In 2006, human papillomavirus (HPV) vaccine was first recommended in the United States to prevent cancers and other diseases caused by HPV; vaccination coverage increased steadily through 2021, and increasing numbers of young women had received HPV vaccine as children or adolescents. Since 2008, CDC has monitored incidence of precancerous lesions (cervical intraepithelial neoplasia [CIN] grades 2-3 and adenocarcinoma in situ [AIS], collectively CIN2+), which are detected through cervical cancer screening and can be used as an intermediate outcome for monitoring vaccination impact, via the five-site Human Papillomavirus Vaccine Impact Monitoring Project. This analysis describes trends in incidence of CIN2+ and CIN3+ (i.e., CIN grade 3 and AIS) lesions during 2008-2022. Among women aged 20-24 years who were screened for cervical cancer, rates during 2008-2022 decreased for CIN2+ by 79%, and for CIN3+ by 80%. In the same period, CIN3+ rates among screened women aged 25-29 years decreased by 37%. These data are consistent with considerable impact of HPV vaccination for preventing cervical precancers among women in the age groups most likely to have been vaccinated, and support existing recommendations to vaccinate children at the routinely recommended ages as a cancer prevention measure.

Numerous studies have investigated vaccine-induced correlates of protection (CoP) against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, but data on infection-induced CoP are limited. Given differences between vaccine- and infection-induced immune responses, in conjunction with low vaccination in many US populations, a better understanding of infection-induced CoP is needed. We used residual sera from a mid-2020 Rhode Island serosurvey of healthcare professionals (HCP) and corresponding state-collected SARS-CoV-2 testing data through February 2021 to generate an analytic cohort of HCP with a first SARS-CoV-2 infection prior to serosurvey blood collection and multiple viral tests after blood collection to assess for reinfection (defined as a positive viral test ≥90 days after their first positive). We tested sera for levels of IgG and IgA targeting ancestral spike (S), receptor-binding domain (RBD), or nucleocapsid (N). We used adjusted Cox proportional hazard ratios to assess the association between categorical antibody level and the risk of subsequent reinfection. Among 170 HCP included in this analysis (median age = 47 years; interquartile range: 35-55 years), 30 were reinfected during the analytic period. Adjusted Cox proportional hazard ratios indicated that higher levels of anti-S or anti-RBD IgG were significantly associated with a lower risk of reinfection. These findings support the use of anti-S or anti-RBD IgG levels as markers of immunologic protection, such as in population serosurveys, or immune-bridging studies in settings of high prevalence of prior infection.  IMPORTANCEThe measurement of antibodies in blood is a relatively simple process and commonly used to estimate overall levels of past infection in populations. But, if someone has antibodies, does this mean that they are protected from being infected again? And are people with higher levels of antibody better protected? There are good data in the literature exploring how antibodies from the coronavirus disease 2019 (COVID-19) vaccination are associated with protection. But, there is still a lot to learn about protection conferred by antibodies that develop after a severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. In our study, we measure the levels of six different antibody types developed after infection and compare levels to the risk of subsequent infection to better understand which antibody types are best associated with protection. Our data are important for improving studies that use antibodies as proxies for protection, such as population immunity estimates, or those assessing new prevention products.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) introduced in childhood national immunization programs lowered vaccine-type invasive pneumococcal disease (IPD), but replacement with non-vaccine-types persisted throughout the PCV10/13 follow-up period. We assessed PCV10/13 impact on pneumococcal meningitis incidence globally. METHODS: The number of cases with serotyped pneumococci detected in cerebrospinal fluid and population denominators were obtained from surveillance sites globally. Site-specific meningitis incidence rate ratios (IRRs) comparing pre-PCV incidence to each year post-PCV10/13 were estimated by age (<5, 5-17 and ≥18 years) using Bayesian multi-level mixed effects Poisson regression, accounting for pre-PCV trends. All-site weighted average IRRs were estimated using linear mixed-effects regression stratified by age, product (PCV10 or PCV13) and prior PCV7 impact (none, moderate, or substantial). Changes in pneumococcal meningitis incidence were estimated overall and for product-specific vaccine-types and non-PCV13-types. RESULTS: Analyses included 10,168 cases <5 y from PCV13 sites and 2849 from PCV10 sites, 3711 and 1549 for 5-17 y and 29,187 and 5653 for ≥18 y from 42 surveillance sites (30 PCV13, 12 PCV10, 2 PCV10/13) in 30 countries, primarily high-income (84%). Six years after PCV10/PCV13 introduction, pneumococcal meningitis declined 48-74% across products and PCV7 impact strata for children <5 y, 35-62% for 5-17 y and 0-36% for ≥18 y. Impact against PCV10-types at PCV10 sites, and PCV13-types at PCV13 sites was high for all age groups (<5 y: 96-100%; 5-17 y: 77-85%; ≥18 y: 73-85%). After switching from PCV7 to PCV10/13, increases in non-PCV13-types were generally low to none for all age groups. CONCLUSION: Pneumococcal meningitis declined in all age groups following PCV10/PCV13 introduction. Plateaus in non-PCV13-type meningitis suggest less replacement than for all IPD. Data from meningitis belt and high-burden settings were limited.

The generation time, representing the interval between infections in primary and secondary cases, is essential for understanding and predicting the transmission dynamics of seasonal influenza, including the real-time effective reproduction number (Rt). However, comprehensive generation time estimates for seasonal influenza, especially since the 2009 influenza pandemic, are lacking. We estimated the generation time utilizing data from a 7-site case-ascertained household study in the United States over two influenza seasons, 2021/2022 and 2022/2023. More than 200 individuals who tested positive for influenza and their household contacts were enrolled within 7 days of the first illness in the household. All participants were prospectively followed for 10 days, completing daily symptom diaries and collecting nasal swabs, which were then tested for influenza via RT-PCR. We analyzed these data by modifying a previously published Bayesian data augmentation approach that imputes infection times of cases to obtain both intrinsic (assuming no susceptible depletion) and realized (observed within household) generation times. We assessed the robustness of the generation time estimate by varying the incubation period, and generated estimates of the proportion of transmission occurring before symptomatic onset, the infectious period, and the latent period. We estimated a mean intrinsic generation time of 3.2 (95 % credible interval, CrI: 2.9-3.6) days, with a realized household generation time of 2.8 (95 % CrI: 2.7-3.0) days. The generation time exhibited limited sensitivity to incubation period variation. Estimates of the proportion of transmission that occurred before symptom onset, the infectious period, and the latent period were sensitive to variations in the incubation period. Our study contributes to the ongoing efforts to refine estimates of the generation time for influenza. Our estimates, derived from recent data following the COVID-19 pandemic, are consistent with previous pre-pandemic estimates, and will be incorporated into real-time Rt estimation efforts.

