David L. Swerdlow

Hospitalized Patients with 2009 H1N1 Influenza in the United States, April–June 2009

BACKGROUND During the spring of 2009, a pandemic influenza A (H1N1) virus emerged and spread globally. We describe the clinical characteristics of patients who were hospitalized with 2009 H1N1 influenza in the United States from April 2009 to mid-June 2009. METHODS Using medical charts, we collected data on 272 patients who were hospitalized for at least 24 hours for influenza-like illness and who tested positive for the 2009 H1N1 virus with the use of a real-time reverse-transcriptase-polymerase-chain-reaction assay. RESULTS Of the 272 patients we studied, 25% were admitted to an intensive care unit and 7% died. Forty-five percent of the patients were children under the age of 18 years, and 5% were 65 years of age or older. Seventy-three percent of the patients had at least one underlying medical condition; these conditions included asthma; diabetes; heart, lung, and neurologic diseases; and pregnancy. Of the 249 patients who underwent chest radiography on admission, 100 (40%) had findings consistent with pneumonia. Of the 268 patients for whom data were available regarding the use of antiviral drugs, such therapy was initiated in 200 patients (75%) at a median of 3 days after the onset of illness. Data suggest that the use of antiviral drugs was beneficial in hospitalized patients, especially when such therapy was initiated early. CONCLUSIONS During the evaluation period, 2009 H1N1 influenza caused severe illness requiring hospitalization, including pneumonia and death. Nearly three quarters of the patients had one or more underlying medical conditions. Few severe illnesses were reported among persons 65 years of age or older. Patients seemed to benefit from antiviral therapy.

H1N1 2009 influenza virus infection during pregnancy in the USA

BACKGROUND Pandemic H1N1 2009 influenza virus has been identified as the cause of a widespread outbreak of febrile respiratory infection in the USA and worldwide. We summarised cases of infection with pandemic H1N1 virus in pregnant women identified in the USA during the first month of the present outbreak, and deaths associated with this virus during the first 2 months of the outbreak. METHODS After initial reports of infection in pregnant women, the US Centers for Disease Control and Prevention (CDC) began systematically collecting additional information about cases and deaths in pregnant women in the USA with pandemic H1N1 virus infection as part of enhanced surveillance. A confirmed case was defined as an acute respiratory illness with laboratory-confirmed pandemic H1N1 virus infection by real-time reverse-transcriptase PCR or viral culture; a probable case was defined as a person with an acute febrile respiratory illness who was positive for influenza A, but negative for H1 and H3. We used population estimates derived from the 2007 census data to calculate rates of admission to hospital and illness. FINDINGS From April 15 to May 18, 2009, 34 confirmed or probable cases of pandemic H1N1 in pregnant women were reported to CDC from 13 states. 11 (32%) women were admitted to hospital. The estimated rate of admission for pandemic H1N1 influenza virus infection in pregnant women during the first month of the outbreak was higher than it was in the general population (0.32 per 100 000 pregnant women, 95% CI 0.13-0.52 vs 0.076 per 100 000 population at risk, 95% CI 0.07-0.09). Between April 15 and June 16, 2009, six deaths in pregnant women were reported to the CDC; all were in women who had developed pneumonia and subsequent acute respiratory distress syndrome requiring mechanical ventilation. INTERPRETATION Pregnant women might be at increased risk for complications from pandemic H1N1 virus infection. These data lend support to the present recommendation to promptly treat pregnant women with H1N1 influenza virus infection with anti-influenza drugs. FUNDING US CDC.

Epidemiology of Escherichia coli O157:H7 Outbreaks, United States, 1982–2002

Surveillance data from 350 U.S. outbreaks of Escherichia coli O157:H7 are analyzed.

Campylobacter jejuni—An Emerging Foodborne Pathogen

Campylobacter jejuni is the most commonly reported bacterial cause of foodborne infection in the United States. Adding to the human and economic costs are chronic sequelae associated with C. jejuni infection—Guillian-Barré syndrome and reactive arthritis. In addition, an increasing proportion of human infections caused by C. jejuni are resistant to antimicrobial therapy. Mishandling of raw poultry and consumption of undercooked poultry are the major risk factors for human campylobacteriosis. Efforts to prevent human illness are needed throughout each link in the food chain.

Investigation of bioterrorism-related anthrax, United States, 2001: epidemiologic findings.

