Objectives. To compare the incidence, case-hospitalization rates, and vaccination rates of COVID-19 between people experiencing sheltered homelessness (PESH) and the broader community in Chicago, Illinois, and describe the impact of a whole community approach to disease mitigation during the public health emergency. Methods. Incidence of COVID-19 among PESH was compared with community-wide incidence using case-based surveillance data from March 1, 2020, to May 11, 2023. Seven-day rolling means of COVID-19 incidence were assessed for the overall study period and for each of 6 distinct waves of COVID-19 transmission. Results. A total of 774 009 cases of COVID-19 were detected: 2579 among PESH and 771 430 in the broader community. Incidence and hospitalization rates per 100 000 in PESH were more than 5 times higher (99.84 vs 13.94 and 16.88 vs 2.14) than the community at large in wave 1 (March 1, 2020-October 3, 2020). This difference decreased through wave 3 (March 7, 2021-June 26, 2021), with PESH having a lower incidence rate per 100 000 than the wider community (8.02 vs 13.03). Incidence and hospitalization of PESH rose again to rates higher than the broader community in waves 4 through 6 but never returned to wave 1 levels. Throughout the study period, COVID-19 incidence among PESH was 2.88 times higher than that of the community (70.90 vs 24.65), and hospitalization was 4.56 times higher among PESH (7.51 vs 1.65). Conclusions. Our findings suggest that whole-community approaches can minimize disparities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission between vulnerable populations and the broader community, and reinforce the benefits of a shared approach that include multiple partners when addressing public health emergencies in special populations. (Am J Public Health. Published online ahead of print August 28, 2024:e1-e9. https://doi.org/10.2105/AJPH.2024.307801).

With 762 laboratories, the Global Measles and Rubella Laboratory Network (GMRLN) is the largest laboratory network coordinated by the World Health Organization (WHO). Like the Global Polio Laboratory Network, the GMRLN has multiple tiers, including global specialized laboratories, regional reference laboratories, national laboratories, and, in some countries, subnational laboratories. Regional networks are supervised by regional laboratory coordinators reporting to a global coordinator at WHO headquarters. Laboratories in the GMRLN have strong links to national disease control and vaccination programs. The GMRLN's goal is to support member states in obtaining timely, complete, and reliable laboratory-based surveillance data for measles and rubella as part of the strategy for achieving measles and rubella elimination. Surveillance data are reported to the national program and are included in annual reports on the status of measles and rubella elimination to national verification committees for review by regional verification commissions. Quality within the GMRLN is ensured by monitoring performance through external quality assurance programs, confirmatory and quality control testing, accreditation, and coordination of corrective action and training where needed. The overall performance of the laboratories has remained high over the years despite many challenges, particularly the COVID-19 pandemic. The GMRLN is well-positioned to support high-quality laboratory-based surveillance for measles and rubella and to transition to supporting laboratory testing for other pathogens, including vaccine-preventable diseases.

BACKGROUND: Hepatitis C virus (HCV) disproportionately affects among people who inject drugs (PWID) globally. Despite carrying a high HCV burden, little is known about transmission dynamics in low-and-middle income countries. METHODS: We recruited PWID from Nairobi and Coastal cities of Mombasa, Kilifi and Malindi in Kenya at needle and syringe programs. Next-generation sequencing data from HCV hypervariable region 1 were analyzed using Global Hepatitis Outbreak and Surveillance Technology (GHOST) to identify transmission clusters. RESULTS: HCV strains belonged to genotype 1a (n=64, 46.0%), 4a (n=72, 51.8%), and were mixed HCV/1a/4a (n=3, 2.2%). HCV/1a was dominant (61.2%) in Nairobi while HCV/4a was dominant in Malindi (85.7%) and Kilifi (60.9%); whereas both genotypes were evenly identified in Mombasa (45.3%, for HCV/1a and 50.9% for HCV/4a). GHOST identified 11 transmission clusters involving 90 cases. Strains in the two largest clusters (n=38 predominantly HCV/4a, and n=32 HCV/1a) were sampled from all four cities. CONCLUSION: Transmission clusters involving 64.7% of cases indicate an effective sampling of major HCV strains circulating among PWID. Large clusters involving 77.8% of strains from Nairobi and Coast suggest successful introduction of two ancestral HCV/1a and HCV/4a strains to PWID, with widely spread progeny. Disruption of the country-wide transmission network is essential for HCV elimination.

