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During February 2021-June 2022, the Georgia Department of Public Health (GDPH) detected five clusters of rapid HIV transmission concentrated among Hispanic or Latino (Hispanic) gay, bisexual, and other men who have sex with men (MSM) in metropolitan Atlanta. The clusters were detected through routine analysis of HIV-1 nucleotide sequence data obtained through public health surveillance (1,2). Beginning in spring 2021, GDPH partnered with health districts with jurisdiction in four metropolitan Atlanta counties (Cobb, DeKalb, Fulton, and Gwinnett) and CDC to investigate factors contributing to HIV spread, epidemiologic characteristics, and transmission patterns. Activities included review of surveillance and partner services interview data, † medical chart reviews, and qualitative interviews with service providers and Hispanic MSM community members. By June 2022, these clusters included 75 persons, including 56% who identified as Hispanic, 96% who reported male sex at birth, 81% who reported male-to-male sexual contact, and 84% of whom resided in the four metropolitan Atlanta counties. Qualitative interviews identified barriers to accessing HIV prevention and care services, including language barriers, immigration- and deportation-related concerns, and cultural norms regarding sexuality-related stigma. GDPH and the health districts expanded coordination, initiated culturally concordant HIV prevention marketing and educational activities, developed partnerships with organizations serving Hispanic communities to enhance outreach and services, and obtained funding for a bilingual patient navigation program with academic partners to provide staff members to help persons overcome barriers and understand the health care system. HIV molecular cluster detection can identify rapid HIV transmission among sexual networks involving ethnic and sexual minority groups, draw attention to the needs of affected populations, and advance health equity through tailored responses that address those needs., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Valeria D. Cantos reported grant support from the National Institute for Allergy and Infectious Diseases, National Institutes of Health (NIH), Gilead Sciences, and Janssen Research. Jane Yoon Scott reported grant support from the NIH’s Centers for AIDS Research. No other potential conflicts of interest were disclosed.

Of 65 cases during a human immunodeficiency virus (HIV) outbreak among persons who inject drugs (PWID) in West Virginia (2019-2021), 61 (94%) had hepatitis C diagnosed a median of 46 months prior to HIV diagnosis. Hepatitis C diagnosis among PWID should trigger improved access to prevention and treatment services., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

As of November 9, 2022, a total of 28,730 cases of monkeypox (mpox) had been reported in the United States,* primarily among adult cisgender men reporting recent male-to-male sexual contact (1). Transgender and gender-diverse persons, who constitute an estimated 0.5% of the U.S. adult population, † face unique health disparities and barriers to care (2-4). However, data on the epidemiologic and clinical features of Monkeypox virus infections in this population are limited (5). CDC analyzed U.S. case surveillance data on mpox cases in transgender and gender-diverse adults reported during May 17-November 4, 2022. During this period, 466 mpox cases in transgender and gender-diverse adults were reported, accounting for 1.7% of reported cases among adults. Most were in transgender women (43.1%) or gender-diverse persons (42.1%); 14.8% were in transgender men. Among 374 (80.3%) mpox cases in transgender and gender-diverse adults with information available on sexual or close intimate contact, 276 (73.8%) reported sexual or close intimate contact with a cisgender male partner during the 3 weeks preceding symptom onset. During the ongoing outbreak, transgender and gender-diverse persons have been disproportionately affected by mpox. Members of this population frequently reported recent sexual or close intimate contact with cisgender men, who might be in sexual networks experiencing the highest incidence of mpox. These findings highlight the importance of tailoring public health prevention and outreach efforts to transgender and gender-diverse communities and could guide strategies to reduce mpox transmission., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

