BACKGROUND: Sub-Saharan Africa region bears the highest chronic hepatitis B virus (HBV) infection burden worldwide. National estimates of HBV burden are necessary for a viral hepatitis program planning. This study estimated the national prevalence of HBV infection in Kenya among people aged 15-64 years. METHODS: Of 27,745 participants age 15-64 years in the Kenya Population-based HIV Impact Assessment (KENPHIA) 2018 household survey, we analyzed data for all persons living with HIV (PLHIV; n = 1,521) and a random sample of HIV-negative persons (n = 1,551), totaling to 3,072 participants. We tested whole blood samples for hepatitis B surface antigen (HBsAg) using Determine™ HBsAg rapid test and used population projections to estimate national disease burden. Pearson chi square was performed and the weighted prevalence proportions presented. FINDINGS: Of the 3,072 participants,124 tested HBsAg positive, resulting in a weighted national HBV prevalence of 3.0% (95% CI: 2.2-3.9%). This translated to an HBV infection burden of 810,600 (95% CI: 582,700-1,038,600) persons age 15-64 years in Kenya. Distribution of HBV prevalence varied widely (p<0.001) by geography, ranging from 0.1% in Eastern Kenya regions to over 5% in northern and western Kenya. Prevalence of HBV infection was higher in PLHIV (4.7%; 95% CI: 3.3-6.0%) compared to HIV-negative persons (3.0%; 95% CI: 2.1-3.9%), and was highest among persons: age 45-54 years (6.4%; 95% CI: 3.3-9.5%), those who reported no formal education (10.7%; 95% CI: 5.1-16.4%), in polygamous marriages (6.8%; 95% CI: 1.7-11.8%), and in the lowest wealth quintile (5.3%; 95% CI: 2.8-7.7). When adjusted for covariates, lack of formal education (aOR = 4.2; 95% CI: 1.5-12.6) was significantly associated with HBV infection. In stratified analysis by HIV status, residing in rural areas and history of blood transfusion were independently associated with HBV infection among PLHIV, while lack of formal education and no history of blood transfusion were associated with HBV infection among HIV-negative participants (p<0.05). INTERPRETATION: HBV prevalence among persons aged 15-64 years in Kenya was 3.0%. Higher prevalence was documented among persons without formal education, in the lowest wealth quintile, and those living in Kenya's North-Eastern, Rift Valley-North and Nyanza regions. Targeted programmatic measures to strengthen interventions against HBV infections including newborn vaccination and treatment of infected adults to limit mother-to-child transmission, would be helpful in reducing burden of HBV-associated viral hepatitis.

Eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis has been reported in several southern U.S. states and Hawai'i. We present the first locally acquired human cases of A. cantonensis meningoencephalitis in three children in Florida, occurring between June 2021 and January 2022. Clinicians should be attuned to this possible diagnosis in this region.

A nationwide serosurvey among adults in 2021 showed a 2.7% (95% confidence interval [CI]: 2.3%-3.4%) prevalence of hepatitis B. Our analysis evaluates knowledge, attitudes and practices (KAP) for hepatitis B virus (HBV) infection among primary healthcare physicians (PHPs) in Georgia. We randomly selected 550 PHPs from medical facilities in Georgia's six largest cities. Using bivariate ordinal regression, we assessed the association of socio-demographic factors with an ordinal knowledge score (low/middle/high). Multivariable logistic regression was performed to calculate adjusted odds ratios (aOR) and 95% CI to determine associations between HBV knowledge score and practices. Of 550 selected PHPs, 506 (92.0%) agreed to participate. Among them, 62.8% scored in the medium or high knowledge tertiles, 72.7% were confident in diagnosing HBV infection, 37.3% were confident in managing patients with hepatitis B; 47.4% reported being screened for and 26.2% reported being vaccinated against HBV infection. Compared to those with low knowledge scores, PHPs with a high score were less likely to recommend activities not supported by evidence, such as: the use of 'hepatoprotective' medications (aOR 0.43, 95% CI 0.25-0.73), caesarean sections (aOR 0.47, 95% CI 0.27-0.82) and withholding breastfeeding (aOR 0.57, 95% CI 0.34-0.96) to prevent HBV transmission. The majority of PHPs were confident in diagnosing HBV infection, but only one in three were confident in managing patients with hepatitis B. PHPs with higher HBV knowledge were less likely to provide inaccurate instructions to their patients. These findings will help to develop awareness and education campaigns supporting HBV elimination in Georgia.