Measles, a highly contagious respiratory virus with the potential to cause severe complications, hospitalization, and death, was declared eliminated from the United States in 2000; however, with ongoing global transmission, infections in the United States still occur. On March 7, 2024, the Chicago Department of Public Health (CDPH) confirmed a case of measles in a male aged 1 year residing in a temporary shelter for migrants in Chicago. Given the congregate nature of the setting, high transmissibility of measles, and low measles vaccination coverage among shelter residents, measles virus had the potential to spread rapidly among approximately 2,100 presumed exposed shelter residents. CDPH immediately instituted outbreak investigation and response activities in collaboration with state and local health departments, health care facilities, city agencies, and shelters. On March 8, CDPH implemented active case-finding and coordinated a mass vaccination campaign at the affected shelter (shelter A), including vaccinating 882 residents and verifying previous vaccination for 784 residents over 3 days. These activities resulted in 93% measles vaccination coverage (defined as receipt of ≥1 recorded measles vaccine dose) by March 11. By May 13, a total of 57 confirmed measles cases associated with residing in or having contact with persons from shelter A had been reported. Most cases (41; 72%) were among persons who did not have documentation of measles vaccination and were considered unvaccinated. In addition, 16 cases of measles occurred among persons who had received ≥1 measles vaccine dose ≥21 days before first known exposure. This outbreak underscores the need to ensure high vaccination coverage among communities residing in congregate settings.

Cardiovascular diseases (CVDs) are a major source of morbidity and mortality worldwide. Despite a decline of ≈30% over the past decade, heart disease remains the leading killer of Americans.1 For rare and familial forms of CVD, we are increasingly recognizing single-gene mutations that impart relatively large effects on individual phenotype. Examples include inherited forms of cardiomyopathy, arrhythmias, and aortic diseases. However, the prevalence of monogenic disorders typically accounts for a small proportion of the total CVD observed in the population. CVDs in the general population are complex diseases, with several contributing genetic and environmental factors. Although recent progress in monogenic disorders has occurred, we have seen a period of intense investigation to identify the genetic architecture of more common forms of CVD and related traits. | | Genomics serves several roles in cardiovascular health and disease, including disease prediction, discovery of genetic loci influencing CVD, functional evaluation of these genetic loci to understand mechanisms, and identification of therapeutic targets. For single-gene CVDs, progress has led to several clinically useful diagnostic tests, extending our ability to inform the management of afflicted patients and their family members. However, there has been little progress in developing genetic testing for complex CVD because individual common variants have only a modest impact on risk. The study of the genomics of complex CVDs is further challenged by the influence of environmental variables, phenotypic heterogeneity, and pathogenic complexity. Characterization of the clinical phenotype requires consideration of the clinical details of the diseases and traits under study.

Hepatitis C Virus sequence studies mainly focus on the viral amplicon containing the Hypervariable region 1 (HVR1) to obtain a sample of sequences from which several population genetics parameters can be calculated. Recent advances in sequencing methods allow for analyzing an unprecedented number of viral variants from infected patients and present a novel opportunity for understanding viral evolution, drug resistance and immune escape. In the present paper, we compared three recent technologies for amplicon analysis: (i) Next-Generation Sequencing; (ii) Clonal sequencing using End-point Limiting-dilution for isolation of individual sequence variants followed by Real-Time PCR and sequencing; and (iii) Mass spectrometry of base-specific cleavage reactions of a target sequence. These three technologies were used to assess intra-host diversity and inter-host genetic relatedness in HVR1 amplicons obtained from 38 patients (subgenotypes 1a and 1b). Assessments of intra-host diversity varied greatly between sequence-based and mass-spectrometry-based data. However, assessments of inter-host variability by all three technologies were equally accurate in identification of genetic relatedness among viral strains. These results support the application of all three technologies for molecular epidemiology and population genetics studies. Mass spectrometry is especially promising given its high throughput, low cost and comparable results with sequence-based methods.

Vaccine development against hepatitis C virus (HCV) is hindered by poor understanding of factors defining cross-immunoreactivity among heterogeneous epitopes. Using synthetic peptides and mouse immunization as a model, we conducted a quantitative analysis of cross-immunoreactivity among variants of the HCV hypervariable region 1 (HVR1). Analysis of 26,883 immunological reactions among pairs of peptides showed that the distribution of cross-immunoreactivity among HVR1 variants was skewed, with antibodies against a few variants reacting with all tested peptides. The HVR1 cross-immunoreactivity was accurately modeled based on amino acid sequence alone. The tested peptides were mapped in the HVR1 sequence space, which was visualized as a network of 11,319 sequences. The HVR1 variants with a greater network centrality showed a broader cross-immunoreactivity. The entire sequence space is explored by each HCV genotype and subtype. These findings indicate that HVR1 antigenic diversity is extensively convergent and effectively limited, suggesting significant implications for vaccine development.