The Centers for Disease Control and Prevention (CDC) and state, territorial, and local health departments have expanded efforts to detect and respond to HIV clusters and outbreaks in the United States. In July 2017, CDC created the HIV Outbreak Coordination Unit (OCU) to ensure consistent and collaborative assessment of requests from health departments for consultation or support on possible HIV clusters and outbreaks of elevated concern. The HIV OCU is a multidisciplinary, cross-organization functional unit within CDC's Division of HIV/AIDS Prevention. HIV OCU members have expertise in areas such as outbreak detection and investigation, prevention, laboratory services, surveillance and epidemiology, policy, communication, and operations. HIV OCU discussions facilitate problem solving, coordination, and situational awareness. Between HIV OCU meetings, designated CDC staff members communicate regularly with health departments to provide support and assessment. During July 2017-December 2019, the HIV OCU reviewed 31 possible HIV clusters and outbreaks (ie, events) in 22 states that were detected by CDC, health departments, or local partners; 17 events involved HIV transmission associated with injection drug use, and other events typically involved sexual transmission or overall increases in HIV diagnoses. CDC supported health departments remotely or on site with planning and prioritization; data collection, management, and analysis; communications; laboratory support; multistate coordination; and expansion of HIV prevention services. The HIV OCU has augmented CDC's support of HIV cluster and outbreak assessment and response at health departments and had important internal organizational benefits. Health departments may benefit from developing or strengthening similar units to coordinate detection and response efforts within and across public health agencies and advance the national Ending the HIV Epidemic initiative.

On May 17, 2022, the Massachusetts Department of Public Health (MDPH) Laboratory Response Network (LRN) laboratory confirmed the presence of orthopoxvirus DNA via real-time polymerase chain reaction (PCR) from lesion swabs obtained from a Massachusetts resident. Orthopoxviruses include Monkeypox virus, the causative agent of monkeypox. Subsequent real-time PCR testing at CDC on May 18 confirmed that the patient was infected with the West African clade of Monkeypox virus. Since then, confirmed cases* have been reported by nine states. In addition, 28 countries and territories, † none of which has endemic monkeypox, have reported laboratory-confirmed cases. On May 17, CDC, in coordination with state and local jurisdictions, initiated an emergency response to identify, monitor, and investigate additional monkeypox cases in the United States. This response has included releasing a Health Alert Network (HAN) Health Advisory, developing interim public health and clinical recommendations, releasing guidance for LRN testing, hosting clinician and public health partner outreach calls, disseminating health communication messages to the public, developing protocols for use and release of medical countermeasures, and facilitating delivery of vaccine postexposure prophylaxis (PEP) and antivirals that have been stockpiled by the U.S. government for preparedness and response purposes. On May 19, a call center was established to provide guidance to states for the evaluation of possible cases of monkeypox, including recommendations for clinical diagnosis and orthopoxvirus testing. The call center also gathers information about possible cases to identify interjurisdictional linkages. As of May 31, this investigation has identified 17 § cases in the United States; most cases (16) were diagnosed in persons who identify as gay, bisexual, or men who have sex with men (MSM). Ongoing investigation suggests person-to-person community transmission, and CDC urges health departments, clinicians, and the public to remain vigilant, institute appropriate infection prevention and control measures, and notify public health authorities of suspected cases to reduce disease spread. Public health authorities are identifying cases and conducting investigations to determine possible sources and prevent further spread. This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy. ¶ ., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Objective: To understand recent patterns in reported baseline HIV drug-resistance testing over time in the United States., Design: Data from the National HIV Surveillance System for persons who were aged at least 13 years at the time of HIV diagnosis during 2014-2019 and resided in one of 12 US jurisdictions with high levels of reporting in 2014 and 2015., Methods: Among persons included in the analysis, we calculated the total proportion of HIV diagnoses occurring during 2014-2019 with a reported baseline sequence by year of diagnosis and sequence type. A baseline sequence was defined as any protease/ reverse transcriptase (PR/RT) or integrase sequence generated from a specimen collected 90 days or less after diagnosis., Results: During 2014-2019, reported levels of baseline PR/RT (with or without integrase) testing varied by year from 46.9% to 51.8% without any clear pattern over time. PR/RT with integrase testing increased (8.3-19.4%) and integrase-only testing remained low (1.9-1.3%)., Conclusion: While reported levels of baseline PR/RT (with or without integrase) testing have remained sufficiently high for the purposes of molecular cluster detection, higher levels would strengthen jurisdictions' and the Centers for Disease Control and Prevention's ability to monitor trends in HIV drug-resistance and detect and respond to HIV molecular clusters. Efforts to increase levels of reported baseline testing likely need to address both gaps in testing as well as reporting., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Transmitted human immunodeficiency virus (HIV) drug resistance can threaten the efficacy of antiretroviral therapy and pre-exposure prophylaxis (PrEP). Drug-resistance testing is recommended at entry to HIV care in the United States and provides valuable insight for clinical decision making and population-level monitoring., Methods: We assessed transmitted drug-resistance-associated mutation (TDRM) prevalence and predicted susceptibility to common HIV drugs among US persons with HIV diagnosed during 2014-2018 who had a drug resistance test performed ≤3 months after HIV diagnosis and reported to the National HIV Surveillance System and who resided in 28 jurisdictions where ≥20% of HIV diagnoses had an eligible sequence during this period., Results: Of 50 747 persons in the analysis, 9616 (18.9%) had ≥1 TDRM. TDRM prevalence was 0.8% for integrase strand transfer inhibitors (INSTIs), 4.2% for protease inhibitors, 6.9% for nucleoside reverse transcriptase inhibitors (NRTIs), and 12.0% for non-NRTIs. Most individual mutations had a prevalence <1.0% including M184V (0.9%) and K65R (0.1%); K103N was most prevalent (8.6%). TDRM prevalence did not increase or decrease significantly during 2014-2018 overall, for individual drug classes, or for key individual mutations except for M184V (12.9% increase per year; 95% confidence interval, 5.6-20.6%)., Conclusions: TDRM prevalence overall and for individual drug classes remained stable during 2014-2018; transmitted INSTI resistance was uncommon. Continued population-level monitoring of INSTI and NRTI mutations, especially M184V and K65R, is warranted amidst expanding use of second-generation INSTIs and PrEP., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

