Currently there is no detailed, internationally agreed protocol defined to evaluate antimicrobial susceptibility testing (AST) for Legionella pneumophila (required to establish epidemiological cut-off value or "ECOFF" boundaries); therefore, antimicrobial resistance in these isolates cannot be defined. AST methods utilising media containing activated charcoal as an ingredient, to enable Legionella growth, are unreliable as noted in an internationally authored opinion paper and a new gold standard is required. Here we define a detailed protocol for broth microdilution (BMD) using defined cell culture collection-deposited control reference strains (Philadelphia-1 and Knoxville-1) as well as two accessible reference strains with moderately (lpeAB-carrying) and markedly (23S rRNA mutation-carrying) elevated azithromycin minimum inhibitory concentration (MIC). The defined protocol enables up to eight L. pneumophila strains to be set up on a single 96-well plate per antimicrobial tested. Initial ranges to routinely capture an MIC for these reference strains using clinically relevant antimicrobials azithromycin (0.01-0.25 mg/L), levofloxacin (0.008-0.03 mg/L), lefamulin (0.01-2 mg/L), rifampicin (0.0002-0.0008 mg/L) and doxycycline (0.25-16 mg/L) following incubation for 48 h at 37 °C in a shaking incubator have been empirically determined. Establishment of this internationally agreed protocol sets the scene for the next step: validation and comparison of antimicrobial ranges between international Legionella reference laboratories to establish putative resistance cut-off thresholds for these clinically relevant antimicrobials.

INTRODUCTION: Variations in cervical cancer incidence rates and trends have been reported by sociodemographic characteristics. However, research on economic characteristics is limited especially among younger women in the United States. METHODS: We analyzed United States Cancer Statistics data to examine age-standardized cervical cancer incidence rates among women aged 15-29 years during 2007-2020. We used an index-based county-level economic classification to rank counties in the top 25 %, middle 25 %-75 %, and bottom 25 %. We assessed differences in incidence using rate ratios and trends using annual percent changes (APCs) from joinpoint regression. Due to impact from the COVID-19 pandemic, trend analysis excluded 2020 data. Analyses were conducted during August-October 2023. RESULTS: During 2007-2020, incidence rates were lower in the top 25 % counties economically than the bottom 25 % or middle 25 %-75 % (1.6 vs 2.1 vs 1.9 per 100,000, respectively). Rates were higher in nonmetropolitan than metropolitan counties across economic groups. Overall, rates declined in all county-level economic strata, especially in the bottom 25 % during 2015-2019 (APC -10.6 %). Rates appeared to decrease in metropolitan counties and women of all races across economic categories. decreases were most evident in the top 25 % of non-Hispanic White women during 2016-2019 and nonmetropolitan counties during 2017-2019. CONCLUSIONS: In women aged 15-29 years, declining rates of cervical cancer during 2007-2019 across county-level economic strata may partly reflect effects of human papillomavirus vaccination and cervical cancer screening. Further observed differences by race and rurality may help inform efforts to increase implementation of preventive measures in populations with the highest burden.

OBJECTIVES: Evidence indicates that people living with HIV (PLHIV) are more impacted by COVID-19. The burden of SARS-CoV-2 infection among PLHIV is unknown in Nigeria. METHODS: We conducted repeated cross-sectional SARS-CoV-2 serosurveys in 14 states and the Federal Capital Territory in Nigeria among PLHIV who had an HIV viral load (VL) test during April 2022 to January 2023. Evidence of SARS-CoV-2 immunoglobulin G (IgG) antibodies was assessed using a multiplex bead assay to measure IgG to spike (S), receptor binding domain (RBD), and nucleocapsid (N) proteins to identify potential infection and/or vaccination status. RESULTS: Between April 2022 and January 2023, 47,614 remnant VL samples were included and tested for SARS-CoV-2 antibodies. Seroprevalence of SARS-CoV-2 infection, defined as IgG antibodies to spike and RBD591 [S+] and nucleocapsid [N+], (S+N+), ranged between 21.1% (95% confidence intervals [CI]: 11.4-31.8) in Ekiti State in January 2023 to 71.4% (95% CI 71.9-81.9) in Gombe State in November 2022, with overall steady trends within and between states over time, across age and sex. CONCLUSION: High rates of SARS-CoV-2 antibody seroprevalence among PLHIV in Nigeria were observed. This underscores the need to understand the association between HIV and SARS-CoV-2 to inform strategies to reduce the threat posed by COVID-19.

BACKGROUND: In Malawi, compared to adults, adolescents have higher rates of high HIV viremia and poorer antiretroviral therapy (ART) outcomes. The Ministry of Health, supported by the Elizabeth Glaser Pediatric AIDS Foundation (EGPAF), implemented the provision of differentiated care clubs for adolescents living with HIV (ALHIV), called "teen clubs," to provide psychosocial support and an HIV care package to improve clinical outcomes. We evaluated teen club attendance and factors associated with unsuppressed viral load (VL) in ALHIV enrolled in these teen clubs. METHODS: This cross-sectional study used program data from 35 health facilities in four districts that offered teen club services. We enrolled all ALHIV receiving ART ages 10-19 years who attended teen clubs between July 2018- September 2019 and had documented viral load results. Unsuppressed VL was defined as HIV RNA = > 1000 copies/mL, and optimal ART adherence was defined as having an expected pill count suggesting that between 95 and 105% of pills prescribed were consumed. We used multivariable logistic regression to identify factors associated with unsuppressed VL, adjusting for sex, age, education, district, adherence assessment, disclosure of one's HIV status, and teen club attendance. RESULTS: Our analysis included 1,162 ALHIV with a median age of 15 years (IQR 13-17). The majority were female (n = 614, 53%) and attended one or two teen club visits (n = 665, 57%). Unsuppressed VL was identified in 28% of ALHIV. ALHIV with sub-optimal ART adherence were twice as likely to have unsuppressed VL (adjusted odds ratio [aOR] 2.0, 95% confidence interval (CI): 1.42-2.62) compared to those with optimal ART adherence. ALHIV on second-line treatments, were nearly four times more likely to have unsuppressed VL (aOR 3.7, 95% CI: 1.64-9.09) compared with those on first-line ART. ALHIV who had attained secondary school education were less likely to have unsuppressed VL (aOR 0.42, 95% CI 0.21-0.81) than those who only attained primary school education. CONCLUSION: Even amongst adolescents enrolled in teen clubs, teen club attendance is low and high HIV viremia prevails. A continual focus on adolescents is needed to promote consistent teen club attendance and consistent ART adherence among the adolescents enrolled in differentiated service delivery.

