INTRODUCTION: Retention in care and antiretroviral therapy (ART) adherence are major clinical and public health challenges in the treatment of HIV in the United States. Traditional data to care (D2C) approaches use health department surveillance data to promote retention in HIV care, with challenges in the timeliness of data and inconclusive findings. Earlier identification of people with HIV who are at risk of loss from care-such as when an ART prescription is not filled-represents a new direction for D2C (D2C-Rx or prescription-based D2C). METHODS: We designed the Antiretroviral Improvement among Medicaid EnrolleeS (AIMS) study, a D2C-Rx initiative in Virginia, which leveraged real-time administrative claims from Virginia Medicaid and HIV surveillance data from Virginia Department of Health (April 2023-June 2024). AIMS was a statewide cluster-randomized, controlled trial comparing a phased, multi-level program of support (intervention) to usual care, among Virginia Medicaid enrollees without current ART prescriptions. Support included a provider-level component for those with no prior ART prescription and patient-level component for those with a > 30-90-day late ART prescription refill(s). We hypothesized that AIMS would increase HIV viral suppression and improve ART adherence at 12 months compared to usual care. We describe the original study protocol and discuss changes implemented to the study design and program implementation. We also consider key methodologic contributions, as well as limitations and challenges to patient- and provider-level enrollment, such as ART prescription data accuracy. ETHICS AND DISSEMINATION: This study was reviewed and approved by the Institutional Review Board of Virginia Commonwealth University (HM20018229). REGISTRATION: The trial is registered at clinicaltrials.gov (NCT05477485).

Rabies is a fatal zoonotic disease caused by Lyssavirus rabies (RABV) and related negative strand RNA viruses from the Lyssavirus genus (family Rhabdoviridae). The LN34 assay targets the highly conserved leader region and nucleoprotein gene of the lyssavirus genome and utilizes degenerate primers and a TaqMan probe containing locked nucleotides to detect RNA across the diverse Lyssavirus genus. A negative finding for rabies should be made only if a full cross-section of the brain stem and three lobes of the cerebellum are examined; however, identification of lyssavirus RNA in any tissue is diagnostic of rabies infection. Tissue is collected and homogenized in TRIzol reagent, which also inactivates the virus. RNA extraction is performed using a spin column-based commercial extraction kit. Master mixes are prepared in a clean space and aliquoted into a 96 well plate before adding sample RNA. In clinical settings, each sample is tested by real-time RT-PCR for the presence of lyssavirus RNA in triplicate and singly for host β -actin mRNA. Positive and negative controls are included at extraction and real-time RT-PCR steps of the protocol. Data analysis involves manual adjustment of the thresholds to standardize Ct values across instrument runs. Positive results are determined by the presence of typical amplification in the pan-lyssavirus assay (Ct ≤ 35). Negative results are determined by the absence of typical amplification in the pan-lyssavirus assay and detection of host β-actin mRNA (Ct ≤ 33). Observation of values outside of these ranges or failure of the assay controls can invalidate the run or result in inconclusive results for a specimen. The protocol should be closely followed to ensure high assay sensitivity and specificity. Procedural modifications can affect assay performance and lead to false positive, false negative, or uninterpretable results.

Human adenovirus (HAdV), especially HAdV species F (HAdV-F) is recognized as a cause of acute gastroenteritis (AGE) worldwide. To assess the global prevalence of HAdV in case-patients of all ages with AGE, we conducted a systematic literature search for studies published in English during 2015-2022. We generated pooled prevalence estimates using generalized linear mixed models. Using data from 147 included articles, the overall pooled prevalence among AGE case-patients of any species of HAdV (pan-HAdV) was 5.8 % and 6.0 % for HAdV-F. The prevalence of HAdV was significantly higher among case-patients < 5 years of age compared with case-patients ≥ 5 years of age (pan-HAdV: 6.6 % vs. 2.0 %, p < 0.0001; HAdV-F: 8.7 % vs. 2.3 %, p = 0.04). Prevalence was significantly higher in high mortality developing countries and lowest in developed countries (pan-HAdV: 9.4 % vs. 4.0 %, p < 0.0001; HAdV-F: 11.6 % vs. 3.2 %, p = 0.0003). Understanding the burden of HAdV-associated AGE may be useful for targeted interventions, including future vaccine development.

Norovirus is the most common cause of foodborne illness outbreaks in the United States. In January 2024, local health jurisdictions and the California Department of Public Health (CDPH) identified two concurrent norovirus outbreaks across eight Southern California local health jurisdictions. CDPH was notified in late December 2023 and early January 2024 of gastrointestinal illnesses in persons who consumed raw oysters from food service facilities in San Diego County (outbreak 1). Additional illness reports came from multiple jurisdictions that included Los Angeles County and other areas in Southern California (outbreak 2). In total, approximately 400 persons across eight local health jurisdictions reported gastrointestinal illness after raw oyster consumption. A multiagency investigation confirmed that outbreaks 1 and 2 were unrelated, and implicated oysters were traced to two separate, nonoverlapping harvest regions in Mexico. A total of 179 outbreak-associated cases, including 24 laboratory-confirmed norovirus cases, were identified. Patient samples from both outbreaks identified norovirus genogroups I and II; other enteric viruses (sapovirus, astrovirus, rotavirus, and adenovirus) were also identified from one or both outbreaks. Noroviruses were genetically related by genotype within each outbreak but dissimilar between outbreaks. In outbreak 2, oysters might have been contaminated at a location separate from the original growing area, also known as wet storage. Concurrent outbreaks with similar modes of transmission can be unrelated, and the source for each should be confirmed through traceback. Proper storage and handling of shellfish is essential to maintaining safety of food products to consumers. Cooking oysters to 145°F (62.8°C) is recommended before consumption.