Exposure to healthcare procedures might be a source of hepatitis C virus (HCV) transmission in Georgia, one of the few countries currently on track to eliminate hepatitis C. While there has been a history of iatrogenic transmission of HCV, the risk of HCV transmission related to endoscopic procedures has not been previously assessed in Georgia. The goal of this study was to assess HCV seroconversion among individuals undergoing endoscopic procedures to estimate the relative role and incidence of HCV infection attributable to endoscopic procedures. A prospective cohort study was conducted in four endoscopy units in two cities (Tbilisi and Kutaisi) of Georgia during April-September, 2021. Recruitment of study participants was conducted using convenience sampling, and every eligible patient was approached and invited to participate in the study. Study population included adults (age ≥ 18 years) who received an endoscopic procedure (gastroscopy, colonoscopy and bronchoscopy) in inpatient or outpatient unit at the study sites. HCV antibody (anti-HCV) testing was conducted using rapid diagnostic test (RDT) on the same day they underwent the endoscopic procedure. Patients with a non-reactive anti-HCV baseline test were retested after 6 months. Patients with reactive baseline tests were excluded from the study and linked to further testing and care. Participants with a reactive result on follow-up RDTs were retested using a lab-based anti-HCV and HCV ribonucleic acid (RNA) test. A total of 981 HCV antibody non-reactive participants were enrolled; 590 (64.8%) of them were reached and retested after 6 months. At retesting, two out of 590 (0.3%) individuals had a reactive anti-HCV result on RDT and both were negative on laboratory-based anti-HCV and HCV RNA tests. Based on the results of this study, endoscopic procedures were not shown to contribute to HCV transmission in Georgia.

BACKGROUND: Hepatitis C virus (HCV) infection can lead to a type of primary liver cancer called hepatocellular carcinoma (HCC). Georgia, a high HCV prevalence country, started an HCV elimination program in 2015. In addition to tracking incidence and mortality, surveillance for the HCV-attributable fraction of HCC is an important indicator of the program's impact. This study assesses HCV infection-attributable HCC in the Georgian population. METHODS: This case-control study utilized HCV programmatic and Georgian Cancer Registry data from 2015-2019. Bivariate logistic regression and age- and sex-stratified analyses assessed HCV and liver cancer association. HCV-attributable liver cancer proportions for the HCV-exposed and total population were calculated. A sub-analysis was performed for HCC cases specifically. RESULTS: The total study population was 3874 with 496 liver cancer cases and 3378 controls. The odds for HCV-infected individuals developing liver cancer was 20.1 (95% confidence interval [CI] 15.97-25.37), and the odds of developing HCC was 16.84 (95% CI 12.01-23.83) compared to the HCV-negative group. Odds ratios varied across strata, with HCV-infected older individuals and women having higher odds of developing both liver cancer and HCC. A large proportion of liver cancer and HCC can be attributed to HCV in HCV-infected individuals; however, in the general population, the burden of liver cancer and HCC cannot be explained by HCV alone. CONCLUSION: HCV was significantly associated with a higher risk of developing liver cancer and HCC in the Georgian population. In addition, given Georgia's high HCV burden, increased HCC monitoring in HCV-infected patients is needed.

About 80% of persons with chronic hepatitis B virus (HBV) infection in the United States are non-US-born. Despite improvements in infant hepatitis B vaccination globally since 2000, work remains to attain the World Health Organization's (WHO) global 2030 goal of 90% vaccination. We explore the impacts on the United States of global progress in hepatitis B vaccination since 2000 and of achieving WHO hepatitis B vaccination goals. We simulated immigrants with HBV infection arriving to the United States from 2000 to 2070 using models of the 10 countries from which the largest numbers of individuals with HBV infection were born. We estimated costs in the United States among these cohorts using a disease simulation model. We simulated three scenarios: a scenario with no progress in infant vaccination for hepatitis B since 2000 (baseline), current (2020) progress and achieving WHO 2030 goals for hepatitis B vaccination. We estimate current hepatitis B vaccination progress since the 2000 baseline in these 10 countries will lead to 468,686 fewer HBV infections, avoid 35,582 hepatitis B-related deaths and save $4.2 billion in the United States through 2070. Achieving the WHO 2030 90% hepatitis B infant vaccination targets could lead to an additional 16,762 fewer HBV infections, 989 fewer hepatitis B-related deaths and save $143 million through 2070. Global hepatitis B vaccination since 2000 reduced prevalence of HBV infection in the United States. Achieving the WHO 2030 infant vaccination goals globally could lead to over one hundred million dollars in additional savings.

Background: Individuals receiving hemodialysis for end-stage kidney disease are at increased risk of infection with hepatitis C virus (HCV) and hepatitis B virus (HBV) due to regular and frequent receipt of invasive medical treatment in a shared space. Aim: This study assessed infection prevention and control practices in dialysis facilities, evaluated HCV and HBV testing practices, and estimated the number of cases of seroconversion for HCV and HBV infection in dialysis facilities in Georgia. Methods: We invited all 27 dialysis centers that provide maintenance dialysis in Georgia to participate in a facility-based survey during April–June 2021. Results: In total, 68.2% (n = 15/22) of facilities performed anti-HCV screening upon admission to the center. At the majority of facilities (n = 21/22, 95.5%), HBV screening was performed upon admission to the center. A total of 329 anti-HCV positive patients were reported from 20 of 22 facilities, 29.5% (n = 97/329) were HCV RNA positive, 18.2% (n = 60/329) were HCV RNA negative, and 52.3% (n = 172/329) were not tested or their result was missing. Overall, 200 HBsAg-positive patients were reported from the same 20 facilities. At 10 facilities: 39 patients from seven facilities seroconverted for HCV infection, and 31 patients from eight dialysis facilities seroconverted for HBV infection. Conclusions: We identified a high number of HBV and HCV seroconversions among dialysis patients in Georgia suggesting serious gaps in infection control practices. Strict adherence to infection prevention and control practices is essential to prevent transmission of HCV and HBV infections through contaminated equipment and surfaces. © The Author(s) 2024.

