Autoimmune hepatitis: Brighton Collaboration case definition and guidelines for data collection, analysis, and presentation of immunisation safety data.

This report introduces a Brighton Collaboration (BC) case definition for autoimmune hepatitis (AIH), which has been classified as a priority adverse event of special interest (AESI), as there were possible cases seen following COVID-19 vaccination. The case definition was developed by a group of subject matter and BC process experts to facilitate safety data comparability across pre- and post-licensure clinical trials, as well as pharmacovigilance activities in multiple settings with diverse resources and healthcare access. The usual BC case definition development process was followed in an expedited manner, and took two months to complete, including finalising the manuscript for publication, instead of the usual 1 year development time. It includes a systematic review of the literature and an expert consensus to define levels of diagnostic certainty for AIH, and provides specific guidelines for data collection and analysis. Histology, serological and biochemical tests and exclusion of alternate diagnosis were considered necessary to define the levels of certainty (definitive, probable and possible). AEFI reports of suspected AIH were independently classified by the WG members to test its useability and these classifications were used to finalise the case definition. The document underwent peer review by external AIH experts and a Reference Group of vaccine safety stakeholders in high-, low- and middle-income countries to ensure case definition useability, applicability, and scientific integrity. The expedited process can be replicated for development of other standardised case definitions for priority AESIs for endemics and epidemics. While applicable to cases reported following immunisation, the case definition is independent of lapsed time following vaccination and, as such, can also be used to determine background incidence for vaccinated and unvaccinated control groups in studies of causal association. While use of this case definition is also appropriate for the study of safety of other products including drugs, it is not meant to guide clinical case management.

Enhanced Vaccine Effectiveness during the Delta Phase of the COVID-19 Pandemic in the Medicare Population Supports a Multilayered Prevention Approach.

Throughout the pandemic, individuals 65 years and older have contributed most COVID-19 related deaths. To best formulate effective vaccination and other prevention policies to protect older adults, large scale observational studies of these higher risk individuals are needed. We conducted a Vaccine Effectiveness (VE) study during the B.1.617.2 Delta variant phase of the pandemic in July and August 2021 in a cohort of 17 million Medicare beneficiaries of which 5.7 million were fully vaccinated. We found that individuals fully vaccinated with the Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273 vaccines in January 2021 had 2.5 times higher breakthrough infections and hospitalizations than those fully vaccinated in March 2021, consistent with waning of vaccine-induced immunity. Measuring VE weekly, we found that VE against hospitalization, and even more so against infection, increased from July 2021 through August 2021, suggesting that in addition to the protective role of vaccination, increased masking or social distancing might have contributed to the unexpected increase in VE. Ongoing monitoring of Medicare beneficiaries should be a priority as new variants continue to emerge, and the VE of the new bivalent vaccines remains to be established. This could be accomplished with a large Medicare claims database and the analytics platform used for this study.

REPRINT OF: Relationship of Childhood Abuse and Household Dysfunction to Many of the Leading Causes of Death in Adults: The Adverse Childhood Experiences (ACE) Study.

BACKGROUND: The relationship of health risk behavior and disease in adulthood to the breadth of exposure to childhood emotional, physical, or sexual abuse, and household dysfunction during childhood has not previously been described. METHODS: A questionnaire about adverse childhood experiences was mailed to 13,494 adults who had completed a standardized medical evaluation at a large HMO; 9,508 (70.5%) responded. Seven categories of adverse childhood experiences were studied: psychological, physical, or sexual abuse; violence against mother; or living with household members who were substance abusers, mentally ill or suicidal, or ever imprisoned. The number of categories of these adverse childhood experiences was then compared to measures of adult risk behavior, health status, and disease. Logistic regression was used to adjust for effects of demographic factors on the association between the cumulative number of categories of childhood exposures (range: 0-7) and risk factors for the leading causes of death in adult life. RESULTS: More than half of respondents reported at least one, and one-fourth reported ≥2 categories of childhood exposures. We found a graded relationship between the number of categories of childhood exposure and each of the adult health risk behaviors and diseases that were studied (P < .001). Persons who had experienced four or more categories of childhood exposure, compared to those who had experienced none, had 4- to 12-fold increased health risks for alcoholism, drug abuse, depression, and suicide attempt; a 2- to 4-fold increase in smoking, poor self-rated health, ≥50 sexual intercourse partners, and sexually transmitted disease; and a 1.4- to 1.6-fold increase in physical inactivity and severe obesity. The number of categories of adverse childhood exposures showed a graded relationship to the presence of adult diseases including ischemic heart disease, cancer, chronic lung disease, skeletal fractures, and liver disease. The seven categories of adverse childhood experiences were strongly interrelated and persons with multiple categories of childhood exposure were likely to have multiple health risk factors later in life. CONCLUSIONS: We found a strong graded relationship between the breadth of exposure to abuse or household dysfunction during childhood and multiple risk factors for several of the leading causes of death in adults.

