IMPORTANCE: Respiratory syncytial virus (RSV) infection can cause severe illness in adults. However, there is considerable uncertainty in the burden of RSV-associated hospitalizations among adults prior to RSV vaccine introduction. OBJECTIVE: To describe the demographic characteristics of adults hospitalized with laboratory-confirmed RSV and to estimate annual rates and numbers of RSV-associated hospitalizations, intensive care unit (ICU) admissions, and in-hospital deaths. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the RSV Hospitalization Surveillance Network (RSV-NET), a population-based surveillance platform that captures RSV-associated hospitalizations in 58 counties in 12 states, covering approximately 8% of the US population. The study period spanned 7 surveillance seasons from 2016-2017 through 2022-2023. Included cases from RSV-NET were nonpregnant hospitalized adults aged 18 years or older residing in the surveillance catchment area and with a positive RSV test result. EXPOSURE: Laboratory-confirmed RSV-associated hospitalization, defined as a positive RSV test result within 14 days before or during hospitalization. MAIN OUTCOMES AND MEASURES: Hospitalization rates per 100 000 adult population, stratified by age group. After adjusting for test sensitivity and undertesting for RSV in adults hospitalized with acute respiratory illnesses, rates were extrapolated to the US population to estimate annual numbers of RSV-associated hospitalizations. Clinical outcome data were used to estimate RSV-associated ICU admissions and in-hospital deaths. RESULTS: From the 2016 to 2017 through the 2022 to 2023 RSV seasons, there were 16 575 RSV-associated hospitalizations in adults (median [IQR] age, 70 [58-81] years; 9641 females [58.2%]). Excluding the 2020 to 2021 and the 2021 to 2022 seasons, when the COVID-19 pandemic affected RSV circulation, hospitalization rates ranged from 48.9 (95% CI, 33.4-91.5) per 100 000 adults in 2016 to 2017 to 76.2 (95% CI, 55.2-122.7) per 100 000 adults in 2017 to 2018. Rates were lowest among adults aged 18 to 49 years (8.6 [95% CI, 5.7-16.8] per 100 000 adults in 2016-2017 to 13.1 [95% CI, 11.0-16.1] per 100 000 adults in 2022-2023) and highest among adults 75 years or older (244.7 [95% CI, 207.9-297.3] per 100 000 adults in 2022-2023 to 411.4 [95% CI, 292.1-695.4] per 100 000 adults in 2017-2018). Annual hospitalization estimates ranged from 123 000 (95% CI, 84 000-230 000) in 2016 to 2017 to 193 000 (95% CI, 140 000-311 000) in 2017 to 2018. Annual ICU admission estimates ranged from 24 400 (95% CI, 16 700-44 800) to 34 900 (95% CI, 25 500-55 600) for the same seasons. Estimated annual in-hospital deaths ranged from 4680 (95% CI, 3570-6820) in 2018 to 2019 to 8620 (95% CI, 6220-14 090) in 2017 to 2018. Adults 75 years or older accounted for 45.6% (range, 43.1%-48.8%) of all RSV-associated hospitalizations, 38.6% (range, 36.7%-41.0%) of all ICU admissions, and 58.7% (range, 51.9%-67.1%) of all in-hospital deaths. CONCLUSIONS AND RELEVANCE: In this cross-sectional study of adults hospitalized with RSV before the 2023 introduction of RSV vaccines, RSV was associated with substantial burden of hospitalizations, ICU admissions, and in-hospital deaths in adults, with the highest rates occurring in adults 75 years or older. Increasing RSV vaccination of older adults has the potential to reduce associated hospitalizations and severe clinical outcomes.

BACKGROUND: Screening for SARS-CoV-2 infection among hospital admissions made interpretation of COVID-19 hospitalization data challenging as SARS-CoV-2-positive persons with mild or asymptomatic infection may be incorrectly identified as COVID-19-associated hospitalizations. The study objective is to estimate the proportion of hospitalizations likely attributable to COVID-19 among SARS-CoV-2-positive hospitalized patients. METHODS: A sample of laboratory-confirmed SARS-CoV-2-positive hospitalizations from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) from June 2020 to September 2023 was analyzed, with a focus on July 2022 to September 2023. Likely COVID-19-attributable hospitalizations were defined as hospitalizations among SARS-CoV-2-positive non-pregnant adults ages ≥ 18 years with COVID-19-related presenting complaint, treatment, or discharge diagnosis. RESULTS: Among 44,816 sampled hospitalizations, 90% met the definition of likely COVID-19-attributable. Among the 9866 admissions occurring during July 2022 to September 2023, 86% were likely COVID-19-attributable; 87% had a COVID-19-related presenting complaint, 64% received steroids or COVID-19-related treatment, 47% had respiratory- and 10% had coagulopathy-related discharge diagnoses, and 39% had COVID-19 as the principal discharge diagnosis code. More than 70% met ≥ 2 criteria. Compared with likely COVID-19-attributable hospitalizations, SARS-CoV-2-positive patients who did not meet the case definition were more likely to be ages 18-49 years (27% vs. 13%), have no underlying medical conditions (14% vs. 4%), or be asymptomatic for COVID-19 upon admission (46% vs. 10%) (all p < 0.05). CONCLUSIONS: Most hospitalizations among SARS-CoV-2-positive adults in a recent period were likely attributable to COVID-19. COVID-19-attributable hospitalizations are less common among younger SARS-CoV-2-positive hospitalized adults but still account for nearly three quarters of all admissions among SARS-CoV-2-positive adults in this age group.