A Borrelia miyamotoi gene with partial homology to bipA of relapsing fever spirochetes Borrelia hermsii and Borrelia turicatae was identified by a GenBank basic alignment search analysis. We hypothesized that this gene product may be an immunogenic antigen as described for other relapsing fever Borrelia (RFB) and could serve as a serological marker for B. miyamotoi infections. The B. miyamotoi gene was a truncated version about half the size of the B. hermsii and B. turicatae bipA with a coding sequence of 894 base pairs. The gene product had a calculated molecular size of 32.7 kDa (including the signal peptide). Amino acid alignments with B. hermsii and B. turicatae BipA proteins and with other B. miyamotoi isolates showed conservation at the carboxyl end. We cloned the B. miyamotoi bipA-like gene (herein named bipM) and generated recombinant protein for serological characterization and for antiserum production. Protease protection analysis demonstrated that BipM was surface exposed. Serologic analyses using anti-B. miyamotoi serum samples from tick bite-infected and needle inoculated mice showed 94 % positivity against BipM. The 4 BipM negative serum samples were blotted against another B. miyamotoi antigen, BmaA, and two of them were seropositive resulting in 97 % positivity with both antigens. Serum samples from B. burgdorferi sensu stricto (s.s.)-infected mice were non-reactive against rBipM by immunoblot. Serum samples from Lyme disease patients were also serologically negative against BipM except for 1 sample which may have indicated a possible co-infection. A recently published study demonstrated that B. miyamotoi BipM was non-reactive against serum samples from B. hermsii, Borrelia parkeri, and B. turicatae infected animals. These results show that BipM has potential for a B. miyamotoi-infection specific and sensitive serodiagnostic to differentiate between Lyme disease and various RFB infections.

BACKGROUND: Alpha-gal syndrome (AGS) is an allergy to galactose-α-1,3-galactose (alpha-gal), a carbohydrate found in most mammals. Evidence indicates that AGS develops following a tick bite, and in the United States, AGS is most associated with bites from Amblyomma americanum (lone star tick); however, not all persons bitten by ticks develop clinical AGS. OBJECTIVE: This study investigated intrinsic risk factors associated with the development of AGS. METHODS: We performed a case-control study among adults presenting for diagnosis or management of AGS at an allergy clinic in North Carolina during 2019-2020 and compared them to controls enrolled from two nearby internal medicine clinics. A questionnaire gathered epidemiologic and tick exposure data and blood was obtained for alpha-gal specific IgE (sIgE) and other testing. RESULTS: The 82 enrolled case patients and 191 controls did not differ significantly by age or sex. Case patients were more likely than controls to have A or O blood types (non-B-antigen), have experienced childhood allergies, and have a family history of AGS and other food allergies. Case patients were also more likely to report experiencing long healing times for insect bites or stings and a family history of allergy to stinging or biting insects. CONCLUSION: This study suggests that intrinsic factors contribute to risk of developing AGS. Some traits are genetic, but common behaviors among households and family units likely also contribute. Identification of these risk factors can inform personal risk, aid healthcare providers in understanding susceptible populations, and contribute to ongoing understanding of AGS epidemiology.

BACKGROUND: The country of Georgia initiated its hepatitis C virus (HCV) elimination program in 2015, at which point a serosurvey showed the adult prevalence of HCV antibody (anti-HCV) and HCV RNA to be 7.7% and 5.4%, respectively. This analysis reports hepatitis C results of a follow-up serosurvey conducted in 2021, and progress towards elimination. METHODS: The serosurvey used a stratified, multistage cluster design with systematic sampling to include adults and children (aged 5-17 years) providing consent (or assent with parental consent). Blood samples were tested for anti-HCV and if positive, HCV RNA. Weighted proportions and 95% confidence intervals (CI) were compared with 2015 age-adjusted estimates. RESULTS: Overall, 7237 adults and 1473 children were surveyed. Among adults, the prevalence of anti-HCV was 6.8% (95% CI, 5.9-7.7). The HCV RNA prevalence was 1.8% (95% CI, 1.3-2.4), representing a 67% reduction since 2015. HCV RNA prevalence decreased among those reporting risk factors of ever injecting drugs (51.1% to 17.8%), and ever receiving a blood transfusion (13.1% to 3.8%; both P < .001). No children tested positive for anti-HCV or HCV RNA. CONCLUSIONS: These results demonstrate substantial progress made in Georgia since 2015. These findings can inform strategies to meet HCV elimination targets.

