major public health problem in India, accounting for more than 300,000 cases per year, Salmonella typhi is the most common etiologic agent (1), but Salmonella paratyphi A, the other causative agent, causes more asymptomatic infections than S. typhi. According to earlier reports from India, S. paratyphi A was implicated as a causative agent in 3%-17% of enteric fever cases (2). However, a large community-based study in an urban slum of Delhi during October 1995 to October 1996 found that S. paratyphi A caused approximately 20%-25% of the cases of enteric fever in this region (3). An outbreak of enteric fever due to a single S. paratyphi A strain in an urban residential area was reported in 1996 from New Delhi, where contaminated water was implicated as the probable source (4,5). This outbreak prompted a retrospective analysis of the laboratory records of the All India Institute of Medical Sciences, New Delhi, over a 5-year period (1994-1998) to study the change, if any, in the etiology of enteric fever in North India.

We evaluated all blood culture records from the institute's clinical bacteriology laboratory for April to October (the months with the highest number of enteric fever cases) each year. Records were from patients residing in New Delhi and the surrounding areas of North India. The blood was collected by a phlebotomist in the outpatient department or by a resident doctor in hospital wards. Blood cultures were carded out by standard laboratory technique (6). Five ml of blood was added to 50 mi of brain heart infusion broth (Hi-Media Laboratory, India) under aseptic conditions. Bacterial identification was accomplished by standard microbiologic protocol (6). Susceptibility to antibiotics (amoxycillin, chloramphenicol, cotrimoxazole, gentamicin, ciprofloxacin, and ceftriaxone) was tested by the comparative disk diffusion method (Stokes method) (7). Chi-square for trend was calculated, and the p value was determined.

The total number of blood cultures performed for enteric fever cases (10,109 in 1994, 12,092 in 1995, 17,652 in 1996, 15,997 in 1997, and 17,012 in 1998) did not change significantly over this period. The isolation of S. typhi changed little (Chi-square = 2.367; p = 0.123; statistically not significant). However, the proportion orS. paratyphi A isolates rose from 6.5% in 1994 to 44.9% in 1998 (Chi-square = 22.20; p [is less than] 0.001; statistically significant). The proportion of $. paratyphi A isolations in enteric fever cases from 1994 to 1998 was 6.5%, 21.2%, 50.5%, 30.7%, and 44.9%, respectively. Even excluding the strains from the 1996 outbreak (4), we found that the proportion of S. paratyphi ,4 in enteric fever cases increased compared with S. typhi (Chi-square = 30.528; p [is less than] 0.001). With our catchment area, case definition of enteric fever, and laboratory methods remaining the same during this period, it appears that the etiology of enteric fever in North India is changing significantly.

The age-wise distribution of S. typhi and S. paratyphi A showed that S. typhi was a significant isolate from children [is less than] 5 years of age, while this distribution was not observed for S. parathyphi A, which involved those [is greater than] 5 years of age. Sex was not significantly associated (mean male to female sex ratio was 32.4:18 for S. typhi and 15.8:10.6 for S. paratyphi A).

S. typhi has become increasingly sensitive to amoxycillin, chloramphenicol, and gentamicin, increasing from 75.1% in 1994 to 96.6% in 1998 for amoxycillin, from 71.9% in 1994 to 91.6% in 1998 for chloramphenicol, and from 96.4% to 100% for gentamicin. S. paratyphi A strains have remained uniformly sensitive (100%) to all antibiotics (amoxycillin, chloramphenicol, and gentamicin, as well as ciprofloxacin and ceftriaxone) used in the treatment of enteric fever. In light of reports of multidrug resistance in S. typhi, especially to quinolones, continued surveillance and monitoring of antimicrobial sensitivity of S. paratyphi A strains are needed.

The increase in proportion of S. paratyphi A cases, which may be due to a high degree of clinical suspicion (with mild fever cases investigated for enteric fever), changing host susceptibility, or even change in the virulence of the organism, should be further investigated.

References

(1.) Richens J. Typhoid and paratyphoid fevers. In: Oxford textbook of medicine. Weatherall DJ, Ledingham JGG, Warrell DA, editors. Vol 1. 3rd ed. London:: Oxford Medical Publication; 1996. p. 560-8.

(2.) Saxena SN, Sen R. Salmonella paratyphi A infection in India: incidence and phage types. Trans Royal Soc Trop Med Hyg 1966;603:409-11.

(3.) Kumar R, Sazawal S, Sinha A, Sood S, Bhan MK. Typhoid fever: contemporary issues as related to the disease in India. Round Table Conference Series on Water Borne Diseases. 12th ed. Ranbaxy Science Foundation, New Delhi, 1997;2:31-6.

(4.) Kapil A, Sood S, Reddaiah VP, Das BK, Seth P. Partyphoid fever due to Salmonella enterica serotype paratyphi A. Emerg Infect Dis 1997;3:407.

(5.) Thong K, Nair S, Chaudhry R, Seth P, Kapil A, Kumar D, et al. Molecular analysis of Salmonella paratyphi A from an outbreak in New Delhi, India. Emerg Infect Dis 1998;4:507-8.

(6.) Collee JG, Duguid JP, Fraser AG, Marmion BP. Mackie and Mc Cartney practical medical microbiology: laboratory strategy in the diagnosis of infective syndromes. 13th ed. London (UK): Churchill Livingstone; 1989. 601-7.

(7.) Stokes EJ, Ridgway GL. Clinical bacteriology: anti-bacterial drugs. 5th ed. London: Edward Arnold; 1980. p. 205-19.

Seema Sood, Arti Kapil, Nihar Dash, Bimal K. Das, Vikas Goel, and Pradeep Seth All India Institute of Medical Sciences, New Delhi, India