Persons who work closely with dairy cows, poultry, or other animals with suspected or confirmed infection with highly pathogenic avian influenza (HPAI) A(H5N1) viruses are at increased risk for infection. In September 2024, the California Department of Public Health was notified of the first human case of HPAI A(H5N1) in California through monitoring of workers on farms with infected cows. During September 30-December 24, 2024, a total of 38 persons received positive test results for HPAI A(H5N1) viruses in California; 37 were dairy farm workers with occupational exposure to sick cows, and one was a child aged <18 years with an undetermined exposure, the first pediatric HPAI A(H5N1) case reported in the United States. All patients had mild illness. The identification of cases associated with occupational exposure to HPAI A(H5N1) viruses on dairy farms highlights the continued risk for persons who work with infected animals. The pediatric case was identified through routine surveillance. Given recent increases in the prevalence of HPAI A(H5N1) viruses among some animal populations, public health agencies should continue to investigate cases of HPAI A(H5N1) in humans as part of control measures, pandemic preparedness, to identify concerning genetic changes, and to prevent and detect potential human-to-human transmission of the virus. To date, no human-to-human transmission of HPAI A(H5N1) virus has been identified in the United States.

OBJECTIVES:  This study aimed to demonstrate real-world use of the Making Electronic Data More Available for Research and Public Health (MedMorph) Reference Architecture (RA) for automated exchange of hepatitis C-related data for public health surveillance and research using Fast Healthcare Interoperability Resources (FHIR). METHODS:  Pilot participants included a public health authority (PHA), research organization (RO), clinical sites, and electronic health record (EHR) vendors. The RA was tested for hepatitis C public health surveillance and research data exchange. A mixed methods evaluation used multiple data sources to assess impact of the RA compared with usual methods. RESULTS:  After implementation of the RA components, there was no burden on clinical staff to report data for public health surveillance or research purposes. Data were successfully transferred and passed from EHR to PHA and RO, which revealed the value of receiving clinical data in addition to laboratory data via electronic laboratory reporting for the PHA and limitations in the Bulk FHIR standard. CONCLUSION:  Initial results indicate potential for long-term reduction of level of effort of reporting while improving the availability and completeness of clinical data for public health surveillance and research. Using a FHIR-based approach that aligns with regulatory health information technology certification requirements and existing infrastructure may reduce implementation burden. The MedMorph approach can enhance public health surveillance and research, resulting in improved data completeness and reduced reporting burden through automated data exchange using industry standards. MedMorph will continue to inform Centers for Disease Control and Prevention's Public Health Data Strategy, which provides the agency's direction for data modernization.

Studies in SIV-infected macaques show that the virus reservoir is particularly refractory to conventional suppressive antiretroviral therapy (ART). We posit that optimized ART regimens designed to have robust penetration in tissue reservoirs and long-lasting antiviral activity may be advantageous for HIV or SIV remission. Here we treat macaques infected with RT-SHIV with oral emtricitabine/tenofovir alafenamide and long-acting cabotegravir/rilpivirine without (n = 4) or with (n = 4) the immune activator vesatolimod after the initial onset of viremia. We document full suppression in all animals during treatment (4-12 months) and no virus rebound after treatment discontinuation (1.5-2 years of follow up) despite CD8 + T cell depletion. We show efficient multidrug penetration in virus reservoirs and persisting rilpivirine in plasma for 2 years after the last dose. Our results document a type of virus remission that is achieved through early treatment initiation and provision of ultra long-lasting antiviral activity that persists after treatment cessation.

Reliable, validated diagnostic tests are critical for rabies control in animals and prevention in people. We present a performance assessment and updates to the LN34 real-time RT-PCR assay for rabies diagnosis in postmortem animal brain samples. In two U.S. laboratories during 2017 to 2022, routine used of the LN34 assay produced excellent diagnostic sensitivity (99.72% to 100%) and specificity (99.99% to 100%) compared to the direct fluorescence antibody test (DFA). Almost all (>90%) DFA indeterminate results caused by non-specific or atypical fluorescence were negative by LN34 testing, representing up to 111 cases where unnecessary post-exposure prophylaxis could be avoided. LN34 assay original primer sequences showed low sensitivity for some rare lyssaviruses. Increased primer concentration combined with new primer formulation showed improved performance for impacted lyssaviruses with no loss in performance across diverse rabies virus variants from clinical samples. The updated LN34 and internal control assays were combined into a single-well LN34 multiplexed (LN34M) format, run at half reagent volumes. The LN34M assay showed similar detection of rabies virus to the singleplexed assay with simplified assay set-up, lower cost, and improved quality controls.