BACKGROUND: To optimize vaccination strategies, it is useful to detect breakthrough infections and assess vaccine effectiveness in programmatic use. Monitoring emerging SARS-CoV-2 variants and vaccine effectiveness against them is also essential to determine the most effective vaccine options. This study aims to monitor SARS-CoV-2 breakthrough infections, the emergence of new SARS-CoV-2 variants, and host immune response during the peri-infection period of COVID-19. The study will also assess the uptake of the COVID-19 vaccine booster doses, and associated barriers or motivations among healthcare workers (HCWs). METHODS: Leveraging an existing HCW cohort in Bangladesh, HCWs will be enrolled from purposively selected health facilities from four different administrative divisions across Bangladesh. We captured cohort data on HCW's demographic information, clinical information, COVID-19 illness, and exposure, and vaccination histories for COVID-19. However, no biological specimens were collected for testing during the first phase of the cohort. In the current study, we plan to follow enrolled HCWs biweekly for suspected COVID-19 illness and capture relevant data including illness outcomes. Respiratory swab samples from symptomatic and a subset of asymptomatic HCWs will be tested for SARS-CoV-2 by rRT-PCR and positive samples will undergo Sanger sequencing to identify the SARS-CoV-2 variants of concern (VOCs). We will also perform Whole Genome Sequencing on a subset of SARS-CoV-2 positive samples with low CT values (Ct ≤ 30) to identify emerging SARS-CoV-2 variants. To examine the antibody response, we will collect blood samples from the participants at 12-week intervals for one year. We will use the EUROIMMUN kit and will also perform in-house ELISA to assess host immune factors with Luminex platform. DISCUSSION: This proposed study will generate useful data on COVID-19 breakthrough infection and the durability of anti-SARS-CoV-2 antibodies among HCWs following vaccination. The findings on booster vaccination intention and uptake will inform government COVID-19 vaccination strategies. Information on circulating and emerging strains of SARS-CoV-2 and vaccine performance against those strains will help understand population-level risks of COVID-19 infection. The study will generate data on facilitators and barriers to COVID-19 booster uptake among HCWs which can inform health communication messaging to improve booster acceptance in this population.

The extent to which semi-quantitative antibody levels confer protection against SARS-CoV-2 infection in populations with heterogenous immune histories is unclear. Two nested case-control studies were designed within the multisite HEROES/RECOVER prospective cohort of frontline workers to study the relationship between antibody levels and protection against first-time post-vaccination infection and reinfection with SARS-CoV-2 from December 2021 to January 2023. All participants submitted weekly nasal swabs for rRT-PCR testing and blood samples quarterly and following infection or vaccination. Cases of first-time post-vaccination infection following a third dose of monovalent (origin strain WA-1) mRNA vaccine (n = 613) and reinfection (n = 350) were 1:1 matched to controls based on timing of blood draw and other potential confounders. Conditional logistic regression models were fit to estimate infection risk reductions associated with 3-fold increases in end titers for receptor binding domain (RBD). In first-time post-vaccination and reinfection study samples, most were female (67%, 57%), non-Hispanic (82%, 68%), and without chronic conditions (65%, 65%). The odds of first-time post-vaccination infection were reduced by 21% (aOR = 0.79, 95% CI = [0.66-0.96]) for each 3-fold increase in RBD end titers. The odds of reinfection associated with a 3-fold increase in RBD end titers were reduced by 23% (aOR = 0.77, 95% CI = [0.65-0.92] for unvaccinated individuals and 58% (aOR = 0.42, 95% CI = [0.22-0.84]) for individuals with three mRNA vaccine doses following their first infection. Frontline workers with higher antibody levels following a third dose of mRNA COVID-19 vaccine were at reduced risk of SARS-CoV-2 during Omicron predominance. Among those with previous infections, the point estimates of risk reduction associated with antibody levels was greater for those with three vaccine doses compared to those who were unvaccinated.

We studied the relationship of frailty and acute lower respiratory infection (ALRI) among a multi-site cohort of community-dwelling older adults aged ≥60 years in India. During January 2019‒January 2020, participants completed the Edmonton Frail Scale (EFS) at baseline and every 3 months at four sites in India, with each participant completing a maximum of four surveys. Participants were categorized as non-frail (0-5 points), vulnerable (6-7 points), and frail (≥8 points) based on EFS score. Project nurses made weekly home visits to identify ALRI episodes with onset during past 7 days. We estimated adjusted hazard ratios (aHR) for having an ALRI episode within 90 days after EFS by frailty category. We also assessed risk of deterioration of frailty during 7-100 days after ALRI episode onset in terms of an increased EFS score by ≥1 point and change of frailty category. Among 5801 participants (median age 65 years, 41% males), 3568 (61·5%) were non-frail, 1507 (26%) vulnerable, and 726 (12·5%) frail at enrolment. Compared with non-frail participants, the hazard of an ALRI episode was higher among vulnerable (aHR: 1·6, (95%CI 1·3-2.0) and frail participants (aHR: 1·7, 95%CI 1·3-2·2). Participants having ALRI within the past 7-100 days were at increased risk of worsening frailty category (aOR: 1.9, 95%CI 1·3-2.8) compared to participants without an ALRI episode during the same period. The association between ALRIs and worsened frailty suggests prevention of ALRIs through vaccination and other strategies may have broad reaching health benefits for older adults.

BACKGROUND: Previous studies have demonstrated associations of persistent organic pollutants (POPs) with sex-related hormones; however, findings were inconsistent. Sex-specific impacts and pathways through which adiposity influences associations are not completely understood. We sought to evaluate sex-specific associations of POPs serum concentration with sex-related hormones and to explore pathways through which adiposity may modify associations. METHODS: We studied 1,073 men and 716 postmenopausal women participating in the "Persistent Organic Pollutants, Endogenous Hormones, and Diabetes in Latinos" ancillary study which is a subcohort of the "Hispanic Community Health Study/Study of Latinos." We use baseline examination data collected from 2008-2011 to investigate associations between eight organochlorine pesticides (OCPs), five polychlorinated biphenyls (PCB) groups, sum of polybrominated diphenyl ethers and polybrominated biphenyl 153 on sex hormone binding globulin (SHBG) and various sex-related hormone levels. We examined associations cross-sectionally using linear and logistic regression models adjusted for complex survey design and confounders. RESULTS: PCBs and select OCPs were associated with increased SHBG in women and decreased estradiol (E2) and/or bioavailable E2 in men. For instance, per quartile increase in serum concentrations of ∑PCBs and oxychlordane were associated with decreased levels of E2 (β=-6.36 pmol/L; 95% CI:-10.7,-2.02 and β=-5.08 pmol/L; 95% CI:-8.11,-2.05) and bioavailable E2 (β=-4.48 pmol/L; 95% CI:-7.22,-1.73 and β=-4.23 pmol/L; 95% CI:-6.17,-2.28), respectively, in men, and increased levels of SHBG (β=7.25 nmol/L; 95% CI:2.02,12.8 and β=9.42 nmol/L; 95% CI:4.08,15.0), respectively, in women. p,p'-DDT and β-HCCH, and o,p'-DDT were also associated with decreased testosterone (T) and bioavailable T (ng/dL) levels in men. Adiposity modified associations in men, revealing stronger inverse associations of PCBs, PBDEs, and several OCPs with LH, SHBG, E2, bioavailable E2, T, and the ratios of LH to FSH and E2 to T in those with below median body mass index and waist-to-hip ratio. CONCLUSION: Distinct patterns of hormone dysregulation with increasing POPs serum concentration were identified in men and post-menopausal women. In men but less so in postmenopausal women, adiposity modified associations of POPs serum concentration with sex-related hormones.