Background Since 2014, the United States has experienced a biennial spike in pediatric acute flaccid myelitis (AFM). Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF) and only inconsistently identified from the respiratory tract, serum, or stool.Methods We interrogated CSF from children with AFM (n=42) and pediatric controls with other neurologic diseases (OND) (n=58). Samples were incubated with T7 bacteriophage expressing 481,966 sixty-two amino acid peptides with a fourteen amino acid overlap tiled across all known vertebrate virus and arbovirus genomes, an adaption of the VirScan method. Antibody-bound phage were deep sequenced to quantify enriched peptides with normalized counts expressed as reads per hundred thousand (rpK). EV antibody findings were confirmed with ELISA using whole viral protein 1 (VP1) from contemporary enterovirus (EV) A71 and D68 strains. Separately, metagenomic next-generation sequencing (mNGS) of CSF RNA, both unbiased and with targeted enrichment for EVs, was performed.Results The most significantly enriched viral family by VirScan of CSF in AFM versus OND controls was Picornaviridae (mean rpK 11,266 versus mean rpK 950, p-adjusted < 0.001, Wilcoxon signed-rank test with Bonferroni adjustment). Enriched Picornaviridae peptides belonged almost entirely to the genus Enterovirus. The mean EV VP1 ELISA signal in AFM (mean OD 0.51) was significantly higher than OND controls (mean OD 0.08, p-value < 0.001, Mann-Whitney test). mNGS did not detect additional enterovirus RNA in CSF.Conclusion Despite the rare detection of EV RNA in the CNS of patients with AFM, a pan-viral serologic assay identified high levels of CSF EV antibodies in AFM CSF compared to CSF from OND controls. These results provide further evidence for a causal role of non-polio enteroviruses in AFM.

Donor-derived transmission of infections is a rare complication of kidney transplant. Hepatitis A virus (HAV) is a common cause of acute viral hepatitis worldwide, but donor-derived transmission to organ recipients has been reported in the literature only twice previously. The timeline for HAV incubation and clearance in transplant recipients is not well understood. METHODS: In 2018, 2 kidneys and a liver were procured from a deceased donor resident of Kentucky, one of many states that was experiencing an HAV outbreak associated with person-to-person transmission through close contact, primarily among people who reported drug use. Both kidney recipients, residents of Virginia, subsequently developed acute HAV infections. We report the results of an investigation to determine the source of transmission and describe the clinical course of HAV infection in the infected kidney recipients. RESULTS: The liver recipient had evidence of immunity to HAV and did not become infected. The donor and both kidney recipients were found to have a genetically identical strain of HAV using a next-generation sequencing-based cyber molecular assay (Global Hepatitis Outbreak Surveillance Technology), confirming donor-derived HAV infections in kidney recipients. At least 1 kidney recipient experienced delayed development of detectable hepatitis A anti-IgM antibodies. By 383 and 198 d posttransplant, HAV RNA was no longer detectable in stool specimens from the left and right kidney recipients, respectively. CONCLUSIONS: Adherence to current guidance for hepatitis A vaccination may prevent future morbidity due to HAV among organ recipients. http://links.lww.com/TXD/A548.

Reconstruction of transmission networks from viral genomes sampled from infected individuals is a major computational problem of genomic epidemiology. For this problem, we propose a maximum likelihood framework SOPHIE (SOcial and PHilogenetic Investigation of Epidemics) based on the integration of phylogenetic and random graph models. SOPHIE is scalable, accounts for intra-host diversity and accurately infers transmissions without case-specific epidemiological data.

Genomic epidemiology is now widely used for viral outbreak investigations. Still, this methodology faces many challenges. First, few methods account for intra-host viral diversity. Second, maximum parsimony principle continues to be employed, even though maximum likelihood or Bayesian models are usually more consistent. Third, many methods utilize case-specific data, such as sampling times or infection exposure intervals. This impedes study of persistent infections in vulnerable groups, where such information has a limited use. Finally, most methods implicitly assume that transmission events are independent, while common source outbreaks violate this assumption. We propose a maximum likelihood framework SOPHIE (SOcial and PHilogenetic Investigation of Epidemics) based on integration of phylogenetic and random graph models. It infers transmission networks from viral phylogenies and expected properties of inter-host social networks modelled as random graphs with given expected degree distributions. SOPHIE is scalable, accounts for intra-host diversity and accurately infers transmissions without case-specific epidemiological data. SOPHIE code is freely available at https://github.com/compbel/SOPHIE/ Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.

