OBJECTIVES: After respiratory syncytial virus (RSV), human metapneumovirus (hMPV) was the second-ranked pathogen attributed to severe pneumonia in the PERCH study. We sought to characterize hMPV-positive cases in high-burden settings, which have limited data, by comparing with RSV-positive and other cases. METHODS: Children aged 1-59 months hospitalized with suspected severe pneumonia and age/season-matched community controls in seven African and Asian countries had nasopharyngeal/oropharyngeal swabs tested by multiplex PCR for 32 respiratory pathogens, among other clinical and lab assessments at admission. Odds ratios adjusted for age and site (adjusted OR [aOR]) were calculated using logistic regression. Aetiologic probability was estimated using Bayesian nested partial latent class analysis. Latent class analysis identified syndromic constellations of clinical characteristics. RESULTS: hMPV was detected more frequently among cases (267/3887, 6.9%) than controls (115/4976, 2.3%), among cases with pneumonia chest X-ray findings (8.5%) than without (5.5%), and among controls with respiratory tract illness (3.8%) than without (1.8%; all p ≤ 0.001). HMPV-positive cases were negatively associated with the detection of other viruses (aOR, 0.18), especially RSV (aOR, 0.11; all p < 0.0001), and positively associated with the detection of bacteria (aORs, 1.77; p 0.03). No single clinical syndrome distinguished hMPV-positive from other cases. Among hMPV-positive cases, 65.2% were aged <1 year and 27.5% had pneumonia danger signs; positive predictive value for hMPV aetiology was 74.5%; mortality was 3.9%, similar to RSV-positive (2.4%) and lower than that among other cases (9.6%). DISCUSSION: HMPV-associated severe paediatric pneumonia in high-burden settings was predominantly in young infants and clinically indistinguishable from RSV. HMPV-positives had low case fatality, similar to that in RSV-positives.

BACKGROUND: There is paucity of information on the role of cytomegalovirus (CMV) infection as a cause of stillbirths or childhood deaths in low-and middle-income countries (LMICs). We investigated attribution of CMV-disease in the causal pathway to stillbirths and deaths in children <5 years of age in seven LMICs participating in the Child Health and Mortality Prevention Surveillance (CHAMPS) network. METHODS: We analyzed stillbirths and decedents enrolled between December 2016 and July 2023. Deaths were investigated using post-mortem minimally invasive tissue sampling with histopathology and molecular diagnostic investigations of tissues and body fluids, along with review of clinical records. Multi-disciplinary expert panels reviewed findings and reported on the causal pathway to death. RESULTS: CMV was detected in 19.5%(1140/5841) of all evaluated deaths, including 5.0% (111/2204), 6.2% (139/2229), 41.2% (107/260), 68.1%(323/474) and 68.2%(460/674) of stillbirths, neonates (deaths 0-<28 days postnatal), young infants (28-<90 days), older infants (90-<365 days) and children (12-<60 months), respectively. CMV-disease was attributed in the causal pathway to death in 0.9%(20/2204) of stillbirths, 0.8%(17/2229) of neonates, 13.1% (34/260) of young infants, 9.7%(46/474) of older infants and 3.3%(22/674) of children. Decedents with CMV-disease compared with those without CMV-disease in the causal pathway, were more likely to have severe microcephaly (38.2% vs. 21.1%; aOR 2.2, 95%CI: 1.3-3.6) and HIV-infected (36.9% vs. 6.2%; aOR: 10.9, 95%CI: 6.5-18.5). CONCLUSIONS: CMV-disease is an important contributor to deaths during infancy and childhood and is often associated with severe microcephaly and HIV-infection. Improving management of CMV in HIV-infected children and a vaccine to prevent CMV are needed interventions.

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

Purpose: To investigate the prevalence, patterns, and predictors of SARS-CoV-2 RNA and culturable virus in tears of a case-ascertained household cohort. Design: Prospective, longitudinal case-ascertained household cohort identified through convenience sampling. MethodsThis analysis was restricted to individuals who were non-hospitalized, symptomatic, and tested positive for SARS-CoV-2 by nasal RT-PCR. Tears and anterior nasal biospecimens were serially collected throughout the acute period. Tears specimens were collected by the study staff using Schirmer test strips, and nasal specimens were self-collected. For both, SARS-CoV-2 RNA was quantified using qRT-PCR, and culturable virus was detected using presence of cytopathic effect (CPE) in tissue culture; positive CPE was confirmed by a qRT-PCR step. A series of cross-sectional unadjusted analyses were performed investigating the relationship between different sociodemographic determinants and biological factors associated with tears RNA positivity.