BACKGROUND: A recent infection testing algorithm (RITA) incorporating case surveillance (CS) with the rapid test for recent HIV infection (RTRI) was integrated into HIV testing services in Thailand as a small-scale pilot project in October 2020. OBJECTIVE: We aimed to describe the lessons learned and initial outcomes obtained after the establishment of the nationwide recent HIV infection surveillance project from April through August 2022. METHODS: We conducted desk reviews, developed a surveillance protocol and manual, selected sites, trained staff, implemented surveillance, and analyzed outcomes. Remnant blood specimens of consenting newly diagnosed individuals were tested using the Asanté HIV-1 Rapid Recency Assay. The duration of HIV infection was classified as RTRI-recent or RTRI-long-term. Individuals testing RTRI-recent with CD4 counts <200 cells/mm3 or those having opportunistic infections were classified as RITA-CS-long-term. Individuals testing RTRI-recent with CD4 counts >200 cells/mm3, no opportunistic infections, and not on antiretroviral treatment were classified as RITA-CS-recent. RESULTS: Two hundred and one hospitals in 14 high-burden HIV provinces participated in the surveillance. Of these, 69 reported ≥1 HIV diagnosis during the surveillance period. Of 1053 newly diagnosed cases, 64 (6.1%) were classified as RITA-CS-recent. On multivariate analysis, self-reporting as transgender women (adjusted odds ratio [AOR] 7.41, 95% CI 1.59-34.53) and men who have sex with men (AOR 2.59, 95% CI 1.02-6.56) compared to heterosexual men, and students compared to office workers or employers (AOR 3.76, 95% CI 1.25-11.35) were associated with RITA-CS-recent infection. The proper selection of surveillance sites, utilizing existing surveillance tools and systems, and conducting frequent follow-up and supervision visits were the most commonly cited lessons learned to inform the next surveillance phase. CONCLUSIONS: Recent HIV infection surveillance can provide an understanding of current epidemiologic trends to inform HIV prevention interventions to interrupt ongoing or recent HIV transmission. The key success factors of the HIV recent infection surveillance in Thailand include a thorough review of the existing HIV testing service delivery system, a streamlined workflow, strong laboratory and health services, and regular communication between sites and the Provincial Health Offices.

OBJECTIVE: The resurgence of syphilis in the United States presents a significant public health challenge. Much of the information needed for syphilis surveillance resides in electronic health records (EHRs). In this manuscript, we describe a surveillance platform for automating the extraction of EHR data, known as SmartChart Suite, and the results from a pilot. MATERIALS AND METHODS: The SmartChart Suite framework has been developed in compliance with the HHS Health IT Alignment Policy. The platform's major functionalities are (1) data retrieval; (2) logical evaluation; (3) standardized data storage; and (4) results display. The SmartChart Suite was deployed in September 2023 at the Grady Health System in Atlanta, Georgia. We established a cohort of likely syphilis patients, randomly selected 50 medical records for manual and automated chart review, and analyzed the results. RESULTS: The SmartChart Suite was successfully deployed and integrated with the Epic EHR system at Grady. The overall performance results were precision of 97.6%, recall of 100.0%, and F-Score of 98.8. DISCUSSION: Automated abstraction of EHR data has significant potential to improve public health surveillance and case investigation processes while reducing the resource burden on health departments and reporters. The SmartChart Suite comprises a flexible open-source solution for registry development and maintenance across a wide spectrum of conditions and use cases. CONCLUSION: SmartChart Suite demonstrates the potential of automated chart abstraction to support disease surveillance. HHS-compliant open-source tools such as SmartChart Suite can support more efficient human review by providing accurate and relevant data for critical public health activities.

Post rotavirus vaccine introduction in Mozambique (September 2015), we documented a decline in rotavirus-associated diarrhoea and genotypes changes in our diarrhoeal surveillance spanning 2008-2021. This study aimed to perform whole-genome sequencing of rotavirus strains from 2009 to 2012 (pre-vaccine) and 2017-2018 (post-vaccine). Rotavirus strains previously detected by conventional PCR as G2P[4], G2P[6], G3P[4], G8P[4], G8P[6], and G9P[6] from children with moderate-to-severe and less-severe diarrhoea and without diarrhoea (healthy community controls) were sequenced using Illumina MiSeq(®) platform and analysed using bioinformatics tools. All these G and P-type combinations exhibited DS-1-like constellation in the rest of the genome segments as, I2-R2-C2-M2-A2-N2-T2-E2-H2. Phylogenetic analysis revealed that strains from children with and without diarrhoea clustered together with other Mozambican and global strains. Notably, the NSP4 gene of strains G3P[4] and G8P[4] in children with diarrhoea clustered with animal strains, such as bovine and caprine, with similarity identities ranging from 89.1 to 97.0% nucleotide and 89.5-97.0% amino acids. Our findings revealed genetic similarities among rotavirus strains from children with and without diarrhoea, as well as with animal strains, reinforcing the need of implementing studies with One Health approach in our setting, to elucidate the genetic diversity of this important pathogen.

BACKGROUND: It is crucial to consider cultural, religious, and socio-behavioural factors that may influence the acceptability of Minimally Invasive Tissues Sampling (MITS). MITS is being used to understand the causes of child death and conducted in nine countries within Africa and South Asia with the highest child mortality. Progress has been made in the development of laboratory infrastructures and training for physicians to do MITS, but many communities are concerned about the religious acceptability of taking samples from deceased children. This paper explores the acceptability of MITS in a predominantly Muslim community. METHODS: A qualitative study was conducted in Kersa and Harar, in Eastern Ethiopia between April 23, 2018 and April 21, 2019 where high child mortality rates have been recorded. The study involved interviews and focus groups with 76 participants, including mothers, elders, and religious leaders. In addition, observations were conducted at burial ceremonies and in grieving families' homes. Grounded theory framework is used in this article to understand the acceptability of postmortem MITS. RESULTS: We explore cultural, religious, and socio-behavioural barriers and facilitators that may influence the acceptability of minimally invasive tissue sampling. We identify three themes relating to the acceptability of MITS: (1) Perceptions and rituals related to child death (2), Religious acceptance of post-mortem investigation, and (3) Fears and suspicions of organ theft and body mutilation. Most participants hypothetically accepted MITS, but suggested that the procedure consider religious practices. Religious leaders and parents stated that they would accept the procedure if it would help reduce child deaths. Acceptance is inconsistent and differs across time and place. Some villages accepted the procedure swiftly, only to change their views when they became aware of suspicions from other villages about the procedure disfiguring the body. Parents of deceased children were concerned that taking samples from the children's bodies would delay the burial. CONCLUSIONS: Mortality surveillance requires a thorough understanding of the cultural, religious, and sociocultural aspects that may affect the acceptability of MITS. MITS research should be conducted close to communities, involving community members, incorporating religious perspectives, and promoting health outreach campaigns to facilitate sociocultural perceptions of the research activities.