During October 2019, the West Virginia Bureau for Public Health (WVBPH) noted that an increasing number of persons who inject drugs (PWID) in Kanawha County received a diagnosis of HIV. The number of HIV diagnoses among PWID increased from less than five annually during 2016-2018 to 11 during January-October 2019 (Figure). Kanawha County (with an approximate population of 180,000*) has high rates of opioid use disorder and overdose deaths, which have been increasing since 2016, † and the county is located near Cabell County, which experienced an HIV outbreak among PWID during 2018-2019 (1,2). In response to the increase in HIV diagnoses among PWID in 2019, WVBPH released a Health Advisory § ; and WVBPH and Kanawha-Charleston Health Department (KCHD) convened an HIV task force, conducted care coordination meetings, received CDC remote assistance to support response activities, and expanded HIV testing and outreach., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

In 2019, the West Virginia Bureau for Public Health (WV BPH), Cabell-Huntington Health Department (CHHD), and CDC collaborated to respond to an HIV outbreak among people who inject drugs (PWID). CDC, WV BPH, and CHHD formed a cross-agency communications team to establish situational awareness, identify knowledge gaps, and establish key audiences for messages, including the general population, PWID, and clinical and social service providers. The team disseminated up-to-date information about the outbreak, and prioritized messages addressing stigma related to drug use, syringe services programs, and HIV. Messages were continually updated to address the evolving situation and to resonate with local values. Messages were disseminated via advertisements, local news media, and directly to PWID, people experiencing homelessness, and providers. The response supplemented CHHD's assets, including strong relationships and community knowledge, with staff capacity and expertise from state and federal agencies. This collaborative approach is a useful model to address communication needs., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Objectives: Before community transmission of COVID-19 was recognized in the United States, cruise ship passengers with high risk for exposure to SARS-CoV-2 were repatriated and quarantined. We describe cases of influenza-like illness (ILI) among responders., Methods: We reviewed situation reports and responder illness reports to characterize ill responders, including illness onset date, symptoms, fever, diagnostic tests, potential breaches in PPE use, and return to work status., Results: Among 339 responders, nine (3%) reported ILI. No breaches in PPE were reported. Three responders with ILI were tested for both SARS-CoV-2 infection and influenza A; none tested positive for SARS-CoV-2 infection and two tested positive for influenza A., Conclusions: Despite an outbreak of ILI among responders, none were diagnosed with COVID-19, suggesting preventive measures in place might have been sufficient to prevent responders from SARS-CoV-2 exposure., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 American College of Occupational and Environmental Medicine.)

