Hepatitis A Virus Transmission Research Articles

Hepatitis A virus infection.

Hepatitis A is a vaccine-preventable infection caused by the hepatitis A virus (HAV). Over 150 million new infections of hepatitis A occur annually. HAV causes an acute inflammatory reaction in the liver that usually resolves spontaneously without chronic sequelae. However, up to 20% of patients experience a prolonged or relapsed course and <1% experience acute liver failure. Host factors, such as immunological status, age, pregnancy and underlying hepatic diseases, can affect the severity of disease. Anti-HAV IgG antibodiesproduced in response to HAV infection persist for life and protect against re-infection; vaccine-induced antibodies against hepatitis A confer long-term protection. The WHO recommends vaccination for individuals at higher risk of infection and/or severe disease in countries with very low and low hepatitis A virus endemicity, and universal childhood vaccination in intermediate endemicity countries. To date, >25 countries worldwide have implemented such programmes, resulting in a reduction in the incidence of HAV infection. Improving hygiene and sanitation, rapid identification of outbreaks and fast and accurate intervention in outbreak control are essential to reducing HAV transmission.

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

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. 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. 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. 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.

Widespread Community Transmission of Hepatitis A Virus Following an Outbreak at a Local Restaurant — Virginia, September 2021–September 2022

Hepatitis A is a vaccine-preventable liver infection caused by the hepatitis A virus (HAV); it is transmitted through ingestion of food or drink that has been contaminated by small amounts of infected stool, or through direct contact, including sexual contact, with a person who is infected (1). After years of historically low rates of hepatitis A in the United States, the incidence began increasing in 2016, with outbreaks characterized by person-to-person HAV transmission among persons who use drugs, persons experiencing homelessness, and men who have sex with men (2,3). As of September 2022, 13 states were experiencing outbreaks, including Virginia (3). In September 2021, the Roanoke City and Alleghany Health Districts (RCAHD) in southwestern Virginia investigated an outbreak of hepatitis A. The outbreak, which resulted in 51 cases, 31 hospitalizations, and three deaths, was associated with a food handler who was infected. After the outbreak, the community experienced ongoing person-to-person transmission of HAV, predominantly among persons who use injection drugs. As of September 30, 2022,* an additional 98 cases had been reported to RCAHD. The initial outbreak and community transmission have exceeded US$3 million in estimated direct costs (4,5). This report describes the initial outbreak and the ongoing community transmission of HAV. Increasing vaccination coverage among persons with risk factors for hepatitis A infection is important, including among those who use drugs. Strengthening community partnerships between public health officials and organizations that employ persons with risk factors for acquisition of HAV could help to prevent infections and outbreaks.

Pediatric Hepatitis A: A Case Report

Background: Hepatitis A is a systemic infection which predominantly inflame the liver due to Hepatitis-A-Virus (HAV) infection. Developing countries have higher prevalence of this disease because of poor sanitation and environment. The transmission of HAV is fecal-oral via contaminated foods or beverages. Case: A 14-year-old boy visited emergency department with yellowish skin on body, nausea, fever, and liver enlargement. He had a bad habit of consuming unhealthy street-foods. Hepatitis A was diagnosed after history taking, physical examination and laboratory testing. Serology test was performed with positive Anti HAV IgM to confirm the disease. Liver enzymes, and bilirubin level were also increased in this patient. Discussion: The transmission of HAV is through fecal-oral via contaminated foods or beverages. This disease can be prevented by having good personal hygiene, avoiding contaminated food, with good access to clean water and environmental sanitation. Habit of consuming street foods is a risk factor of developing HAV infection. The clinical manifestation of HAV infection includes jaundice, nausea, decreased appetite, and vomiting. Conclusion: Diagnosis of hepatitis A requires careful history taking, physical examination and laboratory evaluation. Hepatitis A is a self-limiting disease and currently there is no specific treatment to cure this disease. Supportive treatment, hepato-protector and vitamin supplementation will improve the condition.

Occurrence of Hepatitis A Virus in Water Matrices: A Systematic Review and Meta-Analysis.