BACKGROUND: Respiratory syncytial virus (RSV) can cause severe disease among infants and older adults. Less is known about RSV among pregnant women. METHODS: To analyze hospitalizations with laboratory-confirmed RSV among women aged 18 to 49 years, we used data from the RSV Hospitalization Surveillance Network (RSV-NET), a multistate population-based surveillance system. Specifically, we compared characteristics and outcomes among (1) pregnant and nonpregnant women during the pre-COVID-19 pandemic period (2014-2018), (2) pregnant women with respiratory symptoms during the prepandemic and pandemic periods (2021-2023), and (3) pregnant women with and without respiratory symptoms in the pandemic period. Using multivariable logistic regression, we examined whether pregnancy was a risk factor for severe outcomes (intensive care unit admission or in-hospital death) among women aged 18 to 49 years who were hospitalized with RSV prepandemic. RESULTS: Prepandemic, 387 women aged 18 to 49 years were hospitalized with RSV. Of those, 350 (90.4%) had respiratory symptoms, among whom 33 (9.4%) were pregnant. Five (15.2%) pregnant women and 74 (23.3%) nonpregnant women were admitted to the intensive care unit; no pregnant women and 5 (1.6%) nonpregnant women died. Among 279 hospitalized pregnant women, 41 were identified prepandemic and 238 during the pandemic: 80.5% and 35.3% had respiratory symptoms, respectively (P < .001). Pregnant women were more likely to deliver during their RSV-associated hospitalization during the pandemic vs the prepandemic period (73.1% vs 43.9%, P < .001). CONCLUSIONS: Few pregnant women had severe RSV disease, and pregnancy was not a risk factor for a severe outcome. More asymptomatic pregnant women were identified during the pandemic, likely due to changes in testing practices for RSV.

To assess the importance of index testing in HIV case finding, we analyzed quarterly data from October 2019 to September 2021 from 371 facilities in 12 districts in South Africa. Index testing accounted for 2.6% of all HIV tests (index and non-index) (n = 163,633), but 17.8% of all HIV-positive results, with an HIV-positivity 4-times higher than non-index testing modalities (4.1%). Despite twice as many adult females ≥ 15 years accepting index testing (n = 206,715) compared to adult males ≥ 15 years (n = 102,180), females identified fewer contacts (n = 91,123) than males (n = 113,939). Slightly more than half (51.2%) of all contacts elicited were tested (n = 163,633/319,680), while 19.7% (n = 62,978) of elicited contacts were previously diagnosed as HIV-positive and not eligible for further testing. These findings indicate index testing can be effective in increasing HIV diagnoses in South Africa. Further operational research is needed to address gaps identified in the index testing cascade, including elicitation and testing of contacts.

In 2016, CDC identified a multidrug-resistant (MDR) strain of Salmonella enterica serotype Newport that is now monitored as a persisting strain (REPJJP01). Isolates have been obtained from U.S. residents in all 50 states and the District of Columbia, linked to travel to Mexico, consumption of beef products obtained in the United States, or cheese obtained in Mexico. In 2021, the number of isolates of this strain approximately doubled compared with the 2018-2020 baseline and remained high in 2022. During January 1, 2021- December 31, 2022, a total of 1,308 isolates were obtained from patients, cattle, and sheep; 86% were MDR, most with decreased susceptibility to azithromycin. Approximately one half of patients were Hispanic or Latino; nearly one half reported travel to Mexico during the month preceding illness, and one third were hospitalized. Two multistate outbreak investigations implicated beef products obtained in the United States. This highly resistant strain might spread through travelers, animals, imported foods, domestic foods, or other sources. Isolates from domestic and imported cattle slaughtered in the United States suggests a possible source of contamination. Safe food and drink consumption practices while traveling and interventions across the food production chain to ensure beef safety are necessary in preventing illness.

Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults. In May 2023, two RSV vaccines were approved for prevention of RSV lower respiratory tract disease in adults aged ≥60 years. In June 2023, CDC recommended RSV vaccination for adults aged ≥60 years, using shared clinical decision-making. Using data from the Respiratory Syncytial Virus-Associated Hospitalization Surveillance Network, a population-based hospitalization surveillance system operating in 12 states, this analysis examined characteristics (including age, underlying medical conditions, and clinical outcomes) of 3,218 adults aged ≥60 years who were hospitalized with laboratory-confirmed RSV infection during July 2022-June 2023. Among a random sample of 1,634 older adult patients with RSV-associated hospitalization, 54.1% were aged ≥75 years, and the most common underlying medical conditions were obesity, chronic obstructive pulmonary disease, congestive heart failure, and diabetes. Severe outcomes occurred in 18.5% (95% CI = 15.9%-21.2%) of hospitalized patients aged ≥60 years. Overall, 17.0% (95% CI = 14.5%-19.7%) of patients with RSV infection were admitted to an intensive care unit, 4.8% (95% CI = 3.5%-6.3%) required mechanical ventilation, and 4.7% (95% CI = 3.6%-6.1%) died; 17.2% (95% CI = 14.9%-19.8%) of all cases occurred in long-term care facility residents. These data highlight the importance of prioritizing those at highest risk for severe RSV disease and suggest that clinicians and patients consider age (particularly age ≥75 years), long-term care facility residence, and underlying medical conditions, including chronic obstructive pulmonary disease and congestive heart failure, in shared clinical decision-making when offering RSV vaccine to adults aged ≥60 years.