Introduction: In January 2019, the West Virginia Bureau for Public Health detected increased HIV diagnoses among people who inject drugs in Cabell County. Responding to HIV clusters and outbreaks is 1 of the 4 pillars of the Ending the HIV Epidemic in the U.S. initiative and requires activities from the Diagnose, Treat, and Prevent pillars. This article describes the design and implementation of a comprehensive response, featuring interventions from all pillars., Methods: This study used West Virginia Bureau for Public Health data to identify HIV diagnoses during January 1, 2018-October 9, 2019 among (1) people who inject drugs linked to Cabell County, (2) their sex or injecting partners, or (3) others with an HIV sequence linked to Cabell County people who inject drugs. Surveillance data, including HIV-1 polymerase sequences, were analyzed to estimate the transmission rate and timing of infections using molecular clock phylogenetic analysis. Federal, state, and local partners designed and implemented a comprehensive response during January 2019-October 2019., Results: Of 82 people identified in the outbreak, most were male (60%), were White (91%), and reported unstable housing (80%). In a large molecular cluster containing 56 of 60 (93%) available sequences, 93% of inferred transmissions occurred after January 1, 2018. HIV testing, HIV pre-exposure prophylaxis, and syringe services were rapidly expanded, leading to improved linkage to HIV care and viral suppression., Conclusions: Evidence of rapid transmission in this outbreak galvanized robust collaboration among federal, state, and local partners, leading to critical improvements in HIV prevention and care services. HIV outbreak response requires increased coordination and creativity to improve service delivery to people affected by rapid HIV transmission., (Published by Elsevier Inc.)

Diagnoses of HIV among people who inject drugs have increased in the U.S. during 2014-2018 for the first time in 2 decades, and multiple HIV outbreaks have been detected among people who inject drugs since 2015. These epidemiologic trends pose a significant concern for achieving goals of the federal initiative for Ending the HIV Epidemic in the U.S. Syringe services programs are cost effective, safe, and highly effective in reducing HIV transmission and are an essential component of a comprehensive, integrated approach to addressing these concerns. Yet, geographic coverage of these programs remains limited in the U.S., and many jurisdictions continue to have laws and policies that limit or disallow syringe services programs. An in-depth literature review was conducted on the role of syringe services programs in the Ending the HIV Epidemic initiative. Empirical and model-based evidence consistently shows that syringe services programs have the highest impact in HIV prevention when combined with access to medications for substance use disorder and antiretroviral therapy. Their effectiveness is further maximized when they provide services without restrictions and include proven and innovative strategies to expand access to harm-reduction and clinical services (e.g., peer outreach, telehealth). Increasing geographic and service coverage of syringe services programs requires strong and sustainable policy, funding, and community support and will need to address new challenges related to the COVID-19 pandemic. Syringe services programs have a key role in all 4 Ending the HIV Epidemic initiative strategies-Prevent, Diagnose, Treat, and Respond-and thus are instrumental to its success in preventing disease and saving lives., (Copyright © 2021 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