BACKGROUND: Effective vector control interventions, notably insecticide-treated nets (ITNs) and indoor residual spraying (IRS) are indispensable for malaria control in Tanzania and elsewhere. However, the emergence of widespread insecticide resistance threatens the efficacy of these interventions. Monitoring of insecticide resistance is, therefore, critical for the selection and assessment of the programmatic impact of insecticide-based interventions. METHODS: The study was conducted country-wide across 22 sentinel districts of Tanzania between May and July 2023 using standard World Health Organization susceptibility test with 1×, 5×, and 10× of deltamethrin, permethrin, and alpha-cypermethrin and discriminating concentrations of 0.25% pirimiphos-methyl. Synergist assays were conducted to explore the underlying mechanisms of the observed phenotypic pyrethroid-resistant mosquitoes. Three- to five-day-old wild adult females in the first filiar generation of Anopheles gambiae sensu lato (s.l.) were used for the susceptibility bioassays. RESULTS: Anopheles gambiae s.l. were resistant to all pyrethroids at the discriminating dose in most sentinel districts except in Rorya, which remains fully susceptible, and Ushetu, which remains susceptible to deltamethrin but not permethrin. In 5 sites (Bukombe, Ukerewe, Kilwa, Kibondo, and Kakonko), the An. gambiae s.l. species exhibited strong resistance to pyrethroids surviving the 10 X concentrations (mortality rate < 98%). However, they remained fully susceptible to pirimiphos-methyl in almost all the sites except in Kibondo and Shinyanga. Likewise, there was full restoration to susceptibility to pyrethroid following pre-exposure of An. gambiae s.l. to piperonyl-butoxide (PBO) in 13 out of 16 sites. The 3 sites that exhibited partial restoration include Kakonko, Tandahimba, and Newala. CONCLUSION: The evidence of widespread pyrethroid resistance of the major malaria vector justifies the decision made by the Tanzania National Malaria Control Programme to transition to PBO-based ITNs. Without this switch, the gains achieved in malaria control could be compromised. Equally important, the lack of full restoration to susceptibility observed in three sentinel districts upon pre-exposure to PBO merits close monitoring, as there could be other underlying resistance mechanisms besides oxidase metabolic resistance.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) that are ten-valent (PCV10) and 13-valent (PCV13) became available in 2010. We evaluated their global impact on invasive pneumococcal disease (IPD) incidence in all ages. METHODS: Serotype-specific IPD cases and population denominators were obtained directly from surveillance sites using PCV10 or PCV13 in their national immunisation programmes and with a primary series uptake of at least 50%. Annual incidence rate ratios (IRRs) were estimated comparing the incidence before any PCV with each year post-PCV10 or post-PCV13 introduction using Bayesian multi-level, mixed-effects Poisson regressions, by site and age group. All site-weighted average IRRs were estimated using linear mixed-effects regression, stratified by product and previous seven-valent PCV (PCV7) effect (none, moderate, or substantial). FINDINGS: Analyses included 32 PCV13 sites (488 758 cases) and 15 PCV10 sites (46 386 cases) in 30 countries, primarily high income (39 sites), using booster dose schedules (41 sites). By 6 years after PCV10 or PCV13 introduction, IPD due to PCV10-type serotypes and PCV10-related serotype 6A declined substantially for both products (age <5 years: 83-99% decline; ≥65 years: 54-96% decline). PCV7-related serotype 19A increases before PCV10 or PCV13 introduction were reversed at PCV13 sites (age <5 years: 61-79% decline relative to before any PCV; age ≥65 years: 7-26% decline) but increased at PCV10 sites (age <5 years: 1·6-2·3-fold; age ≥65 years: 3·6-4·9-fold). Serotype 3 IRRs had no consistent trends for either product or age group. Non-PCV13-type IPD increased similarly for both products (age <5 years: 2·3-3·3-fold; age ≥65 years: 1·7-2·3-fold). Despite different serotype 19A trends, all-serotype IPD declined similarly between products among children younger than 5 years (58-74%); among adults aged 65 years or older, declines were greater at PCV13 (25-29%) than PCV10 (4-14%) sites, but other differences between sites precluded attribution to product. INTERPRETATION: Long-term use of PCV10 or PCV13 reduced IPD substantially in young children and more moderately in older ages. Non-vaccine-type serotypes increased approximately two-fold to three-fold by 6 years after introduction of PCV10 or PCV13. Continuing serotype 19A increases at PCV10 sites and declines at PCV13 sites suggest that PCV13 use would further reduce IPD at PCV10 sites. FUNDING: Bill & Melinda Gates Foundation as part of the WHO Pneumococcal Vaccines Technical Coordination Project.

Globally, abuse of older people (AOP) affects one in six individuals aged 60 years and older every year. Despite the widespread prevalence of AOP, evidence-based interventions for preventing and responding to this issue are insufficient. To address this gap, WHO proposed an initiative to accelerate the development of effective interventions for AOP across all country income levels. In the first phase, the initiative identified 89 promising interventions across a total of 101 evaluations or descriptions, which led to the creation of a public database. Most interventions targeted physical, psychological, and financial abuse and neglect, were implemented in the USA, and focused on victims or potential victims. These interventions were primarily delivered by social workers and nurses, usually in health-care facilities and community centres. Face-to-face delivery was common. Additionally, 28 (28%) of the 101 evaluations used randomised controlled trial designs. The results of this Review can be used to identify interventions that are ready for a rigorous outcome evaluation.