Hepatitis A is a common form of viral hepatitis. It is usually transmitted through the ingestion of contaminated food and water. This systematic review was carried out to summarise the overall prevalence of Hepatitis A virus (HAV) in different water matrices: untreated and treated wastewater, surface water, groundwater, drinking water, and others (e.g., irrigation water and floodwater). The literature search was performed in four databases: PubMed, Web of Science, Global Index Medicus, and Excerpta Medica Database. Heterogeneity (I2) was assessed using the χ2 test on the Cochran Q statistic and H parameters. A total of 200 prevalence data from 144 articles were included in this meta-analysis. The overall prevalence of HAV in water matrices was 16.7% (95% CI: 13.4-20.3). The prevalence for individual matrix was as follows: 31.4% (95% CI: 23.0-40.4) untreated wastewater, 18.0% (95% CI: 9.5-28.2) treated wastewater, 15.0% (95% CI: 10.1-20.5) surface water, 2.3% (95% CI: 0.1-6.0) in groundwater, 0.3% (95% CI: 0.0-1.7) in drinking water, and 8.5% (95% CI: 3.1-15.6) in other matrices. The prevalence was higher in low-income economies (29.0%). Africa and Eastern Mediterranean were the regions with higher HAV prevalence values. This study showed a high heterogeneity (I2 &gt; 75%) with a significant publication bias (p value Egger test &lt; 0.001). The results of this review suggest that water matrices could be an important route of HAV transmission even in industrialized countries, despite the lower prevalence compared to less industrialized countries, and the availability of advanced water management systems. More effective water/wastewater treatment strategies are needed in developing countries to limit the environmental circulation of HAV.

Hepatitis A virus (HAV) RNA detection in Polish blood donors and likely transmissions through blood components during the 2017-2019 epidemic.

In Poland, hepatitis A virus (HAV) RNA screening was performed in plasma for fractionation usually immediately before shipment. Our goal was to study epidemiology, rate of transfusion transmitted HAV during epidemic (2017-2019), and viral characteristics of infected plasma donors. HAV RNA was tested in 1,866,590 donations from 1,210,423 donors using RT-PCR in mini pools of 96 (MP96) or TMA in MP16. Virological characteristics included RNA level (RL), antibody testing, and sequencing. Twenty-one HAV infections were identified (1.13/100,000 donations; 95% confidence interval [95% CI]: 0.74-1.72) and (1.73/100,000 donors; 95% CI: 1.35-2.65). The Blood Transfusion Centers were also informed about three donors, who were hospitalized for hepatitis A soon after their blood donation. In addition, we identified a donor, who had reactive result for HAV after receiving HAV vaccination. He tested positive twice 10 days after receiving the first and the second dose. The highest RL was 16 million IU/ml, mean 1,706,905 IU/ml, and median 220 IU/ml. The longest detectable RL lasted for 113 days. HAV-infected donors were seronegative (36%) or IgM positive (64%). We followed up on 12 HAV contaminated blood components issued for transfusion. In two out of seven identified patients viral transmission was confirmed (28.6%). Based on our results, we propose a 6 month deferral after HAV infection and 14 days post HAV vaccination. The infectivity rate was below 30%. The HAV RNA testing could be considered as an additional safeguard against HAV transmission at the time of increased incidence of HAV infections in the general population.

Hepatitis A and E Viruses in Mussels from Cherrat Estuary in Morocco: Detection by Real-Time Reverse Transcription PCR Analysis.

The aim of the present study was to evaluate hepatitis A virus (HAV) and hepatitis E virus (HEV) contamination in mussels (Mytilus galloprovincialis) from Cherrat estuary (Moroccan Atlantic Coast), Morocco. In total, 52 samples (n = 12 mussels/each) were collected at four sites in the estuary, monthly, between March 2019 and March 2020. HAV and HEV were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) according to the ISO/TS 15216 method. HAV was detected in 46.15% of analyzed samples. Conversely, HEV was not detected in any sample. Moreover, the HAV detection rate was significantly associated with seasonal rainfall variations. This qualitative study on HAV and HEV contamination highlights the interest of studying mussel samples from wild areas. As HAV presence in mussels represents a potential health risk, viral contamination surveillance of mussels is necessary to protect consumers. HAV shellfish contamination must be monitored at Cherrat estuary because of the role played by shellfish as HAV reservoirs and/or vehicles in fecal-oral HAV transmission.

