Adeno-associated virus type 2 in US children with acute severe hepatitis.

As of August 2022, clusters of acute severe hepatitis of unknown aetiology in children have been reported from 35 countries, including the USA1,2. Previous studies have found human adenoviruses (HAdVs) in the blood from patients in Europe and the USA3-7, although it is unclear whether this virus is causative. Here we used PCR testing, viral enrichment-based sequencing and agnostic metagenomic sequencing to analyse samples from 16 HAdV-positive cases from 1 October 2021 to 22 May 2022, in parallel with 113 controls. In blood from 14 cases, adeno-associated virus type 2 (AAV2) sequences were detected in 93% (13 of 14), compared to 4 (3.5%) of 113 controls (P < 0.001) and to 0 of 30 patients with hepatitis of defined aetiology (P < 0.001). In controls, HAdV type 41 was detected in blood from 9 (39.1%) of the 23 patients with acute gastroenteritis (without hepatitis), including 8 of 9 patients with positive stool HAdV testing, but co-infection with AAV2 was observed in only 3 (13.0%) of these 23 patients versus 93% of cases (P < 0.001). Co-infections by Epstein-Barr virus, human herpesvirus 6 and/or enterovirus A71 were also detected in 12 (85.7%) of 14 cases, with higher herpesvirus detection in cases versus controls (P < 0.001). Our findings suggest that the severity of the disease is related to co-infections involving AAV2 and one or more helper viruses.

A Case Series of Children with Acute Hepatitis and Human Adenovirus Infection.

BACKGROUND: Human adenoviruses typically cause self-limited respiratory, gastrointestinal, and conjunctival infections in healthy children. In late 2021 and early 2022, several previously healthy children were identified with acute hepatitis and human adenovirus viremia. METHODS: We used International Classification of Diseases, 10th Revision, codes to identify all children (<18 years of age) with hepatitis who were admitted to Children's of Alabama hospital between October 1, 2021, and February 28, 2022; those with acute hepatitis who also tested positive for human adenovirus by whole-blood quantitative polymerase chain reaction (PCR) were included in our case series. Demographic, clinical, laboratory, and treatment data were obtained from medical records. Residual blood specimens were sent for diagnostic confirmation and human adenovirus typing. RESULTS: A total of 15 children were identified with acute hepatitis - 6 (40%) who had hepatitis with an identified cause and 9 (60%) who had hepatitis without a known cause. Eight (89%) of the patients with hepatitis of unknown cause tested positive for human adenovirus. These 8 patients plus 1 additional patient referred to this facility for follow-up were included in this case series (median age, 2 years 11 months; age range, 1 year 1 month to 6 years 5 months). Liver biopsies indicated mild-to-moderate active hepatitis in 6 children, some with and some without cholestasis, but did not show evidence of human adenovirus on immunohistochemical examination or electron microscopy. PCR testing of liver tissue for human adenovirus was positive in 3 children (50%). Sequencing of specimens from 5 children showed three distinct human adenovirus type 41 hexon variants. Two children underwent liver transplantation; all the others recovered with supportive care. CONCLUSIONS: Human adenovirus viremia was present in the majority of children with acute hepatitis of unknown cause admitted to Children's of Alabama from October 1, 2021, to February 28, 2022, but whether human adenovirus was causative remains unclear. Sequencing results suggest that if human adenovirus was causative, this was not an outbreak driven by a single strain. (Funded in part by the Centers for Disease Control and Prevention.).

COVID-19 Incidence and Mortality Among Unvaccinated and Vaccinated Persons Aged ≥12 Years by Receipt of Bivalent Booster Doses and Time Since Vaccination - 24 U.S. Jurisdictions, October 3, 2021-December 24, 2022.