BACKGROUND: Tracking the emergence, introduction and spread of SARS-CoV-2 variants of concern are essential for informing public health strategies. In 2021, Cambodia faced two major epidemic waves of SARS-CoV-2 triggered by the successive rise of the Alpha and Delta variants. METHODS: Phylodynamic analysis of 1,163 complete SARS-CoV-2 genomes from Cambodia, along with global sequences, were conducted between February and September 2021 to infer viral introductions, molecular epidemiology and population dynamics. The relationship between epidemic trends and control strategies were evaluated. Bayesian phylogeographic reconstruction was employed to estimate and contrast the spatiotemporal dynamics of the Alpha and Delta variants over time. RESULTS: Here we reveal that the Alpha variant displays rapid lineage diversification, accompanied by the acquisition of a spike E484K mutation that coincides with the national implementation of mass COVID-19 vaccination. Despite nationwide control strategies and increased vaccination coverage, the Alpha variant was quickly displaced by Delta variants that exhibits a higher effective reproductive number. Phylogeographic inference indicates that the Alpha variant was introduced through south-central region of Cambodia, with strong diffusion rates from the capital of Phnom Penh to other provinces, while the Delta variant likely entered the country via the northern border provinces. CONCLUSIONS: Continual genomic surveillance and sequencing efforts, in combination with public health strategies, play a vital role in effectively tracking and responding to the emergence, evolution and dissemination of future emerging variants. | Tracking how SARS-CoV-2, the virus that causes COVID-19, changes over time is important for public health. In Cambodia, there were two major COVID-19 waves in 2021, driven by the Alpha and Delta variants. We analyzed 1,163 virus samples from Cambodia, plus samples from other places, to understand how these variants spread. We found that the Alpha variant quickly spread and changed as Cambodia started a mass vaccination campaign. Despite efforts to control it, the Delta variant, which spreads more easily, soon took over. The Alpha variant likely came into Cambodia from the south, while the Delta variant probably entered from the north. Monitoring these changes helps us respond better to future outbreaks. | eng

BACKGROUND: Outbreaks of emerging multidrug-resistant organisms (eMDROs), including carbapenem-resistant Enterobacterales, carbapenem-resistant Acinetobacter baumannii, and Candida auris, have been reported among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients. We describe eMDRO clusters in SARS-CoV-2 units and associated infection control (IC) practices early in the SARS-CoV-2 pandemic. METHODS: We conducted a retrospective survey of a convenience sample of health departments in 11 states to describe clusters of eMDROs that began before November 1, 2020 and involved SARS-CoV-2 units. Cluster characteristics and IC practices during the cluster period were assessed using a standardized outbreak report form, and descriptive analyses were performed. RESULTS: Overall, 18 eMDRO clusters (10 carbapenem-resistant Enterobacterales, 6 C auris, 1 carbapenem-resistant Pseudomonas aeruginosa, and 1 carbapenem-resistant A baumannii) in 18 health care facilities involving 397 patients were reported from 10 states. During the cluster period, 60% of facilities reported a shortage of isolation gowns, 69% extended use of gowns, and 67% reported difficulty obtaining preferred disinfectants. Reduced frequency of hand hygiene audits was reported in 85% of acute care hospitals during the cluster period compared with before the pandemic. CONCLUSIONS: Changes in IC practices and supply shortages were identified in facilities with eMDRO outbreaks during the SARS-CoV-2 pandemic and might have contributed to eMDRO transmission.

BACKGROUND: Oral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (F/TDF) has high efficacy against HIV-1 acquisition. Seventy-two prospective studies of daily oral F/TDF PrEP were conducted to evaluate HIV-1 incidence, drug resistance, adherence, and bone and renal safety in diverse settings. METHODS: HIV-1 incidence was calculated from incident HIV-1 diagnoses after PrEP initiation and within 60 days of discontinuation. Tenofovir concentrations in dried blood spots (DBS), drug resistance, and bone/renal safety indicators were evaluated in a subset of studies. RESULTS: Among 17 274 participants, there were 101 cases with new HIV-1 diagnosis (.77 per 100 person-years; 95% confidence interval [CI]: .63-.94). In 78 cases with resistance data, 18 (23%) had M184I or V, 1 (1.3%) had K65R, and 3 (3.8%) had both mutations. In 54 cases with tenofovir concentration data from DBS, 45 (83.3%), 2 (3.7%), 6 (11.1%), and 1 (1.9%) had average adherence of <2, 2-3, 4-6, and ≥7 doses/wk, respectively, and the corresponding incidence was 3.9 (95% CI: 2.9-5.3), .24 (.060-.95), .27 (.12-.60), and .054 (.008-.38) per 100 person-years. Adherence was low in younger participants, Hispanic/Latinx and Black participants, cisgender women, and transgender women. Bone and renal adverse event incidence rates were 0.69 and 11.8 per 100 person-years, respectively, consistent with previous reports. CONCLUSIONS: Leveraging the largest pooled analysis of global PrEP studies to date, we demonstrate that F/TDF is safe and highly effective, even with less than daily dosing, in diverse clinical settings, geographies, populations, and routes of HIV-1 exposure.