Infection with hepatitis D virus leads to liver disease and cancer most rapidly of all hepatitis viruses. However, knowledge about hepatitis D remains poor and the burden and impact are underestimated, even though some 12-15 million people mainly in low- and middle-income countries may be affected. Its epidemiology is changing, with increasing migration leading to increased risks of infection and disease. A recent Viral Hepatitis Prevention Board meeting reviewed the current epidemiological status, improvements in diagnostic testing, advances in the development of novel antiviral agents in phase III trials and the need for a greater public health response, such as new guidelines and recommended testing of all people newly identified as infected with hepatitis B virus for hepatitis D virus infection. It identified issues and needs for attention with regard to prevention, diagnosis and treatment.

During the COVID-19 pandemic, many public schools across the United States shifted from fully in-person learning to alternative learning modalities such as hybrid and fully remote learning. In this study, data from 14,688 unique school districts from August 2020 to June 2021 were collected to track changes in the proportion of schools offering fully in-person, hybrid and fully remote learning over time. These data were provided by Burbio, MCH Strategic Data, the American Enterprise Institute's Return to Learn Tracker and individual state dashboards. Because the modalities reported by these sources were incomplete and occasionally misaligned, a model was needed to combine and deconflict these data to provide a more comprehensive description of modalities nationwide. A hidden Markov model (HMM) was used to infer the most likely learning modality for each district on a weekly basis. This method yielded higher spatiotemporal coverage than any individual data source and higher agreement with three of the four data sources than any other single source. The model output revealed that the percentage of districts offering fully in-person learning rose from 40.3% in September 2020 to 54.7% in June of 2021 with increases across 45 states and in both urban and rural districts. This type of probabilistic model can serve as a tool for fusion of incomplete and contradictory data sources in order to obtain more reliable data in support of public health surveillance and research efforts.

In 2016, World Health Organization (WHO) introduced global targets for the care and management of hepatitis C virus (HCV) infection to eliminate hepatitis C as a public health threat by 2030. Despite significant improvements in testing and treatment, in 2020 only 23% of all persons infected with HCV globally were diagnosed. We explore examples from global hepatitis C programs in Georgia, Rwanda, and Nigeria that have used decentralized and integrated models to increase access to HCV testing. Georgia established the world's first national hepatitis C elimination program in 2015. In 2022, 2.6 million people (80% of the adults) have been screened for antibodies for HCV infection, and 80,000 persons with HCV virus detected were treated. To achieve these results, Georgia implemented HCV core antigen (HCVcAg) testing, utilization of point-of-care HCV RNA, and simplification of HCV viremia detection by qualitative HCV RNA. Rwanda was the first country in sub-Saharan Africa to commit to HCV elimination in 2018, and as of 2022 it has achieved its screening target of 7 million people and initiated approximately 60,000 patients on hepatitis C treatment by rapid decentralization and integration of HCV services. In Nigeria, the integrated near-point-of-care testing approach in Nasarawa state has been effective in expanding access to HCV viremia testing and enabling the possibility of same-day testing and treatment initiation. Examples of decentralization and integration of HCV testing and linkage to care in Georgia, Rwanda and Nigeria could help inform effective strategies to reach 2030 hepatitis C elimination goals in other countries.

BACKGROUND: The reported incidence of acute hepatitis C virus (HCV) infection is increasing among persons of childbearing age in the United States. Infants born to pregnant persons with HCV infection are at risk for perinatal HCV acquisition. In 2020, the United States Preventive Services Task Force and Centers for Disease Control and Prevention recommended that all pregnant persons be screened during each pregnancy for hepatitis C. However, there are limited data on trends in hepatitis C testing during pregnancy. OBJECTIVE: We estimated hepatitis C testing rates in a large cohort of patients with Medicaid and commercial insurance who gave birth during 2015-2019 and described demographic and risk-based factors associated with testing. METHODS: Medicaid and commercial insurance claims for patients aged 15-44 years and who gave birth between 2015 and 2019 were included. Birth claims were identified using procedure and diagnosis codes for vaginal or cesarean delivery. Hepatitis C testing was defined as an insurance claim during the 42 weeks before delivery. Testing rates were calculated among patients who delivered and among the subset of patients who were continuously enrolled for 42 weeks before delivery. We also compared the timing of testing relative to delivery among patients with commercial or Medicaid insurance. Multivariable logistic regression was used to identify factors associated with testing. RESULTS: Among 1,142,770 Medicaid patients and 1,207,132 commercially insured patients, 175,223 (15.3%) and 221,436 (18.3%) were tested for hepatitis C during pregnancy, respectively. Testing rates were 89,730 (21.8%) and 187,819 (21.9%) among continuously enrolled Medicaid and commercially insured patients, respectively. Rates increased from 2015 through 2019 among Medicaid (from 20,758/108,332, 19.2% to 13,971/52,330, 26.8%) and commercially insured patients (from 38,308/211,555, 18.1% to 39,152/139,972, 28%), respectively. Among Medicaid patients, non-Hispanic Black (odds ratio 0.73, 95% CI 0.71-0.74) and Hispanic (odds ratio 0.53, 95% CI 0.51-0.56) race or ethnicity were associated with lower odds of testing. Opioid use disorder, HIV infection, and high-risk pregnancy were associated with higher odds of testing in both Medicaid and commercially insured patients. CONCLUSIONS: Hepatitis C testing during pregnancy increased from 2015 through 2019 among patients with Medicaid and commercial insurance, although tremendous opportunity for improvement remains. Interventions to increase testing among pregnant persons are needed.

