toxin producing Escherichia coli O157:H7 enteritis linked to consumption of contaminated spinach from one California supplier captured the attention

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1 The NEW ENGLAND JOURNAL of MEDICINE Perspective march, 009 Peanut Butter, Peppers, and Nationwide Salmonella Outbreaks Dennis G. Maki, M.D. Two years ago, a nationwide outbreak of Shiga toxin producing Escherichia coli O17:H7 enteritis linked to consumption of contaminated spinach from one California supplier captured the attention of the national media for weeks. It was at least the th reported U.S. outbreak of E. coli infection that had been traced to contaminated leafy green vegetables since 199. Each year, approximately 0,000 persons acquire endemic toxigenic E. coli infection, and 0 of them die, 1 despite greatly intensified efforts during the past decade on the part of our federal food-safety agencies the U.S. Department of Agriculture (USDA), the Food and Drug Administration (FDA), and the Centers for Disease Control and Prevention (CDC) to prevent the spread of such infections. Now we are confronted by two large nationwide outbreaks of salmonella infection (see graphs). Between April and August 008, Salmonella serotype Saintpaul enteritis was diagnosed in 107 persons in states, the District of Columbia, and Canada. Ultimately, 8 patients were hospitalized, and elderly patients died. Initial epidemiologic investigations by state health departments and the CDC suggested that contamination of tomatoes grown in the southwestern United States was the cause, although this was never proved microbiologically. Predictably, tomato consumption plummeted, and the industry lost an estimated $00 million. After several months of investigation, the outbreak strain was isolated from jalapeño and serrano peppers that had been grown on one Mexican farm, and the CDC concluded that the outbreak derived from contamination of peppers that were eaten raw probably in many cases with tomatoes, which might explain the misleading results from the initial case control studies. In a second outbreak, which began on September 1 and is ongoing, S. Typhimurium enteritis had been diagnosed in 00 persons in states and Canada by February 8, 009 (see map and image). The CDC quickly traced the outbreak to contamination of one Georgia producer s peanut butter and the processed foods of other manufacturers that contained the company s peanut butter or paste. More than half the cases have occurred in children, hundreds of patients have been hospitalized, and at least eight have died. Beyond a recall of all peanut products produced by the company since January 1, 008, n engl j med 0;10 nejm.org march,

2 A Salmonella Saintpaul April August 008 No. of Persons April 1, 008 April 8, 008 April 1, 008 April, 008 April 9, 008 May, 008 May 1, 008 May 0, 008 May 7, 008 June, 008 June 10, 008 June 17, 008 June, 008 July 1, 008 July 8, 008 July 1, 008 July, 008 July 9, 008 August, 008 August, 008 August 19, 008 August 8, 008 Date of Illness Onset B Salmonella Typhimurium August 008 February 009 No. of Persons August 1, 008 August, 008 more than 00 food products (including cookies, crackers, cereal, candy, ice cream, and pet foods) have been recalled. Investigations have revealed that salmonella had been isolated from the implicated company s peanut butter or peanut paste in its internal qualitycontrol sampling program on at least occasions during the past August 9, 008 September, 008 September, 008 September 19, 008 September, 008 October, 008 October 10, 008 October 17, 008 October, 008 October 1, 008 November 7, 008 November 1, 008 Salmonella Infections in Two Nationwide Outbreaks in Date of Illness Onset year, but no action was taken to investigate the source of contamination, review sterilization procedures, or reclean the production machinery. The company is now under criminal investigation. It has been estimated that in large salmonella outbreaks, for every case identified by clinical culture, there are approximately November 1, 008 November 8, 008 December, 008 December, 008 December 19, 008 December, 008 January, 009 January 9, 009 January 1, 009 January, 009 January 0, 009 February 8, 009 In the first salmonella outbreak between April and August 008 (Panel A), Salmonella Saintpaul enteritis was diagnosed in 107 persons in U.S. states, the District of Columbia, and Canada; it was traced to contamination of imported jalapeño and serrano peppers grown on a single Mexican farm. In the second outbreak, which officially started on September 1, 008, and is ongoing (Panel B), S. Typhimurium enteritis had been diagnosed in 00 persons from U.S. states and Canada as of February 8, 009; it was traced to contamination of one Georgia producer s peanut butter and hundreds of foods from other manufacturers that used the company s products. The shaded areas in each graph represent illnesses that may not have been included in the final tally for each outbreak. Data are from the CDC ( 8 additional undetected cases meaning that these two outbreaks may each have affected more than 0,000 persons. And these are not rare outbreaks. In 00 and 007, peanut butter contaminated by S. Tennessee sickened tens of thousands of persons in states, and there have been at least other multistate salmonella 90 n engl j med 0;10 nejm.org march, 009