Adults aged ≥65 years remain at elevated risk for severe COVID-19 disease and have higher COVID-19-associated hospitalization rates compared with those in younger age groups. Data from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) were analyzed to estimate COVID-19-associated hospitalization rates during January-August 2023 and identify demographic and clinical characteristics of hospitalized patients aged ≥65 years during January-June 2023. Among adults aged ≥65 years, hospitalization rates more than doubled, from 6.8 per 100,000 during the week ending July 15 to 16.4 per 100,000 during the week ending August 26, 2023. Across all age groups, adults aged ≥65 years accounted for 62.9% (95% CI = 60.1%-65.7%) of COVID-19-associated hospitalizations, 61.3% (95% CI = 54.7%-67.6%) of intensive care unit admissions, and 87.9% (95% CI = 80.5%-93.2%) of in-hospital deaths associated with COVID-19 hospitalizations. Most hospitalized adults aged ≥65 years (90.3%; 95% CI = 87.2%-92.8%) had multiple underlying conditions, and fewer than one quarter (23.5%; 95% CI = 19.5%-27.7%) had received the recommended COVID-19 bivalent vaccine. Because adults aged ≥65 years remain at increased risk for COVID-19-associated hospitalization and severe outcomes, guidance for this age group should continue to focus on measures to prevent SARS-CoV-2 infection, encourage vaccination, and promote early treatment for persons who receive a positive SARS-CoV-2 test result to reduce their risk for severe COVID-19-associated outcomes.

Enterovirus D68 (EV-D68) has been implicated in outbreaks of severe respiratory illness and acute flaccid myelitis (AFM) and is detected in patient respiratory samples and from stool and wastewater, suggesting both respiratory and enteric routes of transmission. Here, we used a panel of EV-D68 isolates, including a historical isolate and multiple contemporary isolates from AFM outbreak years, to define the dynamics of viral replication and the host response to infection in primary human airway cells and stem cell-derived enteroids. We show that some recent EV-D68 isolates have decreased sensitivity to acid and temperature compared with an earlier isolate and that the respiratory, but not intestinal, epithelium induces a robust type III interferon (IFN) response that restricts infection. Our findings define the differential responses of the respiratory and intestinal epithelium to contemporary EV-D68 isolates and suggest that some isolates have the potential to target both the human airway and gastrointestinal tracts.Competing Interest StatementThe authors have declared no competing interest.

Coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other viruses is inevitable as the COVID-19 pandemic continues. This study aimed to evaluate cell lines commonly used in virus diagnosis and isolation for their susceptibility to SARS-CoV-2. While multiple kidney cell lines from monkeys were susceptible and permissive to SARS-CoV-2, many cell types derived from human, dog, mink, cat, mouse, or chicken were not. Analysis of MDCK cells, which are most commonly used for surveillance and study of influenza viruses, demonstrated that they were insusceptible to SARS-CoV-2 and that the cellular barrier to productive infection was due to low expression level of the angiotensin converting enzyme 2 (ACE2) receptor and lower receptor affinity to SARS-CoV-2 spike, which could be overcome by over-expression of canine ACE2 in trans. Moreover, SARS-CoV-2 cell tropism did not appear to be affected by a D614G mutation in the spike protein.Competing Interest StatementThe authors have declared no competing interest.

In August 2016, the Wisconsin Department of Health Services notified the U.S. Centers for Disease Control and Prevention of multidrug-resistant (MDR) Salmonella enterica serovar Heidelberg infections in people who reported contact with dairy calves. Federal and state partners investigated this to identify the source and scope of the outbreak and to prevent further illnesses. Cases were defined as human Salmonella Heidelberg infection caused by a strain that had one of seven pulsed-field gel electrophoresis (PFGE) patterns or was related by whole genome sequencing (WGS), with illness onset from January 1, 2015, through July 2, 2018. Patient exposure and calf purchase information was collected and analyzed; calves were traced back from the point of purchase. Isolates obtained from animal and environmental samples collected on-farm were supplied by veterinary diagnostic laboratories and compared with patient isolates using PFGE and WGS. Antimicrobial susceptibility testing by standardized broth microdilution was performed. Sixty-eight patients from 17 states were identified. Forty (63%) of 64 patients noted cattle contact before illness. Thirteen (33%) of 40 patients with exposure to calves reported that calves were sick or had died. Seven individuals purchased calves from a single Wisconsin livestock market. One hundred forty cattle from 14 states were infected with the outbreak strain. WGS indicated that human, cattle, and environmental isolates from the livestock market were genetically closely related. Most isolates (88%) had resistance or reduced susceptibility to antibiotics of ≥5 antibiotic classes. This resistance profile included first-line antibiotic treatments for patients with severe salmonellosis, including ampicillin, ceftriaxone, and ciprofloxacin. In this outbreak, MDR Salmonella Heidelberg likely spread from sick calves to humans, emphasizing the importance of illness surveillance in animal populations to prevent future spillover of this zoonotic disease.