A custom hepatitis A virus assay for whole-genome sequencing

Since 2016, the United States has experienced a resurgence in the number of hepatitis A virus (HAV) cases and outbreaks. These outbreaks have been sustained by person-to-person transmission with cases occurring predominantly in high-risk populations including intravenous drug users, individuals experiencing homelessness, and men who have sex with men. To investigate HAV transmission, a molecular-surveillance system consisting of real-time RT-PCR (rRT-PCR) for detection, and a conventional RT-PCR assay for genotyping of HAV, was established in New York State (NYS) in 2019. Since then, a total of 271 HAV-positive serum samples collected from cases across NYS between 2019 and 2021 were identified by rRT-PCR. To rapidly and efficiently generate HAV whole-genome sequences, a custom AmpliSeq™ panel was designed in collaboration with Thermo Fisher. To streamline the process, sample preparation was performed on an Ion Chef and sequencing on an Ion S5XL. Of the 271 HAV-positive samples, the whole-genome sequencing (WGS) assay successfully generated 134 near-complete, high-quality HAV sequences. Phylogenetic analysis of the VP1–2A region identified 216 IB, 48 IA, and 2 IIIA genotypes, while 5 were unable to be typed due to poor sequence in this key region. The HAV whole-genome sequencing approach provided a more efficient and streamlined approach for genotyping HAV compared to previous methods and resulted in phylogenetic trees with enhanced resolution compared to the HAV VP1–2A region alone.

Transmission dynamics of the 2016-18 outbreak of hepatitis A among men who have sex with men in England and cost-effectiveness analysis of vaccination strategies to prevent future outbreaks.

SummaryBackgroundDespite being vaccine-preventable, hepatitis A virus (HAV) outbreaks occur among men who have sex with men (MSM). We modelled the cost-effectiveness of vaccination strategies to prevent future outbreaks.MethodsA HAV transmission model was calibrated to HAV outbreak data for MSM in England over 2016-2018, producing estimates for the basic reproduction number (R0) and immunity levels (seroprevalence) post-outbreak. For a hypothetical outbreak in 2023 (same R0 and evolving immunity), the cost-effectiveness of pre-emptive (vaccination between outbreaks among MSM attending sexual health services (SHS)) and reactive (vaccination during outbreak among MSM attending SHS and primary care) vaccination strategies were modelled. Effectiveness in quality-adjusted life-years (QALYs) and costs were estimated (2017 UK pounds) from a societal perspective (10-year time horizon; 3% discount rate). The incremental cost-effectiveness ratio (ICER) was estimated.FindingsR0 for the 2016-2018 outbreak was 3·19 (95% credibility interval (95%CrI) 2·87-3·46); seroprevalence among MSM increased to 70·4% (95%CrI 67·3-72·8%) post-outbreak. For our hypothetical HAV outbreak in 2023, pre-emptively vaccinating MSM over the preceding five-years was cost-saving (compared to no vaccination) if the yearly vaccine coverage rate among MSM attending SHS was <9·1%. Reactive vaccination was also cost-saving compared to no vaccination, but was dominated by pre-emptive vaccination if the yearly vaccination rate was >8%. If the pre-emptive yearly vaccination rate fell below this threshold, it became cost-saving to add reactive vaccination to pre-emptive vaccination.InterpretationAlthough highly transmissible, existing immunity limited the recent HAV outbreak among MSM in England. Pre-emptive vaccination between outbreaks, with reactive vaccination if indicated, is the best strategy for limiting future HAV outbreaks.FundingNIHR.

Exploration of a new hepatitis a surveillance system in Beijing, China: based on molecular epidemiology

BackgroundThe incidence of hepatitis A virus (HAV) infection is low in Beijing, China, but the risk of outbreaks still exists. It is difficult to identify possible sources of infection among sporadic cases based on a routine surveillance system. Therefore, a more effective surveillance system needs to be established.MethodsThe epidemiological data of hepatitis A were obtained from a routine surveillance system. Patients with HAV confirmed at the local hospitals were asked to complete a questionnaire that included additional case information and possible sources of infection. Serum and fecal specimens were also collected for testing HAV RNA by polymerase chain reaction. In addition, the 321-nucleotide segment of the VP1/2A junction region was sequenced to determine the HAV genotype.ResultsIn 2019, 110 HAV cases were reported in Beijing, with an incidence rate of 0.51/100,000. 61(55.5%) of these patients were male. The greatest proportion of these patients were aged from 30 to 60 years. The rate was lower in suburban and rural areas compared to urban areas. Contaminated food consumption, particularly seafood consumption, was the primary potential source of infection. Among the 16 specimens of confirmed HAV cases that could be sequenced, 93.8% were HAV IA, and 6.3% were HAV IB. In addition, the samples collected from all HAV sequences in this investigation showed 89.4–100% nucleotide homology. Two groups (each with three sporadic cases) showed 100% nucleotide homology. The three sporadic cases in one group had the same possible source of infection: contaminated salad with raw vegetables and seafood. In the other group, the three sporadic cases did not have an epidemiological connection.ConclusionsIn a low HAV prevalent area, such as in Beijing, incorporating molecular epidemiology into the routine surveillance system could help inform possible clusters of outbreaks and provide support for earlier control of HAV transmission. Nevertheless, increased sampling from detected cases and improved specimen quality are needed to implement such a system.