3 CA 7 OR WA 17 NV ID 1 AZ UT MT WY NM CO 1 ND 1 MN SD NE 1 TX KS OK IA MO AR LA WI IL MS IN 7 MI 0 KY OH 80 WV PA 17 VA 1 NC TN AL GA SC VT NY NH ME NJ DE MD 8 MA 7 CT 9 1 cases 19 cases RI FL 0 80 cases AK HI Cases of Infection with the Outbreak Strain of S. Typhimurium in the United States, September 1, 008, through February 8, 009. Data are from the National Center for Zoonotic, Vector-Borne, and Enteric Diseases, CDC. outbreaks traced to contaminated tomatoes since Once again, we must ask ourselves how foodborne disease can develop in 7 million residents of one of the world s most technically advanced countries each year, causing 0,000 hospitalizations and 000 deaths and adding $7 billion to our health care costs, despite intensive regulation of food production and distribution. Enormous shifts in food production during the past half century underlie the increased risk and complexity of foodborne disease caused by bacterial enteropathogens originating in food animals in North America. Today, virtually all food consumed domestically is grown and processed on a vast industrial scale or, increasingly, is imported: milk and complex dairy products, eggs and egg products, fresh vegetables and fruits, and the processed snacks and condiments incorporating these foodstuffs. Relatively little of the fresh food we eat is now grown or produced locally. Moreover, Americans like to eat out, and the risk of foodborne disease is considerably higher with food prepared in restaurants than with meals made at home. Although U.S. farmers and companies that process and distribute our food have made considerable progress in reducing the risk of microbial contamination of their products, raw meats and poultry, raw milk, and most vegetables still commonly harbor microorganisms of food-animal origin that are often enteropathogens, such as campylobacter, salmonella, Shiga toxin producing E. coli, and listeria. With centralized production and transcontinental distribution of commercially produced foods, unusually heavy contamination of a basic foodstuff or a failure to remove contaminants in a single production step can result in the shipment of contaminated food to millions of consumers, as these two recent salmonella outbreaks have illustrated. To those who believe that the solution is a return to a pastoral, early-0th-century model with millions of small farms producing more natural food, I would point out that even if the millions of farm workers who would be required were available to produce food on a quasi-boutique scale, the costs would be enormous; it would be impossible to feed 00 million n engl j med 0;10 nejm.org march,

4 Clustered Gram-Negative Salmonella Typhimurium Bacteria. Image is a color-enhanced scanning electron micrograph (,000) of bacteria grown in a pure culture. Americans, let alone the rest of the world. Efficient, industrialized production of huge quantities of food is an inescapable necessity to avoid food shortages and global famine. The challenge is to enhance the quality and safety of industrially produced food. Meeting this challenge will mean building on the success of the USDA s Pathogen Reduction, Hazard Analysis, and Critical Control Point (HACCP) program, which was launched in 199, the same year as FoodNet, a program of more intensive surveillance of foodborne infections in 10 states, and PulseNet, a system for pulsedfield gel electrophoresis DNA subtyping of enteric pathogens identified in U.S. clinical laboratories. The HACCP program needs to be scientifically validated and applied more consistently at all stages of food production actions that might have prevented the current salmonella outbreak. A nationwide expansion of FoodNet could improve the surveillance of documented foodborne disease, but more timely, electronic central reporting (which as done now requires nearly weeks) and expansion of our national program to an international scale are required to permit more effective investigation of disease clusters. PulseNet s pathogen subtyping should be accelerated, and the program should be integrated with similar efforts in other countries. We need more effective programs for monitoring the production and processing of food (including imported food) and assessing its safety. Inspections of food producers and processors by state agencies, the FDA, and the USDA have been limited by insufficient personnel and inadequate budgetary support. Safer food will come only when the federal government commits the resources needed to achieve it. We also need to develop rapid and more sensitive molecular methods for detecting enteropathogens in food, both during processing and in random sampling of final products, and programs applying these technologies need to be developed and implemented for high-risk foods. Requiring bar codes indicating the provenance of all commercial foods would permit immediate tracing of a food item to a specific farm, processing plant, or distribution center. Such a system could have greatly accelerated the resolution of the salmonella outbreak traced to Mexican peppers. Consumers have the right to know the origin of their food, which should be stated on the label of every fresh, perishable food item. But there are further steps that I believe are necessary. We should vigorously pursue promising new approaches to the feeding of poultry, swine, and cattle that can reduce colonization by campylobacter, salmonella, and E. coli. This effort should include an international moratorium on the incorporation into animal feeds of growth-promoting antibiotics, which have been linked to greatly increased antimicrobial resistance in bacterial enteropathogens recovered from human infections and may weaken animals resistance to colonization by enteropathogens. Similarly, we should aim to eliminate all unnecessary use of antimicrobial agents in both human and veterinary medicine. Hygienic food-preparation practices in restaurants, hospitals, nursing homes, and private homes should be improved. We should greatly strengthen the capacities of local and regional health departments to monitor the foodhandling practices of grocery stores, restaurants, and caterers, to pursue suspected problems more vigorously, and to more effectively integrate their activities with the national surveillance and control programs of the CDC, the FDA, and the USDA. Finally, we already have the capacity to improve food safety 9 n engl j med 0;10 nejm.org march, 009