IMPORTANCE: People who have been infected with or vaccinated against SARS-CoV-2 have reduced risk of subsequent infection, but the proportion of people in the US with SARS-CoV-2 antibodies from infection or vaccination is uncertain. OBJECTIVE: To estimate trends in SARS-CoV-2 seroprevalence related to infection and vaccination in the US population. DESIGN, SETTING, AND PARTICIPANTS: In a repeated cross-sectional study conducted each month during July 2020 through May 2021, 17 blood collection organizations with blood donations from all 50 US states; Washington, DC; and Puerto Rico were organized into 66 study-specific regions, representing a catchment of 74% of the US population. For each study region, specimens from a median of approximately 2000 blood donors were selected and tested each month; a total of 1 594 363 specimens were initially selected and tested. The final date of blood donation collection was May 31, 2021. EXPOSURE: Calendar time. MAIN OUTCOMES AND MEASURES: Proportion of persons with detectable SARS-CoV-2 spike and nucleocapsid antibodies. Seroprevalence was weighted for demographic differences between the blood donor sample and general population. Infection-induced seroprevalence was defined as the prevalence of the population with both spike and nucleocapsid antibodies. Combined infection- and vaccination-induced seroprevalence was defined as the prevalence of the population with spike antibodies. The seroprevalence estimates were compared with cumulative COVID-19 case report incidence rates. RESULTS: Among 1 443 519 specimens included, 733 052 (50.8%) were from women, 174 842 (12.1%) were from persons aged 16 to 29 years, 292 258 (20.2%) were from persons aged 65 years and older, 36 654 (2.5%) were from non-Hispanic Black persons, and 88 773 (6.1%) were from Hispanic persons. The overall infection-induced SARS-CoV-2 seroprevalence estimate increased from 3.5% (95% CI, 3.2%-3.8%) in July 2020 to 20.2% (95% CI, 19.9%-20.6%) in May 2021; the combined infection- and vaccination-induced seroprevalence estimate in May 2021 was 83.3% (95% CI, 82.9%-83.7%). By May 2021, 2.1 SARS-CoV-2 infections (95% CI, 2.0-2.1) per reported COVID-19 case were estimated to have occurred. CONCLUSIONS AND RELEVANCE: Based on a sample of blood donations in the US from July 2020 through May 2021, vaccine- and infection-induced SARS-CoV-2 seroprevalence increased over time and varied by age, race and ethnicity, and geographic region. Despite weighting to adjust for demographic differences, these findings from a national sample of blood donors may not be representative of the entire US population.

Enterovirus D68 (EV-D68) has been implicated in outbreaks of severe respiratory illness and is associated with acute flaccid myelitis (AFM). EV-D68 is often detected in patient respiratory samples but has also been detected in stool and wastewater, suggesting the potential for both respiratory and enteric routes of transmission. Here, we used a panel of EV-D68 isolates, including a historical pre-2014 isolate and multiple contemporary isolates from AFM outbreak years, to define the dynamics of viral replication and the host response to infection in primary human airway cells and stem cell-derived enteroids. We show that some recent EV-D68 isolates have decreased sensitivity to acid and temperature compared with earlier isolates and that the respiratory, but not intestinal, epithelium induces a robust type III interferon (IFN) response that restricts infection. Our findings define the differential responses of the respiratory and intestinal epithelium to contemporary EV-D68 isolates and suggest that a subset of isolates have the potential to target both the human airway and gastrointestinal tracts.

Co-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other viruses has been reported. We evaluated cell lines commonly used to isolate viruses and diagnose related diseases for their susceptibility to SARS-CoV-2. Although multiple kidney cell lines from monkeys were susceptible to SARS-CoV-2, we found many cell types derived from humans, dogs, minks, cats, mice, and chicken were not. We analyzed MDCK cells, which are most commonly used for surveillance and study of influenza viruses, and found that they were not susceptible to SARS-CoV-2. The low expression level of the angiotensin converting enzyme 2 receptor and lower receptor affinity to SARS-CoV-2 spike, which could be overcome by overexpression of canine angiotensin converting enzyme 2 in trans, strengthened the cellular barrier to productive infection. Moreover, a D614G mutation in the spike protein did not appear to affect SARS-CoV-2 cell tropism. Our findings should help avert inadvertent propagation of SARS-CoV-2 from diagnostic cell lines.

BACKGROUND: In 2004, in response to high levels of treatment failure associated with sulfadoxine-pyrimethamine (SP) resistance, Benin changed its first-line malaria treatment from SP to artemisinin-based combination therapy for treatment of uncomplicated Plasmodium falciparum malaria. Resistance to SP is conferred by accumulation of single nucleotide polymorphisms (SNPs) in P. falciparum genes involved in folate metabolism, dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps), targeted by pyrimethamine and sulfadoxine, respectively. Because SP is still used for intermittent preventive treatment in pregnant women (IPTp) and seasonal malaria chemoprevention (SMCP) in Benin, the prevalence of Pfdhfr and Pfdhps SNPs in P. falciparum isolates collected in 2017 were investigated. METHODS: This study was carried out in two sites where the transmission of P. falciparum malaria is hyper-endemic: Klouékanmey and Djougou. Blood samples were collected from 178 febrile children 6-59 months old with confirmed uncomplicated P. falciparum malaria and were genotyped for SNPs associated with SP resistance. RESULTS: The Pfdhfr triple mutant IRN (N51I, C59R, and S108N) was the most prevalent (84.6%) haplotype and was commonly found with the Pfdhps single mutant A437G (50.5%) or with the Pfdhps double mutant S436A and A437G (33.7%). The quintuple mutant, Pfdhfr IRN/Pfdhps GE (A437G and K540E), was rarely observed (0.8%). The A581G and A613S mutant alleles were found in 2.6 and 3.9% of isolates, respectively. Six isolates (3.9%) were shown to harbour a mutation at codon I431V, recently identified in West African parasites. CONCLUSIONS: This study showed that Pfdhfr triple IRN mutants are near fixation in this population and that the highly sulfadoxine-resistant Pfdhps alleles are not widespread in Benin. These data support the continued use of SP for chemoprevention in these study sites, which should be complemented by periodic nationwide molecular surveillance to detect emergence of resistant genotypes.