BACKGROUND: Stigma and lack of social support are barriers to HIV prevention, especially among cisgender Black women in the United States. While HIV pre-exposure prophylaxis (PrEP) can decrease HIV transmission, PrEP initiation and adherence remains low among Black women, especially in the U.S. South. OBJECTIVES: The purpose of this study was to characterize experiences with stigma and social support among PrEP-naïve and PrEP-experienced Black cisgender women in Mississippi. DESIGN: Qualitative study in which semi-structured interviews and focus groups were conducted. METHODS: We purposively recruited PrEP-naïve cisgender Black women who met PrEP indications to participate in focus groups and all PrEP-experienced cisgender Black women at a sexual health clinic in Jackson, Mississippi to participate in one-on-one semi-structured interviews. Inductive thematic analysis was used to analyze focus group and interview transcripts. RESULTS: A total of 37 PrEP-naïve Black cisgender women participated across 6 focus groups and 8 PrEP-experienced cisgender Black women completed semi-structured interviews. Four themes were identified: (1) the intersection of gendered racism, discrimination, and HIV stigma, (2) enacted and anticipated PrEP stigma, (3) stigma mitigation strategies and PrEP adherence, and (4) social support's role in PrEP initiation and adherence. PrEP-naïve and -experienced Black women discussed the negative consequence that sexual stigmatization and gendered racism has on HIV testing. PrEP-naïve Black women discussed how HIV stigma decreases PrEP initiation. Conversely, PrEP-experienced Black women were able to identify strategies they utilized to mitigate stigma. PrEP-experienced Black women discussed how differing levels of social support impact their PrEP use. CONCLUSION: Improving social support and stigma mitigation strategies could help improve PrEP initiation and adherence among cisgender Black women at-risk of acquiring HIV in the U.S. South. Educating communities on PrEP, and training providers on stigma-mitigating strategies when serving Black women in the U.S. South who are seeking HIV prevention is paramount. | PrEP initiation and adherence among Black cisgender women in Mississippi: The role of HIV and PrEP stigma and social supportWhy was the study done?Stigma and lack of social support have been demonstrated as barriers to HIV prevention, especially among cisgender Black women in the United States (U.S.). While HIV pre-exposure prophylaxis (PrEP), a HIV prevention medication, has the ability to decrease HIV transmission, rates of starting PrEP remain low among Black women, especially in the U.S. South. Improving PrEP programs for US Black women calls for understanding how stigma and social support impact PrEP use among Black women.What did the researchers do?We recruited cisgender Black women who was eligible for PrEP but have never taken PrEP (PrEP-naïve) to participate in focus groups and cisgender Black women who have taken PrEP (PrEP-experienced) to participate in one-on-one in-depth interviews from healthcare clinics in Jackson, Mississippi. Inductive thematic analysis was used to analyze focus group and interview transcripts.What did the researchers find?A total of 37 Black cisgender women across six groups participated in focus groups and eight cisgender Black women were interviewed. PrEP-naïve women reported: · HIV stigma in the community, which can lead to anticipated PrEP stigma · Experiencing sex-based sexual stigmatization at provider’s offices when seeking HIV testing PrEP-experienced Black women reported: Experiencing stigma when disclosing their PrEP use, such as their family and friends thinking that the woman and/or her partner is living with HIV. PrEP-experienced Black women who were in serodifferent partnership and had others in their network who knew about PrEP received support to take PrEP.What do the findings mean?Improving social support and stigma mitigation strategies could help improve PrEP initiation and adherence among cisgender Black women at-risk of acquiring HIV in the U.S. South. This includes educating communities on HIV and PrEP, and training providers on stigma-mitigating strategies when serving Black women in the U.S. South. | eng

Hospital surfaces are known to contribute to the spread of healthcare-associated antimicrobial pathogens. Environmental sampling can help locate reservoirs and determine intervention strategies, although sampling and detection can be labor intensive. Composite approaches may help reduce time and costs associated with sampling and detection. We investigated optimum surface areas for sampling antimicrobial-resistant organisms (AROs) with a single side of cellulose sponge, created theoretical composites (TC) by adding recovery results from multiple optimum areas, then compared the TC to the standard Centers for Disease Control and Prevention sampling method (one sponge using all sides, whole tool; (WT)). Five AROs were evaluated: carbapenemase-producing KPC+ Klebsiella pneumoniae (KPC), Acinetobacter baumannii (AB), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecalis (VRE) and Clostridioides difficile spores (CD). Steel coupons comprising four surface areas (323; 645; 1,290 and 2,258 cm2) were inoculated, dried, and sampled with one sampling pass using the larger side (face) or the smaller side (edge) of a pre-moistened cellulose sponge tool. Based on the optimum areas determined for each organism, composite areas were 1,290 cm2 for MRSA and VRE, 1,936 cm2 for AB, 2,580 cm2 for CD spores and 3,870 cm2 for KPC. Total colony forming units (CFU) recovered using a composite approach was greater or comparable than using multiple WT samplings (over the same area as the composite) for MRSA, VRE and AB (130%; 144% and 95%) yet less than if using multiple WT samplings for KP and CD (47% and 66%). We propose a conservative composite sampling strategy if the target organism is unknown; 323 cm2 sampling area for each of the four sides of the sponge, (1290 cm2 total). The conservative composite sampling strategy improved the recovery of KP (from 47% to 85% of multiple WT samplings), while MRSA, VRE, AB and CD (131%; 144%; 97% and 66%) remained within 5% to that of the optimum area TC.