Accurate rapid diagnostic tests (RDTs) are needed to diagnose lymphatic filariasis (LF) in global elimination programmes. We evaluated the performance of the new STANDARD Q Filariasis Antigen Test (QFAT) against the Bioline Filariasis Test Strip (FTS) for detecting W. bancrofti antigen (Ag) in laboratory conditions, using serum (n = 195) and plasma (n = 189) from LF-endemic areas (Samoa, American Samoa and Myanmar) and Australian negative controls (n = 46). The prior Ag status of endemic samples (54.9% Ag-positive) was determined by rapid test (ICT or FTS) or Og4C3 ELISA. The proportion of samples testing positive at 10 min was similar for QFAT (44.8%) and FTS (41.3%). Concordance between tests was 93.5% (kappa 0.87, n = 417) at 10 min, and it increased to 98.8% (kappa 0.98) at 24 h. The sensitivities of QFAT and FTS at 10 min compared to the prior results were 92% (95% CI 88.0-96.0) and 86% (95% CI 80.0-90.0), respectively, and they increased to 97% and 99% at 24 h. Specificity was 98% for QFAT and 99% for FTS at 10 min. Both tests showed evidence of cross-reaction with Dirofilaria repens and Onchocerca lupi but not with Acanthochilonema reconditum or Cercopithifilaria bainae. Under laboratory conditions, QFAT is a suitable alternative RDT to FTS.

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.

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

BACKGROUND: Widespread use of pneumococcal conjugate vaccines (PCVs) has reduced vaccine-type invasive pneumococcal disease (IPD). We describe the serotype distribution of IPD after extensive use of ten-valent PCV (PCV10; Synflorix, GSK) and 13-valent PCV (PCV13; Prevenar 13, Pfizer) globally. METHODS: IPD data were obtained from surveillance sites participating in the WHO-commissioned Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project that exclusively used PCV10 or PCV13 (hereafter PCV10 and PCV13 sites, respectively) in their national immunisation programmes and had primary series uptake of at least 70%. Serotype distribution was estimated for IPD cases occurring 5 years or more after PCV10 or PCV13 introduction (ie, the mature period when the serotype distribution had stabilised) using multinomial Dirichlet regression, stratified by PCV product and age group (<5 years, 5-17 years, 18-49 years, and ≥50 years). FINDINGS: The analysis included cases occurring primarily between 2015 and 2018 from 42 PCV13 sites (63 362 cases) and 12 PCV10 sites (6806 cases) in 41 countries. Sites were mostly high income (36 [67%] of 54) and used three-dose or four-dose booster schedules (44 [81%]). At PCV10 sites, PCV10 serotypes caused 10·0% (95% CI 6·3-12·9) of IPD cases in children younger than 5 years and 15·5% (13·4-19·3) of cases in adults aged 50 years or older, while PCV13 serotypes caused 52·1% (49·2-65·4) and 45·6% (40·0-50·0), respectively. At PCV13 sites, PCV13 serotypes caused 26·4% (21·3-30·0) of IPD cases in children younger than 5 years and 29·5% (27·5-33·0) of cases in adults aged 50 years or older. The leading serotype at PCV10 sites was 19A in children younger than 5 years (30·6% [95% CI 18·2-43·1]) and adults aged 50 years or older (14·8% [11·9-17·8]). Serotype 3 was a top-ranked serotype, causing about 9% of cases in children younger than 5 years and 14% in adults aged 50 years or older at both PCV10 and PCV13 sites. Across all age and PCV10 or PCV13 strata, the proportion of IPD targeted by higher-valency PCVs beyond PCV13 was 4·1-9·7% for PCV15, 13·5-36·0% for PCV20, 29·9-53·8% for PCV21, 15·6-42·0% for PCV24, and 31·5-50·1% for PCV25. All top-ten ranked non-PCV13 serotypes are included in at least one higher-valency PCV. INTERPRETATION: The proportion of IPD due to serotypes included in PCVs in use was low in mature PCV10 and PCV13 settings. Serotype distribution differed between PCV10 and PCV13 sites and age groups. Higher-valency PCVs target most remaining IPD and are expected to extend impact. FUNDING: Bill & Melinda Gates Foundation as part of the WHO Pneumococcal Vaccines Technical Coordination Project.

