HNRNPC haploinsufficiency affects alternative splicing of intellectual disability-associated genes and causes a neurodevelopmental disorder.

Heterogeneous nuclear ribonucleoprotein C (HNRNPC) is an essential, ubiquitously abundant protein involved in mRNA processing. Genetic variants in other members of the HNRNP family have been associated with neurodevelopmental disorders. Here, we describe 13 individuals with global developmental delay, intellectual disability, behavioral abnormalities, and subtle facial dysmorphology with heterozygous HNRNPC germline variants. Five of them bear an identical in-frame deletion of nine amino acids in the extreme C terminus. To study the effect of this recurrent variant as well as HNRNPC haploinsufficiency, we used induced pluripotent stem cells (iPSCs) and fibroblasts obtained from affected individuals. While protein localization and oligomerization were unaffected by the recurrent C-terminal deletion variant, total HNRNPC levels were decreased. Previously, reduced HNRNPC levels have been associated with changes in alternative splicing. Therefore, we performed a meta-analysis on published RNA-seq datasets of three different cell lines to identify a ubiquitous HNRNPC-dependent signature of alternative spliced exons. The identified signature was not only confirmed in fibroblasts obtained from an affected individual but also showed a significant enrichment for genes associated with intellectual disability. Hence, we assessed the effect of decreased and increased levels of HNRNPC on neuronal arborization and neuronal migration and found that either condition affects neuronal function. Taken together, our data indicate that HNRNPC haploinsufficiency affects alternative splicing of multiple intellectual disability-associated genes and that the developing brain is sensitive to aberrant levels of HNRNPC. Hence, our data strongly support the inclusion of HNRNPC to the family of HNRNP-related neurodevelopmental disorders.

Expanding the phenotype of children presenting with hypoventilation with biallelic TBCK pathogenic variants and literature review.

Individuals with biallelic TBCK pathogenic variants present in infancy with distinctive facial features, profound hypotonia, severe intellectual impairment and epilepsy. Although rare, it may mimic other neurogenetic disorders leading to extensive investigations. Improved understanding of the clinical phenotype can support early monitoring of complications due to respiratory insufficiency. We present six individuals who were found to have pathogenic biallelic TBCK variants. The clinico-radiological and diagnostic records were reviewed. Five individuals were diagnosed with hypoventilation, requiring respiratory support, highlighting the need for early respiratory surveillance. Characteristic brain imaging in our cohort included periventricular leukomalacia-like changes. We recommend screening for TBCK in hypotonic children with periventricular leukomalacia-like changes, particularly in the absence of prematurity.

Association of Pneumococcal Conjugate Vaccine Use With Hospitalized Pneumonia in Medicare Beneficiaries 65 Years or Older With and Without Medical Conditions, 2014 to 2017.

Importance: The association of 13-valent pneumococcal conjugate vaccine (PCV13) use with pneumonia hospitalization in older adults, especially those with underlying medical conditions, is not well described. Objective: To evaluate the association of PCV13 use with pneumonia, non-health care-associated (non-HA) pneumonia, and lobar pneumonia (LP) hospitalization among US Medicare beneficiaries 65 years or older. Design, Setting, and Participants: This cohort study with time-varying exposure assignment analyzed claims data from US Medicare beneficiaries 65 years or older enrolled in Parts A/B with a residence in the 50 US states or the District of Columbia by September 1, 2014. New Medicare Parts A/B beneficiaries within 6 months after their 65th birthday were continuously included in the cohort after September 1, 2014, and followed through December 31, 2017. Participants were censored if they died, changed enrollment status, or developed a study outcome. Most of the analyses were conducted from 2018 to 2019, and additional analyses were performed from 2021 to 2022. Exposures: Use of PCV13 vaccination 14 days or more before pneumonia hospitalization. Main Outcomes and Measures: Discrete-time survival models were used to estimate the incidence rate ratio (IRR) and number of pneumonia hospitalizations averted through PCV13 use. The adjusted IRR for the association of PCV13 vaccination with pneumonia hospitalization was used to estimate vaccine effectiveness (VE). Results: At the end of follow-up (December 2017), 24 121 625 beneficiaries (13 593 975 women [56.4%]; 418 005 [1.7%] Asian, 1 750 807 [4.8%] Black, 338 044 [1.4%] Hispanic, 111 508 [0.5%] Native American, and 20 700 948 [85.8%] White individuals) were in the cohort; 4 936 185 (20.5%) had received PCV13 only, and 10 646 220 (79.5%) had not received any pneumococcal vaccines. More than half of the beneficiaries in the cohort were younger than 75 years, White, and had either immunocompromising or chronic medical conditions. Coverage with PCV13 increased from 0.8% (September 2014) to 41.5% (December 2017). The VE for PCV13 was estimated at 6.7% (95% CI, 5.9%-7.5%) for pneumonia, 4.7% (95% CI, 3.9%-5.6%) for non-HA pneumonia, and 5.8% (95% CI, 2.6%-8.9%) for LP. From September 2014 through December 2017, an estimated 35 127 pneumonia (95% CI, 33 011-37 270), 24 643 non-HA pneumonia (95% CI, 22 761-26 552), and 1294 LP (95% CI, 797-1819) hospitalizations were averted through PCV13 use. Conclusions and Relevance: The study results suggest that PCV13 use was associated with reduced pneumonia hospitalization among Medicare beneficiaries 65 years or older, many of whom had underlying medical conditions. Increased PCV13 coverage and use of recently approved higher-valent pneumococcal conjugate vaccines may avert additional pneumonia hospitalizations in adults.