Genomic analysis of globally diverse Mycobacterium tuberculosis strains provides insights into the emergence and spread of multidrug resistance.

Multidrug-resistant tuberculosis (MDR-TB), caused by drug-resistant strains of Mycobacterium tuberculosis, is an increasingly serious problem worldwide. Here we examined a data set of whole-genome sequences from 5,310 M. tuberculosis isolates from five continents. Despite the great diversity of these isolates with respect to geographical point of isolation, genetic background and drug resistance, the patterns for the emergence of drug resistance were conserved globally. We have identified harbinger mutations that often precede multidrug resistance. In particular, the katG mutation encoding p.Ser315Thr, which confers resistance to isoniazid, overwhelmingly arose before mutations that conferred rifampicin resistance across all of the lineages, geographical regions and time periods. Therefore, molecular diagnostics that include markers for rifampicin resistance alone will be insufficient to identify pre-MDR strains. Incorporating knowledge of polymorphisms that occur before the emergence of multidrug resistance, particularly katG p.Ser315Thr, into molecular diagnostics should enable targeted treatment of patients with pre-MDR-TB to prevent further development of MDR-TB.

Community-driven standards-based electronic laboratory data-sharing networks.

Public health laboratories (PHLs) are critical components of the nation's healthcare system, serving as stewards of valuable specimens, delivering important diagnostic results to support clinical and public health programs, supporting public health policy, and conducting research. This article discusses the need for and challenges of creating standards-based data-sharing networks across the PHL community, which led to the development of the PHL Interoperability Project (PHLIP). Launched by the Association of Public Health Laboratories and the Centers for Disease Control and Prevention in September 2006, PHLIP has leveraged a unique community-based collaborative process, catalyzing national capabilities to more effectively share electronic laboratory-generated diagnostic information and bolster the nation's health security. PHLIP is emerging as a model of accelerated innovation for the fields of laboratory science, technology, and public health.

The APHL/CDC Public Health Laboratory Interoperability Project Portal: a web-based collaborative tool to establish a national harmonized vocabulary for public health data exchange.

Public health laboratories at all capacity levels are facing challenges in exchanging electronic data among themselves and with their partners. In response to this the Association of Public Health Laboratories working collaboratively with CDC launched an innovative portal development project in January 2006. This portal will enable public health laboratories to collaborate in a web-based environment to establish a standardized vocabulary for test identifications and test results, a cornerstone for creating interoperable information systems.

Safety profile of smallpox vaccine: insights from the laboratory worker smallpox vaccination program.