Genomic epidemiology is now widely used for viral outbreak investigations. Still, this methodology faces many challenges. First, few methods account for intra-host viral diversity. Second, maximum parsimony principle continues to be employed for phylogenetic inference of transmission histories, even though maximum likelihood or Bayesian models are usually more consistent. Third, many methods utilize case-specific data, such as sampling times or infection exposure intervals. This impedes study of persistent infections in vulnerable groups, where such information has a limited use. Finally, most methods implicitly assume that transmission events are independent, although common source outbreaks violate this assumption. We propose a maximum likelihood framework, SOPHIE, based on the integration of phylogenetic and random graph models. It infers transmission networks from viral phylogenies and expected properties of inter-host social networks modeled as random graphs with given expected degree distributions. SOPHIE is scalable, accounts for intra-host diversity, and accurately infers transmissions without case-specific epidemiological data.

Hepatitis C virus (HCV) infections are public health problem across the globe, particularly in developing countries. Pakistan has the second highest prevalence of HCV infection worldwide. Limited data exist from Pakistan about persons who inject drugs (PWID) and are at significant risk of exposure to HCV infection and transmission. Serum specimens (n = 110) collected from PWID residing in four provinces were tested for molecular markers of HCV infection. Next generation sequencing (NGS) of the hypervariable region (HVR1) of HCV and Global Hepatitis Outbreak and Surveillance Technology (GHOST) were used to determine HCV genotype, genetic heterogeneity, and construct transmission networks. Among tested specimens, 47.3% were found anti-HCV positive and 34.6% were HCV RNA-positive and belonged to four genotypes, with 3a most prevalent followed by 1a, 1b and 4a. Variants sampled from five cases formed phylogenetic cluster and a transmission network. One case harbored infection with two different genotypes. High prevalence of infections and presence of various genotypes indicate frequent introduction and transmission of HCV among PWID in Pakistan. Identification of a transmission cluster across three provinces, involving 20% of all cases, suggests the existence of a countrywide transmission network among PWIDs. Understanding the structure of this network should assist in devising effective public health strategies to eliminate HCV infection in Pakistan.

Globally, hepatitis A virus (HAV) is one of the most common agents of acute viral hepatitis and causes approximately 1.4 million cases and 90,000 deaths annually despite the existence of an effective vaccine. In 2019, federal, state, and local partners investigated a multi-state outbreak of HAV infections linked to fresh blackberries sourced from multiple suppliers in Michoacn, Mexico. A total of 20 individuals with outbreak-related HAV infection were reported in seven states, including 11 hospitalizations, and no deaths. The Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and Nebraska State and Douglas County Health Departments conducted a traceback investigation for fresh blackberries reportedly purchased by 16 ill persons. These individuals reported purchasing fresh blackberries from 11 points of service from September 16 through 29, 2019 and their clinical isolates assessed through next-generation sequencing and phylogenetic analysis were genetically similar. The traceback investigation did not reveal convergence on a common grower or packing house within Mexico, but all of the blackberries were harvested from growers in Michoacn, Mexico. FDA did not detect the pathogen after analyzing fresh blackberry samples from four distributors, one consumer, and from nine importers at the port of entry as a result of increased screening. Challenges included gaps in traceability practices and the inability to recover the pathogen from sample testing, which prohibited investigators from determining the source of the implicated blackberries. This multi-state outbreak illustrated the importance of food safety practices for fresh produce that may contribute to foodborne illness outbreaks.

This multi-agency report developed under the Interagency Collaboration for Genomics for Food and Feed Safety (Gen-FS) provides an overview of the use of and transition to Whole-Genome Sequencing (WGS) technology to detect and characterize pathogens transmitted commonly by food and identify their sources. We describe foodborne pathogen analysis, investigation, and harmonization efforts among federal agencies, including the National Institutes of Health (NIH); the Department of Health and Human Services' Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA); and the U.S. Department of Agriculture's Food Safety and Inspection Service (FSIS), Agricultural Research Service (ARS), and Animal and Plant Health Inspection Service (APHIS). We describe single nucleotide polymorphism (SNP), core-genome (cg) and whole-genome multi-locus sequence typing (wgMLST) data analysis methods as used in CDC's PulseNet and FDA's GenomeTrakr networks, underscoring the complementary nature of the results for linking genetically related foodborne pathogens during outbreak investigations while allowing flexibility to meet the specific needs of Gen-FS agency partners. We highlight how we apply WGS to pathogen characterization (virulence and antimicrobial resistance profiles), source attribution efforts, and increasing transparency by making the sequences and other data publicly available through the National Center for Biotechnology Information (NCBI). Finally, we highlight the impact of current trends in the use of culture-independent diagnostics tests (CIDT) for human diagnostic testing on analytical approaches related to food safety. Lastly, we highlight what is next for WGS in food safety.