Bacillus anthracis causes anthrax through virulence factors encoded on two plasmids. However, non-B. anthracis organisms within the closely related, environmentally ubiquitous Bacillus cereus group (BCG) may cause an anthrax-like disease in humans through the partial adoption of anthrax-associated virulence genes, challenging the definition of anthrax disease. To elucidate these phenomena and their evolutionary past, we performed whole-genome sequencing on non-anthracis BCG isolates, including 93 archival (1967-2003) and 5 contemporary isolates (2019-2023). We produced annotated genomic assemblies and performed a pan-genome analysis to identify evidence of virulence gene homology and virulence gene acquisition by linear inheritance or horizontal gene transfer. At least one anthrax-associated virulence gene was annotated in ten isolates. Most homologous sequences in archival isolates showed evidence of pseudogenization and subsequent gene loss. The presence or absence of accessory genes, including anthrax-associated virulence genes, aligned with the phylogenetic structure of the BCG core genome. These findings support the hypothesis that anthrax-associated virulence genes were inherited from a common ancestor in the BCG and were retained or lost across different lineages, and contribute to a growing body of work informing public health strategies related to anthrax surveillance and identification.

BACKGROUND: Individual immune responses to SARS-CoV-2 are well-studied, while the combined effect of these responses on population-level immune dynamics remains poorly understood. Given the key role of population immunity on pathogen transmission, delineation of the factors that drive population immune evolution has critical public health implications. METHODS: We enrolled individuals 5 years and older selected using a multistage cluster survey approach in the Northwest and Southeast of the Dominican Republic. Paired blood samples were collected mid-pandemic (Aug 2021) and late pandemic (Nov 2022). We measured serum pan-immunoglobulin antibodies against the SARS-CoV-2 spike protein. Generalized Additive Models (GAMs) and random forest models were used to analyze the relationship between changes in antibody levels and various predictor variables. Principal component analysis and partial dependence plots further explored the relationships between predictors and antibody changes. FINDINGS: We found a transformation in the distribution of antibody levels from an irregular to a normalized single peak Gaussian distribution that was driven by titre-dependent boosting. This led to the convergence of antibody levels around a common immune setpoint, irrespective of baseline titres and vaccination profile. INTERPRETATION: Our results suggest that titre-dependent kinetics driven by widespread transmission direct the evolution of population immunity in a consistent manner. These findings have implications for targeted vaccination strategies and improved modeling of future transmission, providing a preliminary blueprint for understanding population immune dynamics that could guide public health and vaccine policy for SARS-CoV-2 and potentially other pathogens. FUNDING: The study was primarily funded by the Centers for Disease Control and Prevention grant U01GH002238 (EN). Salary support was provided by Wellcome Trust grant 206250/Z/17/Z (AK) and the Australian National Health and Medical Research Council Investigator grant APP1158469 (CLL).

Interest in utilizing exoskeletons to mitigate the risks of musculoskeletal disorders (MSDs) among construction workers is growing, spurred by encouraging results in other industries. However, it is crucial to carefully examine their impact on workers' stability and balance before implementation. In this study, seven male participants lifted a 35-lb cinder block from a production table to a simulated wall at two heights—elbow and shoulder levels—using three different exoskeleton models on an unstable platform, where their balance and shoulder muscle activity were assessed. Balance-related parameters, included mean distance (MDIST), total excursion (EXCUR), and mean velocity (VEL) of the center of pressure, were derived from force plate data. Muscle activity in six shoulder and upper arm muscles was estimated using electromyography (EMG) data. The results indicated that wearing two of the exoskeletons significantly increased both total and medio-lateral (ML) MDIST compared to not wearing an exoskeleton. Wearing one of the exoskeletons significantly increased total and ML VEL and ML EXCUR. Although lifting level did not have a significant impact on the balance parameters, it did affect the muscle activity in most of the measured muscles. Moreover, only one exoskeleton significantly reduced the activity in a particular shoulder muscle compared to no exoskeleton use. In conclusion, the evaluated shoulder-assist exoskeletons showed limited benefits for preventing upper extremity MSDs and may negatively affect whole-body balance during a block-laying task on an unstable platform. These findings underscore the importance of comprehensive evaluations of balance and effectiveness prior to adopting exoskeletons in construction. © 2024

The continued emergence of deadly human coronaviruses from animal reservoirs highlights the need for pan-coronavirus interventions for effective pandemic preparedness. Here, using linking B cell receptor to antigen specificity through sequencing (LIBRA-seq), we report a panel of 50 coronavirus antibodies isolated from human B cells. Of these, 54043-5 was shown to bind the S2 subunit of spike proteins from alpha-, beta-, and deltacoronaviruses. A cryoelectron microscopy (cryo-EM) structure of 54043-5 bound to the prefusion S2 subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike defined an epitope at the apex of S2 that is highly conserved among betacoronaviruses. Although non-neutralizing, 54043-5 induced Fc-dependent antiviral responses in vitro, including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). In murine SARS-CoV-2 challenge studies, protection against disease was observed after introduction of Leu234Ala, Leu235Ala, and Pro329Gly (LALA-PG) substitutions in the Fc region of 54043-5. Together, these data provide new insights into the protective mechanisms of non-neutralizing antibodies and define a broadly conserved epitope within the S2 subunit.