BACKGROUND: The frequency of mild-to-moderate adverse events following smallpox vaccination was not well documented or reported during the pre-eradication era. This report describes the frequency of such symptoms among 936 adult smallpox vaccinees with and without a history of prior smallpox vaccination. METHODS: Diary cards were distributed to 1006 laboratory workers and members of the Centers for Disease Control and Prevention (CDC) smallpox response team who received smallpox vaccination under an investigational new drug protocol during 2001-2002. Vaccinees were requested to complete the diary card daily and return it to the CDC 28 days after vaccination. The proportion of vaccinees reporting symptoms was determined and compared among subgroups. RESULTS: Ninety-three percent of the diary cards were returned. The most common symptom reported was "itching at vaccination site." Primary vaccines reported statistically higher proportions of the following 11 symptoms: joint pain (25% vs. 11%; P=.0011), muscle pain (46% vs. 19%; P<.0001), fatigue (43% vs. 29%; P=.0161), swelling at vaccination site (58% vs. 33%; P<.0001), itching on the body (31% vs. 17%; P=.0048), abdominal pain (11% vs. 2%; P=.0012), swollen or tender lymph nodes (71% vs. 33%; P<.0001), pain at injection site (48% vs. 30%; P=.0018), headache (40% vs. 25%; P=.0088), backache (17% vs. 7%; P=.0090), and fever (temperature, >or=100 degrees F [37.7 degrees C]; 20% vs. 9%; P=.0047). CONCLUSIONS: This analysis suggests that previously unvaccinated persons aged <30 years experienced more symptoms than did previously vaccinated persons. The findings of increased proportions with joint pain, abdominal pain, backache, and difficulty breathing were unexpected. As with recently described cardiac adverse events, these symptoms are suggestive of systemic involvement and warrant further study.

SARS surveillance during emergency public health response, United States, March-July 2003.

In response to the emergence of severe acute respiratory syndrome (SARS), the United States established national surveillance using a sensitive case definition incorporating clinical, epidemiologic, and laboratory criteria. Of 1,460 unexplained respiratory illnesses reported by state and local health departments to the Centers for Disease Control and Prevention from March 17 to July 30, 2003, a total of 398 (27%) met clinical and epidemiologic SARS case criteria. Of these, 72 (18%) were probable cases with radiographic evidence of pneumonia. Eight (2%) were laboratory-confirmed SARS-coronavirus (SARS-CoV) infections, 206 (52%) were SARS-CoV negative, and 184 (46%) had undetermined SARS-CoV status because of missing convalescent-phase serum specimens. Thirty-one percent (124/398) of case-patients were hospitalized; none died. Travel was the most common epidemiologic link (329/398, 83%), and mainland China was the affected area most commonly visited. One case of possible household transmission was reported, and no laboratory-confirmed infections occurred among healthcare workers. Successes and limitations of this emergency surveillance can guide preparations for future outbreaks of SARS or respiratory diseases of unknown etiology.

Comparison of neonatal thyroid-stimulating hormone levels and indicators of iodine deficiency in school children.

OBJECTIVES: To compare thyroid-stimulating hormone (TSH) levels in neonatal cord blood between study sites in Bangladesh, Guatemala and the United States. Also, to compare neonatal TSH results with indicators of iodine deficiency in school children. DESIGN: Consecutive births and, in school children, cross-sectional surveys. SETTING: Savar, Bangladesh; San Pedro Sacatepequez, Guatemala; and Atlanta, United States. SUBJECTS: In each study site, cord blood was spotted on to filter paper and TSH levels determined using a sensitive monoclonal assay. In the USA, heel stick blood specimens from newborns spotted on to filter paper were also obtained as well as exposure to iodine-containing antiseptics during the birthing process. Urine specimens were collected from mothers of newborns and tested for iodine concentration. School children in the same areas were surveyed for thyroid size by palpation and ultrasonography, and urine specimens collected for iodine concentration. RESULTS: Between 141 and 243 cord blood specimens were collected from each study site. The prevalence of elevated cord blood TSH levels (> 5 mUl(-1)) was high in all study sites, from 58% to 84%. All sites would be categorised as having 'severe' iodine deficiency based on WHO/UNICEF/ICCIDD criteria. Iodine-containing antiseptics were used during 98% of the births in the USA but not in Bangladesh or Guatemala. The neonatal TSH classification indicated more severe iodine deficiency levels than classifications based on urinary iodine and goitre in school children. CONCLUSIONS: In the USA, elevated TSH levels may be partially attributed to use of beta-iodine-containing antiseptics prior to birth. We recommend the cautious interpretation of TSH results in newborns for the assessment of iodine deficiency disorders when iodine-containing antiseptics are used during the birthing process.