BACKGROUND: Although current guidelines recommend implantable cardioverter-defibrillator (ICD) placement in survivors of out-of-hospital cardiac arrest, contemporary data on secondary-prevention ICDs in survivors of out-of-hospital cardiac arrest remain limited. METHODS AND RESULTS: Using 2013 to 2019 CARES (Cardiac Arrest Registry to Enhance Survival) linked to Medicare, we identified 3226 patients aged ≥65 years with an initial shockable rhythm who survived to discharge without severe neurological disability. Multivariable hierarchical regression models were used to examine the association between patient variables and ICD placement and quantify hospital variation in ICD implantation. The mean age was 72.2 years, 23.5% were women, 10% were Black individuals, and 4% were Hispanic individuals. Overall, 997 (30.9%) patients received an ICD before discharge, 1266 (39.2%) at 90 days, and 1287 (39.9%) within 6 months. Older age (≥85 years), female sex, history of diabetes, calendar year, and presentation with acute myocardial infarction were associated with lower odds of ICD implantation, but race or ethnicity was not associated with ICD implantation. Among 297 hospitals, the median proportion of survivors receiving ICD at discharge was 28.6% (interquartile range, 20%-50%). The relative odds of ICD implantation varied by 62% across hospitals (median odds ratio, 1.62 [95% CI, 1.38-1.82]) after adjusting for case mix. CONCLUSIONS: Fewer than 1 in 3 survivors of out-of-hospital cardiac arrest due to a shockable rhythm received a secondary-prevention ICD before discharge. Although patient variables were associated with ICD implantation, there was no difference by race or ethnicity. Even after adjusting for patient case mix, ICD implantation varied markedly across hospitals.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is a highly effective pharmaceutical intervention that prevents HIV infection, but PrEP uptake across the US has been slow among men who have sex with men (MSM), especially among Black/African American (B/AA) and Hispanic /Latino (H/L) MSM. This study investigates the acceptability and essential components of a peer-driven intervention (PDI) for promoting PrEP uptake among MSM, with a specific focus on B/AA and H/L communities. METHODS: We conducted 28 semi-structured, qualitative interviews with MSM in southern New England to explore the components of a PDI, including attitudes, content, and effective communication methods. A purposive sampling strategy was used to recruit diverse participants who reflect the communities with the highest burden of HIV infection. RESULTS: Of 28 study participants, the median age was 28 years (interquartile range [IQR]: 25, 35). The sample comprised B/AA (39%, n = 11) and H/L (50%, n = 14) individuals. Notably, nearly half of the participants (46%) were current PrEP users. We found that many participants were in favor of using a PDI approach for promoting PrEP. Additionally, several participants showed interest in becoming peer educators themselves. They emphasized the need for strong communication skills to effectively teach others about PrEP. Moreover, participants noted that peer education should cover key topics like how PrEP works, how effective it is, and any possible side effects. CONCLUSIONS: Our study shows that effective PDIs, facilitated by well-trained peers knowledgeable about PrEP, could enhance PrEP uptake among MSM, addressing health disparities and potentially reducing HIV transmission in B/AA and H/L communities.

No vaccines and few chemoprophylaxis options exist for the prevention of bacterial sexually transmitted infections (STIs) (specifically syphilis, chlamydia, and gonorrhea). These infections have increased in the United States and disproportionately affect gay, bisexual, and other men who have sex with men (MSM) and transgender women (TGW). In three large randomized controlled trials, 200 mg of doxycycline taken within 72 hours after sex has been shown to reduce syphilis and chlamydia infections by >70% and gonococcal infections by approximately 50%. This report outlines CDC's recommendation for the use of doxycycline postexposure prophylaxis (doxy PEP), a novel, ongoing, patient-managed biomedical STI prevention strategy for a selected population. CDC recommends that MSM and TGW who have had a bacterial STI (specifically syphilis, chlamydia, or gonorrhea) diagnosed in the past 12 months should receive counseling that doxy PEP can be used as postexposure prophylaxis to prevent these infections. Following shared decision-making with their provider, CDC recommends that providers offer persons in this group a prescription for doxy PEP to be self-administered within 72 hours after having oral, vaginal, or anal sex. The recommended dose of doxy PEP is 200 mg and should not exceed a maximum dose of 200 mg every 24 hours.Doxy PEP, when offered, should be implemented in the context of a comprehensive sexual health approach, including risk reduction counseling, STI screening and treatment, recommended vaccination and linkage to HIV PrEP, HIV care, or other services as appropriate. Persons who are prescribed doxy PEP should undergo bacterial STI testing at anatomic sites of exposure at baseline and every 3-6 months thereafter. Ongoing need for doxy PEP should be assessed every 3-6 months as well. HIV screening should be performed for HIV-negative MSM and TGW according to current recommendations.

BACKGROUND: Invasive meningococcal isolates in South Africa have in previous years (<2008) been characterized by serogroup B, C, W and Y lineages over time, with penicillin intermediate resistance (peni) at 6%. We describe the population structure and genomic markers of peni among invasive meningococcal isolates in South Africa, 2016-2021. METHODS: Meningococcal isolates were collected through national, laboratory-based invasive meningococcal disease (IMD) surveillance. Phenotypic antimicrobial susceptibility testing and whole-genome sequencing were performed, and the mechanism of reduced penicillin susceptibility was assessed in silico. RESULTS: Of 585 IMD cases reported during the study period, culture and PCR-based capsular group was determined for 477/585 (82%); and 241/477 (51%) were sequenced. Predominant serogroups included NmB (210/477; 44%), NmW (116/477; 24%), NmY (96/477; 20%) and NmC (48/477; 10%). Predominant clonal complexes (CC) were CC41/44 in NmB (27/113; 24%), CC11 in NmW (46/56; 82%), CC167 in NmY (23/44; 53%), and CC865 in NmC (9/24; 38%). Peni was detected in 16% (42/262) of isolates, and was due to the presence of a penA mosaic, with the majority harboring penA7, penA9 or penA14. CONCLUSION: IMD lineages circulating in South Africa were consistent with those circulating prior to 2008, however peni was higher than previously reported, and occurred in a variety of lineages.

Partner notification services (PNS) offers opportunities to discuss HIV pre-exposure prophylaxis (PrEP) and provide referrals. We evaluated the PrEP care cascade among men who have sex with men (MSM) engaging in PNS within a sexually transmitted infections clinic. Among 121 MSM eligible for PrEP during PNS, 21% subsequently initiated PrEP.