The Respond pillar of the Ending the HIV Epidemic in the U.S. initiative, which consists of activities also known as cluster and outbreak detection and response, offers a framework to guide tailored implementation of proven HIV prevention strategies where transmission is occurring most rapidly. Cluster and outbreak response involves understanding the networks in which rapid transmission is occurring; linking people in the network to essential services; and identifying and addressing gaps in programs and services such as testing, HIV and other medical care, pre-exposure prophylaxis, and syringe services programs. This article reviews the experience gained through 30 HIV cluster and outbreak responses in North America during 2000-2020 to describe approaches for implementing these core response strategies. Numerous jurisdictions that have implemented these response strategies have demonstrated success in improving outcomes related to HIV care and viral suppression, testing, use of prevention services, and reductions in transmission or new diagnoses. Efforts to address important gaps in service delivery revealed by cluster and outbreak detection and response can strengthen prevention efforts broadly through multidisciplinary, multisector collaboration. In this way, the Respond pillar embodies the collaborative, data-guided approach that is critical to the overall success of the Ending the HIV Epidemic in the U.S. initiative., (Published by Elsevier Inc.)

Background: Persons who inject drugs (PWID) have frequent healthcare encounters related to their injection drug use (IDU) but are often not tested for human immunodeficiency virus (HIV). We sought to quantify missed opportunities for HIV testing during an HIV outbreak among PWID., Methods: PWID with HIV diagnosed in 5 Cincinnati/Northern Kentucky counties during January 2017-September 2018 who had ≥1 encounter 12 months prior to HIV diagnosis in 1 of 2 Cincinnati/Northern Kentucky area healthcare systems were included in the analysis. HIV testing and encounter data were abstracted from electronic health records. A missed opportunity for HIV testing was defined as an encounter for an IDU-related condition where an HIV test was not performed and had not been performed in the prior 12 months., Results: Among 109 PWID with HIV diagnosed who had ≥1 healthcare encounter, 75 (68.8%) had ≥1 IDU-related encounters in the 12 months before HIV diagnosis. These 75 PWID had 169 IDU-related encounters of which 86 (50.9%) were missed opportunities for HIV testing and occurred among 46 (42.2%) PWID. Most IDU-related encounters occurred in the emergency department (118/169; 69.8%). Using multivariable generalized estimating equations, HIV testing was more likely in inpatient compared with emergency department encounters (adjusted relative risk [RR], 2.72; 95% confidence interval [CI], 1.70-4.33) and at the healthcare system receiving funding for emergency department HIV testing (adjusted RR, 1.76; 95% CI, 1.10-2.82)., Conclusions: PWID have frequent IDU-related encounters in emergency departments. Enhanced HIV screening of PWID in these settings can facilitate earlier diagnosis and improve outbreak response., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Background: The Coronavirus Disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), evolved rapidly in the United States. This report describes the demographic, clinical, and epidemiologic characteristics of 544 U.S. persons under investigation (PUI) for COVID-19 with complete SARS-CoV-2 testing in the beginning stages of the pandemic from January 17 through February 29, 2020., Methods: In this surveillance cohort, the U.S. Centers for Disease Control and Prevention (CDC) provided consultation to public health and healthcare professionals to identify PUI for SARS-CoV-2 testing by quantitative real-time reverse-transcription PCR. Demographic, clinical, and epidemiologic characteristics of PUI were reported by public health and healthcare professionals during consultation with on-call CDC clinicians and subsequent submission of a CDC PUI Report Form. Characteristics of laboratory-negative and laboratory-positive persons were summarized as proportions for the period of January 17-February 29, and characteristics of all PUI were compared before and after February 12 using prevalence ratios., Results: A total of 36 PUI tested positive for SARS-CoV-2 and were classified as confirmed cases. Confirmed cases and PUI testing negative for SARS-CoV-2 had similar demographic, clinical, and epidemiologic characteristics. Consistent with changes in PUI evaluation criteria, 88% (13/15) of confirmed cases detected before February 12, 2020, reported travel from China. After February 12, 57% (12/21) of confirmed cases reported no known travel- or contact-related exposures., Conclusions: These findings can inform preparedness for future pandemics, including capacity for rapid expansion of novel diagnostic tests to accommodate broad surveillance strategies to assess community transmission, including potential contributions from asymptomatic and presymptomatic infections., Competing Interests: The authors have declared that no competing interests exist.

