Hepatitis C Virus Infection Preceding an Outbreak of Human Immunodeficiency Virus Among Persons Who Inject Drugs-Kanawha County, West Virginia, 2019-2021.

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.

Transmitted Drug Resistance Among Human Immunodeficiency Virus (HIV)-1 Diagnoses in the United States, 2014-2018.

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.

Epidemiologic and Clinical Features of Mpox in Transgender and Gender-Diverse Adults - United States, May-November 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.

Notes from the Field: HIV Outbreak During the COVID-19 Pandemic Among Persons Who Inject Drugs - Kanawha County, West Virginia, 2019-2021.

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.

Monkeypox Outbreak - Nine States, May 2022.

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.¶.

Communicating During an HIV Outbreak Among People Who Inject Drugs-West Virginia 2019.

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.

Responding to Outbreaks of Human Immunodeficiency Virus Among Persons Who Inject Drugs-United States, 2016-2019: Perspectives on Recent Experience and Lessons Learned.

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.

Human Immunodeficiency Virus (HIV) Outbreak Investigation Among Persons Who Inject Drugs in Massachusetts Enhanced by HIV Sequence Data.

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.

Shigella sonnei Outbreak Investigation During a Municipal Water Crisis-Genesee and Saginaw Counties, Michigan, 2016.

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.

Waterborne Disease Outbreaks Associated With Environmental and Undetermined Exposures to Water - United States, 2013-2014.

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.

Influenza-Like Illness Among Personnel Responding to U.S. Quarantine of Cruise Ship Passengers Exposed to SARS-CoV-2.

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.

Syringe Services Programs' Role in Ending the HIV Epidemic in the U.S.: Why We Cannot Do It Without Them.

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.

HIV Cluster and Outbreak Detection and Response: The Science and Experience.

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.

Increasing Capacity to Detect Clusters of Rapid HIV Transmission in Varied Populations-United States.

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.

Response to a Large HIV Outbreak, Cabell County, West Virginia, 2018-2019.

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.

Genetic and pharmacologic alteration of cathepsin expression influences reovirus pathogenesis.

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.