On September 1, 2022, CDC recommended an updated (bivalent) COVID-19 vaccine booster to help restore waning protection conferred by previous vaccination and broaden protection against emerging variants for persons aged ≥12 years (subsequently extended to persons aged ≥6 months).* To assess the impact of original (monovalent) COVID-19 vaccines and bivalent boosters, case and mortality rate ratios (RRs) were estimated comparing unvaccinated and vaccinated persons aged ≥12 years by overall receipt of and by time since booster vaccination (monovalent or bivalent) during Delta variant and Omicron sublineage (BA.1, BA.2, early BA.4/BA.5, and late BA.4/BA.5) predominance.† During the late BA.4/BA.5 period, unvaccinated persons had higher COVID-19 mortality and infection rates than persons receiving bivalent doses (mortality RR = 14.1 and infection RR = 2.8) and to a lesser extent persons vaccinated with only monovalent doses (mortality RR = 5.4 and infection RR = 2.5). Among older adults, mortality rates among unvaccinated persons were significantly higher than among those who had received a bivalent booster (65-79 years; RR = 23.7 and ≥80 years; 10.3) or a monovalent booster (65-79 years; 8.3 and ≥80 years; 4.2). In a second analysis stratified by time since booster vaccination, there was a progressive decline from the Delta period (RR = 50.7) to the early BA.4/BA.5 period (7.4) in relative COVID-19 mortality rates among unvaccinated persons compared with persons receiving who had received a monovalent booster within 2 weeks-2 months. During the early BA.4/BA.5 period, declines in relative mortality rates were observed at 6-8 (RR = 4.6), 9-11 (4.5), and ≥12 (2.5) months after receiving a monovalent booster. In contrast, bivalent boosters received during the preceding 2 weeks-2 months improved protection against death (RR = 15.2) during the late BA.4/BA.5 period. In both analyses, when compared with unvaccinated persons, persons who had received bivalent boosters were provided additional protection against death over monovalent doses or monovalent boosters. Restored protection was highest in older adults. All persons should stay up to date with COVID-19 vaccination, including receipt of a bivalent booster by eligible persons, to reduce the risk for severe COVID-19.

Acute Hepatitis and Adenovirus Infection Among Children - Alabama, October 2021-February 2022.

During October-November 2021, clinicians at a children's hospital in Alabama identified five pediatric patients with severe hepatitis and adenovirus viremia upon admission. In November 2021, hospital clinicians, the Alabama Department of Public Health, the Jefferson County Department of Health, and CDC began an investigation. This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.

Multidrug-Resistant Salmonella Heidelberg Associated with Mechanically Separated Chicken at a Correctional Facility.

We describe multidrug-resistant (MDR) Salmonella Heidelberg infections associated with mechanically separated chicken (MSC) served at a county correctional facility. Twenty-three inmates met the case definition. All reported diarrhea, 19 (83%) reported fever, 16 (70%) reported vomiting, 4 (17%) had fever ≥103°F, and 3 (13%) were hospitalized. A case-control study found no single food item significantly associated with illness. Salmonella Heidelberg with an indistinguishable pulsed-field gel electrophoresis pattern was isolated from nine stool specimens; two isolates displayed resistance to a total of five drug classes, including the third-generation cephalosporin, ceftriaxone. MDR Salmonella Heidelberg might have contributed to the severity of illness. Salmonella Heidelberg indistinguishable from the outbreak subtype was isolated from unopened MSC. The environmental health assessment identified cross-contamination through poor food-handling practices as a possible contributing factor. Proper hand-washing techniques and safe food-handling practices were reviewed with the kitchen supervisor.

Variability among states in investigating foodborne disease outbreaks.

Over 1,100 foodborne disease outbreaks cause over 23,000 illnesses in the United States annually, but the rates of outbreaks reported and successful investigation vary dramatically among states. We used data from the Centers for Disease Control and Prevention's outbreak reporting database, Association of Public Health Laboratories' PulseNet laboratory subtyping network survey and Salmonella laboratory survey, national public health surveillance data, and national surveys to examine potential causes of this variability. The mean rate of reporting of Salmonella outbreaks was higher in states requiring submission of all isolates to the state public health laboratory, compared to those that do not (5.9 vs. 4.1 per 10 million population, p=0.0062). Rates of overall outbreak reporting or successful identification of an etiology or food vehicle did not correlate at the state level with population, rates of sporadic disease reporting, health department organizational structure, or self-reported laboratory or epidemiologic capacity. Foodborne disease outbreak surveillance systems are complex, and improving them will require a multi-faceted approach to identifying and overcoming barriers.

Travel-associated enteric infections diagnosed after return to the United States, Foodborne Diseases Active Surveillance Network (FoodNet), 2004-2009.