Molecular cluster detection analyzes HIV sequences to identify rapid HIV transmission and inform public health responses. We describe changes in the capability to detect molecular clusters and in geographic variation in transmission dynamics. We examined the reporting completeness of HIV-1 polymerase sequences in quarterly National HIV Surveillance System datasets from December 2015 to December 2019. Priority clusters were identified quarterly. To understand populations recently affected by rapid transmission, we described the transmission risk and race/ethnicity of people in clusters first detected in 2018-2019. During December 2015 to December 2019, national sequence completeness increased from 26% to 45%. Of the 1212 people in the 136 clusters first detected in 2018-2019, 69% were men who have sex with men (MSM) and 11% were people who inject drugs (PWID). State-by-state analysis showed substantial variation in transmission risk and racial/ethnic groups in clusters of rapid transmission. HIV sequence reporting has increased nationwide. Molecular cluster analysis identifies rapid transmission in varied populations and identifies emerging patterns of rapid transmission in specific population groups, such as PWID, who, in 2015-2016, comprised only 1% of people in such molecular clusters. These data can guide efforts to focus, tailor, and scale up prevention and care services for these populations.

In 2015, a large human immunodeficiency virus (HIV) outbreak occurred among persons who inject drugs (PWID) in Indiana. During 2016-2019, additional outbreaks among PWID occurred across the United States. Based on information disseminated by responding health departments and Centers for Disease Control and Prevention (CDC) involvement, we offer perspectives about characteristics of and public health responses to 6 such outbreaks. Across outbreaks, injection of opioids (including fentanyl) or methamphetamine predominated; many PWID concurrently used opioids and methamphetamine or cocaine. Commonalities included homelessness or unstable housing, previous incarceration, and hepatitis C virus exposure. All outbreaks occurred in metropolitan areas, including some with substantial harm reduction and medical programs targeted to PWID. Health departments experienced challenges locating case patients and contacts, linking and retaining persons in care, building support to strengthen harm-reduction programs, and leveraging resources. Expanding the concept of vulnerability to HIV outbreaks and other lessons learned can be considered for preventing, detecting, and responding to future outbreaks among PWID., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Background: The Massachusetts Department of Public Health and the Centers for Disease Control and Prevention collaborated to characterize a human immunodeficiency virus (HIV) outbreak in northeastern Massachusetts and prevent further transmission. We determined the contributions of HIV sequence data to defining the outbreak., Methods: Human immunodeficiency virus surveillance and partner services data were analyzed to understand social and molecular links within the outbreak. Cases were defined as HIV infections diagnosed during 2015-2018 among people who inject drugs with connections to northeastern Massachusetts or HIV infections among other persons named as partners of a case or whose HIV polymerase sequence linked to another case, regardless of diagnosis date or geography., Results: Of 184 cases, 65 (35%) were first identified as part of the outbreak through molecular analysis. Twenty-nine cases outside of northeastern Massachusetts were molecularly linked to the outbreak. Large molecular clusters (75, 28, and 11 persons) were identified. Among 161 named partners, 106 had HIV; of those, 40 (38%) diagnoses occurred through partner services., Conclusions: Human immunodeficiency virus sequence data increased the case count by 55% and expanded the geographic scope of the outbreak. Human immunodeficiency virus sequence and partner services data each identified cases that the other method would not have, maximizing prevention and care opportunities for HIV-infected persons and their partners., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Objectives. To investigate a shigellosis outbreak in Genesee County, Michigan (including the City of Flint), and Saginaw County, Michigan, in 2016 and address community concerns about the role of the Flint water system. Methods. We met frequently with community members to understand concerns and develop the investigation. We surveyed households affected by the outbreak, analyzed Shigella isolate data, examined the geospatial distribution of cases, and reviewed available water quality data. Results. We surveyed 83 households containing 158 cases; median age was 10 years. Index case-patients from 55 of 83 households (66%) reported contact with a person outside their household who wore diapers or who had diarrhea in the week before becoming ill; results were similar regardless of household drinking water source. Genomic diversity was not consistent with a point source. In Flint, no space-time clustering was identified, and average free chlorine residual values remained above recommended levels throughout the outbreak period. Conclusions. The outbreak was most likely caused by person-to-person contact and not by the Flint water system. Consistent community engagement was essential to the design and implementation of the investigation.