In October 2001, the first inhalational anthrax case in the United States since 1976 was identified in a media company worker in Florida. A national investigation was initiated to identify additional cases and determine possible exposures to Bacillus anthracis. Surveillance was enhanced through health-care facilities, laboratories, and other means to identify cases, which were defined as clinically compatible illness with laboratory-confirmed B. anthracis infection. From October 4 to November 20, 2001, 22 cases of anthrax (11 inhalational, 11 cutaneous) were identified; 5 of the inhalational cases were fatal. Twenty (91%) case-patients were either mail handlers or were exposed to worksites where contaminated mail was processed or received. B. anthracis isolates from four powder-containing envelopes, 17 specimens from patients, and 106 environmental samples were indistinguishable by molecular subtyping. Illness and death occurred not only at targeted worksites, but also along the path of mail and in other settings. Continued vigilance for cases is needed among health-care providers and members of the public health and law enforcement communities.

Botulism in the united states : A clinical and epidemiologic review

Botulism is a neuroparalytic illness caused by a neurotoxin produced from the anaerobic, spore-forming bacterium Clostridium botulinum [1]. Botulism was recognized as sausage poisoning during the 18th and 19th centuries [2], and the pathogenesis of disease was first described by van Ermengem in 1897 after his investigation of a large outbreak in Ellezelles, Belgium [3]. Because botulinum toxin is so lethal, intensive surveillance and control measures have been mandated in the United States. However, prompt recognition and treatment of botulism by clinicians remain a critical component of surveillance and are the most important steps in reducing rates of death from this disease. Botulism outbreaks are a public health emergency that require rapid recognition to prevent additional cases and to effectively treat patients with mechanical ventilation and early administration of antitoxin. In the event of terrorist use of botulinum toxin, clinicians would also be the first to recognize and treat casualties of intentional botulism poisoning. In this report, we provide a clinical overview of botulism and describe the U.S. Botulism Surveillance System. The Organism Clostridium botulinum is classified as a single species but consists of at least three genetically distinguishable groups of organisms. These are alike in their abilities to produce neurotoxins with similar pharmacologic activities [4] but diverse serologic properties (toxin types A, B, C, D, E, F, and G). Human botulism is primarily caused by the strains of C. botulinum that produce toxin types A, B, and E. Neurotoxigenic strains of C. baratii [5, 6] (which produce type F toxin) and C. butyricum [7] (which produce type E toxin) also have been implicated in human botulism. Strains of C. botulinum that produce type C or type D toxin for the most part cause botulism only in nonhuman species. These neurotoxigenic organisms are anaerobic, gram-positive, spore-forming bacilli and are commonly found in soils throughout the world. Clostridium botulinum organisms cause food poisoning because the heat-resistant spores survive food preservation methods that kill nonsporulating organisms; they subsequently produce a potent neurotoxin under anaerobic, low-acid (pH > 4.6), and low solute conditions [8]. The toxins affect a broad range of vertebrate species, but the evolutionary utility of toxin production to the bacterial host organisms is unclear. The Toxin The seven recognized types of botulinum neurotoxins (types A through G) are distinguished by neutralization of biological activity with type-specific serologic reagents. These types are defined by the International Standards for Clostridium botulinum Antitoxin [9]. The toxins of all types consist of a 100-kd heavy chain joined to a 50-kd light chain by a disulfide bond [10]. After absorption into the bloodstream, botulinum toxin binds irreversibly to the presynaptic nerve endings of the peripheral nervous system and cranial nerves, where it inhibits the release of acetylcholine (Figure 1). The mechanism involves binding to a toxin receptor on the nerve cell membrane at the neuromuscular junction, internalization of a portion (the catalytic portion residing in the light chain) of the toxin molecule [11], and cleavage of protein components of the neuroexocytosis apparatus within the cell [12]. Figure 1. Schematic representation of the action of botulinum toxin (BT) on a neuromuscular junction. Botulinum neurotoxin is considered the most potent lethal substance known. It is 15 000 to 100 000 times more toxic than sarin, the potent organophosphate nerve agent used in a terrorist attack in the subway system in Tokyo [13]. The nucleotide sequences for all seven toxin types have been sequenced [14-22]. Epidemiology Four clinical forms of botulism occur in humans: foodborne botulism; wound botulism; infant botulism (infant intestinal colonization); and, rarely, adult infectious botulism (adult intestinal colonization). Studies in monkeys indicate that, if aerosolized, botulinum toxin also can be absorbed through the lungs [23]; this could occur in the case of a terrorist attack. From 1973 through 1996 in the United States, 724 cases of foodborne botulism (median, 24 cases annually [range, 8 to 86 cases]), 103 cases of wound botulism (median, 3 cases annually [range, 0 to 25 cases]), 1444 cases of infant botulism (median, 71 cases annually [range, 0 to 99 cases]), and 39 