Recommended vaccination at nine months of age with the measles-containing vaccine (MCV1) has been part of Ethiopia's routine immunization program since 1980. A second dose of MCV (MCV2) was introduced in 2019 for children 15 months of age. We examined MCV1 and MCV2 coverage and the factors associated with measles vaccination status. A cross-sectional household survey was conducted among caregivers of children aged 12-35 months in selected districts of Oromia Region. Measles vaccination status was determined using home-based records, when available, or caregivers' recall. We analyzed the association between MCV1 and MCV2 vaccination status and household, caregiver, and child factors using logistic regression. The caregivers of 1172 children aged 12-35 months were interviewed and included in the analysis. MCV1 and MCV2 coverage was 71% and 48%, respectively. The dropout rate (DOR) from the first dose of Pentavalent vaccine to MCV1 was 22% and from MCV1 to MCV2 was 46%. Caregivers were more likely to vaccinate their children with MCV if they gave birth at a health facility, believe that their child had received all recommended vaccines, and know the required number of vaccination visits and doses. MCV2 coverage was low, with a high measles dropout rate (DOR). Caregivers with high awareness of MCV and its schedule were more likely to vaccinate their children. Intensified demand generation, defaulter tracking, and vaccine-stock management should be strengthened to improve MCV uptake.

In 2022, an estimated 5 million persons in the World Health Organization Region of the Americas (AMR) were living with chronic hepatitis B virus (HBV) infection, the leading cause of hepatocellular carcinoma and cirrhosis worldwide. Most chronic infections are acquired through mother-to-child transmission (MTCT) or horizontal transmission during childhood and are preventable with hepatitis B vaccination, including a birth dose (HepB-BD), followed by 2-3 additional doses (HepB3) in infancy. The Pan American Health Organization (PAHO) Elimination of MTCT of HBV infection strategy is intended to reduce chronic HBV infection (measured by hepatitis B surface antigen [HBsAg] seroprevalence) to ≤0.1% among children by achieving 1) ≥95% coverage with HepB-BD and HepB3; and 2) ≥80% of pregnant women received testing for HBsAg, and provision of hepatitis B immunoglobulin to HBV-exposed neonates. By 2012, all 51 AMR countries and territories (countries) provided HepB3 nationwide, and by 2021, 34 (67%) provided HepB-BD nationwide. Mathematical models estimate that HBsAg seroprevalence in children is ≤0.1% in 14 (28%) of 51 countries and at the regional level. Three (6%) of 51 countries met the 95% coverage targets for both HepB3 and HepB-BD during both 2021 and 2022. Of these, two have likely met criteria for the elimination of MTCT of HBV infection. However, in 2022, HepB3 coverage had declined by ≥10 percentage points in 15 (37%) of 41 countries with 2012 coverage data for comparison. These declines in HepB3 coverage, as well as the absence of HepB-BD in the routine immunization schedules in 17 countries, threaten PAHO's progress toward the elimination of MTCT of HBV infection. Efforts to introduce HepB-BD and maintain high HepB3 and HepB-BD coverage are needed.

BACKGROUND: Pig-tailed macaques (PTMs) are commonly used as preclinical models to assess antiretroviral drugs for HIV prevention research. Drug toxicities and disease pathologies are often preceded by changes in blood hematology. To better assess the safety profile of pharmaceuticals, we defined normal ranges of hematological values in PTMs using an Isolation Forest (iForest) algorithm. METHODS: Eighteen female PTMs were evaluated. Blood was collected 1-24 times per animal for a total of 159 samples. Complete blood counts were performed, and iForest was used to analyze the hematology data to detect outliers. RESULTS: Median, IQR, and ranges were calculated for 13 hematology parameters. From all samples, 22 outliers were detected. These outliers were excluded from the reference index. CONCLUSIONS: Using iForest, we defined a normal range for hematology parameters in female PTMs. This reference index can be a valuable tool for future studies evaluating drug toxicities in PTMs.

We present a novel small molecule antiviral chemotype that was identified by an unconventional cell-free protein synthesis and assembly-based phenotypic screen for modulation of viral capsid assembly. Activity of PAV-431, a representative compound from the series, has been validated against infectious viruses in multiple cell culture models for all six families of viruses causing most respiratory diseases in humans. In animals, this chemotype has been demonstrated efficacious for porcine epidemic diarrhoea virus (a coronavirus) and respiratory syncytial virus (a paramyxovirus). PAV-431 is shown to bind to the protein 14-3-3, a known allosteric modulator. However, it only appears to target the small subset of 14-3-3 which is present in a dynamic multi-protein complex whose components include proteins implicated in viral life cycles and in innate immunity. The composition of this target multi-protein complex appears to be modified upon viral infection and largely restored by PAV-431 treatment. An advanced analog, PAV-104, is shown to be selective for the virally modified target, thereby avoiding host toxicity. Our findings suggest a new paradigm for understanding, and drugging, the host-virus interface, which leads to a new clinical therapeutic strategy for treatment of respiratory viral disease.

BACKGROUND: Recently, increasing focus on patient input into research and healthcare improvements has fostered expanded patient-centered advocacy efforts. This first pan-fungal disease summit, part of the MYCology Advocacy, Research, & Education effort, brought together patients, caregivers, and mycology experts to better document patient experiences with invasive fungal disease (IFD) and establish priorities for mycology education, advocacy, and research. METHODS: Patients who had suffered from IFD, their caregivers, clinicians, industry representatives, government officials, and patient advocacy professionals were invited. Patients and caregivers shared their stories and struggles with IFD. Breakout sessions separated mycology experts from patients and caregivers for further discussions to identify commonalities and perceived gaps and to formulate recommendations. The 2 groups then reconvened to develop consensus recommendations. RESULTS: IFD patients and their caregivers shared experiences reflecting the typically lengthy prediagnosis, acute treatment, long-term treatment, and posttreatment recovery stages of IFD. They reported substantial physical, psychological, and financial burdens associated with the IFD experience, particularly related to delayed diagnoses. They reaffirmed a need for coordinated patient-centered education, peer support, and advocacy to document the burden of serious fungal infections. Mycology experts discussed strategies to address gaps in the mycology field, such as insufficient training, inadequate workforce support, and a need to partner more with patient groups. CONCLUSIONS: A summit involving patients with IFD, family caregivers, and mycology experts identified a substantial nonclinical burden of disease associated with IFD. Patients and mycology experts prioritized several goals for education, advocacy, and research to raise awareness of IFD and improve outcomes.

