Prevalence and Types of Drugs Used Among Hepatitis A Patients During Outbreaks Associated with Person-to-Person Transmission, Kentucky, Michigan, and West Virginia, 2016-2019.

Background: People who use drugs are at increased risk for hepatitis A virus infection. Since 1996, the Advisory Committee on Immunization Practices has recommended hepatitis A vaccination for people who use drugs. Since 2016, the U.S. has experienced widespread hepatitis A outbreaks associated with person-to-person transmission. Purpose: To describe the prevalence of drug use, route of use, and drugs used among hepatitis A outbreak-associated patients. Methods: State outbreak and medical records were reviewed to describe the prevalence, type, and route of drug use among a random sample of 812 adult outbreak-associated hepatitis A patients from Kentucky, Michigan, and West Virginia during 2016-2019. Differences in drug-use status were analyzed by demographic and risk-factor characteristics using the X 2 test. Results: Among all patients, residents of Kentucky (55.6%), Michigan (51.1%), and West Virginia (60.1%) reported any drug use, respectively. Among patients that reported any drug use, methamphetamine was the most frequently reported drug used in Kentucky (42.3%) and West Virginia (42.1%); however, opioids were the most frequently reported drug used in Michigan (46.8%). Hepatitis A patients with documented drug use were more likely (p<0.05) to be experiencing homelessness/unstable housing, have been currently or recently incarcerated, and be aged 18-39 years compared to those patients without documented drug use. Implications: Drug use was prevalent among person-to-person hepatitis A outbreak-associated patients, and more likely among younger patients and patients experiencing homelessness or incarceration. Increased hepatitis A vaccination coverage is critical to prevent similar outbreaks in the future.

Prevalence of indications for adult hepatitis A vaccination among hepatitis A outbreak-associated cases, Three US States, 2016-2019.

BACKGROUND: Safe and effective hepatitis A vaccines have been recommended in the United States for at-risk adults since 1996; however, adult vaccination coverage is low. METHODS: Among a random sample of adult outbreak-associated hepatitis A cases from three states that were heavily affected by person-to-person hepatitis A outbreaks, we assessed the presence of documented Advisory Committee on Immunization Practices (ACIP) indications for hepatitis A vaccination, hepatitis A vaccination status, and whether cases that were epidemiologically linked to an outbreak-associated hepatitis A case had received postexposure prophylaxis (PEP). RESULTS: Overall, 74.1% of cases had a documented ACIP indication for hepatitis A vaccination. Fewer than 20% of epidemiologically linked cases received PEP. CONCLUSIONS: Efforts are needed to increase provider awareness of and adherence to ACIP childhood and adult hepatitis A vaccination and PEP recommendations in order to stop the current person-to-person hepatitis A outbreaks and prevent similar outbreaks in the future.

Estimated Medicaid Costs Associated with Hepatitis A During an Outbreak - West Virginia, 2018-2019.

Hepatitis A is a vaccine-preventable disease caused by the hepatitis A virus (HAV). Transmission of the virus most commonly occurs through the fecal-oral route after close contact with an infected person. Widespread outbreaks of hepatitis A among persons who use illicit drugs (injection and noninjection drugs) have increased in recent years (1). The Advisory Committee on Immunization Practices (ACIP) recommends routine hepatitis A vaccination for children and persons at increased risk for infection or severe disease, and, since 1996, has recommended hepatitis A vaccination for persons who use illicit drugs (2). Vaccinating persons who are at-risk for HAV infection is a mainstay of the public health response for stopping ongoing person-to-person transmission and preventing future outbreaks (1). In response to a large hepatitis A outbreak in West Virginia, an analysis was conducted to assess total hepatitis A-related medical costs during January 1, 2018-July 31, 2019, among West Virginia Medicaid beneficiaries with a confirmed diagnosis of HAV infection. Among the analysis population, direct clinical costs ranged from an estimated $1.4 million to $5.6 million. Direct clinical costs among a subset of the Medicaid population with a diagnosis of a comorbid substance use disorder ranged from an estimated $1.0 million to $4.4 million during the study period. In addition to insight on preventing illness, hospitalization, and death, the results from this study highlight the potential financial cost jurisdictions might incur when ACIP recommendations for hepatitis A vaccination, especially among persons who use illicit drugs, are not followed (2).

Factors Associated With Hepatitis A Mortality During Person-to-Person Outbreaks: A Matched Case-Control Study-United States, 2016-2019.