Pre-Exposure Prophylaxis (PrEP) is recommended as an HIV prevention measure for men who have sex with men (MSM). We assessed factors associated with PrEP retention and adherence among MSM in Kigali, Rwanda. We undertook a retrospective cross-sectional study and used a questionnaire to obtain PrEP retention and adherence history from MSM enrolled in the key population (KP) program that attended scheduled follow-up clinics from four (4) health facilities between April 2021 to June 2021. Retention was defined as attending scheduled PrEP follow-up appointments and adherence as taking PrEP medication 95% or more of the time. We used multivariable cox proportion hazard regression to determine factors associated with 3-month retention and principal component analysis (PCA) to determine factors associated with self-reported adherence. Data were analyzed using STATA (version 16.0). We interviewed 439 MSM aged 18 years and above that were initiated on PrEP. Majority were employed (57%, n = 251), between ages 25-34 years (49%, n = 217), close to half completed primary level education (47%, n = 206), were involved in sex work (42%, n = 184), and over a half lived in household of 1-2 members (55%, n = 241). Ninety percent of the MSM respondents (n = 393) were retained on PrEP at 3 months and among those retained, 287 (73%) had good adherence. Multivariable cox regression revealed that MSM more likely to be retained on PrEP, were those that are sex workers (adjusted Hazard Ratio (aHR) = 4.139; 95% Confidence Interval (95%CI): 1.569, 10.921), had more than one (1) regular sexual partners (aHR = 3.949; 95%CI: 2.221, 7.022), lived in households of 3-5 members (aHR = 3.755; 95%CI: 1.706, 8.261), completed secondary school education (aHR = 2.154; 95%CI: 1.130, 4.108), and were circumcised (aHR = 2.218, 95%CI: 1.232, 3.993). Employed MSM had a 66% decreased likelihood to be retained on PrEP (aHR = 0.345; 95%CI: 0.168, 0.707). Similarly, MSM that used condoms consistently had an 85% decreased likelihood to be retained on PrEP (aHR = 0.149; 95%CI: 0.035, 0.632). Principal component regression analysis showed that the component with MSM with higher numbers of regular sexual partners had increased odds of adhering to PrEP (Crude Odds Ratio (cOR) = 1.32; 95%CI: 1.144, 1.530). The study highlighted that MSM using PrEP as the main method of HIV prevention were more likely to be retained and adherent to PrEP. There is need to emphasize PrEP use alongside other HIV prevention methods and targeted STI testing and treatment among PrEP users.

Black women are disproportionately affected by HIV. We analyzed data from two Centers for Disease Control and Prevention's HIV surveillance systems to better understand HIV prevention strategies used by Black women at risk for and with HIV to help inform efforts to end HIV. Among sexually active Black women, we analyzed 2019 National HIV Behavioral Surveillance data on women without HIV (n = 4,033) and 2018-2020 Medical Monitoring Project data on women with HIV (n = 967). We reported percentages of HIV prevention strategies and services used and assessed differences between groups using Rao-Scott chi-square tests. Among Black women without HIV, 39% were aware of pre-exposure prophylaxis (PrEP); of these, 7% discussed PrEP with a healthcare provider, and 1% used PrEP in the past 12 months. Approximately 16% used a condom with their last sex partner; 36% reported that their last sex partner did not have HIV. Among Black women with HIV, 58% had condom-protected sex, 56% reported having sex while having sustained viral suppression, 3% had condomless sex with a partner on PrEP, and 24% had sex with a partner with HIV; 12% engaged in sex without using any HIV prevention strategy. HIV prevention strategies and services differed by selected demographic characteristics and social determinants of health. Although many sexually active Black women reported using HIV prevention strategies, there is room for improvement among those at risk for or with HIV. Tailoring prevention efforts based on individual needs and circumstances is essential for ending the HIV epidemic.

We report a case of Acanthamoeba infection in an HCT recipient with steroid-refractory GVHD. We highlight the multiple challenges that free-living ameba infections present to the clinician, the clinical laboratory, transplant infectious disease for review, hospital epidemiology if nosocomial transmission is considered, and public health officials, as exposure source identification can be a significant challenge. Transplant physicians should include Acanthamoeba infections in their differential diagnosis of a patient with skin, sinus, lung, and/or brain involvement.

Understanding the dynamics of antibody responses following vaccination and SARS-CoV-2 infection is important for informing effective vaccination strategies and other public health interventions. This study investigates SARS-CoV-2 antibody dynamics in a Puerto Rican cohort, analyzing how IgG levels vary by vaccination status and previous infection. We assess waning immunity and the distribution of hybrid immunity with the aim to inform public health strategies and vaccination programs in Puerto Rico and similar settings. We conducted a prospective, longitudinal cohort study to identify SARS-CoV-2 infections and related outcomes in Ponce, Puerto Rico, from June 2020-August 2022. Participants provided self-collected nasal swabs every week and serum every six months for RT-PCR and IgG testing, respectively. IgG reactivity against nucleocapsid (N) antigens, which generally indicate previous infection, and spike (S1) and receptor-binding domain (RBD) antigens, which indicate history of either infection or vaccination, was assessed using the Luminex Corporation xMAP® SARS-CoV-2 Multi-Antigen IgG Assay. Prior infection was defined by positive RT-PCRs, categorized by the predominant circulating SARS-CoV-2 variant at the event time. Demographic information, medical history, and COVID-19 vaccination history were collected through standardized questionnaires. Of 882 participants included in our analysis, 34.0% experienced at least one SARS-CoV-2 infection, with most (78.7%) occurring during the Omicron wave (December 2021 onwards). SARS-CoV-2 antibody prevalence increased over time, reaching 98.4% by the final serum collection, 67.0% attributable to vaccination alone, 1.6% from infection alone, and 31.4% from both. Regardless of prior infection status, RBD and S1 IgG levels gradually declined following two vaccine doses. A third dose boosted these antibody levels and showed a slower decline over time. N-antibody levels peaked during the Omicron surge and waned over time. Vaccination in individuals with prior SARS-CoV-2 infection elicited the highest and most durable antibody responses. N or S1 seropositivity was associated with lower odds of a subsequent positive PCR test during the Omicron period, with N antibodies showing a stronger association. By elucidating the differential decay of RBD and S1 antibodies following vaccination and the complexities of N-antibody response following infection, this study in a Puerto Rican cohort strengthens the foundation for developing targeted interventions and public health strategies.

Background: Vaccination is one of the most effective measures to prevent influenza illness and its complications. Since the 1980s, countries and territories in the Americas have progressively implemented influenza vaccination operations in high-risk priority groups—such as older adults, pregnant persons, persons with comorbidities and health workers. Methods: In this review, we present the history and progress of the seasonal influenza program in the Americas, how the program contributed to the efficient and timely roll-out of the COVID-19 vaccines during the pandemic, and how the program can be used to promote immunization operations across the life span for existing and future vaccines. Results: The influenza A(H1N1)pdm09 pandemic in 2009 and the COVID-19 pandemic in 2020–2023 underscored the importance of having a robust seasonal influenza vaccination program for pandemic preparedness and response. Overall, countries with existing seasonal influenza vaccination programs were better prepared and rolled out the delivery of COVID-19 vaccines more quickly and effectively compared to other countries where the influenza vaccination platform was weak or non-existent. Conclusions: Traditionally, national immunization programs of developing countries have been predominately focused on newborns, children younger than five years and school-aged children while often limiting their investment in effective adult vaccination programs; these programs are typically isolated to high-income countries. Countries in Latin America have been the exception, with strong influenza vaccination programs for adults regardless of national income level. The presence of functional and effective adult influenza vaccination programs can also facilitate the acceptance and uptake of other adult vaccines targeting priority groups at higher risk for severe illness or complications. © 2024 by the authors.