BACKGROUND: SARS-CoV-2, the virus that causes COVID-19 disease, was first identified in Wuhan, China in December 2019, with subsequent worldwide spread. The first U.S. cases were identified in January 2020. METHODS: To determine if SARS-CoV-2 reactive antibodies were present in sera prior to the first identified case in the U.S. on January 19, 2020, residual archived samples from 7,389 routine blood donations collected by the American Red Cross from December 13, 2019 to January 17, 2020, from donors resident in nine states (California, Connecticut, Iowa, Massachusetts, Michigan, Oregon, Rhode Island, Washington, and Wisconsin) were tested at CDC for anti-SARS-CoV-2 antibodies. Specimens reactive by pan-immunoglobulin (pan Ig) enzyme linked immunosorbent assay (ELISA) against the full spike protein were tested by IgG and IgM ELISAs, microneutralization test, Ortho total Ig S1 ELISA, and receptor binding domain / Ace2 blocking activity assay. RESULTS: Of the 7,389 samples, 106 were reactive by pan Ig. Of these 106 specimens, 90 were available for further testing. Eighty four of 90 had neutralizing activity, 1 had S1 binding activity, and 1 had receptor binding domain / Ace2 blocking activity >50%, suggesting the presence of anti-SARS-CoV-2-reactive antibodies. Donations with reactivity occurred in all nine states. CONCLUSIONS: These findings suggest that SARS-CoV-2 may have been introduced into the United States prior to January 19, 2020.

Acute flaccid myelitis (AFM) is a serious neurological illness first recognized in the United States in 2014, with subsequent outbreaks every two years. Following extensive etiologic testing by multiple laboratories of hundreds of specimens collected from patients diagnosed with AFM, no consistent cause of AFM has been identified. However, viruses, including enteroviruses, have been implicated through detection in non-sterile site specimens and antibody studies. Cytokines and chemokines play important roles in the modulation of the innate and adaptive immune response to pathogens. In the current study, we measured levels of cytokines and chemokines in serum and CSF collected from confirmed AFM patients and non-AFM control patients, to identify unique biomarkers as potential hallmarks of AFM pathogenesis. Analysis of ratios of cytokines and chemokines in the CSF compared to the serum indicate that the pro-inflammatory cytokines/chemokines IP-10 and IL-6 were significantly elevated in AFM patients compared to non-AFM patients. These results may provide additional insight into potential etiologies, pathogenic mechanisms, and treatments for AFM.

Objective: Quadrivalent meningococcal conjugate vaccines (MenACWY) have been recommended routinely for adolescents since 2005; in 2015, serogroup B meningococcal (MenB) vaccines were recommended for persons aged 16-23 years based on individual clinical decision making. We surveyed college health providers or administrators to understand current meningococcal vaccine policies. Methods/Participants: In January 2017, we distributed a survey to 985 institutions in partnership with the American College Health Association to assess vaccination policies and outbreak response plans. Results: Overall, 352 (36%) institutions completed the survey. Most either required (N = 186, 53%) or recommended (N = 148, 42%) a meningococcal vaccine; only half (N = 167) had a policy specifically addressing MenB vaccines. Few institutions with a MenB vaccine policy required vaccination (N = 7, 4%); most recommended vaccination (N = 160, 96%). Conclusion: Most institutions have a meningococcal vaccination policy; however, there is substantial diversity in policies. Fewer schools have policies specifically addressing MenB vaccines.

Nearly half of HIV infections in the United States are concentrated among African Americans, and over half of new HIV infections occur in the South. African Americans have poorer outcomes in the entire continua of HIV and PrEP care. Complex social, structural, and behavioral factors contribute to our nation's alarming racial disparities in HIV infection, particularly in the Deep South. Despite the importance of faith, spirituality and religious practice in the lives of many African Americans, there has been little scientific investment exploring how African Americans' religious participation, faith and spirituality may impact our nation's HIV epidemic. This article summarizes the state of the science on this critical issue. We also identify opportunities for new scholarship on how faith, spirituality and religious participation may impact HIV care continuum outcomes in the South and call for greater federal research investment on these issues.

BACKGROUND: The study of Onchocerca volvulus has been limited by its host range, with only humans and non-human primates shown to be susceptible to the full life cycle infection. Small animal models that support the development of adult parasites have not been identified. METHODOLOGY/PRINCIPAL FINDINGS: We hypothesized that highly immunodeficient NSG mice would support the survival and maturation of O. volvulus and alteration of the host microenvironment through the addition of various human cells and tissues would further enhance the level of parasite maturation. NSG mice were humanized with: (1) umbilical cord derived CD34+ stem cells, (2) fetal derived liver, thymus and CD34+ stem cells or (3) primary human skeletal muscle cells. NSG and humanized NSG mice were infected with 100 O. volvulus infective larvae (L3) for 4 to 12 weeks. When necropsies of infected animals were performed, it was observed that parasites survived and developed throughout the infection time course. In each of the different humanized mouse models, worms matured from L3 to advanced fourth stage larvae, with both male and female organ development. In addition, worms increased in length by up to 4-fold. Serum and urine, collected from humanized mice for identification of potential biomarkers of infection, allowed for the identification of 10 O. volvulus-derived proteins found specifically in either the urine or the serum of the humanized O. volvulus-infected NSG mice. CONCLUSIONS/SIGNIFICANCE: The newly identified mouse models for onchocerciasis will enable the development of O. volvulus specific biomarkers, screening for new therapeutic approaches and potentially studying the human immune response to infection with O. volvulus.