BackgroundGeorgia has adopted the World Health Organization European Region's and global goals to eliminate viral hepatitis. A nationwide serosurvey among adults in 2015 showed 2.9% prevalence for hepatitis B virus (HBV) surface antigen (HBsAg) and 25.9% for antibodies against HBV core antigen (anti-HBc). HBV infection prevalence among children had previously not been assessed.AimWe aimed to assess HBV infection prevalence among children and update estimates for adults in Georgia.MethodsThis nationwide cross-sectional serosurvey conducted in 2021 among persons aged ≥ 5 years used multi-stage stratified cluster design. Participants aged 5-20 years were eligible for hepatitis B vaccination as infants. Blood samples were tested for anti-HBc and, if positive, for HBsAg. Weighted proportions and 95% confidence intervals (CI) were calculated for both markers.ResultsAmong 5-17 year-olds (n = 1,473), 0.03% (95% CI: 0-0.19) were HBsAg-positive and 0.7% (95% CI: 0.3-1.6) were anti-HBc-positive. Among adults (n = 7,237), 2.7% (95% CI: 2.3-3.4) were HBsAg-positive and 21.7% (95% CI: 20.4-23.2) anti-HBc-positive; HBsAg prevalence was lowest (0.2%; 95% CI: 0.0-1.5) among 18-23-year-olds and highest (8.6%; 95% CI: 6.1-12.1) among 35-39-year-olds.ConclusionsHepatitis B vaccination in Georgia had remarkable impact. In 2021, HBsAg prevalence among children was well below the 0.5% hepatitis B control target of the European Region and met the ≤ 0.1% HBsAg seroprevalence target for elimination of mother-to-child transmission of HBV. Chronic HBV infection remains a problem among adults born before vaccine introduction. Screening, treatment and preventive interventions among adults, and sustained high immunisation coverage among children, can help eliminate hepatitis B in Georgia by 2030.

BackgroundBetween May 2015 and February 2022, 77,168 hepatitis C virus (HCV)-infected people in Georgia have been treated through an HCV elimination programme. To project the programme's long-term impacts, an HCV infection model was initially developed, based on data from surveys among people who inject drugs and a national serosurvey in 2015.AimAccounting for follow-up surveys in 2021, we validate and update projections of HCV infection prevalence and incidence.MethodWe assessed the initial model projections' accuracy for overall prevalence, by age, sex, and among people who ever injected drugs, compared with 2021 serosurvey data. We used 2021 results to weight model fits and to recalculate the national programme's impact leading up to March 2022 on HCV infection incidence rates. Cases and deaths averted were estimated. The impact of reduced treatment rates during the COVID-19 pandemic was assessed.ResultsThe original model overpredicted adult (≥ 18 years old) chronic HCV infection prevalence for 2021 (2.7%; 95% credible interval (CrI): 1.9-3.5%) compared with a 2021 serosurvey (1.8%; 95% confidence interval (CI): 1.3-2.4%). Weighted model projections estimated a 60% decrease in HCV infection incidence by March 2022, with an absolute incidence of 66 (95% CrI: 34-131) per 100,000 person-years (overall population). Between May 2015 and March 2022, 9,186 (95% CrI: 5,396-16,720) infections and 842 (95% CrI: 489-1,324) deaths were averted. The COVID-19 pandemic resulted in 13,344 (95% CrI: 13,236-13,437) fewer treatments and 438 (95% CrI: 223-744) fewer averted infections by March 2022.ConclusionResults support the programme's high effectiveness. At current treatment rate (406/month), 90% reductions in prevalence and incidence in Georgia are achievable by 2030.

Background Correctional and detention facilities are disproportionately affected by COVID-19 due to shared space, contact between staff and detained persons, and movement within facilities of detained persons, many with pre-existing medical conditions. On March 18, 2020, Cook County Jail, one of the United States’ largest, identified its first suspected case of COVID-19 in a detained person.Methods This analysis includes SARS-CoV-2 cases confirmed by molecular detection among detained persons and Cook County Sheriff’s Office staff. We examined occurrence of symptomatic cases in each building and proportions of asymptomatic detained persons testing positive. We describe timing of interventions including social distancing, mask use, and expanded testing and show outbreak trajectory in the jail versus contemporaneous case counts in Chicago.Results During March 1–April 30, 907 symptomatic and asymptomatic cases of SARS-CoV-2 infection were detected among detained persons (n = 628) and staff (n = 279), with nine deaths. Symptomatic cases occurred in all housing divisions; in 9/13 buildings, staff cases occurred first. Among asymptomatic detained persons in quarantine, 23.6% tested positive. Visitation stopped March 15, programmatic activities were suspended March 23, cells were converted into single occupancy beginning March 26, and universal masking was implemented for staff (April 2) and detained persons (April 13). Cases at the jail declined while cases in Chicago increased.Conclusion Aggressive intervention strategies coupled with widespread diagnostic testing of detained and staff populations can limit introduction and mitigate transmission of SARS-CoV-2 infection in correctional and detention facilities.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNo external funding was received for the execution of this study or manuscript preparation.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This study was reviewed by Centers for Disease Control and Prevention, Chicago Department of Public Health, Cook County Health, and Cook County Sheriff's Office institutional review boards or the equivalent entity and deemed not to be research involving human subjects and public health response.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData were provided by the Cook County Sheriff's Office, Chicago Department of Public Health, Cermak Health Services, and Cook County Health. Access to data submitted into the Illinois' National Electronic Disease Surveillance System was provided by Chicago Department of Public Health. Data represent protected health information (PHI), and cannot be made available in raw form. Results are presented in aggregate in this manuscript. Authors had access to data.