Expanding the phenotype of TAB2 variants and literature review.

TAB2 is a gene located on chromosome 6q25.1 and plays a key role in development of the heart. Existing literature describes congenital heart disease as a common recognized phenotype of TAB2 gene variants, with evidence of a distinct syndromic phenotype also existing beyond this. Here we describe 14 newly identified individuals with nine novel, pathogenic TAB2 variants. The majority of individuals were identified through the Deciphering Developmental Disorders study through trio whole exome sequencing. Eight individuals had de novo variants, the other six individuals were found to have maternally inherited, or likely maternally inherited, variants. Five individuals from the same family were identified following cardiac disease gene panel in the proband and subsequent targeted familial gene sequencing. The clinical features of this cohort were compared to the existing literature. Common clinical features include distinctive facial features, growth abnormalities, joint hypermobility, hypotonia, and developmental delay. Newly identified features included feeding difficulties, sleep problems, visual problems, genitourinary abnormality, and other anatomical variations. Here we report 14 new individuals, including novel TAB2 variants, in order to expand the emerging syndromic clinical phenotype and provide further genotype-phenotype correlation.

Further evidence for attenuated phenotype with variants in the BMPER gene causing DSD: Case report and literature review.

Diaphonospondylodysotosis (DSD) and ischiospinal dysostosis (ISD) are rare skeletal dysplasias with variants in the bone morphogenetic protein-binding endothelial regulator (BMPER). There is a continuum of clinical presentation, with DSD at the severe end of the spectrum whilst ISD is towards the milder end. Both are caused due to pathogenic variants in BMPER. Previous studies have reported 20 patients from 13 families. Common features in the cohort reported so far are spinal and rib anomalies but other findings illustrate phenotypic variation. Survival ranges from death within the neonatal period to alive and well at 19 years. We present three siblings with variable phenotype, adding to the evidence for a single definition of BMPER-related skeletal dysplasia. We highlight the need for ongoing care planning and guarded prognostication, with regular review by clinical teams.

Expanding the phenotype of HNRNPU-related neurodevelopmental disorder with emphasis on seizure phenotype and review of literature.

Pathogenic variants in heterogeneous nuclear ribonucleoprotein U (HNRNPU) results in a novel neurodevelopmental disorder recently delineated. Here, we report on 17 previously unpublished patients carrying HNRNPU pathogenic variants. All patients were found to harbor de novo loss-of-function variants except for one individual where the inheritance could not be determined, as a parent was unavailable for testing. All patients had seizures which started in early childhood, global developmental delay, intellectual disability, and dysmorphic features. In addition, hypotonia, behavioral abnormalities (such as autistic features, aggression, anxiety, and obsessive-compulsive behaviors), and cardiac (septal defects) and/or brain abnormalities (ventriculomegaly and corpus callosum thinning/agenesis) were frequently observed. We have noted four recurrent variants in the literature (c.1089G>A p.(Trp363*), c.706_707del p.(Glu236Thrfs*6), c.847_857del p.(Phe283Serfs*5), and c.1681dels p.(Gln561Serfs*45)).