INTRODUCTION: Data on ethnic and racial differences in symptoms and health-related impacts following SARS-CoV-2 infection are limited. We aimed to estimate the ethnic and racial differences in symptoms and health-related impacts 3 and 6 months after the first SARS-CoV-2 infection. METHODS: Participants included adults with SARS-CoV-2 infection enrolled in a prospective multicenter US study between 12/11/2020 and 7/4/2022 as the primary cohort of interest, as well as a SARS-CoV-2-negative cohort to account for non-SARS-CoV-2-infection impacts, who completed enrollment and 3-month surveys (N = 3,161; 2,402 SARS-CoV-2-positive, 759 SARS-CoV-2-negative). Marginal odds ratios were estimated using GEE logistic regression for individual symptoms, health status, activity level, and missed work 3 and 6 months after COVID-19 illness, comparing each ethnicity or race to the referent group (non-Hispanic or white), adjusting for demographic factors, social determinants of health, substance use, pre-existing health conditions, SARS-CoV-2 infection status, COVID-19 vaccination status, and survey time point, with interactions between ethnicity or race and time point, ethnicity or race and SARS-CoV-2 infection status, and SARS-CoV-2 infection status and time point. RESULTS: Following SARS-CoV-2 infection, the majority of symptoms were similar over time between ethnic and racial groups. At 3 months, Hispanic participants were more likely than non-Hispanic participants to report fair/poor health (OR: 1.94; 95%CI: 1.36-2.78) and reduced activity (somewhat less, OR: 1.47; 95%CI: 1.06-2.02; much less, OR: 2.23; 95%CI: 1.38-3.61). At 6 months, differences by ethnicity were not present. At 3 months, Other/Multiple race participants were more likely than white participants to report fair/poor health (OR: 1.90; 95% CI: 1.25-2.88), reduced activity (somewhat less, OR: 1.72; 95%CI: 1.21-2.46; much less, OR: 2.08; 95%CI: 1.18-3.65). At 6 months, Asian participants were more likely than white participants to report fair/poor health (OR: 1.88; 95%CI: 1.13-3.12); Black participants reported more missed work (OR, 2.83; 95%CI: 1.60-5.00); and Other/Multiple race participants reported more fair/poor health (OR: 1.83; 95%CI: 1.10-3.05), reduced activity (somewhat less, OR: 1.60; 95%CI: 1.02-2.51; much less, OR: 2.49; 95%CI: 1.40-4.44), and more missed work (OR: 2.25; 95%CI: 1.27-3.98). DISCUSSION: Awareness of ethnic and racial differences in outcomes following SARS-CoV-2 infection may inform clinical and public health efforts to advance health equity in long-term outcomes.

OBJECTIVES: Effective health communication can increase intent to vaccinate. We compared 8 messages that may influence parents' intent to vaccinate their children against COVID-19. METHODS: In a cross-sectional survey of adults in the United States administered online in August 2021, 1837 parents and legal guardians were exposed to 8 messages (individual choice, gain/practical benefits, nonexpert, health care provider recommendation, altruism/community good, safety/effectiveness, safety, and effectiveness) to determine message reception and influence on intent to vaccinate their children. Parents responded to 10 questions using a Likert scale. We computed odds ratios (ORs) for each message, with an OR >1.0 indicating greater observed odds of participant agreement with the follow-up statement as compared with a reference message. We compared outcomes individually across messages with ordinal logistic regression fit using generalized estimating equations. RESULTS: The individual choice message had the highest odds of agreement for understanding intent (OR = 2.10; 95% CI, 1.94-2.27), followed by the health care provider recommendation message (OR = 1.58; 95% CI, 1.46-1.71). The individual choice message had the highest odds of memorability, relatability, and trustworthiness. The altruism/community good message was at or near second best. The altruism/community good message had the highest or near-highest odds of increasing parents' intent to vaccinate their children, asking friends and family for their thoughts, and searching for additional information. The message that most motivated parents to vaccinate their children depended on parental intent to vaccinate prior to being exposed to the tested messages. CONCLUSIONS: Messages with themes of individual choice, health care provider recommendation, and altruism/community good may be used in future message campaigns. Further research is needed to refine message concepts related to altruism/community good.

OBJECTIVE: We investigated concurrent outbreaks of Pseudomonas aeruginosa carrying bla(VIM) (VIM-CRPA) and Enterobacterales carrying bla(KPC) (KPC-CRE) at a long-term acute-care hospital (LTACH A). METHODS: We defined an incident case as the first detection of bla(KPC) or bla(VIM) from a patient's clinical cultures or colonization screening test. We reviewed medical records and performed infection control assessments, colonization screening, environmental sampling, and molecular characterization of carbapenemase-producing organisms from clinical and environmental sources by pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing. RESULTS: From July 2017 to December 2018, 76 incident cases were identified from 69 case patients: 51 had bla(KPC,) 11 had bla(VIM,) and 7 had bla(VIM) and bla(KPC). Also, bla(KPC) were identified from 7 Enterobacterales, and all bla(VIM) were P. aeruginosa. We observed gaps in hand hygiene, and we recovered KPC-CRE and VIM-CRPA from drains and toilets. We identified 4 KPC alleles and 2 VIM alleles; 2 KPC alleles were located on plasmids that were identified across multiple Enterobacterales and in both clinical and environmental isolates. CONCLUSIONS: Our response to a single patient colonized with VIM-CRPA and KPC-CRE identified concurrent CPO outbreaks at LTACH A. Epidemiologic and genomic investigations indicated that the observed diversity was due to a combination of multiple introductions of VIM-CRPA and KPC-CRE and to the transfer of carbapenemase genes across different bacteria species and strains. Improved infection control, including interventions that minimized potential spread from wastewater premise plumbing, stopped transmission.

BACKGROUND: Most studies on bystander cardiopulmonary resuscitation (CPR) for out-of-hospital cardiac arrest (OHCA) have focused on in-hospital or short-term survival. OBJECTIVES: The purpose of this study was to examine the association between bystander CPR and long-term survival outcomes for OHCA. METHODS: Within the Cardiac Arrest Registry to Enhance Survival, we identified 152,653 patients with OHCA ≥65 years of age or older. Using multivariable hierarchical logistic regression, we first examined the association between bystander CPR and in-hospital survival. Then, among those surviving to discharge and linked to Medicare files, we evaluated the association between bystander CPR and long-term mortality over 5 years using multivariable Cox regression. RESULTS: Overall, 58,464 (38.3%) received bystander CPR. Patients receiving bystander CPR were more likely to have an OHCA that was witnessed, in a public location, and with an initial shockable rhythm. Bystander CPR was associated with a 24% higher likelihood of surviving to hospital discharge (10.2% vs 5.5%; adjusted relative risk: 1.24 [95% CI: 1.19-1.29]; P < 0.001), and this survival benefit was similar (interaction P = 0.24) for those who were 65 to 74, 75 to 84, and ≥85 years of age. Among patients surviving to hospital discharge (median follow-up of 31 months), bystander CPR was additionally associated with lower long-term mortality vs those without bystander CPR (adjusted hazard ratio: 0.78 [95% CI: 0.73-0.84]; P < 0.001), and this benefit was also consistent across age groups (interaction P = 0.13). CONCLUSIONS: In older adults with OHCA, bystander CPR was associated with higher rates of in-hospital survival. This survival benefit was not attenuated by competing mortality risks but increased in magnitude after hospital discharge.