Hepatitis A virus (HAV) is an emerging public health concern and there is an urgent need for ways to rapidly identify cases so that outbreaks can be managed effectively. Conventional testing for HAV relies on anti-HAV IgM seropositivity. However, studies estimate that 10-30% of patients may not be diagnosed by serology. Molecular assays that can directly detect viral nucleic acids have the potential to improve diagnosis, which is key to prevent the spread of infections. In this study, we developed a real-time PCR (RT-PCR) assay to detect HAV RNA for the identification of acute HAV infection. Primers were designed to target the conserved 5'-untranslated region (5'-UTR) of HAV, and the assay was optimized on both the Qiagen Rotor-Gene and the BD MAX. We successfully detected HAV from patient serum and stool samples with moderate differences in sensitivity and specificity depending on the platform used. Our results highlight the clinical utility of using a molecular assay to detect HAV from various specimen types that can be implemented in hospitals to assist with diagnostics, treatment and prevention.

Industrial hog operation (IHO) workers can be occupationally exposed to Staphylococcus aureus and may carry the bacteria in their nares. Workers may persistently carry S. aureus or transition between different states of nasal carriage over time: no nasal carriage, nasal carriage of a human-associated strain, and nasal carriage of a livestock-associated strain. We developed a mathematical model to predict the proportion of IHO workers in each nasal carriage state over time, accounting for IHO worker mask use. We also examined data sufficiency requirements to inform development of models that produce reliable predictions. We used nasal carriage data from a cohort of 101 IHO workers in North Carolina, sampled every two weeks for four months, to develop a three state Markov model that describes the transition dynamics of IHO worker nasal carriage status over the study period and at steady state. We also stratified models by mask use to examine its impact on worker transition dynamics. If conditions remain the same, our models predicted that 49.1% of workers will have no nasal carriage of S. aureus, 28.2% will carry livestock-associated S. aureus, and 22.7% will carry human-associated S. aureus at steady state. In stratified models, at steady state, workers who reported only occasional mask (<80% of the time) use had a higher predicted proportion of individuals with livestock-associated S. aureus nasal carriage (39.2%) compared to workers who consistently (80% of the time) wore a mask (15.5%). We evaluated the amount of longitudinal data that is sufficient to create a Markov model that accurately predicts future nasal carriage states by creating multiple models that withheld portions of the collected data and compared the model predictions to observed data. Our data sufficiency analysis indicated that models created with a small subset of the dataset (approximately 1/3 of observed data) perform similarly to models created using all observed data points. Markov models may have utility in predicting worker health status over time, even when limited longitudinal data are available.

Hepatitis A virus (HAV) genotype IA was most common among strains tested in US outbreak investigations and surveillance during 1996-2015. However, HAV genotype IB gained prominence during 2016-2019 person-to-person multistate outbreaks. Detection of previously uncommon strains highlights the changing molecular epidemiology of HAV infection in the United States.

BACKGROUND: We investigated patients with potential SARS-CoV-2 reinfection in the United States during May-July 2020. METHODS: We conducted case finding for patients with potential SARS-CoV-2 reinfection through the Emerging Infections Network. Cases reported were screened for laboratory and clinical findings of potential reinfection followed by requests for medical records and laboratory specimens. Available medical records were abstracted to characterize patient demographics, comorbidities, clinical course, and laboratory test results. Submitted specimens underwent further testing, including RT-PCR, viral culture, whole genome sequencing, subgenomic RNA PCR, and testing for anti-SARS-CoV-2 total antibody. RESULTS: Among 73 potential reinfection patients with available records, 30 patients had recurrent COVID-19 symptoms explained by alternative diagnoses with concurrent SARS-CoV-2 positive RT-PCR, 24 patients remained asymptomatic after recovery but had recurrent or persistent RT-PCR, and 19 patients had recurrent COVID-19 symptoms with concurrent SARS-CoV-2 positive RT-PCR but no alternative diagnoses. These 19 patients had symptom recurrence a median of 57 days after initial symptom onset (interquartile range: 47 - 76). Six of these patients had paired specimens available for further testing, but none had laboratory findings confirming reinfections. Testing of an additional three patients with recurrent symptoms and alternative diagnoses also did not confirm reinfection. CONCLUSIONS: We did not confirm SARS-CoV-2 reinfection within 90 days of the initial infection based on the clinical and laboratory characteristics of cases in this investigation. Our findings support current CDC guidance around quarantine and testing for patients who have recovered from COVID-19.