Report of two children with global developmental delay in association with de novo TLK2 variant and literature review.

We describe clinical details, including novel findings, of two further children with the newly defined TLK2-related disorder. One patient was recruited to the Deciphering Developmental Delay (DDD) Study to identify underlying etiology of global developmental delay. The other was detected on whole-exome sequencing as part of second line investigations following normal microarray. Both patients were found to have de novo heterozygous pathogenic TLK2 variants. A novel c.6del p.(Glu3Lysfs*) loss-of-function frameshift variant was found in Patient 1. A c.1121+1G>A splice-donor variant was detected in Patient 2. TLK2-related neurodevelopmental disorder is a specific syndrome that has been recently described. Global developmental delay, behavioral problems, gastrointestinal disorders, and typical facial dysmorphism are common features. Neuropsychiatric disorders, ophthalmic, musculoskeletal and cranial abnormalities, as well as short stature, have also all been described. The novel findings we describe include sleep disturbance, nondifferentiation of lateral semi-circular canals (where asymmetric semi-circular canals were a feature in the previous cohort), vesico-ureteric reflux, and bilateral periauricular skin tags. Here, we report a novel TLK2 variant and previously undescribed features of TLK2-related disorder, to expand the clinical phenotype and provide further genotype-phenotype correlation.

Intrapartum group B Streptococcal prophylaxis and childhood weight gain.

OBJECTIVE: To determine the difference in rate of weight gain from birth to 5 years based on exposure to maternal group B streptococcal (GBS) intrapartum antibiotic prophylaxis (IAP). DESIGN: Retrospective cohort study of 13 804 infants. SETTING: Two perinatal centres and a primary paediatric care network in Philadelphia. PARTICIPANTS: Term infants born 2007-2012, followed longitudinally from birth to 5 years of age. EXPOSURES: GBS IAP defined as penicillin, ampicillin, cefazolin, clindamycin or vancomycin administered ≥4 hours prior to delivery to the mother. Reference infants were defined as born to mothers without (vaginal delivery) or with other (caesarean delivery) intrapartum antibiotic exposure. OUTCOMES: Difference in rate of weight change from birth to 5 years was assessed using longitudinal rate regression. Analysis was a priori stratified by delivery mode and adjusted for relevant covariates. RESULTS: GBS IAP was administered to mothers of 2444/13 804 (17.7%) children. GBS IAP-exposed children had a significantly elevated rate of weight gain in the first 5 years among vaginally-born (adjusted rate difference 1.44% (95% CI 0.3% to 2.6%)) and caesarean-born (3.52% (95% CI 1.9% to 5.2%)) children. At 5 years, the rate differences equated to an additional 0.24 kg among vaginally-born children and 0.60 kg among caesarean-born children. CONCLUSION: GBS-specific IAP was associated with a modest increase in rate of early childhood weight gain. GBS IAP is an effective intervention to prevent perinatal GBS disease-associated morbidity and mortality. However, these findings highlight the need to better understand effects of intrapartum antibiotic exposure on childhood growth and support efforts to develop alternate prevention strategies.

Intrapartum Antibiotic Exposure and Body Mass Index in Children.