cases of botulism of undetermined type were reported to the Centers for Disease Control and Prevention (CDC) (Figure 2) (CDC. Unpublished data). In the United States, approximately half of the cases of foodborne botulism are caused by toxin type A; the remaining foodborne cases are almost equally divided between toxins type E and type B [24]. Among cases of infant botulism, approximately half are caused by toxin type A and half by toxin type B; among cases of wound botulism, approximately 80% are caused by toxin type A and 20% by toxin type B (CDC. Unpublished data). In the United States, type A botulism is most common west of the Mississippi River, and type B is most common east of the Mississippi River [25]. Type E outbreaks are most common in Alaska [26, 27]. Figure 2. Annual incidence of botulism in the United States, 1973 to 1996. Important changes in the epidemiology of botulism have emerged in the past few decades. Recently identified vehicles for foodborne botulism include homemade salsa [24], baked potatoes sealed in aluminum foil [28], cheese sauce [29], sauteed onions held under a layer of butter [30], garlic in oil [31], and traditionally prepared salted or fermented fish [26] (Table 1). From 1976 through 1984, restaurant-associated outbreaks accounted for a large proportion of botulism cases (42%), although only 4% of all outbreaks were restaurant-associated [32]. The largest of these outbreaks were caused by jalapeno peppers in Michigan in 1977, potato salad in New Mexico in 1978, sauteed onions in Illinois in 1983, and skordalia made with baked potatoes in Texas in 1994 [33]. Table 1. Vehicles Associated with Foodborne Botulism In 1995 and 1996, the occurrence of wound botulism increased [34], with a total of 42 cases (CDC. Unpublished data). Most of these cases occurred among heroin users in California who injected the drug subcutaneously. Although it is unclear what factors contributed to this epidemic, a shift to the use of black tar heroin produced in Mexico may have played a role [35]. Purified botulinum toxin is used to treat various medical conditions, such as strabismus, blepharospasm, torticollis, oromandibular dystonia, spasmodic dysphonia, and achalasia. Systemic symptoms of botulism-like illness have been reported after therapeutic administration of botulinum toxin [36] but are unlikely to have resulted from this procedure. It is estimated that for most patients, at least 10 times the treatment dose would be required to enter the circulation for systemic symptoms to result ([37]; CDC. Unpublished data). The potential for intentional poisoning with botulinum toxin has come into clearer focus in recent years. As many as 17 countries are suspected to include or to be developing biological agents in their offensive weapons programs [38]. Botulinum toxin often is one of these agents because it is relatively easy to produce and is highly lethal in small quantities. In August 1995, Iraq revealed that during the Persian Gulf War, 11 200 L of botulinum toxin preparation was loaded into specially designed SCUD missile warheads [39]. In addition, before the Aum Shinrikyo used sarin in the 1995 terrorist attack on the Tokyo subway system, the cult had produced botulinum toxin [40]. Clinical Features Foodborne Botulism Foodborne botulism is caused by ingestion of preformed toxin produced in food by C. botulinum. The most frequent source is home-canned foods, in which spores that survive an inadequate cooking and canning process germinate, reproduce, and produce toxin in the anaerobic environment of the canned food. In the event of intentional foodborne poisoning with botulinum toxin, the signs and symptoms developing after ingestion would probably resemble those of naturally occurring foodborne botulism. If aerosolized toxin was inhaled, the incubation period might be slightly longer [23], and gastrointestinal symptoms might not occur. The clinical syndrome of foodborne botulism is dominated by neurologic symptoms and signs resulting from a toxin-induced blockade of the voluntary motor and autonomic cholinergic junctions (Table 2). Although the syndrome is similar for each toxin type, type A toxin has been associated with more severe disease and a higher fatality rate than type B or type E toxin [41]. Symptoms from any toxin type may range from subtle motor weakness or cranial nerve palsies to rapid respiratory arrest. The initial symptoms of foodborne botulism may be gastrointestinal and can include nausea, vomiting, abdominal cramps, or diarrhea; after the onset of neurologic symptoms, constipation is more typical. Dry mouth, blurred vision, and diplopia are usually the earliest neurologic symptoms. These initial symptoms may be followed by dysphonia, dysarthria, dysphagia, and peripheral muscle weakness. Symmetric descending paralysis is characteristic of botulism; paralysis begins with the cranial nerves, then affects the upper extremities, the respiratory muscles, and, finally, the lower extremities in a proximal-to-distal pattern. Onset usually occurs 18 to 36 hours after exposure (range, 6 hours to 8 days) [42]. In severe cases, extensive respiratory muscle paralysis leads to ventilatory failure and death unless supportive care is provided. Patients have required ventilatory support for up to 7 months before the return of muscular function, but ventilatory support is most commonly needed for 2 to 8 weeks [43]. Table 2. Commonly Reported Clinical Symptoms and Physical Findings in Botulism* Clinical recovery generally occurs over weeks to m

A Waterborne Outbreak in Missouri of Escherichia coli O157:H7 Associated with Bloody Diarrhea and Death