BACKGROUND: Global progress on malaria control has stalled recently, partly due to challenges in universal access to malaria diagnosis and treatment. Community health workers (CHWs) can play a key role in improving access to malaria care for children under 5 years (CU5), but national policies rarely permit them to treat older individuals. We conducted a two-arm cluster randomized trial in rural Madagascar to assess the impact of expanding malaria community case management (mCCM) to all ages on health care access and use. METHODS: Thirty health centers and their associated CHWs in Farafangana District were randomized 1:1 to mCCM for all ages (intervention) or mCCM for CU5 only (control). Both arms were supported with CHW trainings on malaria case management, community sensitization on free malaria care, monthly supervision of CHWs, and reinforcement of the malaria supply chain. Cross-sectional household surveys in approximately 1600 households were conducted at baseline (Nov-Dec 2019) and endline (Nov-Dec 2021). Monthly data were collected from health center and CHW registers for 36 months (2019-2021). Intervention impact was assessed via difference-in-differences analyses for survey data and interrupted time-series analyses for health system data. RESULTS: Rates of care-seeking for fever and malaria diagnosis nearly tripled in both arms (from less than 25% to over 60%), driven mostly by increases in CHW care. Age-expanded mCCM yielded additional improvements for individuals over 5 years in the intervention arm (rate ratio for RDTs done in 6-13-year-olds, RR(RDT6-13 years) = 1.65; 95% CIs 1.45-1.87), but increases were significant only in health system data analyses. Age-expanded mCCM was associated with larger increases for populations living further from health centers (RR(RDT6-13 years) = 1.21 per km; 95% CIs 1.19-1.23). CONCLUSIONS: Expanding mCCM to all ages can improve universal access to malaria diagnosis and treatment. In addition, strengthening supply chain systems can achieve significant improvements even in the absence of age-expanded mCCM. TRIAL REGISTRATION: The trial was registered at the Pan-African Clinical Trials Registry (#PACTR202001907367187).

INTRODUCTION: the increasing number of people receiving antiretroviral therapy (ART) in sub-Saharan Africa has stressed already overburdened health systems. A care model utilizing community-based peer-groups (ART Co-ops) facilitated by community health workers (CHW) was implemented (2016-2018) to address these challenges. In 2018, a post-intervention study assessed perceptions of the intervention. METHODS: forty participants were engaged in focus group discussions consisting of ART Co-op clients, study staff, and health care providers from Kitale HIV clinic. Data were analyzed thematically for content on the intervention, challenges, and recommendations for improvement. RESULTS: all participants liked the intervention. However, some reported traveling long distances to attend ART Co-op meetings and experiencing stigma with ART Co-ops participation. The ART Co-op inclusion criteria were considered appropriate; however, additional outreach to deliberately include spouses living with HIV, the disabled, the poor, and HIV pregnant women was recommended. Participants liked CHW-directed quarterly group meetings which included ART distribution, adherence review, and illness identification. The inability of the CHW to provide full clinical care, inconvenient meeting venues, poor timekeeping, and non-attendance behaviors were noted as issues. Participants indicated that program continuation, regular CHW training, rotating meetings at group members´ homes, training ART Co-ops leaders to assume CHW tasks, use of pill diaries to check adherence, nutritional support, and economically empowering members through income generation projects would be beneficial. CONCLUSION: the intervention was viewed positively by both clinic staff and clients. They identified specific challenges and generated actionable key considerations to improve access and acceptability of the community-based model of care.

Introduction: on March 21, 2020, the first case of COVID-19 was confirmed in Uganda. A total lockdown was initiated on March 30 which was gradually lifted May 5-June 30. On March 25, a toll-free call center was organized at the Kampala Capital City Authority to respond to public concerns about COVID-19 and the lockdown. We documented the set-up and use of the call center and analyzed key concerns raised by the public. Methods: two hotlines were established and disseminated through media platforms in Greater Kampala. The call center was open 24 hours a day and 7 days a week. We abstracted data on incoming calls from March 25 to June 30, 2020. We summarized call data into categories and conducted descriptive analyses of public concerns raised during the lockdown. Results: among 10,167 calls, two-thirds (6,578; 64.7%) involved access to health services, 1,565 (15.4%) were about social services, and 1,375 (13.5%) involved COVID-19-related issues. Approximately one-third (2,152; 32.7%) of calls about access to health services were requests for ambulances for patients with non-COVID-19-related emergencies. About three-quarters of calls about social services were requests for food and relief items (1,184; 75.7%). Half of the calls about COVID-19 (730; 53.1%) sought disease-related information. Conclusion: the toll-free call center was used by the public during the COVID-19 lockdown in Kampala. Callers were more concerned about access to essential health services, non-related to COVID-19 disease. It is important to plan for continuity of essential services before a public health emergency-related lockdown. © 2024, African Field Epidemiology Network. All rights reserved.