BACKGROUND: Intrapartum antibiotic prophylaxis (IAP) reduces a newborn's risk of group B streptococcal infection (GBS) but may lead to an increased childhood body mass index (BMI). METHODS: This was a retrospective cohort study of infants (n = 223 431) born 2007-2015 in an integrated healthcare system. For vaginal delivery, we compared children exposed to GBS-IAP and to any other type or duration of intrapartum antibiotics to no antibiotic exposure. For cesarean delivery, we compared children exposed to GBS-IAP to those exposed to all other intrapartum antibiotics, including surgical prophylaxis. BMI over 5 years was compared using nonlinear multivariate models with B-spline functions, stratified by delivery mode and adjusted for demographics, maternal factors, breastfeeding, and childhood antibiotic exposure. RESULTS: In vaginal deliveries, GBS-IAP was associated with higher BMI from 0.5 to 5.0 years of age compared to no antibiotics (P < .0001 for all time points, ΔBMI at age 5 years 0.12 kg/m2, 95% confidence interval [CI]: .07-.16 kg/m2). Other antibiotics were associated with higher BMI from 0.3 to 5.0 years of age. In cesarean deliveries, GBS-IAP was associated with increased BMI from 0.7 years to 5.0 years of age (P < .05 for 0.7-0.8 years, P < .0001 for all other time points) compared to other antibiotics (ΔBMI at age 5 years 0.24 kg/m2, 95% CI: .14-.34 kg/m2). Breastfeeding did not modify these associations. CONCLUSIONS: GBS-IAP was associated with a small but sustained increase in BMI starting at very early age. This association highlights the need to better understand the effects of perinatal antibiotic exposure on childhood health.

Invasive Group A Streptococcal Infections Among People Who Inject Drugs and People Experiencing Homelessness in the United States, 2010-2017.

BACKGROUND: Reported outbreaks of invasive group A Streptococcus (iGAS) infections among people who inject drugs (PWID) and people experiencing homelessness (PEH) have increased, concurrent with rising US iGAS rates. We describe epidemiology among iGAS patients with these risk factors. METHODS: We analyzed iGAS infections from population-based Active Bacterial Core surveillance (ABCs) at 10 US sites from 2010 to 2017. Cases were defined as GAS isolated from a normally sterile site or from a wound in patients with necrotizing fasciitis or streptococcal toxic shock syndrome. GAS isolates were emm typed. We categorized iGAS patients into four categories: injection drug use (IDU) only, homelessness only, both, and neither. We calculated annual change in prevalence of these risk factors using log binomial regression models. We estimated national iGAS infection rates among PWID and PEH. RESULTS: We identified 12 386 iGAS cases; IDU, homelessness, or both were documented in ~13%. Skin infections and acute skin breakdown were common among iGAS patients with documented IDU or homelessness. Endocarditis was 10-fold more frequent among iGAS patients with documented IDU only versus those with neither risk factor. Average percentage yearly increase in prevalence of IDU and homelessness among iGAS patients was 17.5% and 20.0%, respectively. iGAS infection rates among people with documented IDU or homelessness were ~14-fold and 17- to 80-fold higher, respectively, than among people without those risks. CONCLUSIONS: IDU and homelessness likely contribute to increases in US incidence of iGAS infections. Improving management of skin breakdown and early recognition of skin infection could prevent iGAS infections in these patients.

Meningococcal carriage 7 years after introduction of a serogroup A meningococcal conjugate vaccine in Burkina Faso: results from four cross-sectional carriage surveys.

BACKGROUND: In the first 2 years after a nationwide mass vaccination campaign of 1-29-year-olds with a meningococcal serogroup A conjugate vaccine (MenAfriVac) in Burkina Faso, carriage and disease due to serogroup A Neisseria meningitidis were nearly eliminated. We aimed to assess the long-term effect of MenAfriVac vaccination on meningococcal carriage and herd immunity. METHODS: We did four cross-sectional studies of meningococcal carriage in people aged 9 months to 36 years in two districts of Burkina Faso between May 2, 2016, and Nov 6, 2017. Demographic information and oropharyngeal swabs were collected. Meningococcal isolates were characterised using whole-genome sequencing. FINDINGS: Of 14 295 eligible people, 13 758 consented and had specimens collected and laboratory results available, 1035 of whom were meningococcal carriers. Accounting for the complex survey design, prevalence of meningococcal carriage was 7·60% (95% CI 5·67-9·52), including 6·98% (4·86-9·11) non-groupable, 0·48% (0·01-0·95) serogroup W, 0·10% (0·01-0·18) serogroup C, 0·03% (0·00-0·80) serogroup E, and 0% serogroup A. Prevalence ranged from 5·44% (95% CI 4·18-6·69) to 9·14% (6·01-12·27) by district, from 4·67% (2·71-6·64) to 11·17% (6·75-15·59) by round, and from 3·39% (0·00-8·30) to 10·43% (8·08-12·79) by age group. By clonal complex, 822 (88%) of 934 non-groupable isolates were CC192, all 83 (100%) serogroup W isolates were CC11, and nine (69%) of 13 serogroup C isolates were CC10217. INTERPRETATION: Our results show the continued effect of MenAfriVac on serogroup A meningococcal carriage, for at least 7 years, among vaccinated and unvaccinated cohorts. Carriage prevalence of epidemic-prone serogroup C CC10217 and serogroup W CC11 was low. Continued monitoring of N meningitidis carriage will be crucial to further assess the effect of MenAfriVac and inform the vaccination strategy for future multivalent meningococcal vaccines. FUNDING: Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance.