5 by adopting a technology that can protect against safety breakdowns during production, preparation, or cooking: routine irradiation of the final commercial product in the case of poultry and hamburger, processed foods containing eggs or milk, and selected leafy and other vegetables eaten raw could greatly reduce the incidence of bacterial foodborne disease. Research has shown that irradiation kills pathogens or markedly reduces pathogen counts without impairing the nutritional value of food or making it toxic, carcinogenic, or radioactive. Food irradiation has been endorsed by the World Health Organization, the CDC, the FDA, the USDA, the American Medical Association, and the European Commission s Scientific Committee on Food and is already used in many other countries. In the United States, irradiation of fresh meat has been allowed since 1997; last August, the FDA approved the irradiation of iceberg lettuce and spinach. The CDC has estimated that irradiation of high-risk foods could prevent up to a million cases of bacterial foodborne disease each year in North America. I believe it is time to launch a major effort to gain public acceptance of irradiation of high-risk foods. It is time to stop reliving history. No potential conflict of interest relevant to this article was reported. Dr. Maki is a professor of medicine at the University of Wisconsin School of Medicine and Public Health and a hospital epidemiologist at the University of Wisconsin Hospital and Clinics both in Madison. This article (10.10/NEJMp0807) was published at NEJM.org on February, Maki DG. Don t eat the spinach controlling foodborne infectious disease. N Engl J Med 00;:19-.. Investigation of outbreak of infections caused by Salmonella Saintpaul. Atlanta: Centers for Disease Control and Prevention, August, 008. (Accessed February 1, 009, at saintpaul/archive/0808.html.). Investigation update: outbreak of Salmonella typhimurium infections, Atlanta: Centers for Disease Control and Prevention, February 9, 009. (Accessed February 1, 009, at typhimurium/update.html.). DuPont HL. The growing threat of foodborne bacterial enteropathogens of animal origin. Clin Infect Dis 007;:1-1.. Osterholm MT, Norgan AP. The role of irradiation in food safety. N Engl J Med 00; 0: Copyright 009 Massachusetts Medical Society. Global Transmission of Oseltamivir-Resistant Influenza Anne Moscona, M.D. Seemingly from one influenza season to the next, we have lost the use of our leading antiviral influenza drug because of resistance. This winter, the circulating strain of seasonal influenza A virus (H1N1) is resistant to the neuraminidase inhibitor osel tamivir. Moreover, rather than emerging under selective pressure of drug use, as many antibiotic-resistant bacteria do and as has been the concern for influenza, this resistant strain seems to be a natural, spontaneously arising variant. Nevertheless, science has given us the tools with which to anticipate these events and should allow us to develop new clinical solutions that build on our knowledge of the biology of RNA viruses. Neuraminidase cleaves sialic acid residues on the cellular receptor that bind the newly formed virions to the cell and to one another, enabling infection to spread to new host cells and ongoing infection to be established. The neuraminidase inhibitors mimic neuraminidase s natural substrate and bind to the active site, preventing the enzyme from cleaving host-cell receptors, thereby preventing infection of new host cells and halting the spread of infection. The two licensed neuraminidase inhibitors, zanamivir (Relenza) and oseltamivir (Tamiflu), have very little toxicity and are effective against all neuraminidase subtypes and, therefore, against all strains of influenza virus. But the possibility of widespread oseltamivir resistance has been a concern for several years. Structural analysis of the influenza neuraminidase predicted that resistance to oseltamivir would be feasible and more likely to arise than resistance to zanamivir. 1 Although the concern was focused on the emergence of resistance under the selective pressure of drug treatment, the same principles apply to natural variants: mutations could arise that would inhibit oseltamivir s action while leaving viral fitness and zanamivir activity unaffected. These predictions were borne out by clinical data during the past several years, as resistance to oseltamivir in influenza A isolates from treated patients, especially children, has grown more common. However, some complacency about the clinical significance of n engl j med 0;10 nejm.org march, 009 9