BACKGROUND: Group B Streptococcus (GBS) is a leading cause of neonatal meningitis and sepsis and an important cause of disease in adults. Capsular polysaccharide and protein-based GBS vaccines are currently under development. METHODS: Through national laboratory-based surveillance, invasive GBS isolates were collected from patients of all ages between 2019 and 2020. Phenotypic serotyping and antimicrobial susceptibility testing were conducted, followed by whole-genome sequencing for analysis of population structure and surface protein and resistance genes. RESULTS: 1748 invasive GBS cases were reported. Of these, 661 isolates underwent characterization, with 658 yielding both phenotypic and genotypic results. Isolates (n=658) belonged to five clonal complexes (CC1, CC8/10, CC17, CC19, and CC23) and six serotypes were detected: III (42.8%), Ia (27.9%), V (11.9%), II (8.4%), Ib (6.7%), and IV (2.3%). Phenotypically, only one isolate exhibited reduced penicillin susceptibility (MIC 0.25ug/ml). Phenotypic resistance to erythromycin, clindamycin, and tetracycline was observed in 16.1%, 3.8%, and 91.5% of isolates, respectively. ermTR (34.9%) and mefA/E (30.1%) genes were most common among erythromycin-resistant isolates, while ermB predominated clindamycin-resistant isolates (32.0%). tetM accounted for 95.8% of tetracycline resistance. All isolates carried at least one of the three pilus gene clusters, one of the four homologous alpha/Rib family determinants, and 98% harbored one of the serine-rich repeat protein genes. hvgA was found exclusively in CC17 isolates. CONCLUSION: In our setting, β-lactam antibiotics remain appropriate for GBS treatment and polysaccharide and protein-based vaccines under development are expected to provide good coverage.

IMPORTANCE: Increasing the understanding of vaccine effectiveness (VE) against levels of severe influenza in children could help increase uptake of influenza vaccination and strengthen vaccine policies globally. OBJECTIVE: To investigate VE in children by severity of influenza illness. DESIGN, SETTING, AND PARTICIPANTS: This case-control study with a test-negative design used data from 8 participating medical centers located in geographically different US states in the New Vaccine Surveillance Network from November 6, 2015, through April 8, 2020. Participants included children 6 months through 17 years of age who were hospitalized or presented to an emergency department (ED) with acute respiratory illness. EXPOSURES: Receipt of at least 1 dose of the current season's influenza vaccine. MAIN OUTCOMES AND MEASURES: Demographic and clinical characteristics of patients presenting to the hospital or ED with or without influenza were recorded and grouped by influenza vaccination status. Estimated VE against severe influenza illness was calculated using multiple measures to capture illness severity. Data were analyzed between June 1, 2022, and September 30, 2023. RESULTS: Among 15 728 children presenting for care with acute respiratory illness (8708 [55.4%] male; 13 450 [85.5%] 6 months to 8 years of age and 2278 [14.5%] 9-17 years of age), 2710 (17.2%) had positive influenza tests and 13 018 (82.8%) had negative influenza tests (controls). Of the influenza test-positive cases, 1676 children (61.8%) had an ED visit, 896 children (33.1%) required hospitalization for noncritical influenza, and 138 children (5.1%) required hospitalization for critical influenza. About half (7779 [49.5%]) of the children (both influenza test positive and test negative) were vaccinated. Receiving at least 1 influenza vaccine dose was estimated to have a VE of 55.7% (95% CI, 51.6%-59.6%) for preventing influenza-associated ED visits or hospitalizations among children of all ages. The estimated VE was similar across severity levels: 52.8% (95% CI, 46.6%-58.3%) for ED visits, 52.3% (95% CI, 44.8%-58.8%) for noncritical hospitalization, and 50.4% (95% CI, 29.7%-65.3%) for critical hospitalization. CONCLUSIONS AND RELEVANCE: Findings from this case-control study with a test-negative design involving children with a spectrum of influenza severity suggest that influenza vaccination protects children against all levels of severe influenza illness.

BACKGROUND: Despite South Africa's well-established Civil Registration and Vital Statistics system (CRVS) and good completeness of death registration, challenges persist in terms of the quality of cause of death information and the delayed availability of mortality statistics. The introduction of an electronic medical certification of cause of death (eMCCD) system may offer opportunities to improve both the quality and timeliness of this information. METHODS: This study used an exploratory mixed methods design to investigate perceptions surrounding an electronic solution for registering deaths in South Africa. We conducted 14 key informant interviews from 23 key informants invited, surveyed 208 out of 250 targeted health workers and engaged with more than 500 South African health professionals in a participatory workshop about the acceptability of introducing an eMCCD. Mentimeter was used to obtain feedback from the participants. Rapid qualitative analysis methods were used to analyse the key informant interviews and descriptive statistics for the survey and workshop data. During the interpretation phase, qualitative and quantitative data were integrated according to key themes that emerged from the data. RESULTS: During the qualitative interviews, the underlying factors mentioned as contributing to inadequate mortality data quality included insufficient MCCD training, diseases subjected to stigma, limited access to and quality of patient health information, and a significant proportion of deaths occurring outside medical facilities. More than 80.8% of the surveyed health professionals (168/208) rated the importance of mortality statistics as high, but the current quality was rated as low or very low by 29.3% (61/208). An eMCCD appeared to be acceptable to most workshop participants who registered on Mentimeter and was perceived as a means to strengthen the timeliness of mortality information. However, 43.0% (68/158) of the workshop participants who responded to this question on Mentimeter saw poor internet use as the main barrier to introducing an online system. CONCLUSIONS: Our results shed light on critical aspects surrounding cause of death information in South Africa, as well as the challenges faced in maintaining the quality of such data. The findings suggest that the implementation of an eMCCD system could provide opportunities to strengthen the cause of death information in South Africa if it is designed to integrate into the current system and provide supplementary functionalities.

Bullying and cyberbullying are major public health issues affecting youth. One potential protective mechanism within schools is positive school climate. We examine how bullying, cyberbullying, and school climate are associated with substance use, emotional problems, and prosocial behavior using data from 5,143 middle school students and 1,584 educators. We found bullying and cyberbullying experiences are associated with all student outcomes, finding a stronger relationship with cyberbullying for some outcomes. Student perceptions of clear school rules and consequences were consistently protective across all outcomes. Educator’s perceptions of school conflict were associated with more substance use and less prosocial behavior. More research is needed to identify aspects of school climate that may be protective and how schools can promote them. © This work was authored as part of the Contributor’s official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 U.S.C. 105, no copyright protection is available for such works under U.S. Law.