Estimating vaccination threshold and impact in the 2017–2019 hepatitis A virus outbreak among persons experiencing homelessness or who use drugs in Louisville, Kentucky, United States

BackgroundBetween September 2017 and June 2019, an outbreak of hepatitis A virus (HAV) occurred in Louisville, Kentucky, resulting in 501 cases and 6 deaths, predominantly among persons who experience homelessness or who use drugs (PEH/PWUD). The critical vaccination threshold (Vc) required to achieve herd immunity in this population is unknown. We investigated Vc and vaccination impact using epidemic modeling. MethodsTo determine which population subgroups had high infection risks, we employed a technique based on comparing the proportion of cases arising before and after the epidemic peak, across subgroups. We also developed a dynamic deterministic model of HAV transmission among PEH/PWUD to estimate the basic reproduction number (R0), herd immunity threshold, Vc and the effect of timing of the vaccination intervention on epidemic and economic outcomes. ResultsOf the 501 confirmed or probable cases, 385 (76.8%) were among PEH/PWUD. Among PEH/PWUD and within the general population, homelessness was a significant risk factor for infection in the initial stages of the outbreak (odds ratios for homeless versus not homeless: 2.62; 95% confidence interval (CI): 1.62–4.25 for PEH/PWUD and 2.39; 95% CI: 1.51–3.78 for all detected cases). Our estimate for R0 ranges between 2.85 and 3.54, corresponding to an estimate of 69% (95% CI: 65–72) for herd immunity threshold and 76% (95% CI: 72%-80%) for Vc, assuming a vaccine with 90% efficacy. The observed vaccination program was estimated to have averted 30 hospitalizations (95% CI: 19–43), associated with over US$490 000 (95% CI: $310 000–700 000) in hospitalization cost. Greater impact was observed with earlier and faster vaccination implementation. ConclusionsVaccination coverage of at least 77% is likely required to prevent outbreaks of HAV among PEH/PWUD in Louisville, assuming a 90% vaccine efficacy. Proactive hepatitis A vaccination programs among PEH/PWUD will maximize health and economic benefits of these programs and reduce the likelihood of another outbreak.

Hepatitis A Virus Infections Among Men Who Have Sex with Men — Eight U.S. States, 2017–2018

During 1995-2011, the overall incidence of hepatitis A decreased by 95% in the United States from 12 cases per 100,000 population during 1995 to 0.4 cases per 100,000 population during 2011, and then plateaued during 2012─2015. The incidence increased by 294% during 2016-2018 compared with the incidence during 2013-2015, with most cases occurring among populations at high risk for hepatitis A infection, including persons who use illicit drugs (injection and noninjection), persons who experience homelessness, and men who have sex with men (MSM) (1-3). Previous outbreaks among persons who use illicit drugs and MSM led to recommendations issued in 1996 by the Advisory Committee on Immunization Practices (ACIP) for routine hepatitis A vaccination of persons in these populations (4). Despite these long-standing recommendations, vaccination coverage rates among MSM remain low (5). In 2017, the New York City Department of Health and Mental Hygiene contacted CDC after public health officials noted an increase in hepatitis A infections among MSM. Laboratory testing* of clinical specimens identified strains of the hepatitis A virus (HAV) that subsequently matched strains recovered from MSM in other states. During January 1, 2017-October 31, 2018, CDC received reports of 260 cases of hepatitis A among MSM from health departments in eight states, a substantial increase from the 16 cases reported from all 50 states during 2013-2015. Forty-eight percent (124 of 258) of MSM patients were hospitalized for a median of 3 days. No deaths were reported. In response to these cases, CDC supported state and local health departments with public health intervention efforts to decrease HAV transmission among MSM populations. These efforts included organizing multistate calls among health departments to share information, providing guidance on developing targeted outreach and managing supplies for vaccine campaigns, and conducting laboratory testing of clinical specimens. Targeted outreach for MSM to increase awareness about hepatitis A infection and improve access to vaccination services, such as providing convenient locations for vaccination, are needed to prevent outbreaks among MSM.