BACKGROUND: Egg-based inactivated quadrivalent seasonal influenza vaccine (eIIV4), cell culture-based inactivated quadrivalent seasonal influenza vaccine (ccIIV4), and recombinant haemagglutinin (HA)-based quadrivalent seasonal influenza vaccine (RIV4) have been licensed for use in the USA. In this study, we used antigen-specific serum proteomics analysis to assess how the molecular composition and qualities of the serological antibody repertoires differ after seasonal influenza immunisation by each of the three vaccines and how different vaccination platforms affect the HA binding affinity and breadth of the serum antibodies that comprise the polyclonal response. METHODS: In this comparative, prospective, observational cohort study, we included female US health-care personnel (mean age 47·6 years [SD 8]) who received a single dose of RIV4, eIIV4, or ccIIV4 during the 2018-19 influenza season at Baylor Scott & White Health (Temple, TX, USA). Eligible individuals were selected based on comparable day 28 serum microneutralisation titres and similar vaccination history. Laboratory investigators were blinded to assignment until testing was completed. The preplanned exploratory endpoints were assessed by deconvoluting the serological repertoire specific to A/Singapore/INFIMH-16-0019/2016 (H3N2) HA before (day 0) and after (day 28) immunisation using bottom-up liquid chromatography-mass spectrometry proteomics (referred to as Ig-Seq) and natively paired variable heavy chain-variable light chain high-throughput B-cell receptor sequencing (referred to as BCR-Seq). Features of the antigen-specific serological repertoire at day 0 and day 28 for the three vaccine groups were compared. Antibodies identified with high confidence in sera were recombinantly expressed and characterised in depth to determine the binding affinity and breadth to time-ordered H3 HA proteins. FINDINGS: During September and October of the 2018-19 influenza season, 15 individuals were recruited and assigned to receive RIV4 (n=5), eIIV4 (n=5), or ccIIV4 (n=5). For all three cohorts, the serum antibody repertoire was dominated by back-boosted antibody lineages (median 98% [95% CI 88-99]) that were present in the serum before vaccination. Although vaccine platform-dependent differences were not evident in the repertoire diversity, somatic hypermutation, or heavy chain complementarity determining region 3 biochemical features, antibodies boosted by RIV4 showed substantially higher binding affinity to the vaccine H3/HA (median half-maximal effective concentration [EC50] to A/Singapore/INFIMH-16-0019/2016 HA: 0·037 μg/mL [95% CI 0·012-0·12] for RIV4; 4·43 μg/mL [0·030-100·0] for eIIV4; and 18·50 μg/mL [0·99-100·0] μg/mL for ccIIV4) and also the HAs from contemporary H3N2 strains than did those elicited by eIIV4 or ccIIV4 (median EC50 to A/Texas/50/2012 HA: 0·037 μg/mL [0·017-0·32] for RIV4; 1·10 μg/mL [0·045-100] for eIIV4; and 12·6 μg/mL [1·8-100] for ccIIV4). Comparison of B-cell receptor sequencing repertoires on day 7 showed that eIIV4 increased the median frequency of canonical egg glycan-targeting B cells (0·20% [95% CI 0·067-0·37] for eIIV4; 0·058% [0·050-0·11] for RIV4; and 0·035% [0-0·062] for ccIIV4), whereas RIV4 vaccination decreased the median frequency of B-cell receptors displaying stereotypical features associated with membrane proximal anchor-targeting antibodies (0·062% [95% CI 0-0·084] for RIV4; 0·12% [0·066-0·16] for eIIV4; and 0·18% [0·016-0·20] for ccIIV4). In exploratory analysis, we characterised the structure of a highly abundant monoclonal antibody that binds to both group 1 and 2 HAs and recognises the HA trimer interface, despite its sequence resembling the stereotypical sequence motif found in membrane-proximal anchor binding antibodies. INTERPRETATION: Although all three licensed seasonal influenza vaccines elicit serological antibody repertoires with indistinguishable features shaped by heavy imprinting, the RIV4 vaccine selectively boosts higher affinity monoclonal antibodies to contemporary strains and elicits greater serum binding potency and breadth, possibly as a consequence of the multivalent structural features of the HA immunogen in this vaccine formulation. Collectively, our findings show advantages of RIV4 vaccines and more generally highlight the benefits of multivalent HA immunogens in promoting higher affinity serum antibody responses. FUNDING: Centers for Disease Control and Prevention, National Institutes of Health, and Bill & Melinda Gates Foundation.

INTRODUCTION: Malnutrition contributes to 45% of all childhood deaths globally, but these modelled estimates lack direct measurements in countries with high malnutrition and under-5 mortality rates. We investigated malnutrition's role in infant and child deaths in the Child Health and Mortality Prevention Surveillance (CHAMPS) network. METHODS: We analysed CHAMPS data from seven sites (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone and South Africa) collected between 2016 and 2023. An expert panel assessed each death to determine whether malnutrition was an underlying, antecedent or immediate cause or other significant condition. Malnutrition was further classified based on postmortem anthropometry using WHO growth standards for underweight (z-scores for weight-for-age <-2), stunting (length-for-age <-2), and wasting (weight-for-length or MUAC Z-scores <-2). RESULTS: Of 1601 infant and child deaths, malnutrition was considered a causal or significant condition in 632 (39.5%) cases, including 85 (13.4%) with HIV infection. Postmortem measurements indicated 90.1%, 61.2% and 94.1% of these cases were underweight, stunted and wasted, respectively. Most malnutrition-related deaths (n=632) had an infectious cause (89.1%). The adjusted odds of having malnutrition as causal or significant condition were 2.4 (95% CI 1.7 to 3.2) times higher for deaths involving infectious diseases compared with other causes. Common pathogens in the causal pathway for malnutrition-related deaths included Klebsiella pneumoniae (30.4%), Streptococcus pneumoniae (21.5%), Plasmodium falciparum (18.7%) and Escherichia coli/Shigella (17.2%). CONCLUSION: Malnutrition was identified as a causal or significant factor in 39.5% of under-5 deaths in the CHAMPS network, often in combination with infectious diseases. These findings highlight the need for integrated interventions addressing both malnutrition and infectious diseases to effectively reduce under-5 mortality.