Treponema pallidum subsp. pertenue (TPE) is the causative agent of yaws. The disease was subject to global eradication efforts in the mid 20th century but reemerged in West Africa, Southern Asia, and the Pacific region. Despite its importance for eradication, detailed data on possible nonhuman disease reservoirs are missing. A number of African nonhuman primates (NHPs) have been reported to show skin ulcerations suggestive of treponemal infection in humans. Furthermore antibodies against Treponema pallidum (TP) have been repeatedly detected in wild NHP populations. While genetic studies confirmed that NHPs are infected with TP strains, subspecies identification was only possible once for a strain isolated in 1966, pinpointing the involvement of TPE. We therefore collected a number of recently isolated simian TP strains and determined eight whole genome sequences using hybridization capture or long-range PCR combined with next-generation sequencing. These new genomes were compared with those of known human TP isolates. Our results show that naturally occurring simian TP strains circulating in three African NHP species all cluster with human TPE strains and show the same genomic structure as human TPE strains. These data indicate that humans are not the exclusive host for the yaws bacterium and that a One Health approach is required to achieve sustainable eradication of human yaws.

The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, resulting in >300,000 reported cases worldwide as of March 21st, 2020. Here we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 in Northern California using samples from returning travelers, cruise ship passengers, and cases of community transmission with unclear infection sources. Virus genomes were sampled from 29 patients diagnosed with COVID-19 infection from Feb 3rd through Mar 15th. Phylogenetic analyses revealed at least 8 different SARS-CoV-2 lineages, suggesting multiple independent introductions of the virus into the state. Virus genomes from passengers on two consecutive excursions of the Grand Princess cruise ship clustered with those from an established epidemic in Washington State, including the WA1 genome representing the first reported case in the United States on January 19th. We also detected evidence for presumptive transmission of SARS-CoV-2 lineages from one community to another. These findings suggest that cryptic transmission of SARS-CoV-2 in Northern California to date is characterized by multiple transmission chains that originate via distinct introductions from international and interstate travel, rather than widespread community transmission of a single predominant lineage. Rapid testing and contact tracing, social distancing, and travel restrictions are measures that will help to slow SARS-CoV-2 spread in California and other regions of the USA.

Sosuga virus (SOSV) is a recently discovered paramyxovirus with a single known human case of disease. There has been little laboratory research on SOSV pathogenesis or immunity, and no approved therapeutics or vaccines are available. Here, we report the discovery of human monoclonal antibodies (mAbs) from the circulating memory B cells of the only known human case and survivor of SOSV infection. We isolated six mAbs recognizing the functional attachment protein (HN) and 18 mAbs against the fusion (F) protein. The anti-HN mAbs all target the globular head of the HN protein and can be organized into 4 competition-binding groups that exhibit epitope diversity. The anti-F mAbs can be divided into pre- or post-fusion conformation-specific categories and further into 8 competition-binding groups. Generally, pre-fusion conformation-specific anti-F mAbs showed higher potency in neutralization assays than did mAbs only recognizing the post-fusion conformation of F protein. Most of the anti-HN mAbs were more potently neutralizing than the anti-F mAbs, with mAbs in one of the HN competition-binding groups possessing ultra-potent (<1 ng/mL) half maximal inhibitory (IC50) virus neutralization values. These findings provide insight into the molecular basis for human antibody recognition of paramyxovirus surface proteins and the mechanisms of SOSV neutralization. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

The application of statistical analysis software programs has proven useful for the investigation of rockfall runout distance along a designed slope. Rockfall modeling programs are continually being upgraded with more sophisticated analysis tools, such as the use of the rigid body versus lump mass models. Engineers at mine sites utilizing the software may have varied experience related to these models, their associated input parameters, and how to interpret the generated results. To address this concern, researchers at the Spokane Mining Research Division (SMRD) of the US National Institute for Occupational Safety and Health (NIOSH) investigated the influence of slope height, slope angle, slope material, and rock size for both rigid body and lump mass models in a 2-D statistical analysis program. Based on a literature search and industry input, specific ranges common to that of an open pit mining environment were chosen for each of the input parameters to determine 90% rock runout distance as well as their sensitivity to change. Data collected from this numerical analysis and simulation will be compared to empirical rockfall data gathered through the duration of the Highwall Safety project conducted by NIOSH from 2022–2026. © 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