Impact of 13-Valent Pneumococcal Conjugate Vaccine on Meningitis and Pneumonia Hospitalizations in Children aged <5 Years in Senegal, 2010-2016.

BACKGROUND: Senegal introduced a 13-valent pneumococcal conjugate vaccine (PCV13) in October 2013, given at 6, 10, and 14 weeks of age. We document trends of meningitis and pneumonia after the PCV13 introduction. METHODS: From October 2010-October 2016, hospitalization data for clinical meningitis and pneumonia in children aged <5 years were collected from logbooks at a large, tertiary, pediatric hospital in Dakar. We used a set of predetermined keywords to define hospitalizations for extraction from hospital registers. We conducted a time-series analysis and compared hospitalizations before and after the PCV13 introduction, accounting for seasonality. The initial PCV13 uptake period (October 2013-September 2014) was considered to be transitional and was excluded. RESULTS: Over the 7-year period, 1836 and 889 hospitalizations with a discharge diagnosis of pneumonia and meningitis, respectively, occurred in children aged <5 years. In children aged <12 months, a small, significant reduction in pneumonia was observed post-PCV13 (-3.8%, 95% confidence interval [CI] -1.5 to -5.9%). No decline was observed among children aged 12-59 months (-0.7%, 95% CI -0.8 to 2.2%). Meningitis hospitalizations remained stable for children aged <12 months (1.8%, 95% CI -0.9 to 4.4%) and 12-59 months (-0.5%, 95% CI -3.6 to 2.6%). CONCLUSIONS: We used data from 1 hospital to detect a small, significant reduction in all-cause pneumonia hospitalizations 2 years post-PCV13 introduction in infants; the same trend was not measurable in children aged 12-59 months or in meningitis cases. There is a need for continued surveillance to assess the long-term impact of sustained PCV13 use and to monitor how pneumococcus is causing disease in the meningitis belt.

Our health counts: population-based measures of urban Inuit health determinants, health status, and health care access.

OBJECTIVE: Health determinants and outcomes are not well described for the growing population of Inuit living in southern urban areas of Canada despite known and striking health disparities for Inuit living in the north. The objective of this study was to work in partnership with Tungasuvvingat Inuit (TI) to develop population prevalence estimates for key indicators of health, including health determinants, health status outcomes, and health services access for Inuit in Ottawa, Canada. METHODS: We employed community-based respondent driven sampling (RDS) and a comprehensive health assessment survey to collect primary data regarding health determinants, status, and service access. We then linked with datasets held by the Institute for Clinical Evaluative Sciences (ICES), including hospitalization, emergency room, and health screening records. Adjusted population-based prevalence estimates and rates were calculated using custom RDS software. RESULTS: We recruited 341 Inuit adults living in Ottawa. The number of Inuit living, working or accessing health and social services in the City of Ottawa was estimated to be 3361 (95% CI 2309-4959). This population experiences high rates of poverty, unemployment, household crowding, and food insecurity. Prevalence of hypertension (25%; 95% CI 18.1-33.9), chronic obstructive pulmonary disease (6.7%; 95% CI 3.1-10.6), cancer (6.8%; 95% CI 2.7-11.9), and rates of emergency room access were elevated for Inuit in Ottawa compared to the general population. Access to health services was rated fair or poor by 43%. Multiple barriers to health care access were identified. CONCLUSIONS: Urban Inuit experience a heavy burden of adverse health determinants and poor health status outcomes. According to urban Inuit in Ottawa, health services available to Inuit at the time of the study were inadequate.

HIV Infection and HIV-Associated Behaviors Among Persons Who Inject Drugs - 20 Cities, United States, 2015.