2020 will go down in history as the year when the global community was awakened to the fragility of human health and the interdependence of the ecosystem, economy, and humanity. Amid the COVID-19 pandemic, the vulnerability of people with diabetes during a public health emergency became evident by their at least 2 times increased risk of severe disease or death, especially in individuals with poorly controlled diabetes, comorbidities, or both. The disease burden caused by COVID-19, exacerbated by chronic conditions like diabetes, has inflicted a heavy toll on health-care systems and the global economy. | | In this Lancet Commission on diabetes, which embodies 4 years of extensive work on data curation, synthesis, and modelling, we urge policy makers, payers, and planners to collectively change the ecosystem, build capacity, and improve the clinical practice environment. Such actions will enable practitioners to systematically collect data during routine practice and to use these data effectively to diagnose early, stratify risks, define needs, improve care, evaluate solutions, and drive changes at patient, system, and policy levels to prevent and control diabetes and other non-communicable diseases. Emerging evidence regarding the possible damaging effects of severe acute respiratory syndrome coronavirus 2 on pancreatic islets implies the potential worsening of the COVID-19 pandemic and the diabetes epidemic, adding to the urgency of these collective actions. | | Prevention, early detection, prompt diagnosis, and continuing care with regular monitoring and ongoing evaluation are key elements in reducing the growing burden of diabetes. Given the silent and progressive nature of diabetes, it is epidemiological analyses that have provided a framework for identifying populations and subgroups at risk of diabetes and its complications. Although the total prevalence of diabetes reflects disease burden, incidence rates might reflect the effects of interventions among determinant factors that include, but are not limited to, political, socioeconomical, and technological changes within a population, area, or both. | | In 2019, 463 million people had diabetes worldwide, with 80% from low-income and middle-income countries. Over 70% of global deaths are due to non-communicable diseases, including diabetes, cardiovascular disease, cancer, and respiratory disease. On average, diabetes reduces life expectancy in people aged 40–60 years by 4–10 years and independently increases the risk of death from cardiovascular disease, renal disease, and cancer by 1·3–3·0 times. Diabetes is among the leading causes of non-traumatic lower extremity amputation and blindness, especially in people of working age. The co-occurrence of these morbidities severely impairs quality of life, reduces productivity, and causes major suffering.

Since February 12, 2020, approximately 6.5 million cases of SARS-CoV-2 infection, the cause of coronavirus disease 2019 (COVID-19), and 190,000 SARS-CoV-2-associated deaths have been reported in the United States (1,2). Symptoms associated with SARS-CoV-2 infection are milder in children compared with adults (3). Persons aged <21 years constitute 26% of the U.S. population (4), and this report describes characteristics of U.S. persons in that population who died in association with SARS-CoV-2 infection, as reported by public health jurisdictions. Among 121 SARS-CoV-2-associated deaths reported to CDC among persons aged <21 years in the United States during February 12-July 31, 2020, 63% occurred in males, 10% of decedents were aged <1 year, 20% were aged 1-9 years, 70% were aged 10-20 years, 45% were Hispanic persons, 29% were non-Hispanic Black (Black) persons, and 4% were non-Hispanic American Indian or Alaska Native (AI/AN) persons. Among these 121 decedents, 91 (75%) had an underlying medical condition,* 79 (65%) died after admission to a hospital, and 39 (32%) died at home or in the emergency department (ED).(†) These data show that nearly three quarters of SARS-CoV-2-associated deaths among infants, children, adolescents, and young adults have occurred in persons aged 10-20 years, with a disproportionate percentage among young adults aged 18-20 years and among Hispanics, Blacks, AI/ANs, and persons with underlying medical conditions. Careful monitoring of SARS-CoV-2 infections, deaths, and other severe outcomes among persons aged <21 years remains particularly important as schools reopen in the United States. Ongoing evaluation of effectiveness of prevention and control strategies will also be important to inform public health guidance for schools and parents and other caregivers.

BACKGROUND: Understanding hepatitis C virus (HCV) transmission among people who inject drugs (PWID) is essential for HCV elimination. We aimed to differentiate reinfections from treatment failures and to identify transmission linkages and associated factors in a cohort of PWID receiving opioid agonist therapy (OAT). METHODS: We analyzed baseline and follow-up specimens from 150 PWID from three OAT clinics in the Bronx, NY. NGS data from the hypervariable region 1 of HCV were analyzed using Global Hepatitis Outbreak and Surveillance Technology. RESULTS: There were three transmission linkages between study participants. Nine participants did not achieve sustained virologic response (SVR): seven had follow-up specimens with similar sequences to baseline and two passed away. Four additional participants achieved SVR but became viremic at later follow-up: two were reinfected with different strains, one had a late treatment failure, and one was transiently viremic 17 months post-treatment. All transmission linkages were from the same OAT clinic and involved spousal or common-law partnerships. CONCLUSION: This study highlights the use of next generation sequencing (NGS) as an important tool for identifying viral transmission and to help distinguish relapse and reinfection among PWID. Results reinforce the need for harm reduction interventions among couples and those who report ongoing risk factors following SVR.

Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)(1-6). Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)(2). CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM.

BACKGROUND: Hepatitis A is a vaccine-preventable viral disease transmitted by the fecal-oral route. During 2016-2018, the County of San Diego investigated an outbreak of hepatitis A infections primarily among people experiencing homelessness (PEH) to identify risk factors and support control measures. At the time of the outbreak, homelessness was not recognized as an independent risk factor for the disease. METHODS: We tested the association between homelessness and infection with hepatitis A virus (HAV) using a test-negative study design comparing patients with laboratory-confirmed hepatitis A with control subjects who tested negative for HAV infection. We assessed risk factors for severe hepatitis A disease outcomes, including hospitalization and death, using multivariable logistic regression. We measured the frequency of indications for hepatitis A vaccination according to Advisory Committee on Immunization Practice (ACIP) guidelines. RESULTS: Among 589 outbreak-associated cases reported, 291 (49%) occurred among PEH. Compared with those who were not homeless, PEH were at 3.3 (95% CI: 1.5-7.9) times higher odds of HAV infection, 2.5 (95% CI: 1.7-3.9) times higher odds of hospitalization, and 3.9 (95% CI: 1.1-16.9) times higher odds of death associated with hepatitis A. Among PEH, 212 (73%) patients recorded other ACIP indications for hepatitis A vaccination. CONCLUSIONS: PEH were at higher risk for infection with HAV and higher risk for severe hepatitis A disease outcomes compared with those not experiencing homelessness. Approximately one-fourth of PEH had no other ACIP indication for hepatitis A vaccination. These findings support the recent ACIP recommendation to add homelessness as an indication for hepatitis A vaccination.

During January 22-March 23, 2018, a local health department in Washington was notified of two patients who received a diagnosis of acute hepatitis C virus (HCV) infection. Neither patient had behavioral risk factors associated with HCV acquisition; however, both had received injectable narcotic (opioid) drugs from the same nurse during separate visits to an emergency department (ED) at a local hospital on December 6 and December 16, 2017. Investigation revealed that the nurse had accessed the automated drug dispensing system at a higher frequency than had other staff members, admitted diverting* patients' injectable narcotic and antihistamine drugs for personal use, and tested positive for HCV antibodies (anti-HCV) on March 19, 2018, but did not have quantifiable HCV RNA. Specimens from both patients were sent to CDC for genetic testing, and HCV viral variants analysis found a significant level of genetically similar HCV variants in both patients, indicating a common source of infection. Further investigation was conducted to confirm the infection source, identify other potentially exposed patients, and treat any new patients who received an HCV diagnosis. Monitoring frequency of access to drug dispensing systems can help identify staff members with abnormal dispensing patterns, including diversion activities (1). U.S. health care facilities are required to prevent, identify, and report any loss, diversion, or theft of controlled substances (2).

We evaluated clinical outcomes among organ recipients with donor-derived hepatitis B virus (HBV) or hepatitis C virus (HCV) infections investigated by CDC from 2014-2017 in the United States. We characterized new HBV infections in organ recipients if donors tested negative for total anti-HBc, HBsAg and HBV DNA, and new recipient HCV infections if donors tested negative for anti-HCV and HCV RNA. Donor risk behaviors were abstracted from next-of-kin interviews and medical records. During 2014-2017, seven new recipient HBV infections associated with seven donors were identified; six (86%) recipients survived. At last follow-up, all survivors had functioning grafts and five (83%) had started antiviral therapy. Twenty new recipient HCV infections associated with nine donors were identified; 19 (95%) recipients survived. At last follow-up, 18 (95%) survivors had functioning grafts and 14 (74%) had started antiviral treatment. Combining donor next-of kin interviews and medical records, 11/16 (69%) donors had evidence of injection drug use and all met Public Health Service increased risk donor (IRD) criteria. IRD designation led to early diagnosis of recipient infection, and prompt implementation of therapy, likely reducing the risk of graft failure, liver disease and death. This article is protected by copyright. All rights reserved.