BACKGROUND: Serology for dengue viruses (DENV) and Zika virus (ZIKV) has been hindered by antibody cross-reactivity, which limits the utility of these tests for surveillance and assessment of sero-status. Our aim was to develop a multiplexed IgG-based assay with increased accuracy to assess the history of previous DENV and ZIKV infections. METHODS: We developed and assessed the analytical performance of a sample-sparing, multiplexed, microsphere-based serological assay using domain III of the envelope protein (EDIII) of DENV serotypes 1-4 and ZIKV, the most variable region between each virus. We used a reference panel of well-characterised serum samples from US-based travellers or residents of southeast Asia, central America, or Puerto Rico, who were naive or immune to either or both DENV and ZIKV, to develop an algorithm for detecting previous exposure to DENV and ZIKV and identify optimal positivity cutoffs to maximise assay performance. To independently confirm the performance of the assay and algorithm, we used a second test set of previously collected samples from healthy children (aged 9-16 years) living in Puerto Rico, whose DENV and ZIKV serostatus had been defined using the gold-standard virus neutralisation assay. We evaluated the performance of the multiplex assay compared with the gold-standard assay by estimating sensitivity and specificity for identification of past exposure to ZIKV and DENV. FINDINGS: The multiplexed EDIII assay showed reproducible results over different days and a linearity range from μg to pg levels for various EDIII antigens. Using a reference panel of serum samples from individuals who were DENV naive (n=136), DENV immune (n=38), ZIKV naive (n=67), and ZIKV immune (n=28), we optimised the assay and developed a testing algorithm that was 94·9% (95% CI 83·1-99·1) sensitive and 97·1% (92·7-98·9) specific for identifying previous exposure to DENV, and 100% (95% CI 88·0-100) sensitive and 97·0% (89·8-99·5) specific for identifying previous exposure to ZIKV. In an analysis with an independent test set of 389 samples, the assay and algorithm had 94·2% (89·9-97·1) sensitivity and 92·9% (87·3-96·5) specificity for DENV, and 94·1% (88·7-97·4) sensitivity and 95·0% (90·0-98·0) specificity for ZIKV. INTERPRETATION: The multiplexed EDIII serology assay can accurately identify the history of previous infection with either DENV or ZIKV. This high-throughput and sample-sparing assay is a promising new tool for supporting flavivirus surveillance, epidemiological and clinical studies, and serological testing for dengue vaccine eligibility. Further studies are needed to reduce the cost of the assay, eliminate high background in some samples, and to assess performance in DENV-endemic and ZIKV-endemic countries. FUNDING: US National Institutes of Health.

Acute Q fever diagnosis via paired serology is problematic because it requires follow-up for convalescent sample collection; as such, it cannot provide a diagnosis to inform a treatment decision at the time of acute presentation. Real-time polymerase chain reaction (PCR) may be a useful approach for the diagnosis of acute Q fever in endemic settings. Among febrile patients enrolled in a sentinel surveillance study for Q fever at two referral hospitals in Moshi, Tanzania, from 2012 to 2014, we analyzed those with paired sera for IgG to Coxiella burnetii (C. burnetii) phase II antigens using immunofluorescent antibody (IFA) testing, and acute serum was tested for C. burnetii with PCR. Acute Q fever was defined as a fourfold or greater rise from the acute to convalescent sample in IFA reciprocal titer or PCR detection that was confirmed through repeat testing. Test characteristics were tabulated. Among 496 participants tested using both paired IFA and PCR testing, 463 (93.3%) tested negative on both IFA and PCR, five (1.0%) tested positive for Q fever on both IFA and PCR, and 28 (5.6%) tested positive for Q fever on IFA alone. The sensitivity of PCR testing using paired IFA testing as an index was 0.15 (5/33), and the specificity was 1 (463/463). C. burnetii PCR testing provides a clinically specific method that may aid in timely diagnosis in settings in which acute Q fever is a common cause of febrile illness. However, we found a low clinical sensitivity of PCR testing on serum when compared with paired IFA serology.

BACKGROUND: Hemoglobin and hematocrit are the two most common biomarkers used to identify anemia in clinical settings, but their results do not always agree. OBJECTIVE: To examine agreement between hemoglobin and hematocrit in identifying anemia among children aged 1-<5 years and pregnant persons. METHODS: Pregnant persons and children aged 1-<5 years with hemoglobin and hematocrit results from the same whole blood sample in National Health and Nutrition Examination Survey (NHANES,1999-2020) were included. We used the Centers for Disease Control and Prevention (CDC) anemia cutoff values for children, pregnancy status, trimester, and smoking adjustments. We examined concordance of anemia, sensitivity, and specificity among those with anemia based on at least one test overall and by race/ethnicity, sex, and income level. Cohen's kappa was used to measure concordance. RESULTS: Analytic samples included 7,052 children and 1,437 pregnant persons, of which 1,119 had trimester data. Among children, anemia prevalence was 3.7% (95% CI: 3.1-4.3) based on hemoglobin and 5.5% (95% CI: 4.7-6.3) based on hematocrit. Among pregnant persons, anemia prevalence based on hemoglobin was 7.7% (95% CI: 5.9-9.5) and 12.4% (95% CI: 10.1-14.6) based on hematocrit. Kappa scores overall and by sociodemographic characteristics ranged from 0.64-0.75 (moderate concordance) among children and 0.53-0.78 (weak to moderate concordance) among pregnant persons. Among those with anemia on at least one test, 53.5% of children and 61.5% of pregnant persons had anemia based on both tests. CONCLUSIONS: We found substantial discordance between the two biomarkers; about 50% of children and 40% of pregnant women were identified by only one of the two biomarkers. Because hemoglobin and hematocrit may be used interchangeably in the clinical setting, individuals with anemia may be missed, not receive treatment, and therefore be at higher risk of adverse pregnancy, birth, and developmental outcomes.

Early-onset sepsis (EOS) is a significant cause of neonatal morbidity and mortality.1 EOS pathogenesis typically involves ascending infection of the fetal compartment by maternal colonizing gastrointestinal and genitourinary microbial flora or exposure during labor and delivery with subsequent neonatal colonization and infection.2 Signs of neonatal EOS can be difficult to distinguish from clinical instability associated with prematurity and from newborn physiologic transition to extrauterine life.3 EOS is defined by the isolation of pathogenic microbial species from blood or spinal fluid culture in the first 3 days after birth, although definitions vary and may extend to the first week after birth. Sensitivity of neonatal cultures is high, but concerns persist about maternal antibiotic exposures and small blood volumes affecting results.4 Limitations of EOS risk assessment and diagnosis, in addition to substantial infection-attributable morbidity and mortality, have led to high rates of antibiotic use among newborns.5,6 | Several advancements have been made over the last decades in the prevention, diagnosis, and treatment of neonatal EOS.7 Prevention efforts have focused on detecting maternal vaginal-rectal colonization with group B Streptococcus (GBS) and administering intrapartum antibiotic prophylaxis (IAP). Targeted prevention strategies do not exist for other organisms, such as Escherichia coli. Automated culture technology has improved diagnostic yield, though limitations remain for the newborn population. Treatment primarily consists of antimicrobials and supportive (often intensive) care. Increases in drug-resistant infections have led to debate about the risks and benefits of broad versus narrow empiric antibiotic regimens for suspected EOS. | Here, we review the contemporary epidemiology and microbiology of neonatal EOS in the United States and highlight differences between term and preterm newborns and across international settings. We explore 4 current controversies in neonatal EOS: (1) the pros and cons of IAP, (2) options for the current plateau in EOS prevention, (3) optimal empiric treatment regimen, and (4) ongoing disparities in EOS.