BACKGROUND: The role of meningitis in causing deaths and in children under 5 is unclear, especially since widespread use of vaccines to prevent common causes of meningitis. Child Health and Mortality Prevention Surveillance (CHAMPS) uses post-mortem minimally invasive tissue sampling (MITS) and ante-mortem data to explore death causes. We aimed to assess meningitis's contribution to mortality and identify causative pathogens in children under 5 within CHAMPS Network sites. METHOD: In this observational study, we analyzed deaths in live-born children <5 years of age that occurred between December 16, 2016, and December 31, 2023, in CHAMPS catchments in six sub-Saharan African countries (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, South Africa) and Bangladesh. MITS was conducted within 24-72hours of death, including blood and cerebrospinal fluid (CSF) culture, multi-organism targeted nucleic acid amplification tests on blood, CSF and lung tissue, and histopathology of lung, liver and brain. Expert panels at each site reviewed data to attribute causes of death following ICD-10 standards. RESULT: Meningitis was in the causal pathway for 7.0% (270/3857) of deaths; in 4.8% (13/270) meningitis was considered the underlying condition. Neonates accounted for 65.9% (178/270) and infants or children 34.1% (92/270). Among neonatal meningitis deaths, 55.6% (99/178) occurred ≥72hours post-hospital admission; and common pathogens were Acinetobacter baumannii (49.5%, 49/99; mainly from South Africa) and Klebsiella pneumoniae (40.4%, 40/99). Forty-four percent (79/178) of neonatal meningitis deaths were community-associated, primarily due to K. pneumoniae (35.4%, 28/79) and Escherichia coli (13.9%, 11/79). Among infant and child meningitis deaths, 43.5% (40/92) occurred ≥72hours post-admission; and common pathogens were K. pneumoniae (42.5%,17/40) and A. baumannii (17.5%, 7/40). Among community-associated meningitis deaths in infants and children (56.5%, 52/92), Streptococcus pneumoniae (34.6%, 18/52) and K. pneumoniae (19.2%, 10/52) were common pathogens. Pathogen prevalence varied by region. CONCLUSION: Our study highlights meningitis as a significant contributor to under-5 mortality in low-middle-income countries. The prominent role of K. pneumoniae and A. baumannii, particularly in healthcare settings and specific regions, highlights the need for better infection control, targeted interventions, and more effective treatment strategies.

BACKGROUND: The COVID-19 pandemic has generated a demand for timely data, resulting in a surge of mobile phone surveys for tracking the impacts of and responses to the pandemic. Mobile phone surveys have become a preferred mode of data collection across low- and middle-income countries. OBJECTIVE: This study piloted 2 population-based, cross-sectional mobile phone surveys among Sri Lankan residents in 2020 and 2021 during the COVID-19 pandemic. The surveys aimed to gather data on knowledge, attitudes, and practices, vaccine acceptability, availability, and barriers to COVID-19 testing, and use of a medicine distribution service. METHODS: The study used Surveda, an open-source survey tool developed by the NCD (noncommunicable disease) Mobile Phone Survey Data 4 Health Initiative, for data collection and management. The surveys were conducted through interactive voice response using automated, prerecorded messages in Sinhala, Tamil, and English. The sample design involved random sampling of mobile phone numbers, stratified by sex, proportional to the general population. Eligibility criteria varied between surveys, targeting adults aged 35 years and older with any noncommunicable disease for the first survey and all adults for the second survey. The data were adjusted to population estimates, and statistical analysis was conducted using SAS (SAS Institute) and R software (R Core Team). Descriptive statistics, Rao-Scott chi-square tests, and z tests were used to analyze the data. Response rates, cooperation rates, and productivity of the sampling approach were calculated. RESULTS: In the first survey, n=5001, the overall response rate was 7.5%, with a completion rate of 85.6%. In the second survey, n=1250, the overall response rate was 10.9%, with a completion rate of 61.9%. Approximately 3 out of 4 adults reported that they avoided public places (888/1175, 75.6%), more than two-thirds avoided public transportation (808/1173, 68.9%), and 9 out of 10 practiced physical distancing (1046/1167, 89.7%). Approximately 1 out of 10 Sri Lankan persons reported being tested for COVID-19, and the majority of those received a polymerase chain reaction test (112/161, 70%). Significantly more males than females reported being tested for COVID-19 (98/554, 17.8% vs 61/578, 10.6%, respectively; P<.001). Finally, the majority of adult Sri Lankan people reported that they definitely or probably would get the COVID-19 vaccination (781/1190, 65.7%). CONCLUSIONS: The surveys revealed that, overall, the adult Sri Lankan population adhered to COVID-19 mitigation strategies. These findings underscore the use of mobile phone surveys in swiftly and easily providing essential data to inform a country's response during the COVID-19 pandemic, obviating the need for face-to-face data collection.

<sec><title>BACKGROUND</title>Understanding the motivations behind clinical trial participation can help enhance recruitment strategies and determine the generalizability of trial results. This study focuses on the reasons for participating in or declining the Tuberculosis Trials Consortium Study 33 (iAdhere), a clinical trial on the treatment of latent tuberculosis infection (LTBI).</sec><sec><title>METHODS</title>A quantitative evaluation was conducted among screened patients to ascertain their reasons for participating or not in the iAdhere trial. The study gathered data from enrolled participants and those who chose not to enroll.</sec><sec><title>RESULTS</title>Among 1,002 enrolled individuals, 290 participants provided 749 reasons for enrolling. The most common reasons included access to shorter treatment regimens (56%), avoiding progression to TB disease (45%), and improving health (21%). Of the 670 eligible persons who chose not to enroll, 551 individuals provided 800 reasons, with the most common being a preference for standard therapy (17%), disinterest in study medication or TB therapy (both 13%), and the inconvenience of daily observed treatment (12%).</sec><sec><title>CONCLUSION</title>The desire for shorter treatment options and preventing active disease motivates participation in LTBI trials. The diverse reasons for declining enrolment suggest the importance of developing targeted recruitment strategies. These findings support exploring shorter treatment regimens and can guide future recruitment efforts.</sec>.