BACKGROUND: Microneedle patches (MNPs) have been ranked as the highest global priority innovation for overcoming immunisation barriers in low-income and middle-income countries. This trial aimed to provide the first data on the tolerability, safety, and immunogenicity of a measles and rubella vaccine (MRV)-MNP in children. METHODS: This single-centre, phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial was conducted in The Gambia. To be eligible, all participants had to be healthy according to prespecified criteria, aged 18-40 years for the adult cohort, 15-18 months for toddlers, or 9-10 months for infants, and to be available for visits throughout the follow-up period. The three age cohorts were randomly assigned in a 2:1 ratio (adults) or 1:1 ratio (toddlers and infants) to receive either an MRV-MNP (Micron Biomedical, Atlanta, GA, USA) and a placebo (0·9% sodium chloride) subcutaneous injection, or a placebo-MNP and an MRV subcutaneous injection (MRV-SC; Serum Institute of India, Pune, India). Unmasked staff ransomly assigned the participants using an online application, and they prepared visually identical preparations of the MRV-MNP or placebo-MNP and MRV-SC or placebo-SC, but were not involved in collecting endpoint data. Staff administering the study interventions, participants, parents, and study staff assessing trial endpoints were masked to treatment allocation. The safety population consists of all vaccinated participants, and analysis was conducted according to route of MRV administration, irrespective of subsequent protocol deviations. The immunogenicity population consisted of all vaccinated participants who had a baseline and day 42 visit result available, and who had no protocol deviations considered to substantially affect the immunogenicity endpoints. Solicited local and systemic adverse events were collected for 14 days following vaccination. Unsolicited adverse events were collected to day 180. Age de-escalation between cohorts was based on the review of the safety data to day 14 by an independent data monitoring committee. Serum neutralising antibodies to measles and rubella were measured at baseline, day 42, and day 180. Analysis was descriptive and included safety events, seroprotection and seroconversion rates, and geometric mean antibody concentrations. The trial was registered with the Pan African Clinical Trials Registry PACTR202008836432905, and is complete. FINDINGS: Recruitment took place between May 18, 2021, and May 27, 2022. 45 adults, 120 toddlers, and 120 infants were randomly allocated and vaccinated. There were no safety concerns in the first 14 days following vaccination in either adults or toddlers, and age de-escalation proceeded accordingly. In infants, 93% (52/56; 95% CI 83·0-97·2) seroconverted to measles and 100% (58/58; 93·8-100) seroconverted to rubella following MRV-MNP administration, while 90% (52/58; 79·2-95·2) and 100% (59/59; 93·9-100) seroconverted to measles and rubella respectively, following MRV-SC. Induration at the MRV-MNP application site was the most frequent local reaction occurring in 46 (77%) of 60 toddlers and 39 (65%) of 60 infants. Related unsolicited adverse events, most commonly discolouration at the application site, were reported in 35 (58%) of 60 toddlers and 57 (95%) of 60 infants that had received the MRV-MNP. All local reactions were mild. There were no related severe or serious adverse events. INTERPRETATION: The safety and immunogenicity data support the accelerated development of the MRV-MNP. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: Wearing protective helmets is an important prevention strategy to reduce work-related traumatic brain injuries. The existing standardized testing systems are used for quality control and do not provide a quantitative measure of the helmet performance. OBJECTIVE: To analyze the failure characterizations of Type I industrial helmets and develop a generalized approach to quantify the shock absorption performance of Type I industrial helmets based on the existing standardized setups. METHODS: A representative basic Type I construction helmet model was selected for the study. Top impact tests were performed on the helmets at different drop heights using two different impactor masses (3.6 and 5.0 kg). RESULTS: When the helmets were impacted with potential impact energies smaller than the critical potential impact energy values, there was a consistent relationship between the peak impact force and the potential impact energy. When the helmets were impacted under potential impact energies greater than the critical potential impact energy values, the peak impact forces increased steeply with increasing potential impact energy. CONCLUSION: A concept of safety margin for construction helmets based on potential impact energy was introduced to quantify the helmets' shock absorption performance. The proposed method will help helmet manufacturers improve their product quality.

BACKGROUND: Vaccine effectiveness (VE) is essential to monitor the performance of vaccines and generate strategic information to guide decision making. We pooled data from six Latin American countries to estimate the effectiveness of COVID-19 vaccines in preventing laboratory-confirmed SARS-CoV-2 hospitalisation during three different pandemic waves from February 2021 to September 2022. METHODS: We used a test-negative case-control design in hospitalised adults in Chile, Costa Rica, Ecuador, Guatemala, Paraguay, and Uruguay. We estimated adjusted VE by age group (18-64 and ≥65 years), vaccine type and product for primary series vaccination and booster vaccination and by time since last dose during the Omicron variant dominant period. We used mixed effects logistic regression models adjusting for sex, age, week of onset of symptom onset and pre-existing conditions with country fit as a random effect term. FINDINGS: We included 15,241 severe acute respiratory infection (SARI) patients in the analysis. Among adults 18-64 years, VE estimates for primary series vaccination during pre-Delta and Delta periods ranged by product from 66.5% to 95.1% and from 33.5% to 88.2% for older adults. During the Omicron period, VE estimates for primary series were lower and decreased by time since last vaccination, but VE increased to between 26.4% and 57.4% when a booster was administered. INTERPRETATION: mRNA and viral vector vaccines presented higher VE for both primary series and booster. While VE decreased over time, protection against severe COVID-19-associated hospitalisation increased when booster doses were administered. Vaccination with additional doses should be recommended, particularly for persons at increased risk of developing severe COVID-19. FUNDING: This work was supported by a grant from the U.S. Centers for Disease Control and Prevention (CDC) through cooperative agreements with the Pan American Health Organization/World Health Organization.