In The Netherlands, newborn screening (NBS) for tyrosinemia type 1 (TT1) uses dried blood spot (DBS) succinylacetone (SUAC) as a biomarker. However, high false-positive (FP) rates and a false-negative (FN) case show that the Dutch TT1 NBS protocol is suboptimal. In search of optimization options, we evaluated the protocols used by other NBS programs and their performance. We distributed an online survey to NBS program representatives worldwide (N = 41). Questions focused on the organization and performance of the programs and on changes since implementation. Thirty-three representatives completed the survey. TT1 incidence ranged from 1/13,636 to 1/750,000. Most NBS samples are taken between 36 and 72 h after birth. Most used biomarkers were DBS SUAC (78.9%), DBS Tyrosine (Tyr; 5.3%), or DBS Tyr with second tier SUAC (15.8%). The pooled median cut-off for SUAC was 1.50 µmol/L (range 0.3-7.0 µmol/L). The median cut-off from programs using laboratory-developed tests was significantly higher (2.63 µmol/L) than the medians from programs using commercial kits (range 1.0-1.7 µmol/L). The pooled median cut-off for Tyr was 216 µmol/L (range 120-600 µmol/L). Overall positive predictive values were 27.3% for SUAC, 1.2% for Tyr solely, and 90.1% for Tyr + SUAC. One FN result was reported for TT1 NBS using SUAC, while three FN results were reported for TT1 NBS using Tyr. The NBS programs for TT1 vary worldwide in terms of analytical methods, biochemical markers, and cut-off values. There is room for improvement through method standardization, cut-off adaptation, and integration of new biomarkers. Further enhancement is likely to be achieved by the application of post-analytical tools.

Parenteral nutrition (PN) is a nutrient solution administered intravenously (IV) to premature babies. PN causes elevations of some amino acids in blood samples that are also biomarkers used in newborn screening (NBS). Therefore, PN status must be annotated by clinicians on dried blood spot (DBS) cards to reduce NBS laboratory burdens associated with potential false results; however, NBS laboratories continue to receive DBSs with misannotated PN status. N-acetyltyrosine (NAT), a water-soluble tyrosine analog used to increase tyrosine bioavailability in PN solutions, can be used as a blood-based biomarker of PN administration in NBS assays. Residual DBS specimens and manufactured DBSs were used in analyses. The assay was developed and validated using flow injection analysis tandem mass spectrometry (FIA-MS/MS) for the detection of NAT. NAT was only present in neonate DBSs with annotated PN administration and was multiplexed into first-tier newborn screening assays. NAT was highly correlated with amino acids present in PN solutions, such as arginine, leucine, methionine, phenylalanine, and valine. In our sample cohort, we determined an NAT cutoff could aid the identification of misannotated neonates administered PN. We also report the Amadori rearrangement product valine-hexose (Val-Hex) was quantifiable in neonates administered PN, which we suspect forms in the PN solution and/or IV lines. Here, we present the first known use of NAT as a biomarker of PN administration, which is currently being piloted by two U.S. NBS laboratories. NAT and Val-Hex can aid the identification of misannotated DBSs from neonates administered PN, thus decreasing false positive rates.

Background: Crystalline silica particles are fibrogenic agents and established carcinogens, but the mechanisms for disease initiation and progression are not well understood. Previous studies demonstrate that the tumor suppressor gene, programmed cell death 4 (PDCD4), and its upstream regulator, microRNA 21 (miR-21), may be oncogenes for novel cancer prevention or anticancer therapies. Methods: This study examined the alterations of miR-21-PDCD4 signaling in mouse epidermal JB6 cells after exposure to freshly fractured silica particles. Results: The results demonstrate that exposure to crystalline silica caused PDCD4 inhibition in JB6 cells and a significant increase in miR-21 expression. Inhibition of phosphorylated extracellular signal-regulated kinases (ERKs) or phosphorylated p38 with U0126 or SB 203580 reversed silica-induced PDCD4 inhibition. Reactive oxygen species (ROS) scavengers and N-acetyl-l-cysteine also reversed the inhibitory effect of silica on PDCD4 expression. Human lung epithelial BEAS-2B or JB6 cells chronically exposed to low-dose silica resulted in neoplastic transformation as assayed by soft agar. Discussion: These findings demonstrate that freshly fractured silica particles may induce miR-21 expression and PDCD4 inhibition, which may be mediated through ROS and ERK pathways. Unraveling the complex mechanisms associated with these events may provide insights into the initiation and progression of silica-induced carcinogenesis.

Blastomycosis is a fungal disease caused by inhalation of Blastomyces spores from the environment that can result in severe pulmonary illness and high hospitalization rates. In early March 2023, Public Health Delta and Menominee Counties (Michigan) reported a cluster of blastomycosis cases among paper mill workers to the Michigan Department of Health and Human Services (MDHHS). MDHHS subsequently notified CDC. On March 17, paper mill management requested a health hazard evaluation (HHE) from CDC&#8217;s National Institute for Occupational Safety and Health (NIOSH) to investigate potential workplace exposures to Blastomyces and recommend prevention and control measures at the mill. The workplace epidemiologic investigation combined a NIOSH HHE medical survey consisting of a questionnaire on work and health with Blastomyces urine antigen testing of specimens obtained from workers to assist in case finding, with additional case information from MDHHS blastomycosis surveillance data. Assessment of 645 mill workers identified 162 cases of blastomycosis with illness onset during November 1, 2022-May 15, 2023, with the weekly case count peaking at 21 cases in early March 2023. HHE environmental sampling in and around the mill did not identify the source of workers' Blastomyces exposure in the mill. This outbreak was the largest documented blastomycosis outbreak in the United States, and the first associated with a paper mill or an industrial setting. A coordinated public health response facilitated swift prevention measures with recommendations focused on reducing workers' exposure to Blastomyces, including hazard communication, respiratory protection, mill cleaning, and ventilation system improvements.

Inhalation exposure to respirable crystalline silica (RCS) during the fabrication of engineered stone-based kitchen countertops has been on the rise in recent years and has become a significant occupational health problem in the United States and globally. Little is known about the presence of nanocrystalline silica (NCS), i.e., particles below 100 nm. We present a methodology to quantify the crystalline silica content in the sub-100 nm size fraction of the aerosol released during engineered stone fabrication using X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. Aerosol was generated in a test chamber designed per EN 1093-3 and sampled using cascade impactors. XRD and FTIR analysis showed the presence of both α-quartz (15-60%) and cristobalite (10-50%) polymorphs in all size fractions. With increasing particle size, the cristobalite content increased. Seventy percent of the total aerosol mass in the sub-100 nm fraction was found to be crystalline silica, qualitatively confirmed by electron diffraction and electron energy loss spectroscopy. The presence of other minerals was detected in all size fractions; no polymeric resin binder was detected in the sub-100 nm fraction. Although the sub-100 nm fraction was about 1% of the aerosol mass, it accounted for 4-24% of the aerosol surface area based on the total lung deposition. If the surface area is a more relevant exposure metric, the assessment of the efficacy of current engineering control systems using mass as an exposure metric may not provide adequate protection.