Rotavirus is the leading global cause of diarrheal mortality for unvaccinated children under five years of age. The outer capsid of rotavirus virions consists of VP7 and VP4 proteins, which determine viral G and P types, respectively, and are primary targets of neutralizing antibodies. Successful vaccination depends upon generating broadly protective immune responses following exposure to rotaviruses presenting a limited number of G and P type antigens. Vaccine introduction resulted in decreased rotavirus disease burden but also coincided with emergence of uncommon G and P genotypes, including G12. To gain insight into the recent predominance of G12P[8] rotaviruses in the U.S., we evaluated 142 complete rotavirus genome sequences and metadata from 151 clinical specimens collected in Nashville, TN from 2011-2013 through the New Vaccine Surveillance Network. Circulating G12P[8] strains were found to share many segments with other locally circulating strains but to have distinct constellations. Phylogenetic analyses of G12 sequences and their geographic sources provided evidence for multiple separate introductions of G12 segments into Nashville, TN. Antigenic epitopes of VP7 proteins of G12P[8] strains circulating in Nashville, TN differ markedly from those of vaccine strains. Fully vaccinated children were found to be infected with G12P[8] strains more frequently than with other rotavirus genotypes. Multiple introductions and significant antigenic mismatch may in part explain the recent predominance of G12P[8] strains in the U.S. and emphasize need for continued monitoring of rotavirus vaccine efficacy against emerging rotavirus genotypes.IMPORTANCERotavirus is an important cause of childhood diarrheal disease worldwide. Two immunodominant proteins of rotavirus, VP7 and VP4, determine G and P genotypes, respectively. Recently, G12P[8] rotaviruses have become increasingly predominant. By analyzing rotavirus genome sequences from stool specimens obtained in Nashville, TN from 2011-2013 and globally circulating rotaviruses, we found evidence of multiple introductions of G12 genes into the area. Based on sequence polymorphisms, VP7 proteins of these viruses are predicted to present themselves very differently to the immune system compared to those of vaccine strains. Many of the sick children with G12P[8] rotavirus in their diarrheal stools also were fully vaccinated. Our findings emphasize the need for continued monitoring of circulating rotaviruses and the effectiveness of the vaccines against strains with emerging G and P genotypes.

Background: Neonatal herpes is a rare, devastating consequence of herpes simplex virus type 1 (HSV-1) or 2 (HSV-2) infection during pregnancy. The risk of neonatal infection is higher among pregnant women seronegative for HSV-1 or HSV-2 who acquire their first HSV infection near delivery. Methods: We estimated HSV-1 and HSV-2 seroprevalence among pregnant women aged 20-39 years in 1999-2014, assessed HSV seroprevalence changes between 1999-2006 and 2007-2014, and compared HSV seroprevalence between pregnant women and sexually active, non-pregnant women aged 20-39 years in 2007-2014 using National Health and Nutrition Examination Survey data. Results: Among pregnant women in 1999-2014, HSV-1 seroprevalence was 59.3%, HSV-2 seroprevalence was 21.1%, and HSV seronegativity was 30.6%. Between 1999-2006 and 2007-2014, HSV-1 and HSV-2 seroprevalence among pregnant women remained stable. However, among pregnant women with </=3 sex partners (approximately 40% of all pregnant women), seronegativity for both HSV-1 and HSV-2 increased from 35.6% to 51.4% (P<.05). In 2007-2014, non-pregnant women who were 1) unmarried, 2) living below poverty level, or 3) had >/=4 sex partners were more likely than pregnant women to be seronegative for both HSV-1 and HSV-2 (P<.05). Conclusions: HSV-1 and HSV-2 seroprevalence among U.S. pregnant women remained stable between 1999-2014. However, pregnant women with fewer sex partners were increasingly seronegative for both HSV-1 and HSV-2, indicating an increasing proportion of pregnant women who are vulnerable to primary HSV acquisition in pregnancy which confers an increased risk of transmitting HSV to their neonates.

Impoundments formed by microdams in rural areas of Africa are important sources of water for people, but they provide potential larval habitats for Anopheles (Diptera: Culicidae) mosquitoes that are vectors of malaria. To study this association, the perimeters of 31 microdam impoundments in western Kenya were sampled for Anopheles larvae in three zones (patches of floating and emergent vegetation, shorelines of open water, and aggregations of cattle hoofprints) across dry and rainy seasons. Of 3,169 larvae collected, most (86.8%) were collected in the rainy season. Of 2,403 larvae successfully reared to fourth instar or adult, nine species were identified; most (80.2%) were Anopheles arabiensis Patton, sampled from hoofprint zones in the rainy season. Other species collected were Anopheles coustani Laveran, Anopheles gambiae s.s. Giles, Anopheles funestus Giles, and Anopheles rivulorum Leeson, Anopheles pharoensis Theobald, Anopheles squamosus Theobald, Anopheles rufipes (Gough), and Anopheles ardensis (Theobald). Larvae of An. funestus were uncommon (1.5%) in both dry and rainy seasons and were confined to vegetated zones, suggesting that microdam impoundments are not primary habitats for this important vector species, although microdams may provide a dry season refuge habitat for malaria vectors, contributing to population persistence through the dry season. In this study, microdam impoundments clearly provided habitat for the malaria vector An. arabiensis in the rainy season, most of which was within the shallow apron side of the impoundments where people brought cattle for watering, resulting in compacted soil with aggregations of water-filled hoofprints. This observation suggests a potential conflict between public health concerns about malaria and people's need for stable and reliable sources of water.

Strongyloides stercoralis hyperinfection causes high mortality rates in humans, and, while hyperinfection can be induced by immunosuppressive glucocorticoids, the pathogenesis remains unknown. Since immunocompetent mice are resistant to infection with S. stercoralis, we hypothesized that NSG mice, which have a reduced innate immune response and lack adaptive immunity, would be susceptible to the infection and develop hyperinfection. Interestingly, despite the presence of large numbers of adult and first-stage larvae in S. stercoralis-infected NSG mice, no hyperinfection was observed even when the mice were treated with a monoclonal antibody to eliminate residual granulocyte activity. NSG mice were then infected with third-stage larvae and treated for 6 wk with methylprednisolone acetate (MPA), a synthetic glucocorticoid. MPA treatment of infected mice resulted in 50% mortality and caused a significant >10-fold increase in the number of parasitic female worms compared with infected untreated mice. In addition, autoinfective third-stage larvae, which initiate hyperinfection, were found in high numbers in MPA-treated, but not untreated, mice. Remarkably, treatment with Delta7-dafachronic acid, an agonist of the parasite nuclear receptor Ss-DAF-12, significantly reduced the worm burden in MPA-treated mice undergoing hyperinfection with S. stercoralis Overall, this study provides a useful mouse model for S. stercoralis autoinfection and suggests a therapeutic strategy for treating lethal hyperinfection.

