Determining Herd Immunity Thresholds for Hepatitis A Virus Transmission to Inform Vaccination Strategies Among People Who Inject Drugs in 16†US States.

BACKGROUND: Widespread outbreaks of person-to-person transmitted hepatitis A virus (HAV), particularly among people who inject drugs (PWID), continue across the United States and globally. However, the herd immunity threshold and vaccination coverage required to prevent outbreaks are unknown. We used surveillance data and dynamic modeling to estimate herd immunity thresholds among PWID in 16 US states. METHODS: We used a previously published dynamic model of HAV transmission calibrated to surveillance data from outbreaks involving PWID in 16 states. Using state-level calibrated models, we estimated the basic reproduction number (R0) and herd immunity threshold for PWID in each state. We performed a meta-analysis of herd immunity thresholds to determine the critical vaccination coverage required to prevent most HAV outbreaks among PWID. RESULTS: Estimates of R0 for HAV infection ranged from 2.2 (95% confidence interval [CI], 1.9-2.5) for North Carolina to 5.0 (95% CI, 4.5-5.6) for West Virginia. Corresponding herd immunity thresholds ranged from 55% (95% CI, 47%-61%) for North Carolina to 80% (95% CI, 78%-82%) for West Virginia. Based on the meta-analysis, we estimated a pooled herd immunity threshold of 64% (95% CI, 61%-68%; 90% prediction interval, 52%-76%) among PWID. Using the prediction interval upper bound (76%) and assuming 95% vaccine efficacy, we estimated that vaccination coverage of 80% could prevent most HAV outbreaks. CONCLUSIONS: Hepatitis A vaccination programs in the United States may need to achieve vaccination coverage of at least 80% among PWID in order to prevent most HAV outbreaks among this population.

Protection and antibody levels 35 years after primary series with hepatitis B vaccine and response to a booster dose.

BACKGROUND AND AIMS: The duration of protection from hepatitis B vaccination in children and adults is not known. In 1981, we used three doses of plasma-derived hepatitis B vaccine to immunize a cohort of 1578 Alaska Native adults and children from 15 Alaska communities who were ≥6 months old. APPROACH AND RESULTS: We tested persons for antibody to hepatitis B surface antigen (anti-HBs) levels 35 years after receiving the primary series. Those with levels <10 mIU/ml received one booster dose of recombinant hepatitis B vaccine 2-4 weeks later and were then evaluated on the basis of anti-HBs measurements 30 days postbooster. Among the 320 recruited, 112 persons had not participated in the 22- or 30-year follow-up study (group 1), and 208 persons had participated but were not given an HBV booster dose (group 2). Among the 112 persons in group 1 who responded to the original primary series, 53 (47.3%) had an anti-HBs level ≥10 mIU/ml. Among group 1, 73.7% (28 of 38) of persons available for a booster dose responded to it with an anti-HBs level ≥10 mIU/ml at 30 days. Initial anti-HBs level after the primary series was correlated with higher anti-HBs levels at 35 years. Among 8 persons who tested positive for antibody to hepatitis B core antigen, none tested positive for HBsAg or HBV DNA. CONCLUSIONS: Based on anti-HBs level ≥10 mIU/ml at 35 years and a 73.7% booster dose response, we estimate that 86% of participants had evidence of protection 35 years later. Booster doses are not needed in the general population at this time.

Assessing the Cost-Utility of Universal Hepatitis B Vaccination Among Adults.

BACKGROUND: Although effective against hepatitis B virus (HBV) infection, hepatitis B (HepB) vaccination is only recommended for infants, children, and adults at higher risk. We conducted an economic evaluation of universal HepB vaccination among US adults. METHODS: Using a decision analytic model with Markov disease progression, we compared current vaccination recommendations (baseline) with either 3-dose or 2-dose universal HepB vaccination (intervention strategies). In simulated modeling of 1 million adults distributed by age and risk groups, we quantified health benefits (quality-adjusted life years, QALYs) and costs for each strategy. Multivariable probabilistic sensitivity analyses identified key inputs. All costs reported in 2019 US dollars. RESULTS: With incremental base-case vaccination coverage up to 50% among persons at lower risk and 0% increment among persons at higher risk, each of 2 intervention strategies averted nearly one-quarter of acute HBV infections (3-dose strategy, 24.8%; 2-dose strategy, 24.6%). Societal incremental cost per QALY gained of $152 722 (interquartile range, $119 113-$235 086) and $155 429 (interquartile range, $120 302-$242 226) were estimated for 3-dose and 2-dose strategies, respectively. Risk of acute HBV infection showed the strongest influence. CONCLUSIONS: Universal adult vaccination against HBV may be an appropriate strategy for reducing HBV incidence and improving resulting health outcomes.