Associations Between Environmental and Sociodemographic Data and Hepatitis-A Transmission in Pará State (Brazil).

Hepatitis‐A is a waterborne infectious disease transmitted by the eponymous hepatitis‐A virus (HAV). Due to the disease's sociodemographic and environmental characteristics, this study applied public census and remote sensing data to assess risk factors for hepatitis‐A transmission. Municipality‐level data were obtained for the state of Pará, Brazil. Generalized linear and nonlinear models were evaluated as alternative predictors for hepatitis‐A transmission in Pará. The Histogram Gradient Boost (HGB) regression model was deemed the best choice (RMSE= 2.36, and higher R2 = 0.95) among the tested models. Partial dependence analysis and permutation feature importance analysis were used to investigate the partial dependence and the relative importance values of the independent variables in the disease transmission prediction model. Results indicated a complex relationship between the disease transmission and the sociodemographic and environmental characteristics of the study area. Population size, lack of sanitation, urban clustering, year of notification, insufficient public vaccination programs, household proximity to open‐air dumpsites and storm‐drains, and lack of access to healthcare facilities and hospitals were sociodemographic parameters related to HAV transmission. Turbidity and precipitation were the environmental parameters closest related to disease transmission. Based on HGB model, a hepatitis‐A risk map was built for Pará state. The obtained risk map can be thought of as an auxiliary tool for public health strategies. This study reinforces the need to incorporate remote sensing data in epidemiological modelling and surveillance plans for the development of early prevention strategies for hepatitis‐A.

A Cross Sectional Study to Evaluate Awareness About Hepatitis A &amp; E Among Students in Lahore

Background: The aim and objectives of the study were to determine the knowledge, attitude and practices among biological and non-biological students regarding Hepatitis A virus (HAV) and Hepatitis E virus (HEV). Methods: The present study was conducted by the Department of Microbiology, Pakistan kidney &amp; liver institute and research center (PKLI &amp; RC) at University of Veterinary and Animal Sciences (UVAS), Lahore, Pakistan. The study was conducted in November, 2019 to January, 2020. A total of 326 respondents (students) participated in the present study. Respondents filled a pre-tested structured questionnaire. The variables accessed were knowledge of the diseases including etiology, mode of transmission, and prevention and control measures. Results: Most 81.56% of respondents from biological sciences (B-S) group and 51.70% from non-biological sciences (N-B-S) had awareness about HAV/HEV. Furthermore, 72.06% of respondents from BS group and 13.60% of respondents from NBS group had knowledge about the mode of transmission and spread of HAV and HEV infection. Only 16.20% of students from B-S group were aware about importance of vaccination against HAV/HEV. While a very low prevalence was found about vaccination in N-B-S group that is only 4.76%. Conclusion: The study shows significance difference in the awareness level among students from biological sciences and non-biological sciences background. Respondents were found to misunderstand the hepatitis A &amp; E infections with hepatitis B &amp; C, which suggests that there is need to spread awareness about the differences in their spread and severity of these infections. Awareness campaigns should be conducted to make people aware of the ways HAV/HEV spreads, its mode of transmission, severity of infection and preventive measures to minimize its spread as well as chances to acquire HAV/HEV infections.

Risk factors for sporadic hepatitis A infection: A systematic review and meta-analysis