Sickle cell disease (SCD) remains a public health priority in the United States because of its association with complex health needs, reduced life expectancy, lifelong disabilities, and high cost of care. A cross-sectional analysis was conducted to calculate the crude and race-specific birth prevalence for SCD using state newborn screening program records during 2016-2020 from 11 Sickle Cell Data Collection program states. The percentage distribution of birth mother residence within Social Vulnerability Index quartiles was derived. Among 3,305 newborns with confirmed SCD (including 57% with homozygous hemoglobin S or sickle β-null thalassemia across 11 states, 90% of whom were Black or African American [Black], and 4% of whom were Hispanic or Latino), the crude SCD birth prevalence was 4.83 per 10,000 (one in every 2,070) live births and 28.54 per 10,000 (one in every 350) non-Hispanic Black newborns. Approximately two thirds (67%) of mothers of newborns with SCD lived in counties with high or very high levels of social vulnerability; most mothers lived in counties with high or very high levels of vulnerability for racial and ethnic minority status (89%) and housing type and transportation (64%) themes. These findings can guide public health, health care systems, and community program planning and implementation that address social determinants of health for infants with SCD. Implementation of tailored interventions, including increasing access to transportation, improving housing, and advancing equity in high vulnerability areas, could facilitate care and improve health outcomes for children with SCD.

INTRODUCTION: Highly sensitive acute flaccid paralysis (AFP) surveillance is critical for detection of poliovirus circulation and documentation for polio-free certification. The reverse cold chain (RCC) is a system designed to maintain stool specimens in appropriate temperature for effective detection of poliovirus in the laboratory. We monitored the RCC of AFP surveillance in Nigeria to determine its effectiveness in maintaining viability of enterovirus. METHODS: A descriptive cross-sectional study was conducted from November 2017 to December 2019. We included AFP cases from 151 Local Government Areas and monitored RCC of paired stool specimens from collection to arrival at laboratories. The national guideline recommends RCC temperature of +2 to +8°C and a non-polio enterovirus (NPENT) detection rate of ≥10%. We analyzed data with Epi Info 7, and presented results as frequencies and proportions, using Chi-square statistic to test for difference in enterovirus isolation. RESULTS: Of the 1,042 tracked paired stool specimens, 1,038(99.6%) arrived at the laboratory within 72 hours of collection of second specimen, 824(79.1%) were maintained within recommended temperature range, and 271(26%) yielded enteroviruses: 200(73.8%) NPENT, 66(24.4%) Sabin, 3(1.1%) vaccine derived poliovirus type 2 and 2(0.7%) mixture of Sabin and NPENT. The NPENT and Sabin rates were 19.2% and 6.7% respectively. Twenty-five percent of 824 specimens maintained within recommended temperature range, compared with 29.8% of 218 specimens with temperature excursion yielded enteroviruses (P=0.175). CONCLUSION: the RCC of AFP surveillance system in the study area was optimal and effective in maintaining the viability of enteroviruses. It was unlikely that poliovirus transmission was missed during the intervention.

INTRODUCTION: Routine Immunization (RI) is a key strategy in prevention of vaccine-preventable diseases (VPD). The Nigerian Demographic and Health survey 2013 showed that only 55% of children were fully immunized in Osun State. Historically, efforts to improve uptake of RI focused on health system factors with little attention on maternal related factors. This study assessed mothers´ knowledge, attitude, and perception towards the RI program in Atakumosa West Local Government Area (LGA) of Osun State. METHODS: A total of 750 mothers were enrolled in a household survey using WHO cluster sampling in Atakumosa West LGA. Semi-structured questionnaires were used to obtain data on sociodemographic characteristics, knowledge on RI, attitudes, and perception of mothers towards RI program. Knowledge scores of ≥ 4 points based on six-point domain questions were regarded as good. RESULTS: The mean (±SD) age of the mothers was 27.9 (± 6.1) years; 76% (571/750) had good knowledge of RI and VPD and a majority demonstrated a positive attitude towards the RI program. Antenatal care (ANC) attendance [OR 3.7; 95% CI (2.0 - 6.7)] health facility delivery [OR 1.7 (1.2 - 2.7)]; higher level of education [OR 1.9; 95% CI (1.4 - 2.5)], and mothers´ tetanus toxoid immunization status [OR 4.0 (2.3 - 7.2)] were significantly associated with having good knowledge of the RI program. CONCLUSION: A high proportion of mothers in Atakumosa West LGA of Osun State have good knowledge on childhood RI program. Current efforts at health education in ANC should be sustained and other strategies to improve knowledge on immunization need to be identified.