Two serogroup B meningococcal (MenB) vaccines are currently licensed for use in persons aged 10-25 years in the United States. The two vaccines are MenB-FHbp (Trumenba, Pfizer, Inc.) (1) and MenB-4C (Bexsero, GlaxoSmithKline Biologicals, Inc.) (2). In February 2015, the Advisory Committee on Immunization Practices (ACIP) recommended use of MenB vaccines among certain groups of persons aged ≥10 years who are at increased risk for serogroup B meningococcal disease* (Category A) (3), and in June 2015, ACIP recommended that adolescents and young adults aged 16-23 years may be vaccinated with MenB vaccines to provide short-term protection against most strains of serogroup B meningococcal disease (Category Bdagger) (4). Consistent with the original Food and Drug Administration (FDA) licensure for the two available MenB vaccines, ACIP recommended either a 3-dose series of MenB-FHbp or a 2-dose series of MenB-4C. Either MenB vaccine can be used when indicated; ACIP does not state a product preference. The two MenB vaccines are not interchangeable; the same vaccine product must be used for all doses in a series. In April 2016, changes to the dosage and administration of MenB-FHbp were approved by FDA to allow for both a 2-dose series (administered at 0 and 6 months) and a 3-dose series (administered at 0, 1-2, and 6 months) (5,6). In addition, the package insert now states that the choice of dosing schedule depends on the patient's risk for exposure and susceptibility to serogroup B meningococcal disease. These recommendations are regarding use of the 2- and 3-dose schedules of MenB-FHbp vaccine (Trumenba) and replace previous ACIP recommendations for use of MenB-FHbp vaccine published in 2015 (3,4). Recommendations regarding use of MenB-4C (Bexsero) are unchanged (3,4).

BACKGROUND: Rectal STI coinfection models enhance the understanding of rectal HIV transmission risk factors. MATERIALS AND METHODS: Rhesus macaques (n=9) were exposed to one of three rectal Chlamydia trachomatis (CT) challenges: C. trachomatis L2 (CT-L2 ); C. trachomatis serovar E (CT-E), followed by CT-L2 ; or CT-E, treatment/clearance, then CT-L2 . Infections were monitored by PCR. Weekly blood and rectal secretion/lavage samples were collected for cytokine analyzes and/or epithelial sloughing, occult, and overt blood determinations. RESULTS: Chlamydial infections were successfully established in each animal, with varying degrees of persistence. Mucosal IL-1beta was upregulated in animals consecutively infected with CT-E then CT-L2 (P=.05). Epithelial sloughing was also significantly increased post-infection in this group (P=.0003). CONCLUSIONS: This study demonstrates successful rectal infection of rhesus macaques with CT-E and CT-L2 and describes measures of assessing rectal inflammation and pathology. Different infection strategies yield varying inflammatory and pathologic outcomes, providing well-described models for future SIV/SHIV susceptibility studies.

At its June 2016 meeting, the Advisory Committee on Immunization Practices (ACIP) recommended routine use of meningococcal conjugate vaccine (serogroups A, C, W, and Y; including MenACWY-D [Menactra, Sanofi Pasteur] or MenACWY-CRM [Menveo, GlaxoSmithKline]) for persons aged ≥2 months with human immunodeficiency virus (HIV) infection. ACIP has previously recommended routine vaccination of persons aged ≥2 months who have certain medical conditions that increase risk for meningococcal disease (1), including persons who have persistent (e.g., genetic) deficiencies in the complement pathway (e.g., C3, properdin, Factor D, Factor H, or C5-C9); persons receiving eculizumab (Soliris, Alexion Pharmaceuticals) for treatment of atypical hemolytic uremic syndrome or paroxysmal nocturnal hemoglobinuria (because the drug binds C5 and inhibits the terminal complement pathway); and persons with functional or anatomic asplenia (including persons with sickle cell disease). Routine vaccination with meningococcal conjugate vaccine is also recommended for all healthy adolescents in the United States (1). This report summarizes the evidence considered by ACIP in recommending vaccination for HIV-infected persons, and provides recommendations and guidance for use of meningococcal conjugate vaccines (serogroups A, C, W, and Y) among HIV-infected persons aged ≥2 months; the majority of meningococcal disease among HIV-infected persons is caused by these four serogroups.

BACKGROUND: Gonorrhea screening is recommended for women at risk and men who have sex with men; expanded screening is encouraged based on local epidemiology. In response to a substantial increase in gonorrhea cases at an urban medical center serving American Indians, gonorrhea screening of all sexually active patients aged 14 to 45 years was initiated in March 2013. We describe gonorrhea screening coverage and case finding before and after implementation of expanded screening. METHODS: In March 2013, provider training, electronic health record prompts, and bundled laboratory orders were implemented to facilitate gonorrhea screening of all sexually active patients aged 14 to 45 years. We assessed the proportions of patients screened and testing positive for gonorrhea in the 2 years before (March 2011–February 2012 [indicated as 2011], March 2012–February 2013 [2012]) and 1 year after (March 2013–February 2014 [2013]) expanded screening measures. RESULTS: Gonorrhea screening coverage increased from 22% (2012) to 38% (2013); coverage increased 50% among females and 202% among males. Screening coverage increased in nearly all clinics. Gonorrhea case finding increased 68% among females in 2013 (n = 104) compared with 2012 (n = 62), primarily among women aged 25 to 29 years. No corresponding increase in gonorrhea case finding occurred among males. Most increased case finding occurred in the emergency department. CONCLUSIONS: After introduction of expanded gonorrhea screening, there was a significant increase in gonorrhea screening coverage and a subsequent increase in gonorrhea case finding among females. Despite increased screening in all clinics, increased case finding only occurred in the emergency department.