BACKGROUND: Approximately 40% of US travelers to less developed countries experience diarrheal illness. Using data from the Foodborne Diseases Active Surveillance Network (FoodNet), we describe travel-associated enteric infections during 2004-2009, characterizing the patients, pathogens, and destinations involved. METHODS: FoodNet conducts active surveillance at 10 US sites for laboratory-confirmed infections with 9 pathogens transmitted commonly through food. Travel-associated infections are infections diagnosed in the United States but likely acquired abroad based on a pathogen-specific time window between return from international travel to diagnosis. We compare the demographic, clinical, and exposure-related characteristics of travelers with those of nontravelers and estimate the risk of travel-associated infections by destination, using US Department of Commerce data. RESULTS: Of 64,039 enteric infections reported to FoodNet with information about travel, 8270 (13%) were travel associated. The pathogens identified most commonly in travelers were Campylobacter (42%), nontyphoidal Salmonella (32%), and Shigella (13%). The most common travel destinations were Mexico, India, Peru, Dominican Republic, and Jamaica. Most travel-associated infections occurred in travelers returning from Latin America and the Caribbean (LAC). Risk was greatest after travel to Africa (75.9 cases per 100,000 population), followed by Asia (22.7 cases per 100,000), and LAC (20.0 cases per 100,000). CONCLUSIONS: The Latin America and Caribbean region accounts for most travel-associated enteric infections diagnosed in the United States, although travel to Africa carries the greatest risk. Although FoodNet surveillance does not cover enterotoxigenic Escherichia coli, a common travel-associated infection, this information about other key enteric pathogens can be used by travelers and clinicians in pre- and posttravel consultations.

Sporadic campylobacter infection in infants: a population-based surveillance case-control study.

BACKGROUND: Campylobacter is an important cause of foodborne illness in infants (younger than 1 year of age), but little is known about the sources of infection in this age group. METHODS: Eight sites in the Foodborne Diseases Active Surveillance Network (FoodNet) participated in a 24-month population-based case-control study conducted in 2002-2004. Cases were infants with laboratory-confirmed Campylobacter infection ascertained through active laboratory surveillance, and controls were infants in the community. RESULTS: We enrolled 123 cases and 928 controls. Infants 0-6 months of age with Campylobacter infection were less likely to be breast-fed than controls [odds ratio (OR); 0.2; 95% confidence interval (CI), 0.1-0.6]. Risk factors for infants 0-6 months of age included drinking well water (OR 4.4; CI, 1.4-14) and riding in a shopping cart next to meat or poultry (OR 4.0; CI, 1.2-13.0). Risk factors for infants 7-11 months of age included visiting or living on a farm (OR 6.2; CI, 2.2-17), having a pet with diarrhea in the home (OR 7.6; CI, 2.1-28) and eating fruits and vegetables prepared in the home (OR 2.5, CI 1.2-4.9). Campylobacter infection was associated with travel outside the United States at all ages (OR 19.3; CI, 4.5-82.1). CONCLUSIONS: Several unique protective and risk factors were identified among infants, and these risk factors vary by age, suggesting that prevention measures be targeted accordingly. Breast-feeding was protective for the youngest infants and should continue to be encouraged.

Determinants of influenza vaccination, 2003-2004: shortages, fallacies and disparities.

BACKGROUND: The influenza outbreak of 2003-2004 received substantial media attention, including widespread reports of a severe season and vaccine shortages. Understanding the determinants of vaccine receipt is important for guiding immunization policies. METHODS: From February through June 2004, we administered a structured telephone survey to Tennessee residents, using random-digit dialing methodology. RESULTS: Questionnaires were completed by 4028 persons, of whom 2077 (52%) had received influenza vaccination during the previous outbreak season. Of these 2077 vaccine recipients, 63% received vaccine at a private medical clinic, 14% at a workplace, 11% at a health department, and 7% at a pharmacy. Three-fourths of respondents reported a risk factor for which the Centers for Disease Control and Prevention recommends vaccination; of those, 41% went unvaccinated, including 26% who had seen a medical provider for other reasons during the influenza season. More than 40% of persons aged >or=50, more than half of health care workers, and 70% of pregnant women were not immunized. Blacks, rural residents, and lower-income respondents were significantly less likely to be immunized than were comparison groups. Of respondents who were vaccinated, 6% reported difficulties obtaining vaccination (most commonly, they reported that vaccine was not readily available). One-fourth of unvaccinated persons had been offered vaccination but had declined it; of these, 35% thought it unnecessary and 33% believed it would make them ill. Of those not vaccinated, 8% reported requesting vaccination but not receiving it, most commonly because it was unavailable. CONCLUSIONS: Many barriers contribute to disparities in rates of influenza vaccination, of which inadequate supply is only one component. Myths regarding influenza vaccination persist tenaciously. A multifaceted approach to increasing immunization rates is critical.