BACKGROUND: In western Kenya, a cluster-randomized trial is assessing the impact of attractive targeted sugar baits (ATSBs) on malaria in children enrolled in three consecutive cohorts. Here, characteristics of children and households at enrolment, and factors associated with baseline malaria prevalence are described. METHODS: Children aged 1 to < 15 years were randomly selected by cluster (n = 70) from a census database. Cohorts were enrolled in March-April 2022, September-October 2022, and March-April 2023. ATSBs were deployed in March 2022. At enrolment, all participants were tested for malaria by rapid diagnostic test (RDT). After enrolment a household survey was conducted. Household structures were classified as 'improved' (finished walls and roofs, and closed eaves) or 'traditional' (all other construction). A generalized linear mixed model was used to assess factors associated with malaria prevalence. RESULTS: Of 3705 children screened, 220 declined and 523 were excluded, due to plans to leave the study area (n = 392), ineligible age (n = 64) or other reason (n = 67). Overall, 2962 children were enrolled. Bed net use the previous night was more common in children aged 1-4 years (746/777 [96%]) than those aged 5-<15 years (1806/2157 [84%], p < 0.001). Of the 2644 households surveyed (for 2,886 participants), information on house construction was available for 2595. Of these, only 199 (8%) were categorized as 'improved', as most houses had open eaves. While 99% of households owned at least one bed net, only 51% were adequately covered (one net per two household residents). Among 999 children enrolled in the first cohort (baseline), 498 (50%) tested positive by RDT. In an adjusted multivariable analysis, factors associated with RDT positivity included sub-county (Alego-Usonga vs Rarieda, adjusted odds ratio [aOR] 4.81; 95% CI: 2.74-8.45; p < 0.001), house construction (traditional vs improved, aOR 2.80; 95% CI: 1.59-4.95; p < 0.001), and age (5-< 15 vs 1-4 years, aOR 1.64; 95% CI: 1.13-2.37; p = 0.009). CONCLUSIONS: In western Kenya, the burden of malaria in children remains high. Most households owned a bed net, but coverage was inadequate. Residents of Alego-Usonga sub-county, those living in traditionally constructed households, and older children were more likely to test positive by RDT. Additional tools are needed to effectively control malaria in this area. Trial registration The ATSB trial is registered under Clinicaltrials.gov NCT05219565.

Characterization of serological responses to Plasmodium falciparum (Pf) is of interest to understand disease burden and transmission dynamics; however, their interpretation is challenging. Dried blood spots from 30,815 participants aged 6 months to 15 years from the 2018 Nigeria HIV/AIDS Indicator and Impact Survey were analyzed by multiplex bead-based assay to measure immunoglobulin G (IgG) to Pf-stage-specific MSP-1, AMA-1, GLURPR0, LSA-1, and CSP. These IgG levels were analyzed by principal component analysis (PCA). PC1 and PC2 scores explained 41% and 17% of the total variance, respectively. PC1 unit vectors represented seropositivity. PC2 unit vectors for blood-stage antigens were in opposite directions to liver-stage and sporozoite antigens. PC2 scores were correlated with MSP-1 positively (R = 0.52, P < 0.001) and CSP negatively (R=-0.65, P < 0.001) and may help identify areas with prior exposure but higher risk for increased infections or epidemics. PCA of Pf serology can provide summary scores to possibly inform future programmatic interventions.

BACKGROUND: People who inject drugs (PWID) are especially vulnerable to harms from opioid use disorder (OUD). Medications for OUD (MOUD) effectively reduce overdose and infectious disease transmission risks. OBJECTIVE: We investigate whether state Medicaid coverage for methadone and buprenorphine is related to past-year MOUD use among PWID using cross-sectional, multilevel analyses with individual-level data on PWID from the Centers for Disease Control and Prevention's 2018 National HIV Behavioral Surveillance. The sample included 8,142 PWID aged 18-64 who reported daily opioid use from 22 U.S. metropolitan areas. Our outcome was any self-reported MOUD use in the past 12 months. Exposures were state Medicaid coverage and prior authorization requirements for methadone and buprenorphine. We interacted these exposures with PWID race/ethnicity, insurance status, and spatial access to treatment and harm reduction resources. RESULTS: Compared with PWID in states without Medicaid methadone coverage, odds of past-year MOUD use were 73% (p<0.05) higher among PWID in states with methadone coverage requiring prior authorization and 80% (p<0.05) higher among PWID in states with coverage without prior authorization. Insured PWID were twice as likely to report MOUD use than uninsured PWID, with no statistically significant differences between Medicaid versus other insurance. Medicaid prior authorization requirements for buprenorphine were not significantly associated with MOUD use. Non-Hispanic Black PWID were significantly less likely to use MOUD than non-Hispanic White and Hispanic PWID. CONCLUSIONS: State Medicaid methadone coverage was strongly associated with higher odds that PWID utilized MOUD, suggesting that expanding methadone insurance coverage could improve MOUD treatment in a vulnerable population.

BACKGROUND: Highly pathogenic avian influenza A(H5N1) viruses have caused widespread infections in dairy cows and poultry in the United States, with sporadic human cases. We describe characteristics of human A(H5N1) cases identified from March through October 2024 in the United States. METHODS: We analyzed data from persons with laboratory-confirmed A(H5N1) virus infection using a standardized case-report form linked to laboratory results from the Centers for Disease Control and Prevention influenza A/H5 subtyping kit. RESULTS: Of 46 case patients, 20 were exposed to infected poultry, 25 were exposed to infected or presumably infected dairy cows, and 1 had no identified exposure; that patient was hospitalized with nonrespiratory symptoms, and A(H5N1) virus infection was detected through routine surveillance. Among the 45 case patients with animal exposures, the median age was 34 years, and all had mild A(H5N1) illness; none were hospitalized, and none died. A total of 42 patients (93%) had conjunctivitis, 22 (49%) had fever, and 16 (36%) had respiratory symptoms; 15 (33%) had conjunctivitis only. The median duration of illness among 16 patients with available data was 4 days (range, 1 to 8). Most patients (87%) received oseltamivir; oseltamivir was started a median of 2 days after symptom onset. No additional cases were identified among the 97 household contacts of case patients with animal exposures. The types of personal protective equipment (PPE) that were most commonly used by workers exposed to infected animals were gloves (71%), eye protection (60%), and face masks (47%). CONCLUSIONS: In the cases identified to date, A(H5N1) viruses generally caused mild illness, mostly conjunctivitis, of short duration, predominantly in U.S. adults exposed to infected animals; most patients received prompt antiviral treatment. No evidence of human-to-human A(H5N1) transmission was identified. PPE use among occupationally exposed persons was suboptimal, which suggests that additional strategies are needed to reduce exposure risk. (Funded by the Centers for Disease Control and Prevention.).

Tularemia is a rare nationally notifiable zoonosis, caused by the tier-1 select agent Francisella tularensis, that has been reported from all U.S. states except Hawaii. Clinical manifestations typically include fever and localized symptoms that vary by route of infection. The case fatality rate of tularemia is typically <2% but can be higher depending on clinical manifestation and infecting strain. Tularemia is treatable with antibiotics. During 2011-2022, a total of 47 states reported 2,462 tularemia cases, but four central states (Arkansas, Kansas, Missouri, and Oklahoma) accounted for 50% of all reported cases. Incidence was highest among children aged 5-9 years (0.083 per 100,000 population) and adult males aged 65-84 years (range = 0.133-0.161). Incidence among American Indian or Alaska Native persons (0.260) was approximately five times that among White persons (0.057). The average annual incidence of tularemia in the United States during 2011-2022 (0.064) was 56% higher than that reported during 2001-2010 (0.041), largely resulting from increased reporting of probable cases. These findings might reflect an actual increase in human infection or improved case detection amid changes in commercially available laboratory tests during this period. Reducing tularemia incidence will require tailored prevention education; mitigating morbidity and mortality will require health care provider education, particularly among providers serving tribal populations, regarding early and accurate diagnosis and treatment.