To explore pediatricians' perspectives on supporting intimate partner violence (IPV) survivors, including (a) clinical practices and resource use, (b) ideal resources, and (c) barriers to the use of existing resources, we conducted dyadic and individual virtual interviews with pediatricians recruited through Twitter and the American Academy of Pediatrics Council, section, and chapter listservs. The interviews were approximately 60 minutes in length, audio recorded, and transcribed verbatim. We used a thematic analysis approach and hybrid deductive–inductive coding. Twenty-three pediatricians participated in 14 interviews. We identified four themes. Participants' current practices primarily focused on IPV screening and response to disclosure. They described strategies for IPV resource provision and decision-making involving child protective services. They identified multilevel barriers to addressing IPV, including barriers, such as time, identified in previous studies as well as barriers related to the COVID-19 pandemic, telehealth, the electronic health record, and disclosure-focused approaches. The participants desired provider-facing and caregiver-facing resources to strengthen the capacity to address IPV; some were unaware of currently available resources. They noted the need for continued attention to optimizing systems to enhance their capacity to support IPV survivors. Pediatricians report varying practices to address IPV and identify several surmountable barriers to supporting IPV survivors. Our study suggests that disclosure-driven clinical practices, confidentiality concerns, and lack of resources limit pediatricians' capacity to address IPV. Additional resource development and dissemination efforts are needed to improve the awareness of IPV resources currently available to pediatricians and families.

BACKGROUND: To monitor the progress of lymphatic filariasis (LF) elimination programmes, field surveys to assess filarial antigen (Ag) prevalence require access to reliable, user-friendly rapid diagnostic tests. We aimed to evaluate the performance of the new Q Filariasis Antigen Test (QFAT) with the currently recommended Filariasis Test Strip (FTS) for detecting the Ag of Wuchereria bancrofti, the causative agent of LF, under field laboratory conditions. METHODOLOGY/PRINCIPAL FINDINGS: During an LF survey in Samoa, 344 finger-prick blood samples were tested using FTS and QFAT. Microfilariae (Mf) status was determined from blood slides prepared from any sample that reported Ag-positive by either Ag-test. Each test was re-read at 1 hour and the next day to determine the stability of results over time. Overall Ag-positivity by FTS was 29.0% and 30.2% by QFAT. Concordance between the two tests was 93.6% (kappa = 0.85). Of the 101 Mf slides available, 39.6% were Mf-positive, and all were Ag-positive by both tests. Darker test line intensities from Ag-positive FTS were found to predict Mf-positivity (compared to same/lighter line intensities). QFAT had significantly higher reported test result changes than FTS, mostly reported the next day, but fewer changes were reported between 10 minutes to 1-hour. The field laboratory team preferred QFAT over FTS due to the smaller blood volume required, better usability, and easier readability. CONCLUSION/SIGNIFICANCE: QFAT could be a suitable and user-friendly diagnostic alternative for use in the monitoring and surveillance of LF in field surveys based on its similar performance to FTS under field laboratory conditions.

In resource-limited settings where vital registration and medical death certificates are unavailable or incomplete, verbal autopsy (VA) is often used to attribute causes of death (CoD) and prioritize resource allocation and interventions. We aimed to determine the CoD concordance between InterVA and CHAMPS's method. The causes of death (CoDs) of children <5 were determined by two methods using data from seven low- and middle-income countries (LMICs) enrolled in the Child Health and Mortality Prevention Surveillance (CHAMPS) network. The first CoD method was from the DeCoDe panel using data from Minimally Invasive Tissue Sampling (MITS), whereas the second method used Verbal Autopsy (VA), which utilizes the InterVA software. This analysis evaluated the agreement between the two using Lin's concordance correlation coefficient. The overall concordance of InterVA4 and DeCoDe in assigning causes of death across surveillance sites, age groups, and causes of death was poor (0.75 with 95% CI: 0.73-0.76) and lacked precision. We found substantial differences in agreement by surveillance site, with Mali showing the lowest and Mozambique and Ethiopia the highest concordance. The InterVA4 assigned CoD agrees poorly in assigning causes of death for U5s and stillbirths. Because VA methods are relatively easy to implement, such systems could be more useful if algorithms were improved to more accurately reflect causes of death, for example, by calibrating algorithms to information from programs that used detailed diagnostic testing to improve the accuracy of COD determination.

The Centers for Disease Control and Prevention (CDC) responds to public health emergencies at various levels within its organization. Overtime, CDC's response capabilities have matured across the organization due to years of emergency management investment and experience across the agency. In 2019, CDC began to implement the Graduated Response Framework to formalize an approach for managing public health emergencies that recognizes its response capabilities and meets the evolving needs of the country. This brief report summarizes CDC's Graduated Response Framework structure, and how response management escalates and de-escalates according to resource needs and complexity.