Salmonellosis outcomes differ substantially by serotype.

BACKGROUND: Most human infections are caused by closely related serotypes within 1 species of Salmonella. Few data are available on differences in severity of disease among common serotypes. METHODS: We examined data from all cases of Salmonella infection in FoodNet states during 1996-2006. Data included serotype, specimen source, hospitalization, and outcome. RESULTS: Among 46,639 cases, 687 serotypes were identified. Overall, 41,624 isolates (89%) were from stool specimens, 2524 (5%) were from blood, and 1669 (4%) were from urine; 10,393 (22%) cases required hospitalization, and death occurred in 219 (0.5%). The case fatality rate for S. Newport (0.3%) was significantly lower than for Typhimurium (0.6%); Dublin (3.0%) was higher. With respect to invasive disease, 13 serotypes had a significantly higher proportion than Typhimurium (6%), including Enteritidis (7%), Heidelberg (13%), Choleraesuis (57%), and Dublin (64%); 13 serotypes were significantly less likely to be invasive. Twelve serotypes, including Enteritidis (21%) and Javiana (21%), were less likely to cause hospitalization than Typhimurium (24%); Choleraesuis (60%) was significantly more so. CONCLUSIONS: Salmonella serotypes are closely related genetically yet differ significantly in their pathogenic potentials. Understanding the mechanisms responsible for this may be key to a more general understanding of the invasiveness of intestinal bacterial infections.

A case-control study of the epidemiology of sporadic Salmonella infection in infants.

OBJECTIVE: Rates of Salmonella infection are highest in infants, but little is known about potential sources of infection in this high-risk population. We performed a case-control study to identify dietary and environmental risk factors for sporadic salmonellosis among infants. PATIENTS AND METHODS: In 2002-2004, the Foodborne Diseases Active Surveillance Network conducted a population-based, case-control study of sporadic salmonellosis among infants <1 year of age in 8 states. Cases were identified via active laboratory-based surveillance. Healthy controls were frequency matched by age and identified through birth registries or published birth announcements. We assessed diet and environmental exposures in the 5 days before illness onset or interview. Data were analyzed by using logistic regression adjusting for age. RESULTS: The study enrolled 442 subjects and 928 controls. Compared with healthy controls, infants with Salmonella infection were less likely to have been breastfed and more likely to have had exposure to reptiles, to have ridden in a shopping cart next to meat or poultry, or to have consumed concentrated liquid infant formula during the 5-day exposure period. Travel outside the United States was associated with illness in infants 3 to 6 and >6 months of age. Attending day care with a child with diarrhea was associated with salmonellosis in infants >6 months of age. CONCLUSIONS: We identified a number of modifiable protective and risk factors for salmonellosis in infants. Attention should be directed at developing effective preventive measures for this high-risk population.

Restaurant inspection scores and foodborne disease.

Restaurants in the United States are regularly inspected by health departments, but few data exist regarding the effect of restaurant inspections on food safety. We examined statewide inspection records from January 1993 through April 2000. Data were available from 167,574 restaurant inspections. From 1993 to 2000, mean scores rose steadily from 80.2 to 83.8. Mean inspection scores of individual inspectors were 69-92. None of the 12 most commonly cited violations were critical food safety hazards. Establishments scoring <60 had a mean improvement of 16 points on subsequent inspections. Mean scores of restaurants experiencing foodborne disease outbreaks did not differ from restaurants with no reported outbreaks. A variety of factors influence the uniformity of restaurant inspections. The restaurant inspection system should be examined to identify ways to ensure food safety.