In the United States, 9% of human immunodeficiency virus (HIV) infections diagnosed in 2015 were attributed to injection drug use (1). In 2015, 79% of diagnoses of HIV infection among persons who inject drugs occurred in urban areas (2). To monitor the prevalence of HIV infection and associated behaviors among persons who inject drugs, CDC's National HIV Behavioral Surveillance (NHBS) conducts interviews and HIV testing in selected metropolitan statistical areas (MSAs) (3). The prevalence of HIV infection among persons who inject drugs in 20 MSAs in 2015 was 7%. In a behavioral analysis of HIV-negative persons who inject drugs, an estimated 27% receptively shared syringes and 67% had condomless vaginal sex in the previous 12 months. During the same period, 58% had tested for HIV infection and 52% received syringes from a syringe services program. Given the increased number of persons newly injecting drugs who are at risk for HIV infection because of the recent opioid epidemic (2,4), these findings underscore the importance of continuing and expanding health services, HIV prevention programs, and community-based strategies, such as those provided by syringe services programs, for this population.

Detailed Transmission Network Analysis of a Large Opiate-Driven Outbreak of HIV Infection in the United States.

In January 2015, an outbreak of undiagnosed human immunodeficiency virus (HIV) infections among persons who inject drugs (PWID) was recognized in rural Indiana. By September 2016, 205 persons in this community of approximately 4400 had received a diagnosis of HIV infection. We report results of new approaches to analyzing epidemiologic and laboratory data to understand transmission during this outbreak. HIV genetic distances were calculated using the polymerase region. Networks were generated using data about reported high-risk contacts, viral genetic similarity, and their most parsimonious combinations. Sample collection dates and recency assay results were used to infer dates of infection. Epidemiologic and laboratory data each generated large and dense networks. Integration of these data revealed subgroups with epidemiologic and genetic commonalities, one of which appeared to contain the earliest infections. Predicted infection dates suggest that transmission began in 2011, underwent explosive growth in mid-2014, and slowed after the declaration of a public health emergency. Results from this phylodynamic analysis suggest that the majority of infections had likely already occurred when the investigation began and that early transmission may have been associated with sexual activity and injection drug use. Early and sustained efforts are needed to detect infections and prevent or interrupt rapid transmission within networks of uninfected PWID.

Injection-Related Risk Behavior and Engagement in Outreach, Intervention and Prevention Services Across 20 US Cities.

BACKGROUND: Monitoring the effects of HIV prevention efforts on risk behaviors among persons who inject drugs is a key to inform prevention programs and policy. METHODS: Using data from the 2012 National HIV Behavioral Surveillance interviews with persons who inject drugs across 20 US cities (n = 10,171), we conducted latent class analysis to identify injection risk classes and assess the relationship between engagement in prevention services and injection-related risk behavior. We conducted stratified analyses to examine the consistency of these associations across different geographical regions. RESULTS: The latent class analysis identified 6 distinct classes of injection-related risk behavior. The class structure was consistent across regions of the United States, but the distribution of risk classes varied significantly across regions. With covariate adjustment, the South had the most high-risk behavior (21%) and the Midwest had the least (6%). Participation in syringe access services and other prevention services was the lowest in the South. Syringe access was associated with a significantly lower likelihood of membership in the highest risk class in all regions except the Midwest. Participation in individual or group intervention with a practical skills component was associated with less risky injection behavior in all regions except the Northeast. Interventions that featured only safer injection information and discussion had no relationship with risk class. CONCLUSIONS: Our findings support evidence of the effectiveness of syringe service programs and safer injection skills training in reducing high-risk injection behavior and underscore the need to improve access to these prevention interventions in the South of the United States.

HIV Infection Linked to Injection Use of Oxymorphone in Indiana, 2014-2015.