The goals of the Association for Molecular Pathology (AMP) Clinical Practice Committee's Pharmacogenomics (PGx) Working Group are to define the key attributes of pharmacogenetic alleles recommended for clinical testing and a minimum set of variants that should be included in clinical PGx genotyping assays. This document series provides recommendations for a minimum set of variant alleles (Tier 1) and an extended list of variant alleles (Tier 2) that will aid clinical laboratories when designing assays for PGx testing. The AMP PGx Working Group considered the functional impact of the variant alleles, allele frequencies in multiethnic populations, the availability of reference materials, and other technical considerations for PGx testing when developing these recommendations. The goal of this Working Group is to promote standardization of PGx testing across clinical laboratories. This document will focus on clinical DPYD PGx testing that may be applied to all DPD-related medications. These recommendations are not to be interpreted as prescriptive but to provide a reference guide.

BACKGROUND: The majority of recent estimates on the direct medical cost attributable to hospital-onset infections (HOIs) has focused on device- or procedure-associated HOIs. The attributable costs of HOIs that are not associated with device use or procedures have not been extensively studied. OBJECTIVE: We developed simulation models of attributable cost for 16 HOIs and estimated the total direct medical cost, including nondevice-related HOIs in the USA for 2011 and 2015. DATA AND METHODS: We used total discharge costs associated with HOI-related hospitalization from the National Inpatient Sample and applied an analogy costing methodology to develop simulation models of the costs attributable to HOIs. The mean attributable cost estimate from the simulation analysis was then multiplied by previously published estimates of the number of HOIs for 2011 and 2015 to generate national estimates of direct medical costs. RESULTS: After adjusting all estimates to 2017 US dollars, attributable cost estimates for select nondevice-related infections attributable cost estimates ranged from $7661 for ear, eye, nose, throat, and mouth (EENTM) infections to $27,709 for cardiovascular system infections in 2011; and from $8394 for EENTM to $26,445 for central nervous system infections in 2016 (based on 2015 incidence data). The national direct medical costs for all HOIs were $14.6 billion in 2011 and $12.1 billion in 2016. Nondevice- and nonprocedure-associated HOIs comprise approximately 26-28% of total HOI costs. CONCLUSION: Results suggest that nondevice- and nonprocedure-related HOIs result in considerable costs to the healthcare system.

BACKGROUND: U.S. construction workers experience high rates of injury that can lead to chronic pain. This pilot study examined nonpharmacological (without medication prescribed by healthcare provider) and pharmacological (e.g., prescription opioids) pain management approaches used by construction workers. METHODS: A convenience sample of U.S. construction workers was surveyed, in partnership with the U.S. National Institute for Occupational Safety and Health (NIOSH) Construction Sector Program. Differences in familiarity and use of nonpharmacological and pharmacological pain management approaches, by demographics, were assessed using logistic regression models. A boosted regression tree model examined the most influential factors related to pharmacological pain management use, and potential reductions in use were counterfactually modeled. RESULTS: Of 166 (85%) of 195 participants reporting pain/discomfort in the last year, 72% reported using pharmacological pain management approaches, including 19% using opioids. There were significant differences in familiarity with nonpharmacological approaches by gender, education, work experience, and job title. Among 37 factors that predicted using pharmacological and non-pharmacological pain management approaches, training on the risks of opioids, job benefits for unpaid leave and paid disability, and familiarity with music therapy, meditation or mindful breathing, and body scans were among the most important predictors of potentially reducing use of pharmacological approaches. Providing these nonpharmacological approaches to workers could result in an estimated 23% (95% CI: 16%-30%) reduction in pharmacological pain management approaches. CONCLUSION: This pilot study suggests specific factors related to training, job benefits, and worker familiarity with nonpharmacological pain management approaches influence use of these approaches.

CONTEXT: Contributing to the evidence base, by disseminating findings through written products such as journal articles, is a core competency for public health practitioners. Disseminating practice-based evidence that supports improving cardiovascular health is necessary for filling literature gaps, generating health policies and laws, and translating evidence-based strategies into practice. However, a gap exists in the dissemination of practice-based evidence in public health. Public health practitioners face various dissemination barriers (eg, lack of time and resources, staff turnover) which, more recently, were compounded by the COVID-19 pandemic. PROGRAM: The Centers for Disease Control and Prevention's Division for Heart Disease and Stroke Prevention (DHDSP) partnered with the National Network of Public Health Institutes to implement a multimodal approach to build writing capacity among recipients funded by three DHDSP cooperative agreements. This project aimed to enhance public health practitioners' capacity to translate and disseminate their evaluation findings. IMPLEMENTATION: Internal evaluation technical assistance expertise and external subject matter experts helped to implement this project and to develop tailored multimodal capacity-building activities. These activities included online peer-to-peer discussion posts, virtual writing workshops, resource documents, one-to-one writing coaching sessions, an online toolkit, and a supplemental issue in a peer-reviewed journal. EVALUATION: Findings from an informal process evaluation demonstrate positive results. Most participants were engaged and satisfied with the project's activities. Across eight workshops, participants reported increased knowledge (≥94%) and enhanced confidence in writing (≥98%). The majority of participants (83%) reported that disseminating evaluation findings improved program implementation. Notably, 30 abstracts were submitted for a journal supplement and 23 articles were submitted for consideration. DISCUSSION: This multimodal approach serves as a promising model that enhances public health practitioners' capacity to disseminate evaluation findings during times of evolving health needs.