Updated (bivalent) COVID-19 vaccines were first recommended by CDC on September 1, 2022.* An analysis of case and death rates by vaccination status shortly after authorization of bivalent COVID-19 vaccines showed that receipt of a bivalent booster dose provided additional protection against SARS-CoV-2 infection and associated death (1). In this follow-up report on the durability of bivalent booster protection against death among adults aged ≥65 years, mortality rate ratios (RRs) were estimated among unvaccinated persons and those who received a bivalent booster dose by time since vaccination during three periods of Omicron lineage predominance (BA.5 [September 18–November 5, 2022], BQ.1/BQ.1.1 [November 6, 2022–January 21, 2023], and XBB.1.5 [January 22–April 1, 2023]).† | | During September 18, 2022–April 1, 2023, weekly counts of COVID-19–associated deaths§ among unvaccinated persons and those who received a bivalent booster dose¶ were reported from 20 U.S. jurisdictions** that routinely link case surveillance data to immunization registries and vital registration databases (1). Vaccinated persons who did not receive a bivalent COVID-19 booster dose were excluded. Rate denominators were calculated from vaccine administration data and 2019 U.S. intercensal population estimates,†† with numbers of unvaccinated persons estimated by subtracting numbers of vaccinated persons from the 2019 intercensal population estimates, as previously described§§ (1). Average weekly mortality rates were estimated based on date of specimen collection¶¶ during each variant period by vaccination status and time since bivalent booster dose receipt. RRs were calculated by dividing rates among unvaccinated persons by rates among bivalent booster dose recipients; after detrending the underlying linear changes in weekly rates, 95% CIs were estimated from the remaining variation in rates observed*** (1). SAS (version 9.4; SAS Institute) and R (version 4.1.2; R Foundation) software were used to conduct all analyses. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.†††

Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread throughout the world. On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Genome sequencing of SARS-CoV-2 strains allows for the reconstruction of transmission history connecting these infections. Here, we analyze 346 SARS-CoV-2 genomes from samples collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We found that the large majority of SARS-CoV-2 infections sampled during this time frame appeared to have derived from a single introduction event into the state in late January or early February 2020 and subsequent local spread, strongly suggesting cryptic spread of COVID-19 during the months of January and February 2020, before active community surveillance was implemented. We estimate a common ancestor of this outbreak clade as occurring between 18 January and 9 February 2020. From genomic data, we estimate an exponential doubling between 2.4 and 5.1 days. These results highlight the need for large-scale community surveillance for SARS-CoV-2 introductions and spread and the power of pathogen genomics to inform epidemiological understanding.

BACKGROUND: Nucleic acid amplification (NAA) tests rapidly detect Mycobacterium tuberculosis complex directly from clinical specimens, providing valuable results for those evaluated for tuberculosis. METHODS: We analyzed characteristics of cases with NAA testing performed, compared cases with positive and negative NAA test results, and calculated turnaround time and time to treatment for all verified cases reported to the National Tuberculosis Surveillance System in the United States during 2011-2017. RESULTS: Among 67082 verified tuberculosis cases with NAA testing information, 30820 (45.9%) were reported as not having an NAA test performed; the proportion without NAA testing declined annually, from 60.5% in 2011 to 33.6% in 2017. Of 67082 verified cases, 27912 (41.6%) had positive, 8215 (12.2%) had negative, and 135 (0.2%) had indeterminate NAA test results. Among the 33937 cases with an acid-fast bacilli (AFB) smear-positive result, 24093 (70.9%) had an NAA test performed; 11490 of the 30244 (38.0%) with an AFB smear-negative result had an NAA test performed. Although sputum was the most common specimen type tested, 79.8% (7023/8804) of nonsputum specimen types had a positive NAA test result. Overall, 63.7% of cases with laboratory testing had NAA test results reported <6 days following specimen collection; for 13891 cases not yet on treatment, median time to treatment after the laboratory report date was 2 days. CONCLUSIONS: Our analyses demonstrate increased NAA test utilization between 2011 and 2017. However, a large proportion of cases did not have an NAA test performed, reflecting challenges in broader uptake, suggesting an opportunity to expand use of this diagnostic methodology.