OBJECTIVE To describe and determine the source of a large outbreak of Escherichia coli O157:H7 (ECO157) infections in Missouri. DESIGN A case-control study and a household survey. SETTING A small city in a rural Missouri township that had an unchlorinated water supply. PATIENTS Case patients were residents of or visitors to Burdine Township with bloody diarrhea or diarrhea and abdominal cramps occurring between 15 December 1989 and 20 January 1990. MEASUREMENTS Escherichia coli O157 was isolated from 21 stool specimens. All isolates were resistant to sulfisoxazole, tetracycline, and streptomycin; produced Shiga-like toxins I and II; and had one 60-megadalton plasmid. RESULTS Among the 243 case patients, 86 had bloody stools, 32 were hospitalized, 4 died, and 2 had the hemolytic uremic syndrome. In the case-control study, no food was associated with illness, but ill persons had drunk more municipal water than had controls (P = 0.04). The survey showed that, during the peak of the outbreak, bloody diarrhea was 18.2 times more likely to occur in persons living inside the city and using municipal water than in persons living outside the city and using private well water (P = 0.001). Shortly before the peak of the outbreak, 45 water meters were replaced, and two water mains ruptured. The number of new cases declined rapidly after residents were ordered to boil water and after chlorination of the water supply. CONCLUSIONS This was the largest outbreak of ECO157 infections, the first due to a multiply resistant organism, and the first shown to be transmitted by water. System-wide chlorination as well as hyperchlorination during repairs might have prevented this outbreak. Both bloody and nonbloody diarrhea may be common manifestations of this infection, which is probably underdiagnosed because of the failure of routine stool cultures to identify the organism. Cities with deteriorating water systems using untreated water risk widespread illness from contaminated drinking water.

Estimates of the Prevalence of Pandemic (H1N1) 2009, United States, April–July 2009

Through July 2009, a total of 43,677 laboratory-confirmed cases of influenza A pandemic (H1N1) 2009 were reported in the United States, which is likely a substantial underestimate of the true number. Correcting for under-ascertainment using a multiplier model, we estimate that 1.8 million–5.7 million cases occurred, including 9,000–21,000 hospitalizations.

Epidemiology of Seafood-Associated Infections in the United States

SUMMARY Seafood is part of a healthful diet, but seafood consumption is not risk-free. Seafood is responsible for an important proportion of food-borne illnesses and outbreaks in the United States. Seafood-associated infections are caused by a variety of bacteria, viruses, and parasites; this diverse group of pathogens results in a wide variety of clinical syndromes, each with its own epidemiology. Some seafood commodities are inherently more risky than others, owing to many factors, including the nature of the environment from which they come, their mode of feeding, the season during which they are harvested, and how they are prepared and served. Prevention of seafood-associated infections requires an understanding not only of the etiologic agents and seafood commodities associated with illness but also of the mechanisms of contamination that are amenable to control. Defining these problem areas, which relies on surveillance of seafood-associated infections through outbreak and case reporting, can lead to targeted research and help to guide control efforts. Coordinated efforts are necessary to further reduce the risk of seafood-associated illnesses. Continued surveillance will be important to assess the effectiveness of current and future prevention strategies.

Clinical, epidemiological, and microbiological features of Vibrio vulnificus biogroup 3 causing outbreaks of wound infection and bacteraemia in Israel

Summary Background Vibrio vulnificus is a gram-negative bacterium that causes septicaemia and wound infection. Cases occur sporadically, and no previous outbreaks due to a common source or a clonal strain have been reported. In the summer and autumn of 1996 and 1997, an outbreak of invasive V vulnificus infection occurred in Israel in people who had recently handled fresh, whole fish purchased from artificial fish-ponds. Methods We reviewed clinical and epidemiological information, and undertook an environmental investigation to assess disease characteristics, modes of transmission, phenotypic characteristics of the bacterium, and fish-marketing policy. The clonal nature of 19 isolates was studied by biotyping, pulsed-field gel electrophoresis, and restriction-fragment length polymorphism (RFLP) analysis of a PCR fragment. Findings During 1996–97, 62 cases of wound infection and bacteraemia occurred. 57 patients developed cellulitis, four had necrotising fasciitis, and one developed osteomyelitis. In all cases, the fish were cultivated in inland fish-ponds. In the summer of 1996, fish-pond managers initiated a new marketing policy, in which fish were sold alive instead of being packed in ice. Phenotypically, the isolates had five atypical biochemical test results. The isolates were non-typeable by pulsed-field gel electrophoresis, and all had the same PCR-RFLP pattern which had not been seen previously. Interpretation The cause of the outbreak was a new strain of V vulnificus , classified as biogroup 3. A new fish-marketing policy that began in 1996 may have exposed susceptible people to the organism.