OBJECTIVE: To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with disease-modifying antirheumatic drugs (DMARDs) as part of an integrative management approach for people with rheumatoid arthritis (RA). METHODS: An interprofessional guideline development group constructed clinically relevant Population, Intervention, Comparator, and Outcome (PICO) questions. A literature review team then completed a systematic literature review and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the certainty of evidence. An interprofessional Voting Panel (n = 20 participants) that included 3 individuals with RA achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: The Voting Panel achieved consensus on 28 recommendations for the use of integrative interventions in conjunction with DMARDs for the management of RA. Consistent engagement in exercise received a strong recommendation. Of 27 conditional recommendations, 4 pertained to exercise, 13 to rehabilitation, 3 to diet, and 7 to additional integrative interventions. These recommendations are specific to RA management, recognizing that other medical indications and general health benefits may exist for many of these interventions. CONCLUSION: This guideline provides initial ACR recommendations on integrative interventions for the management of RA to accompany DMARD treatments. The broad range of interventions included in these recommendations illustrates the importance of an interprofessional, team-based approach to RA management. The conditional nature of most recommendations requires clinicians to engage persons with RA in shared decision-making when applying these recommendations.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs.

OBJECTIVE: Public health agencies have a critical role in providing effective messaging about mitigation strategies during a public health emergency. The objectives of this study were (1) to understand perceptions of COVID-19 vaccines, including concerns about side effects, safety, and effectiveness and how these perceptions influence vaccine decision-making among US adults and (2) to learn what messages might motivate vaccine uptake. METHODS: In April and May 2021, we conducted 14 online focus groups with non-Hispanic English-speaking and English- and Spanish-speaking Hispanic adults (N = 99) not vaccinated against COVID-19. We oversampled adults aged 18-39 years and rural residents and systematically assessed 10 test messages. Researchers used a standardized guide and an a priori codebook for focus group discussions, coding transcripts, and thematic analysis. RESULTS: Vaccine hesitancy factors included fear of the unknown; long-term side effects, including infertility; and beliefs that the vaccines were developed too quickly and were not sufficiently effective. Motivating factors for receiving vaccination included the ability to safely socialize and travel. Health care providers were considered important trusted messengers. Participants were critical of most messages tested. Messages that came across as "honest" about what is not yet known about COVID-19 vaccines were perceived more positively than other messages tested. Messages were seen as ineffective if perceived as vague or lacking in data and specificity. CONCLUSIONS: Messages that were simple and transparent about what is unknown about vaccines relative to emerging science were viewed most favorably. Health care providers, friends, and family were considered influential in vaccination decision-making. Findings underscore the benefits of research-informed strategies for developing and disseminating effective messages addressing critical issues in a public health emergency.

BACKGROUND: Sexually transmitted infections (STIs) such as syphilis, gonorrhea, and chlamydia have significantly increased over the past decade in the United States. Doxycycline as chemoprophylaxis (i.e., post-exposure prophylaxis [PEP]) offers promise for addressing bacterial STIs. The goal of the current study was to evaluate the safety of longer-term doxycycline use (defined as eight or more weeks) in the context of potential use as STI chemoprophylaxis through a systematic literature review and meta-analysis. METHODS: This review used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to search MEDLINE/PubMed for clinical studies published from August 2003 through January 2023 that reported on adverse events with doxycycline use with a focus on side-effects and metabolic effects of long-term use. RESULTS: A total of 67 studies were included in the systematic review. Overall, studies on longer-term doxycycline use reported 0% to over 50% adverse events ranging from mild to severe. Most common adverse events included gastrointestinal symptoms (i.e., nausea, vomiting, and abdominal pain), dermatologic (i.e., rash), and neurological (i.e., headache and dizziness) symptoms. Discontinuation of doxycycline due to adverse events was relatively uncommon in most studies. A meta-analysis of placebo controlled clinical trials (N = 18) revealed gastrointestinal and dermatological adverse events were more likely to occur in the doxycycline group. CONCLUSION: Longer-term (8+ weeks) doxycycline use is generally safe and may be associated with minor side-effects. Further research is needed on the potential metabolic impact of longer-term doxycycline use.

The Centers for Disease Control and Prevention (CDC)'s Division of Reproductive Health and Harvard T.H. Chan School of Public Health (HSPH) Program Evaluation Practicum (CDC/HSPH Practicum) is a mutually beneficial workforce development partnership formed to provide state, local, and tribal public health organizations with an evaluation plan for a maternal and child health (MCH) program. State, local, and tribal public health organizations submit an MCH program in need of evaluation for inclusion consideration. Student pairs are matched with the selected programs in a 3-week practical field-based experience. This Practicum provides didactic training for both program staff and students followed by field work at the public health organizations. Students provide organizations with comprehensive evaluation plans, complete with logic model, methodology, and indicators. Since the Practicum's inception in 2013, 104 HSPH graduate students have been trained and 30 states and 1 territory have participated and received evaluation plans for their MCH programs. The utility and importance of the CDC/HSPH Practicum is evidenced by program staff and student feedback. Multiple states have implemented the plans designed by the students, with some evaluations leading to program enhancements. The CDC/HSPH Practicum prepares students for the workforce and adds much needed capacity to public health organizations by providing them with evaluation knowledge and skills, and usable evaluation plans to improve MCH-a win-win for all.