BACKGROUND: Mortality related to hepatitis C virus (HCV) infection is a key indicator for elimination. We assessed the impact of HCV infection and treatment on mortality in the country of Georgia during 2015-2020. METHODS: We conducted a population-based cohort study using data from Georgia's national HCV Elimination Program and death registry. We calculated all-cause mortality rates in six cohorts: 1) Negative for anti-HCV; 2) anti-HCV positive, unknown viremia status; 3) current HCV infection and untreated; 4) discontinued treatment; 5) completed treatment, no SVR assessment; 6) completed treatment and achieved SVR. Cox proportional hazards models were used to calculate adjusted hazards ratios and confidence intervals. We calculated the cause-specific mortality rates attributable to liver-related causes. RESULTS: After a median follow-up of 743 days, 100,371 (5.7%) of 1,764,324 study participants died. The highest mortality rate was observed among HCV infected patients who discontinued treatment (10.62 deaths per 100 PY, 95%CI: 9.65, 11.68), and untreated group (10.33 deaths per 100 PY, 95%CI: 9.96, 10.71). In adjusted Cox proportional hazards model, the untreated group had almost six-times higher hazard of death compared to treated groups with or without documented SVR (aHR=5.56, 95%CI: 4.89, 6.31). Those who achieved SVR had consistently lower liver-related mortality compared to cohorts with current or past exposure to HCV. CONCLUSION: This large population-based cohort study demonstrated the marked beneficial association between hepatitis C treatment and mortality. The high mortality rates observed among HCV infected and untreated persons highlights the need to prioritize linkage to care and treatment to achieve elimination goals.

BACKGROUND: In 2015, the country of Georgia initiated its hepatitis C virus (HCV) elimination program. Given a high background incidence of HCV infection, centralized nucleic acid testing (NAT) of blood donations was prioritized for implementation. STUDY DESIGN AND METHODS: Multiplex NAT screening for HIV, HCV and hepatitis B virus (HBV) was launched in January 2020. An analysis was conducted of serological and NAT donor/donation data for the first year of screening (through December 2020). RESULTS: A total of 54,116 donations representing 39,164 unique donors were evaluated. Overall, 671 donors (1.7%) tested positive for at least one infectious marker by serology or NAT, with the highest prevalence among donors aged 40-49 years (2.5%; n=200), male (1.9%; n=524), replacement (2.8%; n=153) and first time (2.1%; n=642) donors. Sixty donations were seronegative but NAT positive, and therefore would not have been found by traditional serology testing alone. These were more likely among female vs. male (adjusted odds ratio [aOR] 2.06; 95% confidence interval [95%CI]: 1.05-4.05), paid (aOR 10.15; 95%CI: 2.80-36.86) or voluntary (aOR 4.30; 95%CI: 1.27-14.56) vs replacement, and repeat vs. first time (aOR 13.98; 95%CI: 4.06-48.12) donors. On repeat serological testing (including HBV core antibody [HBcAb] testing), 6 HBV+ donations, 5 HCV+ donations and 1 HIV+ donations were deemed NAT yield (detected through the implementation of NAT, and would have otherwise been missed by serology screening alone). CONCLUSION: This analysis offers a regional model for NAT implementation, demonstrating the feasibility and clinical utility in a nationwide blood program.

Borrelia miyamotoi is a tick-transmitted spirochete that is genetically grouped with relapsing fever Borrelia and possesses multiple archived pseudogenes that encode variable major proteins (Vmps). Vmps are divided into two groups based on molecular size; variable large proteins (Vlps) and variable small proteins (Vsps). Relapsing fever Borrelia undergo Vmp gene conversion at a single expression locus to generate new serotypes by antigenic switching which is the basis for immune evasion that causes relapsing fever in patients. This study focused on B. miyamotoi vmp expression when spirochetes were subjected to antibody killing selection pressure. We incubated a low passage parent strain with mouse anti-B. miyamotoi polyclonal antiserum which killed the majority population, however, antibody-resistant reisolates were recovered. PCR analysis of the gene expression locus in the reisolates showed vsp1 was replaced by Vlp-encoded genes. Gel electrophoresis protein profiles and immunoblots of the reisolates revealed additional Vlps indicating that new serotype populations were selected by antibody pressure. Sequencing of amplicons from the expression locus of the reisolates confirmed the presence of a predominant majority serotype population with minority variants. These findings confirm previous work demonstrating gene conversion in B. miyamotoi and that multiple serotype populations expressing different vmps arise when subjected to antibody selection. The findings also provide evidence for spontaneous serotype variation emerging from culture growth in the absence of antibody pressure. Validation and determination of the type, number, and frequency of serotype variants that arise during animal infections await further investigations.

Sosuga virus (SOSV) is a recently discovered paramyxovirus with a single known human case of disease. There has been little laboratory research on SOSV pathogenesis or immunity, and no approved therapeutics or vaccines are available. Here, we report the discovery of human monoclonal antibodies (mAbs) from the circulating memory B cells of the only known human case and survivor of SOSV infection. We isolated six mAbs recognizing the functional attachment protein hemagglutinin-neuraminidase (HN) and 18 mAbs against the fusion (F) protein. The anti-HN mAbs all target the globular head of the HN protein and can be organized into 4 competition-binding groups that exhibit epitope diversity. The anti-F mAbs can be divided into pre- or postfusion conformation-specific categories and further into 8 competition-binding groups. The only antibody in the panel that did not display neutralization activity was the single, postfusion-specific anti-F mAb. Most of the anti-HN mAbs were more potently neutralizing than the anti-F mAbs, with mAbs in one of the HN competition-binding groups possessing ultra-potent (<1 ng/mL) half maximal inhibitory (IC50) virus neutralization values. These findings provide insight into the molecular basis for human antibody recognition of paramyxovirus surface proteins and the mechanisms of SOSV neutralization.