Dengue is the most prevalent mosquito-borne viral disease in humans, and cases are continuing to rise globally. In particular, islands in the Caribbean have experienced more frequent outbreaks, and all four dengue virus (DENV) serotypes have been reported in the region, leading to hyperendemicity and increased rates of severe disease. However, there is significant variability regarding virus surveillance and reporting between islands, making it difficult to obtain an accurate understanding of the epidemiological patterns in the Caribbean. To investigate this, we used travel surveillance and genomic epidemiology to reconstruct outbreak dynamics, DENV serotype turnover, and patterns of spread within the region from 2009-2022. We uncovered two recent DENV-3 introductions from Asia, one of which resulted in a large outbreak in Cuba, which was previously under-reported. We also show that while outbreaks can be synchronized between islands, they are often caused by different serotypes. Our study highlights the importance of surveillance of infected travelers to provide a snapshot of local introductions and transmission in areas with limited local surveillance and suggests that the recent DENV-3 introductions may pose a major public health threat in the region.

OBJECTIVE: To examine the relationship between stroke care infrastructure and stroke quality-of-care outcomes at 29 spoke hospitals participating in the <name concealed for blinding purposes> hub-and-spoke telestroke network. MATERIALS AND METHODS: Encounter-level data from <name concealed for blinding purposes> telestroke patient registry were filtered to include encounters during 2015-2022 for patients aged 18 and above with a clinical diagnosis of acute ischemic stroke, and who received intravenous tissue plasminogen activator. Unadjusted and adjusted generalized estimating equations assessed associations between time-related stroke quality-of-care metrics captured during the encounter and the existence of the two components of stroke care infrastructure-stroke coordinators and stroke center certifications-across all hospitals and within hospital subgroups defined by size and rurality. RESULTS: Telestroke encounters at spoke hospitals with stroke coordinators and stroke center certifications were associated with shorter door-to-needle (DTN) times (60.9 min for hospitals with both components and 57.3 min for hospitals with one, vs. 81.2 min for hospitals with neither component, p <.001). Similar patterns were observed for the percentage of encounters with DTN time of ≤60 min (63.8% and 68.9% vs. 32.0%, p <.001) and ≤45 min (34.0% and 38.4% vs. 8.42%, p <.001). Associations were similar for other metrics (e.g., door-to-registration time), and were stronger for smaller (vs. larger) hospitals and rural (vs. urban) hospitals. CONCLUSIONS: Stroke coordinators or stroke center certifications may be important for stroke quality of care, especially at spoke hospitals with limited resources or in rural areas.

INTRODUCTION: In 2012, the World Health Organization revised treatment guidelines for childhood pneumonia with lower chest wall indrawing (LCWI) but no 'danger signs', to recommend home-based treatment. We analysed data from children hospitalized with LCWI pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) study to identify sub-groups with high odds of mortality, who might continue to benefit from hospital management but may not be admitted by staff implementing the 2012 guidelines. We compare the proportion of deaths identified using the criteria in the 2012 guidelines, and the proportion of deaths identified using an alternative set of criteria from our model. METHODS: PERCH enrolled a cohort of 2189 HIV-negative children aged 2-59 months who were admitted to hospital with LCWI pneumonia (without obvious cyanosis, inability to feed, vomiting, convulsions, lethargy or head nodding) between 2011-2014 in Kenya, Zambia, South Africa, Mali, The Gambia, Bangladesh, and Thailand. We analysed risk factors for mortality among these cases using predictive logistic regression. Malnutrition was defined as mid-upper-arm circumference <125mm or weight-for-age z-score <-2. RESULTS: Among 2189 cases, 76 (3·6%) died. Mortality was associated with oxygen saturation <92% (aOR 3·33, 1·99-5·99), HIV negative but exposed status (4·59, 1·81-11·7), moderate or severe malnutrition (6·85, 3·22-14·6) and younger age (infants compared to children 12-59 months old, OR 2·03, 95%CI 1·05-3·93). At least one of three risk factors: hypoxaemia, HIV exposure, or malnutrition identified 807 children in this population, 40% of LCWI pneumonia cases and identified 86% of the children who died in hospital (65/76). Risk factors identified using the 2012 WHO treatment guidelines identified 66% of the children who died in hospital (n = 50/76). CONCLUSIONS: Although it focuses on treatment failure in hospital, this study supports the proposal for better risk stratification of children with LCWI pneumonia. Those who have hypoxaemia, any malnutrition or those who were born to HIV positive mothers, experience poorer outcomes than other children with LCWI pneumonia. Consistent identification of these risk factors should be prioritised and children with at least one of these risk factors should not be managed in the community.