BACKGROUND: The Centers for Disease Control and Prevention recommends annual sexually transmitted infection (STI) and HIV testing and counseling for men who have sex with men (MSM) in the United States. We estimated the annual total direct medical cost of providing recommended STI and HIV testing and counseling services for MSM in the United States. METHODS: We included costs for 9 STI (including anatomic site-specific) tests recommended by the Centers for Disease Control and Prevention (HIV, syphilis, gonorrhea, chlamydia, hepatitis B viral infection, and herpes simplex virus type 2), office visits, and counseling. We included nongenital tests for MSM with exposure at nongenital sites. All cost data were obtained from the 2012 MarketScan outpatient claims database. Men were defined as MSM if they had a male sex partner within the last 12 months, which was estimated at 2.9% (2.6%-3.2%) of the male population in a 2012 study. All costs were updated to 2014 US dollars. RESULTS: The estimated average costs were as follows: HIV ($18 [$9-$27]), hepatitis B viral infection ($23 [$12-$35]), syphilis ($8 [$4-$11]), gonorrhea and chlamydia ($45 [$22-$67]) per anatomic site), herpes simplex virus type 2 ($27 [$14-$41]), office visit ($100 [$50-$149]), and counseling ($29 [$15-$44]). We estimated that the total annual direct cost of a universal STI and HIV testing and counseling program was $1.1 billion ($473 million-$1.7 billion) for all MSM and $756 (range, $338-$1.2 billion) when excluding office visit cost. CONCLUSIONS: These estimates provide the potential costs associated with universal STI and HIV testing and counseling for MSM in the United States. This information may be useful in future cost and/or cost-effectiveness analyses that can be used to evaluate STI and HIV prevention efforts.

OBJECTIVE: To estimate prenatal sexually transmitted disease-human immunodeficiency virus (HIV) screening rates among insured women with prenatal care and the association of chlamydia and gonorrhea screening with Pap testing. METHODS: We estimated prenatal screening rates for syphilis, hepatitis B, HIV, chlamydia, and gonorrhea among women aged 15-44 years using a 2009-2010 U.S. administrative claims database that captures information for health services provided for both Medicaid- and commercially insured persons. Procedural and diagnostic codes were used to identify pregnant women with a live birth in 2010 with continuous insurance coverage at least 210 days before delivery and at least one typical prenatal blood test. Strengths of association between chlamydia and gonorrhea screening and Pap testing were measured using a chi test of independence. RESULTS: Among 98,709 Medicaid-insured pregnant women, 95,064 (96.3%) were screened for syphilis, 95,082 (96.3%) for hepatitis B, 81,339 (82.4%) for HIV, 82,047 (83.1%) for chlamydia, and 73,799 (74.8%) for gonorrhea. Among 266,012 commercially insured women, 260,079 (97.8%) were screened for syphilis, 257,675 (96.8%) for hepatitis B, 227,276 (85.4%) for HIV, 187,071 (70.3%) for chlamydia, and 182,400 (68.6%) for gonorrhea. Prenatal screening for chlamydia and gonorrhea among both groups of women was more likely to be performed if a Pap test was also done (P<.001). CONCLUSION: Prenatal screening for syphilis and hepatitis B was nearly universal among Medicaid- and commercially insured women; HIV screening rates were much lower and varied by insurance type and demographic characteristics. Chlamydia screening was suboptimal and most often occurred with Pap testing. LEVEL OF EVIDENCE: III.

BACKGROUND: Personal lubricant use is common during anal intercourse. Some water-based products with high osmolality and low pH can damage genital and rectal tissues, and the polymer polyquaternium 15 (PQ15) can enhance HIV replication in vitro. This has raised concerns that lubricants with such properties may increase STD/HIV infection risk, although in vivo evidence is scarce. We use a macaque model to evaluate rectal cytotoxicity and SHIV infection risk after use of a highly osmolar (>8,000 mOsm/kg) water-based lubricant with pH of 4.4, and containing PQ15. METHODS: Cytotoxicity was documented by measuring inflammatory cytokines and epithelial tissue sloughing during six weeks of repeated, non-traumatic lubricant or control buffer applications to rectum and anus. We measured susceptibility to SHIVSF162P3 infection by comparing virus doses needed for rectal infection in twenty-one macaques treated with lubricant or control buffer 30 minutes prior to virus exposure. RESULTS: Lubricant increased pro-inflammatory cytokines and tissue sloughing while control buffer (phosphate buffered saline; PBS) did not. However, the estimated AID50 (50% animal infectious dose) was not different in lubricant- and control buffer-treated macaques (p = 0.4467; logistic regression models). CONCLUSIONS: Although the test lubricant caused acute cytotoxicity in rectal tissues, it did not increase susceptibility to infection in this macaque model. Thus neither the lubricant-induced type/extent of inflammation nor the presence of PQ15 affected infection risk. This study constitutes a first step in the in vivo evaluation of lubricants with regards to HIV transmission.