Hepatitis A virus (HAV) is responsible for common acute viral hepatitis worldwide. Improvement in sanitation and use of efficient vaccines have reduced HAV incidence in developed countries. However, naive adult population are most susceptible to severe outcomes, and high endemic areas persist in developing regions. The transmission of HAV through the fecal-oral route is established. However, considering evolving consumption habits and global market exchange of food, investigations on risk factors associated with HAV infection are needed. Thus, a systematic review and a meta-analysis of case-control, cohort and transversal studies was performed to determine the main risk factors associated with sporadic HAV infection. Relevant scientific articles were identified through systematic literature search and subjected to a methodological quality assessment. Mixed-effects meta-analyses models were adjusted by population type to appropriate data partitions. HAV infections are defined by serological testing. The quality assessment stage selected 78 studies investigating risk factors for sporadic infections with hepatitis A conducted between 1985 and 2013. This meta-analysis confirmed that HAV infections are mostly related to inter-human transmissions, either due to contact with an ill person, through oral-anal sex practice, or lack of personal hygiene. Travel to endemic countries, occupational exposure such as working in child daycare, and exposure to wastewater were associated with HAV infection. As HAV can persist in the environment, it was not surprising that consumption of untreated drinking water, shellfish consumed raw, and crop products were risk factors. Food contamination could be due to the use of contaminated water (fruits, vegetables) or originate from infected food handlers at every point of the food chain (from picking to serving). Eating or drinking outside were associated with HAV infection. A lack of recent case-control studies was identified, with only three studies eligible between 2011 and 2017. Case-control studies required a more precise definition of risk factors such as type of crop product, and storing/preparation information (e.g. washed, frozen). The frequency of consumption or duration of environmental exposure could also better inform relationship between exposure and risk of infection. In a context of epidemiological change of HAV, international travel and trade of foods, future case-control studies are needed and should focus on populations at risk of severe infections and acute cases.

Hepatitis A Virus Survival on Drug Paraphernalia

Background: The ongoing hepatitis A outbreak in the United States has concerned public health authorities since March 2017. The outbreak has already spread throughout 30 states and includes primarily homeless individuals and persons who use drugs, including persons who inject drugs (PWIDs). Contaminated drug injection paraphernalia and sharing of these items are suspected to be one of multiple causes of hepatitis A virus (HAV) transmission in those populations. Methods: We used a standard plaque assay to investigate HAV infectivity. Liquid suspensions of HAV were tested to examine the effects of time and temperature on viral infectivity. We also examined HAV survival on commonly used drug paraphernalia, such as needles, syringes, cookers, tourniquets, and cotton balls/filters frequently shared among PWIDs. We investigated the effect of low pH on HAV survival using citric acid, which is frequently used by PWIDs during dose preparation. We also compared the plaque assay results with those concurrently obtained by RT-PCR to establish whether viral HAV RNA levels could be used as surrogates for plaque assay results. Results: We found that HAV suspended in PBS at room temperature was able to infect FRhk4 cells for &gt;17 weeks. HAV remained viable in syringes and needles (ie, semidry conditions) for up to 10 weeks depending on the size of the needles and the syringe dead volume. HAV survival in dry conditions on cooker, tourniquet, and cotton balls/filter surfaces did not exceed 4 weeks. HAV retained its infectivity for &gt;10 weeks at pH as low as 2. PCR results suggest that RNA is amplified from both infectious and noninfectious HAV. Conclusions: Our findings show that HAV can survive and remain infective in the PWID setting for 4–10 weeks depending on the type of paraphernalia examined. These findings suggest that sharing drug paraphernalia by the homeless and PWIDs can potentially facilitate the transmission of HAV within these populations. Moreover, our results confirm that the plaque assay is currently the only reliable method to determine the infectivity of HAV in vitro.Funding: NoneDisclosures: None

Application of an Optimized Direct Lysis Method for Viral RNA Extraction Linking Contaminated Dates to Infection With Hepatitis A Virus

Consumption of dates has not been considered a common risk of hepatitis A virus (HAV) infection. In January 2018, an outbreak of hepatitis was identified with cases resident in all regions of Denmark. All the detected strains belonged to HAV genotype 3A. Epidemiological investigations through patients’ interviews, case-control and trace-back studies pointed toward different batches of dates from a single producer as the vehicle of infection. Boxes of dates from suspected batches were collected from homes of patients and healthy families and analyzed using a recently reported optimized direct lysis method, consisting of simultaneous viral RNA elution and extraction from dates followed by purification of the nucleic acids. Extracts were analyzed for HAV and norovirus (NoV) RNA using RT-qPCR, while detected HAV were genotyped by Sanger sequencing. Among 20 nucleic acid extracts representing eight batches of dates, RNA of HAV (9.3 × 102 genome copies/g) and NoV genogroup (G)II (trace amounts) were detected in one batch, while NoV GII RNA (trace amounts) was detected in another. Average extraction efficiency of spiked process control murine norovirus was 20 ± 13% and the inhibitions of RT-qPCR detection of NoV GI, NoV GII, and HAV were 31 ± 34, 9 ± 9, and 3 ± 7%, respectively. The HAV genome detected in the dates matched by sequence 100% to the HAV genotype 3A detected in stool samples from cases implicated in the outbreak. This confirmed, to our knowledge, for the first time a sequence link between HAV infection and consumption of contaminated dates, suggesting dates to be an important vehicle of HAV transmission.