Severe Acute Respiratory Syndrome Coronavirus 2 Transmission in a Georgia School District-United States, December 2020-January 2021.

BACKGROUND: To inform prevention strategies, we assessed the extent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and settings in which transmission occurred in a Georgia public school district. METHODS: During 1 December 2020-22 January 2021, SARS-CoV-2-infected index cases and their close contacts in schools were identified by school and public health officials. For in-school contacts, we assessed symptoms and offered SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) testing; performed epidemiologic investigations and whole-genome sequencing to identify in-school transmission; and calculated secondary attack rate (SAR) by school setting (eg, sports, elementary school classroom), index case role (ie, staff, student), and index case symptomatic status. RESULTS: We identified 86 index cases and 1119 contacts, 688 (61.5%) of whom received testing. Fifty-nine of 679 (8.7%) contacts tested positive; 15 of 86 (17.4%) index cases resulted in ≥2 positive contacts. Among 55 persons testing positive with available symptom data, 31 (56.4%) were asymptomatic. Highest SARs were in indoor, high-contact sports settings (23.8% [95% confidence interval {CI}, 12.7%-33.3%]), staff meetings/lunches (18.2% [95% CI, 4.5%-31.8%]), and elementary school classrooms (9.5% [95% CI, 6.5%-12.5%]). The SAR was higher for staff (13.1% [95% CI, 9.0%-17.2%]) vs student index cases (5.8% [95% CI, 3.6%-8.0%]) and for symptomatic (10.9% [95% CI, 8.1%-13.9%]) vs asymptomatic index cases (3.0% [95% CI, 1.0%-5.5%]). CONCLUSIONS: Indoor sports may pose a risk to the safe operation of in-person learning. Preventing infection in staff members, through measures that include coronavirus disease 2019 vaccination, is critical to reducing in-school transmission. Because many positive contacts were asymptomatic, contact tracing should be paired with testing, regardless of symptoms.

Evaluating the cost-effectiveness of hepatitis B vaccination strategies in high-impact settings for adults.

Adults at increased risk for hepatitis B virus (HBV) infection are recommended to receive vaccination. We conducted a cost utility analysis to evaluate approaches for implementing that recommendation in selected high-risk settings: community outreach events with a large proportion of immigrants, syringe service programs, substance use treatment centres, sexually transmitted infection (STI) clinics, tuberculosis (TB) clinics and jails. We utilized a decision tree framework with a Markov disease progression model to compare quality adjusted life-years and cost in 2021 United States dollars from four strategies: a 3-dose vaccination regimen with prevaccination screening and testing (PVST; baseline comparison); PVST at the initial encounter followed by a 2-dose series (Intervention 1); PVST with the first dose of a 2-dose vaccination series at the initial encounter (Intervention 2); and a 2-dose vaccination series without PVST (Intervention 3). In all settings, Intervention 1 resulted in worse health outcomes compared with the baseline strategy. Intervention 2 averted incident chronic HBV infections in all settings (range -9.4% in TB clinics, -14.8% in syringe service programs) and was a cost-saving approach in settings with higher risk of infection (i.e. jails, -$266 per person; syringe service programs, -$597; substance use treatment centres, -$130). Providing a 2-dose vaccination series without any screening (Intervention 3) averted incident HBV infections and was cost-saving in all settings but resulted in more HBV-related deaths in settings with higher HBV prevalence. These results demonstrate a 2-dose vaccine series is a cost-effective approach in these high-impact settings, even if prevaccination testing is not possible.

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.

Universal Hepatitis B Vaccination in Adults Aged 19-59 Years: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2022.