BACKGROUND: To characterize neurodevelopmental abnormalities in children up to 36 months of age with congenital Zika virus exposure. METHODS: From the U.S. Zika Pregnancy and Infant Registry, a national surveillance system to monitor pregnancies with laboratory evidence of Zika virus infection, pregnancy outcomes and presence of Zika associated birth defects (ZBD) were reported among infants with available information. Neurologic sequelae and developmental delay were reported among children with ≥1 follow-up exam after 14 days of age or with ≥1 visit with development reported, respectively. RESULTS: Among 2248 infants, 10.1% were born preterm, and 10.5% were small-for-gestational age. Overall, 122 (5.4%) had any ZBD; 91.8% of infants had brain abnormalities or microcephaly, 23.0% had eye abnormalities, and 14.8% had both. Of 1881 children ≥1 follow-up exam reported, neurologic sequelae were more common among children with ZBD (44.6%) vs. without ZBD (1.5%). Of children with ≥1 visit with development reported, 46.8% (51/109) of children with ZBD and 7.4% (129/1739) of children without ZBD had confirmed or possible developmental delay. CONCLUSION: Understanding the prevalence of developmental delays and healthcare needs of children with congenital Zika virus exposure can inform health systems and planning to ensure services are available for affected families. IMPACT: We characterize pregnancy and infant outcomes and describe neurodevelopmental abnormalities up to 36 months of age by presence of Zika associated birth defects (ZBD). Neurologic sequelae and developmental delays were common among children with ZBD. Children with ZBD had increased frequency of neurologic sequelae and developmental delay compared to children without ZBD. Longitudinal follow-up of infants with Zika virus exposure in utero is important to characterize neurodevelopmental delay not apparent in early infancy, but logistically challenging in surveillance models.

Background: Wastewater represents a composite biological sample from the entire contributing population. People infected with monkeypox virus (MPXV)1 may excrete viral DNA into wastewater via multiple ways such as in feces, urine, skin lesions, and/or saliva. We describe results from rapid establishment of wastewater surveillance in selected regions in California within a month of the first reported case of monkeypox in the United States. Method(s): PCR assays targeting genomic DNA from MPXV were deployed in an ongoing wastewater surveillance program in California. MPXV DNA concentrations were measured daily in settled solids samples from nine wastewater plants. Results over a four-week period were validated across different MPXV assays, compared using influent and solids samples, and correlated using non-parametric methods (Kendall's tau) with the number of monkeypox cases reported from each sewershed. Result(s): MPXV DNA was detected at all nine sites between June 19 and August 1, 2022; 5 of 9 sites detected MPXV DNA prior to or within a day of the first case identified in the source sewershed. At the four sites with >10 positive detections, we observed a positive, statistically significant correlation (p <0.001) between MPXV DNA in wastewater solids and incidence rate of reported cases. Conclusion(s): Our findings suggest wastewater can be used to effectively detect the introduction of MPXV and monitor its circulation in the community to inform public health and clinical response. This flexible wastewater surveillance infrastructure may be rapidly leveraged to monitor other pathogens of public health importance that are shed into wastewater. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.

The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, resulting in >300,000 reported cases worldwide as of March 21st, 2020. Here we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 in Northern California using samples from returning travelers, cruise ship passengers, and cases of community transmission with unclear infection sources. Virus genomes were sampled from 29 patients diagnosed with COVID-19 infection from Feb 3rd through Mar 15th. Phylogenetic analyses revealed at least 8 different SARS-CoV-2 lineages, suggesting multiple independent introductions of the virus into the state. Virus genomes from passengers on two consecutive excursions of the Grand Princess cruise ship clustered with those from an established epidemic in Washington State, including the WA1 genome representing the first reported case in the United States on January 19th. We also detected evidence for presumptive transmission of SARS-CoV-2 lineages from one community to another. These findings suggest that cryptic transmission of SARS-CoV-2 in Northern California to date is characterized by multiple transmission chains that originate via distinct introductions from international and interstate travel, rather than widespread community transmission of a single predominant lineage. Rapid testing and contact tracing, social distancing, and travel restrictions are measures that will help to slow SARS-CoV-2 spread in California and other regions of the USA.

Carbapenem-resistant Enterobacterales (CRE) are among the most concerning antibiotic resistance threats due to high rates of multidrug resistance, transmissibility in health care settings, and high mortality rates. We evaluated the potential for regional genomic surveillance to track the spread of bla(KPC)-carrying CRE (KPC-CRE) by using isolate collections from health care facilities in three U.S. states. Clinical isolates were collected from Connecticut (2017 to 2018), Minnesota (2012 to 2018), and Tennessee (2016 to 2017) through the U.S. Centers for Disease Control and Prevention's Multi-site Gram-negative Surveillance Initiative (MuGSI) and additional surveillance. KPC-CRE isolates were whole-genome sequenced, yielding 255 isolates from 214 patients across 96 facilities. Case report data on patient comorbidities, facility exposures, and interfacility patient transfer were extracted. We observed that in Connecticut, most KPC-CRE isolates showed evidence of importation from outside the state, with limited local transmission. In Minnesota, cases were mainly from sporadic importation and transmission of bla(KPC)-carrying Klebsiella pneumoniae ST258, and clonal expansion of bla(KPC)-carrying Enterobacter hormaechei ST171, primarily at a single focal facility and its satellite facilities. In Tennessee, we observed transmission of diverse strains of bla(KPC)-carrying Enterobacter and Klesbiella, with evidence that most derived from the local acquisition of bla(KPC) plasmids circulating in an interconnected regional health care network. Thus, the underlying processes driving KPC-CRE burden can differ substantially across regions and can be discerned through regional genomic surveillance. This study provides proof of concept that integrating genomic data with information on interfacility patient transfers can provide insights into locations and drivers of regional KPC-CRE burden that can enable targeted interventions.