Hepatitis A virus survival on drug paraphernalia.

The ongoing hepatitis A outbreaks in multiple states in the United States have concerned public health authorities since March 2017. The outbreaks have spread throughout 30 states and include primarily persons who use drugs, including persons who inject drugs (PWID) and persons experiencing homelessness. Contaminated drug injection paraphernalia and sharing of these items could potentially aid in transmission of hepatitis A virus (HAV) among these populations. We examined HAV survival on drug paraphernalia frequently shared among PWIDs. The effect of low pH on HAV survival using citric acid, which is frequently used by PWIDs during dose preparation, was investigated. We compared the plaque assay results with those concurrently obtained by qRT-PCR to establish whether HAV RNA levels could be used as surrogates for plaque assay results. HAV suspended in minimal essential media at room temperature infected FRhK4 cells for more than 17weeks. HAV remained viable in syringes/needles for up to 10weeks depending on the gauge of the needles and the syringe dead volumes, and on cookers, tourniquets and cotton balls/filter surfaces for up to 4weeks. HAV retained its infectivity for more than 10weeks at pH as low as 2. In conclusion, our findings show that HAV survives and remains infective in or on injection drug use equipment for 1 to 10weeks depending on the type of paraphernalia examined and environmental conditions. These findings suggest that contaminated drug paraphernalia can potentially facilitate the transmission of HAV within populations who share these items.

The National Hepatitis A Outbreaks: Experience from the Epicenter

Historically, outbreaks of hepatitis A virus (HAV) have been associated with contaminated food. Through vaccination and sanitation, the annual incidence of HAV had plummeted until the recent outbreak. We investigated the demographic features and clinical course of HAV cases during 2017–2018 in West Virginia. We performed a retrospective chart review on 482 patients confirmed with HAV. We found them to be predominantly Caucasian males with a mean age of 42. Forty-nine percent were intravenous drug users with methamphetamine being the substance of choice (52%). There was evidence of geographic clustering. Two patients with chronic liver disease died of hepatic failure secondary to HAV, and a third patient died of lone HAV. Our data shows a strong association of HAV with illicit substance use, specifically methamphetamine. These persons at risk should be targeted for vaccination. The increased transmission of HAV in drug users warrants investigation.

Household transmission and disease transmissibility of a large HAV outbreak in Lazio, Italy, 2016–2017

A major outbreak of Hepatitis A Virus (HAV) has swept through Europe between mid-2016 and 2017, mainly within the community of men who have sex with men (MSM). Over the same period, about 1000 outbreak-related cases of acute Hepatitis A (AHA) were recorded in Lazio region, Italy.We calibrated a Bayesian model to reconstruct likely transmission events within all 44 households where multiple infections were recorded, representing a total of 103 cases from the HAV outbreak in Lazio. Based on information on the observed times of symptom onset, we estimated the probability distribution function of the HAV generation time and used it to compute the effective and instantaneous reproduction numbers for the considered outbreak from the overall epidemic curve (N = 998 cases).We estimated a mean generation time of 30.2 days (95%CI: 25.2–33.0) and an effective reproduction number of about 1.63 (95% CI: 1.35–1.94). Transmissibility peaked in January 2017, shortly before targeted awareness and vaccination campaigns were put in place by health authorities; however, transmission remained above the epidemic threshold until June 2017. Within households, children (0–15) and young adults (16–30) infected preferentially individuals of the same age class, whereas transmission within older age groups was substantially homogeneous.These results suggest that the implemented interventions were able to slow down HAV transmission, but not to bring it rapidly to a halt. According to our estimates of the HAV transmissibility, about 50% of the at-risk persons should be immunized to prevent similar outbreaks in the future. Our results also indicate spillover from community transmission to household members, suggesting the opportunity of vaccinating household contacts of cases to prevent further spread of the epidemics.