Hepatitis B (HepB) vaccines have demonstrated safety, immunogenicity, and efficacy during the past 4 decades (1,2). However, vaccination coverage among adults has been suboptimal, limiting further reduction in hepatitis B virus (HBV) infections in the United States. This Advisory Committee on Immunization Practices (ACIP) recommendation expands the indicated age range for universal HepB vaccination to now include adults aged 19-59 years. Removing the risk factor assessment previously recommended to determine vaccine eligibility in this adult age group (2) could increase vaccination coverage and decrease hepatitis B cases.

Widespread Hepatitis A Outbreaks Associated with Person-to-Person Transmission - United States, 2016-2020.

Hepatitis A is a vaccine-preventable disease typically acquired through fecal-oral transmission. Hepatitis A virus (HAV) infection rates in the United States declined approximately 97% during 1995-2015 after the introduction and widespread pediatric use of hepatitis A vaccines (1). Since 2016, hepatitis A outbreaks have been reported in 37 states, involving approximately 44,650 cases, 27,250 hospitalizations, and 415 deaths as of September 23, 2022 (2). A report describing early outbreaks in four states during 2017 noted that most infections occurred among persons reporting injection or noninjection drug use or experiencing homelessness; this finding signaled a shift in HAV infection epidemiology from point-source outbreaks associated with contaminated food to large community outbreaks associated with person-to-person transmission (3). CDC analyzed interim data from 33 outbreak-affected states to characterize demographic, risk factor, and clinical outcome data from 37,553 outbreak-associated hepatitis A cases reported during August 1, 2016-December 31, 2020. Among persons with available risk factor or clinical outcome information, 56% reported drug use, 14% reported experiencing homelessness, and 61% had been hospitalized; 380 outbreak-associated deaths were reported. The most effective means to prevent and control hepatitis A outbreaks is through hepatitis A vaccination, particularly for persons at increased risk for HAV infection (4). The epidemiologic shifts identified during these outbreaks led to a 2019 recommendation by the Advisory Committee on Immunization Practices (ACIP) for vaccination of persons experiencing homelessness and reinforcement of existing vaccination recommendations for persons who use drugs (4). Substantial progress in the prevention and control of hepatitis A has been made; the number of outbreak-affected states has been reduced from 37 to 13 (2). Increased hepatitis A vaccination coverage, particularly through implementation of successful, nontraditional vaccination strategies among disproportionately affected populations (5), is needed to continue progress in halting current outbreaks and preventing similar outbreaks in the future.

Supporting syringe services programs in the initiation and scale-up of vaccine administration: findings from in-depth interviews.

BACKGROUND: Vaccine-hesitant persons who inject drugs are at increased risk for several vaccine-preventable diseases. However, vaccination rates among this population remain low. While syringe services programs (SSPs) are places where persons who inject drugs feel comfortable accessing services, few offer vaccination services. This study describes facilitators and barriers to vaccination at SSPs. METHODS: We used convenience sampling to conduct semi-structured, qualitative in-depth interviews with 21 SSPs in the USA from June to August 2021. Interview questions asked SSPs about their perceptions, priorities, barriers, facilitators, and the effects of partnerships and policies on vaccine administration. We used deductive thematic analysis to identify the main themes. RESULTS: Eight (n = 8) SSPs offered vaccinations, and thirteen (n = 13) did not offer vaccinations. Most SSPs believed offering vaccination services was important, although addressing SSP participants' immediate needs often took precedence. Staffing, physical space, and logistical issues were the most common barriers to vaccine administration reported by SSPs, followed by SSP participant-related barriers. Facilitators of vaccine administration included access to a tracking system, partnering with agencies or other organizations providing vaccines, and having a licensed vaccination provider on-site. Partnerships provided SSPs opportunities to expand capacity but could also restrict how SSPs operate. Recommended policy changes to facilitate vaccine administration included subsidizing the cost of vaccinations and addressing restrictions around who could administer vaccinations. CONCLUSIONS: Increasing the availability of vaccination services at SSPs requires addressing the varying capacity needs of SSPs, such as tracking systems, licensed vaccinators, and free or low-cost vaccination supplies. While these needs can be met through partnerships and supportive policies, both must consider and reflect cultural competence around the lived experiences of persons who inject drugs.

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.