BACKGROUND: Characteristics of US blood donors with recent (RBI) or occult (OBI) hepatitis B virus (HBV) infection are not well defined. METHODS: Donors with RBI and OBI were identified by nucleic acid and serologic testing among 34.4 million donations during 2009-2015. Consenting donors were interviewed and their HBV S-gene sequenced. RESULTS: The overall rate of HBV-infected donors was 7.95 per 100,000; of these, 0.35 per 100,000 and 1.70 per 100,000 were RBI and OBI, respectively. RBI (n = 120) and OBI (n = 583) donors constituted 26% of all HBV-infected (n = 2735) donors. Detection of HBV DNA in 92% of OBI donors required individual donation nucleic acid testing. Donors with OBI compared to RBI were older (mean age, 48 vs 39 years; p < 0.0001) with lower median viral loads (9 vs. 529 IU/mL; p < 0.0001). A higher proportion of OBI than RBI donors were born or resided in an endemic country (39% vs. 5%; p = 0.0078). Seventy-seven percent of all RBI and OBI donors had multiple sex partners, an HBV-risk factor. Of 40 RBI and 10 OBI donors whose S gene was sequenced, 33 (83%) and 6 (60%), respectively, carried HBV subgenotype A2; 18 (55%) and 2 (33%), respectively, shared an identical sequence. Infection with 1 or more putative HBV-immune-escape mutants was identified in 5 (50%) of OBI but no RBI donors. CONCLUSION: RBI and OBI continue to be identified at low rates, confirming the importance of comprehensive HBV DNA screening of US blood donations. HBV-infected donors require referral for care and evaluation and contact tracing; their HBV strains may provide important information on emergent genotypes.

BACKGROUND: A high prevalence (92.3%) of hepatitis C virus (HCV) co-infection among HIV patients identified during a large HIV outbreak associated with injection of oxymorphone in Indiana prompted genetic analysis of HCV strains. METHODS: Molecular epidemiological analysis of HCV-positive samples included genotyping, sampling intra-host HVR1 variants by next-generation sequencing (NGS) and constructing transmission networks using Global Hepatitis Outbreak and Surveillance Technology (GHOST). FINDINGS: Results from the 492 samples indicate predominance of HCV genotypes 1a (72.2%) and 3a (20.4%), and existence of 2 major endemic NS5B clusters involving 49.8% of the sequenced strains. Among 76 HIV co-infected patients, 60.5% segregated into 2 endemic clusters. NGS analyses of 281 cases identified 826,917 unique HVR1 sequences and 51 cases of mixed subtype/genotype infections. GHOST mapped 23 transmission clusters. One large cluster (n=130) included 50 cases infected with >/=2 subtypes/genotypes and 43 cases co-infected with HIV. Rapid strain replacement and superinfection with different strains were found among 7 of 12 cases who were followed up. INTERPRETATION: GHOST enabled mapping of HCV transmission networks among persons who inject drugs (PWID). Findings of numerous transmission clusters, mixed-genotype infections and rapid succession of infections with different HCV strains indicate a high rate of HCV spread. Co-localization of HIV co-infected patients in the major HCV clusters suggests that HIV dissemination was enabled by existing HCV transmission networks that likely perpetuated HCV in the community for years. Identification of transmission networks is an important step to guiding efficient public health interventions for preventing and interrupting HCV and HIV transmission among PWID. FUND: US Centers for Disease Control and Prevention, and US state and local public health departments.

During 2017, CDC received 1,521 reports of acute hepatitis A virus (HAV) infections from California, Kentucky, Michigan, and Utah; the majority of infections were among persons reporting injection or noninjection drug use or homelessness. Investigations conducted by local and state health departments indicated that direct person-to-person transmission of HAV infections was occurring, differing from other recent, large HAV outbreaks attributed to consumption of contaminated commercial food products. Outbreaks with direct HAV transmission among persons reporting drug use or homelessness signals a shift in HAV infection epidemiology in the United States, and vaccination of these populations at high risk can prevent future outbreaks.

The End TB Strategy envisions a world free of tuberculosis-zero deaths, disease and suffering due to tuberculosis by 2035. This requires reducing the global tuberculosis incidence from >1250 cases per million people to <100 cases per million people within the next two decades. Expanding testing and treatment of tuberculosis infection is critical to achieving this goal. In high-burden countries, like India, the implementation of tuberculosis preventive treatment (TPT) remains a low priority. In this analysis article, we explore potential challenges and solutions of implementing TPT in India. The next chapter in tuberculosis elimination in India will require cost-effective and sustainable interventions aimed at tuberculosis infection. This will require constant innovation, locally driven solutions to address the diverse and dynamic tuberculosis epidemiology and persistent programme monitoring and evaluation. As new tools, regimens and approaches emerge, midcourse adjustments to policy and practice must be adopted. The development and implementation of new tools and strategies will call for close collaboration between local, national and international partners-both public and private-national health authorities, non-governmental organisations, research community and the diagnostic and pharmaceutical industry. Leading by example, India can contribute to global knowledge through operational research and programmatic implementation for combating tuberculosis infection.