BACKGROUND: In January 2015, a total of 11 new diagnoses of human immunodeficiency virus (HIV) infection were reported in a small community in Indiana. We investigated the extent and cause of the outbreak and implemented control measures. METHODS: We identified an outbreak-related case as laboratory-confirmed HIV infection newly diagnosed after October 1, 2014, in a person who either resided in Scott County, Indiana, or was named by another case patient as a syringe-sharing or sexual partner. HIV polymerase (pol) sequences from case patients were phylogenetically analyzed, and potential risk factors associated with HIV infection were ascertained. RESULTS: From November 18, 2014, to November 1, 2015, HIV infection was diagnosed in 181 case patients. Most of these patients (87.8%) reported having injected the extended-release formulation of the prescription opioid oxymorphone, and 92.3% were coinfected with hepatitis C virus. Among 159 case patients who had an HIV type 1 pol gene sequence, 157 (98.7%) had sequences that were highly related, as determined by phylogenetic analyses. Contact tracing investigations led to the identification of 536 persons who were named as contacts of case patients; 468 of these contacts (87.3%) were located, assessed for risk, tested for HIV, and, if infected, linked to care. The number of times a contact was named as a syringe-sharing partner by a case patient was significantly associated with the risk of HIV infection (adjusted risk ratio for each time named, 1.9; P<0.001). In response to this outbreak, a public health emergency was declared on March 26, 2015, and a syringe-service program in Indiana was established for the first time. CONCLUSIONS: Injection-drug use of extended-release oxymorphone within a network of persons who inject drugs in Indiana led to the introduction and rapid transmission of HIV. (Funded by the state government of Indiana and others.).

Low HIV testing among persons who inject drugs-National HIV Behavioral Surveillance, 20 U.S. cities, 2012.

INTRODUCTION: Persons who inject drugs (PWID) continue to be disproportionately affected by HIV. HIV testing is key to reducing HIV transmission by increasing awareness of HIV status and linking HIV-positive persons to care. Using data from PWID participating in CDC's National HIV Behavioral Surveillance (NHBS) system, we examined prevalence of recent HIV testing among PWID by certain characteristics to guide interventions to increase HIV testing. METHODS: We analyzed NHBS data from PWID 18 years or older recruited via respondent-driven sampling in 20 US cities in 2012. We examined demographic and behavioral factors associated with recent HIV testing (within 12 months before interview) using a Poisson model to calculate adjusted prevalence ratios (aPRs). RESULTS: Of 9555 PWID, 53% had recently tested for HIV. In multivariable analysis, HIV testing was more frequent among participants who visited a healthcare provider (aPR 1.50, P<0.001), participated in alcohol or drug treatment (aPR 1.21, P<0.001), or received an HIV prevention intervention (aPR 1.26, P<0.001). HIV testing was also more frequent among participants who received free sterile syringes (aPR 1.12, P<0.001). DISCUSSION: Only half of PWID participating in NHBS in 2012 reported recent HIV testing. HIV testing was more frequent among participants who accessed health and HIV prevention services. To increase HIV testing among PWID, it is important for providers in healthcare and HIV prevention settings to proactively assess risk factors for HIV, including injection drug use, and offer a wide range of appropriate interventions, such as HIV testing.

Factors Associated With Recent Human Immunodeficiency Virus Testing Among Men Who Have Sex With Men in Puerto Rico, National Human Immunodeficiency Virus Behavioral Surveillance System, 2011.

BACKGROUND: Annual human immunodeficiency virus (HIV) testing is considered a key strategy for HIV prevention for men who have sex with men (MSM). In Puerto Rico, HIV research has primarily focused on injection drug use, yet male-to-male sexual transmission has been increasing in recent years. METHODS: Cross-sectional data from the National HIV Behavioral Surveillance system collected in 2011 in San Juan, Puerto Rico, were analyzed to identify factors associated with HIV testing in the past 12 months (recent testing). RESULTS: Overall, 50% of participants were tested recently. In the multivariate analysis, testing recently was associated with having multiple partners in the past 12 months (adjusted prevalence ratio [aPR] [≥4 vs 1 partner] = 1.5; 95% confidence interval [95% CI], 1.2-2.0), visiting a health care provider in the past 12 months (aPR, 1.4; 95% CI, 1.04-1.8), and disclosing male-male attraction/sex to a health care provider (aPR< 1.4; 95% CI, 1.1-1.7). CONCLUSIONS: Human immunodeficiency virus testing was suboptimal among MSM in San Juan. Strategies to increase HIV testing among MSM may include promoting HIV testing for all sexually active MSM including those with fewer partners, increasing utilization of the healthcare system, and improving patient-provider communication.