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U.S. Department of Health and Human Services

Animal & Veterinary

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CVM SENDS EPIDEMIOLOGIST TO U.K. TO RESEARCH SALMONELLA TYPHIMURIUM DT104

by Kathy Hollinger Godon, D.V.M., MPH
FDA Veterinarian Newsletter January/February 1998 Volume XIII, No I

Earlier this year, I was fortunate to spend 4-1/2 months on temporary duty assignment at the Epidemiology Department, Central Veterinary Laboratories (CVL) of the Veterinary Laboratories Agency, an Executive Agency of the Ministry of Agriculture Fisheries and Food (MAFF) in the United Kingdom (U.K.) As an epidemiology training fellow at CVM in the, Division of Epidemiology and Surveillance, this was an excellent opportunity to work with scientists at the Epidemiology Department at CVL, a research agency within MAFF. The work contracted by the Epidemiology Department is varied and reflects public health, animal health, and animal welfare concerns related to animal production in the U.K. Activities of the Department include the monitoring of animal disease, the proposal, design, and conduct of research studies and risk assessments, the participation in education programs directed at veterinary practitioners, animal producers, and the public, and the reporting of findings to the Minister, the public, and in the scientific literature.

Some current areas of study in the Department include BSE predictive modeling, determination of scrapie prevalence at slaughter, pre-slaughter and farm-based predictors of zoonotic pathogen carriage in food animals, tuberculosis control and eradication, the effectiveness of biosecurity for the prevention of campylobacter in poultry, conditions promoting the growth of listeria in baled silage, risk assessment for the transmission of bovine leukosis, and the prevalence of E. coli in cattle, among many others.

In the U.K. there is an epidemic of Salmonella Typhimurium DT104 (StmDT104) occurring in humans and a diverse range of animal species. The epidemic strain is resistant to five antimicrobials (ampicillin, chloramphenicol, streptomycin, sulphonamides and tetracycline), and this resistance is unique as it is chromosomally borne. Currently StmDT104 is the second most commonly isolated cause of human salmonellosis, after S. enteriditis, and is the predominate salmonella isolated from cattle. Recently resistance in StmDT104 has been identified to two additional classes of drugs: trimethoprim and fluoroquinolones. The organism has been isolated from a diverse range of wild and domestic animal species in the U.K. and more recently identified in the U.S. Transmission from animals to man has been demonstrated in the U.K. to occur primarily via foodborne routes, as well as through direct and indirect contact with animals, especially ill farm animals.

Concern about the existence and evidence of the spread of the organism in the U.S. prompted CVM to send an epidemiologist to assist CVL with the description of the U.K. epidemic and the construction of a study to determine factors associated with recurrent clinical disease in cattle caused by StmDT104. The proposed study of StmDT104 was to follow-up a case control study of cattle herds with StmDT104 done by Dr. Sarah Evans in 1994-1995.

Upon arrival and orientation to the various databases, I carried out a descriptive analysis of the epidemic detailing the seasonality and temporality of the epidemic, including projections into the next year. A historical review of the StmDT104 isolates, from laboratory day books, gave me an opportunity to experience "shoe-leather" epidemiology, though my eyes and fingers, not the soles of my shoes, were worn after leafing through 7 years of day books for StmDT104 listings. Results of this research provided new information about the early StmDT104 isolates. Early isolates of the epidemic strain (R type ACSSuT) between 1984-1988 were identified primarily from birds; both seagulls and exotic imported psitticines. The early cattle epidemic was described and appeared sporadic due to the low incidence and geographic distribution of isolates from 1988 to 1991. In 1991, the isolation rate in cattle increased dramatically and continued to increase through 1996. Also, the index herd from which the epidemic strain was isolated in 1988 was identified and characterized.

In addition to the historical data, the susceptibility profiles from the bacteriology database were tabulated for food animal species. The proportion of isolates that were the epidemic strain appeared to be increasing through 1996 in most species, with a concurrent decrease in other phage types of Salmonella Typhimurium. Cattle isolates with nalidixic acid resistance, an indicator of fluoroquinolone resistance, have increased from 0.3 percent in 1994 to 9.7 percent in preliminary 1997 data. Trimethoprim resistance has also shown an increase from 3.6 percent in 1994 to 11.9 percent in preliminary 1997 cattle data.

Calculation of the incidence of StmDT104 in cattle herds was complicated by the lack of a valid denominator, as census data was considered to overestimate the number of cattle herds in the U.K. A sample population, using the control herds from the previous 1994-1995 case control study, was used to estimate the incidence and disease recurrence rates. Other animal and herd characteristics such as age of the index case in an affected herd, morbidity, and severity of disease were described.

After researching the literature and describing the epidemic using the database available information, we began planning and designing the study. The case and control definition, the sample size, power, and potential biases and many other factors were considered in the design of the study and the construction of the questionnaire.

The questionnaire was piloted in the field in ten on-farm visits throughout the southern and western regions of England. Three of the farms visited had episodes of human disease on the farm following the illness in the cattle. On one farm the organism was isolated from the family dog, which was the proposed route of exposure to an ill child. One farm was also able to isolate the organism from the bulk milk tank for four months after the episode of clinical disease in the herd. These farm visits were informative resulting in improvements in clarity and construction of the questionnaire. In addition to the farm visits, the questionnaire was tested in two separate mailings to develop strategies that would improve the response rate and structure of the questionnaire. Strategies that improved response rate included mailing the questionnaire on a Friday for a Saturday delivery, mailing the questionnaire when farmer harvest activity level was low, when the weather was wet, and the inclusion of a handwritten note. Incorporation of these strategies for the second mailing resulted in an improved response rate from 55 percent to 70 percent.

The protocol for the case control study of recurrent disease in cattle was completed in mid-August. Currently, the questionnaire is being mailed and data entry of returned questionnaires is ongoing. I look forward to participating in the data analysis of this study. While in the U.K., I also visited sister agencies, including the Veterinary Medicines Directorate and the European Medicines Evaluation Agency, representing the U.K. and the EU drug evaluation agencies, establishing valuable contacts with the staff of these agencies.