INTRODUCTION: High quality, timely and complete immunization data are essential for program planning and decision-making. In Nigeria, the National Health Management Information System (NHMIS) Routine Immunization (RI) module and dashboard (on the District Health Information System version 2 (DHIS2) platform) support the use of real time RI data. We deployed an automated short message service (SMS) notification system that works with the existing RI module to facilitate improvements in RI data in the DHIS2. METHODS: A pilot project was performed using intervention and control local government areas (LGAs). A mixed methods approach using both qualitative and quantitative methods was used to evaluate the system. We assessed changes in reporting rates across different reports. The evaluation also included baseline and post-intervention surveys of health facility (HF) staff. RESULTS: Reporting timeliness (76% pre and 99% post intervention) and completeness (83% pre and 99% post intervention) were consistently higher during the post-intervention than the pre-intervention period for facilities in the intervention LGA while reporting timeliness (65% pre and 66% post intervention) and completeness (71% and 77% post intervention) for facilities in the control LGA showed no change. Users reported that the SMS system was easy to understand and helped to facilitate improvements in consistency of data and timeliness of reporting. Inability of health care workers to effect changes at the HF level and the lack of immediate feedback were reported as key challenges to timeliness and quality of reports. CONCLUSION: An SMS-based intervention improved timeliness and completeness of health data reporting. However, the intervention should be evaluated on a larger scale over a longer time period before considering a national implementation.

INTRODUCTION: the National Primary Health Care Development Agency, African Field Epidemiology Network, United States Centers for Disease Control and Prevention and the Bill and Melinda Gates Foundation are implementing a Routine Immunization (RI) Module as part of their Routine Health Data Management System based on the 2013 - 2015 Accountability Framework for RI in Nigeria. To inform planning and evidence-based decision making, a data management needs assessment was conducted in Bauchi state which was one of the states selected for the deployment of the DHIS2 RI module. METHODS: desk reviews were conducted, and a semi-structured questionnaire was administered in four Local Government Areas (LGAs) in Bauchi state that were selected based on the initial evaluation of the performance of all 20 Bauchi LGAs. Ganjuwa and Shira were selected as high-performing LGAs and Alkaleri and Bogoro as low-performing LGAs. Four Health Facilities (HF) were selected in each LGA based on rural or urban classification, type of HFs (private or public), security and accessibility. RESULTS: local Immunization Officers (LIOs) prepare monthly reports in high-performing LGAs, and Community Health Care workers are mostly (69%) responsible for report compilation at the HFs. Shira and Alkaleri met 77% and 44% of training indicator targets, respectively, in the previous 12 months. Data recording and reporting was the type of training received the most by health facility personnel. Functioning refrigerators were in all visited LGAs, working thermometer and updated temperature monitoring charts were available in all the cold chain stores. However, no health facility reported having available computers for data-related activities. CONCLUSION: this assessment provided an improved understanding of the Bauchi state Routine Health Data Management System and informed the content of the state-wide scale-up.

INTRODUCTION: Operational gaps in the Global Polio Eradication Initiative implementation had been partly responsible for inadequate population immunity and the continued transmission of wild poliovirus in Nigeria before the African Region was declared polio-free in 2020. Missed opportunities to provide services in nomadic populations due to frequent mobility, lack of inclusion in microplans and the remoteness of their settlements were the major challenges. During May 2013 we conducted immunization outreach to nomadic and other underserved communities in Rabah LGA, Sokoto state, and Ardo Kola LGA, Taraba state, in Nigeria to identify and vaccinate children missed during supplemental immunization activities while identifying missed acute flaccid paralysis cases. METHODS: An enumeration checklist and data collection instruments on Android cell phones were used to capture socio-demographic data and GPS coordinates on nomadic settlements, households, number of children aged <5 years, children previously missed for vaccination and their locations. Local guides led trained enumerators to underserved communities for the enumeration and vaccination. Data were analyzed using Microsoft Excel 2007. RESULTS: A total of 324 settlements were listed for the two states, and 111 (34.3%) of these were identified as missed when compared with micro-planning for the most recent SIA. In these settlements, 3,533 households and 9,385 children aged <5 years were listed. We administered oral poliovirus vaccine to all 1,946 missed children during the recent or any supplemental immunization activities. Of these, 527 (27.1%) had never been vaccinated. We found no missed acute flaccid paralysis cases. CONCLUSION: Nomadic populations continue to be underserved, especially for vaccination services. This results in pockets of populations with low herd immunity and increased risk for poliovirus transmission. Community leaders and nomadic settlements should be included in the micro-planning of all supplemental immunization activities to ensure all children receive vaccination services.

INTRODUCTION: In July 2012, the National Stop Transmission of Polio (NSTOP) program was established to support the Government of Nigeria in interrupting transmission of poliovirus and strengthen routine immunization (RI). NSTOP has approximately 300 staff members with the majority based at the Local Government Area (LGA) level in northern Nigeria. METHODS: An internal assessment of NSTOP was conducted from November 2015 to February 2016 to document the program´s contribution to Nigeria´s immunization program and plan future NSTOP engagement. A mixed methods design was used, with data gathered from health facility, LGA, state, and national levels, through structured surveys, interviews, focus group discussions, and review of program records. Survey and expenditure data were summarized by frequency and trends over time, while interview and focus group data were analyzed qualitatively for key themes. RESULTS: The majority of the 111 non-NSTOP LGA respondents reported that NSTOP officers supported polio campaigns (100%) and supervised RI sessions (99.1%). Out of 181 respondents at health facility level, the majority reported that NSTOP trainings improved their knowledge (83.3%) and skills (76.2%) on RI, and NSTOP officers regularly supervised their RI sessions (96.7%). Most respondents reported that there would be a negative impact on immunization activities if NSTOP officers were withdrawn. CONCLUSION: Future implementation of NSTOP should be realigned to (a) give highest priority to mentoring LGA staff to build institutional capacity, (b) ensure increased capacity translates to improved provision of RI services, and (c) improve routine review of program monitoring data to assess progress in both polio and RI programs.