BACKGROUND AND AIMS: During 2016-2020, the United States experienced person-to-person hepatitis A outbreaks that are unprecedented in the vaccine era, during which case-fatality ratios reported by some jurisdictions exceeded those historically associated with hepatitis A. APPROACH AND RESULTS: To identify factors associated with hepatitis A-related mortality, we performed a matched case-control study (matched on age [±5 years] and county of residence in a 1:4 ratio) using data collected from health department and hospital medical records of outbreak-associated patients in Kentucky, Michigan, and West Virginia. Controls were hepatitis A outbreak-associated patients who did not die. There were 110 cases (mean age 53.6 years) and 414 matched controls (mean age 51.9 years); most cases (68.2%) and controls (63.8%) were male. Significantly (P < 0.05) higher odds of mortality were associated with preexisting nonviral liver disease (adjusted odds ratio [aOR], 5.2), history of hepatitis B (aOR, 2.4), diabetes (aOR, 2.2), and cardiovascular disease (aOR, 2.2), as well as initial Model for End-Stage Liver Disease (MELD) score ≥ 30 (aOR, 10.0), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio > 2 (aOR, 10.3), and platelet count < 150,000/µL (aOR, 3.7) among hepatitis A outbreak-associated patients in the independent multivariable conditional logistic regression analyses (each model adjusted for sex). CONCLUSIONS: Preexisting liver disease, diabetes, cardiovascular disease, and initial MELD score ≥ 30, AST/ALT ratio ≥ 1, and platelet count < 150,000/µL among hepatitis A patients were independently associated with higher odds of mortality. Providers should be vigilant for such features and have a low threshold to escalate care and consider consultation for liver transplantation. Our findings support the recommendation of the Advisory Committee on Immunization Practices to vaccinate persons with chronic liver disease, though future recommendations to include adults with diabetes and cardiovascular disease should be considered.

Hepatitis A Person-to-Person Outbreaks: Epidemiology, Morbidity Burden, and Factors Associated With Hospitalization-Multiple States, 2016-2019.

BACKGROUND: Since 2016, the United States has experienced person-to-person hepatitis A outbreaks unprecedented in the vaccine era. The proportion of cases hospitalized in these outbreaks exceeds historical national surveillance data. METHODS: We described the epidemiology, characterized the reported increased morbidity, and identified factors associated with hospitalization during the outbreaks by reviewing a 10% random sample of outbreak-associated hepatitis A cases in Kentucky, Michigan, and West Virginia-3 heavily affected states. We calculated descriptive statistics and conducted age-adjusted log-binomial regression analyses to identify factors associated with hospitalization. RESULTS: Participants in the random sample (n = 817) were primarily male (62.5%) with mean age of 39.0 years; 51.8% were hospitalized. Among those with available information, 73.2% reported drug use, 14.0% were experiencing homelessness, 29.7% were currently or recently incarcerated, and 61.6% were epidemiologically linked to a known outbreak-associated case. Residence in Michigan (adjusted risk ratio [aRR] = 1.8), being a man who has sex with men (aRR = 1.5), noninjection drug use (aRR = 1.3), and homelessness (aRR = 1.3) were significantly (P < .05) associated with hepatitis A-related hospitalization. CONCLUSIONS: Our findings support current Advisory Committee on Immunization Practices recommendations to vaccinate all persons who use drugs, men who have sex with men, and persons experiencing homelessness against hepatitis A.

Acute Health Effects After the Elk River Chemical Spill, West Virginia, January 2014.

OBJECTIVES: On January 9, 2014, approximately 10 000 gallons of a mixture of 4-methylcyclohexanemethanol and propylene glycol phenyl ether spilled into West Virginia's Elk River, contaminating the potable water supply of about 300 000 West Virginia residents. This study sought to describe acute health effects after the chemical spill. METHODS: We conducted a descriptive analysis using 3 complementary data sources: (1) medical records of patients who visited an emergency department during January 9-23, 2014, with illness potentially related to the spill; (2) West Virginia Poison Center caller records coded as "contaminated water" during January 9-23, 2014; and (3) answers to household surveys about health effects from a Community Assessment for Public Health Emergency Response (CASPER) questionnaire administered 3 months after the spill. RESULTS: In the 2 weeks after the spill, 2000 people called the poison center reporting exposure to contaminated water, and 369 people visited emergency departments in the affected area with reports of exposure and symptoms potentially related to the spill. According to CASPER weighted cluster analyses, an estimated 25 623 households (21.7%; 95% confidence interval [CI], 14.4%-28.9%) had ≥1 person with symptoms who felt that they were related to the spill in the 3 months after it. Reported health effects across all 3 data sources included mild skin, respiratory, and gastrointestinal symptoms that resolved with no or minimal treatment. CONCLUSIONS: Medical records, poison center data, and CASPER household surveys were inexact but useful data sources to describe overall community health effects after a large-scale chemical spill. Analyzing multiple data sources could inform epidemiologic investigations of similar events.

Bortezomib Effects on Human Microvascular Endothelium in vitro.

Cellular oxidative stress in the endothelium of blood vessels leads to several pathophysiological sequelae, including vascular damage and dysfunction, inflammation and atherosclerosis. Heme oxygenase-1 (HO-1) provides protection against oxidative stress-induced cell death and plays a crucial role in the regulation of cyclooxygenase-2 (COX-2) in endothelial cells. In the present study, we have investigated the effects of bortezomib, a clinically used proteasome inhibitor, on the regulation of HO-1 and COX-2 in cultured human microvascular endothelial cells (HMECs). Bortezomib treatment of HMECS induced dose- and time-dependent expression of HO-1 and COX-2 mRNA and protein, and triggered nuclear translocation of nuclear factor erythroid 2-related transcription factor (Nrf2). These findings suggest that HO-1/COX-2-mediated induction of antioxidant mechanisms via Nrf2 activation may contribute to the cytoprotective effects of bortezomib in microvascular endothelium.