BACKGROUND: Shigellosis mainly affects children under 5 years of age living in low- and middle-income countries, who are the target population for vaccination. There are, however, limited data available to define the appropriate timing for vaccine administration in this age group. Information on antibody responses following natural infection, proxy for exposure, could help guide vaccination strategies. METHODS: We undertook a retrospective analysis of antibodies to five of the most prevalent Shigella serotypes among children aged <5 years in Kenya. Serum samples from a cross-sectional serosurvey in three Kenyan sites (Nairobi, Siaya, and Kilifi) were analyzed by standardized ELISA to measure IgG against Shigella sonnei and Shigella flexneri 1b, 2a, 3a, and 6. We identified factors associated with seropositivity to each Shigella serotype, including seropositivity to other Shigella serotypes. RESULTS: A total of 474 samples, one for each participant, were analyzed: Nairobi (n = 169), Siaya (n = 185), and Kilifi (n = 120). The median age of the participants was 13.4 months (IQR 7.0-35.6), and the male:female ratio was 1:1. Geometric mean concentrations (GMCs) for each serotype increased with age, mostly in the second year of life. The overall seroprevalence of IgG antibodies increased with age except for S. flexneri 6 which was high across all age subgroups. In the second year of life, there was a statistically significant increase of antibody GMCs against all five serotypes (p = 0.01-0.0001) and a significant increase of seroprevalence for S. flexneri 2a (p = 0.006), S. flexneri 3a (p = 0.006), and S. sonnei (p = 0.05) compared with the second part of the first year of life. Among all possible pairwise comparisons of antibody seropositivity, there was a significant association between S. flexneri 1b and 2a (OR = 6.75, 95% CI 3-14, p < 0.001) and between S. flexneri 1b and 3a (OR = 23.85, 95% CI 11-54, p < 0.001). CONCLUSION: Children living in low- and middle-income settings such as Kenya are exposed to Shigella infection starting from the first year of life and acquire serotype-specific antibodies against multiple serotypes. The data from this study suggest that Shigella vaccination should be targeted to infants, ideally at 6 or at least 9 months of age, to ensure children are protected in the second year of life when exposure significantly increases.

BACKGROUND: Inhalation injuries due to acute occupational exposures to chemicals are preventable. National surveillance of acute inhalation exposures is limited. This study identified the most common acute inhalation exposure-related incidents by industry sector among US workers. METHODS: To characterize inhalation-related injuries and their exposures during April 2011-March 2022, state and federal records from the Occupational Safety and Health Administration (OSHA) Occupational Safety and Health Information System (OIS) accident database were analyzed. Industry-specific injury, hospitalization, and fatality rates were calculated. RESULTS: The most frequent acute inhalation incidents investigated by OSHA were caused by inorganic gases (52.9%) such as carbon monoxide (CO) or acids, bases, and oxidizing chemical agents (12.9%) such as anhydrous ammonia. The largest number of fatal and nonfatal injuries were reported in the manufacturing (28.6%) and construction (17.2%) sectors. CONCLUSIONS: Workers were affected by acute inhalation exposures in most industries. Using this surveillance, employers can recognize frequently-occurring preventable acute inhalation exposures by industry, such as inorganic gases in the manufacturing sector, and implement prevention measures. Training of workers on exposure characteristics and limits, adverse health effects, and use of protective equipment by exposure agent can prevent inhalation injuries.

Delays in illness recognition, healthcare seeking, and in the provision of appropriate clinical care are common in resource-limited settings. Our objective was to determine the frequency of delays in the "Three Delays-in-Healthcare", and factors associated with delays, among deceased infants and children in seven countries with high childhood mortality. We conducted a retrospective, descriptive study using data from verbal autopsies and medical records for infants and children aged 1-59 months who died between December 2016 and February 2022 in six sites in sub-Saharan Africa and one in South Asia (Bangladesh) and were enrolled in Child Health and Mortality Prevention Surveillance (CHAMPS). Delays in 1) illness recognition in the home/decision to seek care, 2) transportation to healthcare facilities, and 3) the receipt of clinical care in healthcare facilities were categorized according to the "Three Delays-in-Healthcare". Comparisons in factors associated with delays were made using Chi-square testing. Information was available for 1,326 deaths among infants and under 5 children. The majority had at least one identified delay (n = 854, 64%). Waiting >72 hours after illness recognition to seek health care (n = 422, 32%) was the most common delay. Challenges in obtaining transportation occurred infrequently when seeking care (n = 51, 4%). In healthcare facilities, prescribed medications were sometimes unavailable (n = 102, 8%). Deceased children aged 12-59 months experienced more delay than infants aged 1-11 months (68% vs. 61%, P = 0.018). Delays in seeking clinical care were common among deceased infants and children. Additional study to assess the frequency of delays in seeking clinical care and its provision among children who survive is warranted.

Cardiovascular diseases (CVDs) are a major source of morbidity and mortality worldwide. Despite a decline of ≈30% over the past decade, heart disease remains the leading killer of Americans.1 For rare and familial forms of CVD, we are increasingly recognizing single-gene mutations that impart relatively large effects on individual phenotype. Examples include inherited forms of cardiomyopathy, arrhythmias, and aortic diseases. However, the prevalence of monogenic disorders typically accounts for a small proportion of the total CVD observed in the population. CVDs in the general population are complex diseases, with several contributing genetic and environmental factors. Although recent progress in monogenic disorders has occurred, we have seen a period of intense investigation to identify the genetic architecture of more common forms of CVD and related traits. | | Genomics serves several roles in cardiovascular health and disease, including disease prediction, discovery of genetic loci influencing CVD, functional evaluation of these genetic loci to understand mechanisms, and identification of therapeutic targets. For single-gene CVDs, progress has led to several clinically useful diagnostic tests, extending our ability to inform the management of afflicted patients and their family members. However, there has been little progress in developing genetic testing for complex CVD because individual common variants have only a modest impact on risk. The study of the genomics of complex CVDs is further challenged by the influence of environmental variables, phenotypic heterogeneity, and pathogenic complexity. Characterization of the clinical phenotype requires consideration of the clinical details of the diseases and traits under study.