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Waterborne disease outbreaks in the United States are associated with a wide variety of water exposures and are reported annually to CDC on a voluntary basis by state and territorial health departments through the National Outbreak Reporting System (NORS). A majority of outbreaks arise from exposure to drinking water (1) or recreational water (2), whereas others are caused by an environmental exposure to water or an undetermined exposure to water. During 2013-2014, 15 outbreaks associated with an environmental exposure to water and 12 outbreaks with an undetermined exposure to water were reported, resulting in at least 289 cases of illness, 108 hospitalizations, and 17 deaths. Legionella was responsible for 63% of the outbreaks, 94% of hospitalizations, and all deaths. Outbreaks were also caused by Cryptosporidium, Pseudomonas, and Giardia, including six outbreaks of giardiasis caused by ingestion of water from a river, stream, or spring. Water management programs can effectively prevent outbreaks caused by environmental exposure to water from human-made water systems, while proper point-of-use treatment of water can prevent outbreaks caused by ingestion of water from natural water systems.

Human milk contains many bioactive components, including secretory IgA, oligosaccharides, and milk-associated proteins. We assessed the antiviral effects of several components of milk against mammalian reoviruses. We found that glucocerebroside (GCB) inhibited the infectivity of reovirus strain type 1 Lang (T1L), whereas gangliosides GD3 and GM3 and 3'-sialyllactose (3SL) inhibited the infectivity of reovirus strain type 3 Dearing (T3D). Agglutination of erythrocytes mediated by T1L and T3D was inhibited by GD3, GM3, and bovine lactoferrin. Additionally, α-sialic acid, 3SL, 6'-sialyllactose, sialic acid, human lactoferrin, osteopontin, and α-lactalbumin inhibited hemagglutination mediated by T3D. Using single-gene reassortant viruses, we found that serotype-specific differences segregate with the gene encoding the viral attachment protein. Furthermore, GD3, GM3, and 3SL inhibit T3D infectivity by blocking binding to host cells, whereas GCB inhibits T1L infectivity post-attachment. These results enhance an understanding of reovirus cell attachment and define a mechanism for the antimicrobial activity of human milk., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The cathepsin family of endosomal proteases is required for proteolytic processing of several viruses during entry into host cells. Mammalian reoviruses utilize cathepsins B (Ctsb), L (Ctsl), and S (Ctss) for disassembly of the virus outer capsid and activation of the membrane penetration machinery. To determine whether cathepsins contribute to reovirus tropism, spread, and disease outcome, we infected 3-day-old wild-type (wt), Ctsb(-/-), Ctsl(-/-), and Ctss(-/-) mice with the virulent reovirus strain T3SA+. The survival rate of Ctsb(-/-) mice was enhanced in comparison to that of wt mice, whereas the survival rates of Ctsl(-/-) and Ctss(-/-) mice were diminished. Peak titers at sites of secondary replication in all strains of cathepsin-deficient mice were lower than those in wt mice. Clearance of the virus was delayed in Ctsl(-/-) and Ctss(-/-) mice in comparison to the levels for wt and Ctsb(-/-) mice, consistent with a defect in cell-mediated immunity in mice lacking cathepsin L or S. Cathepsin expression was dispensable for establishment of viremia, but cathepsin L was required for maximal reovirus growth in the brain. Treatment of wt mice with an inhibitor of cathepsin L led to amelioration of reovirus infection. Collectively, these data indicate that cathepsins B, L, and S influence reovirus pathogenesis and suggest that pharmacologic modulation of cathepsin activity diminishes reovirus disease severity.