BACKGROUND: Evaluation of optimal dosing has generally been inadequate during TB drug development. Fluoroquinolones are central to TB treatment. We aimed to determine the dose of levofloxacin needed to achieve maximal efficacy and acceptable safety and tolerability as part of a multidrug TB regimen. METHODS: Opti-Q was an international, multi-center, randomized, placebo-controlled, phase II trial. Eligible participants with TB resistant to isoniazid and rifampicin but susceptible to fluoroquinolones (MDR-TB) were randomized to receive one of four weight-adjusted once-daily doses of levofloxacin given for 24 weeks(168 doses): 11mg/kg(750mg), 14mg/kg(750mg/1000mg), 17 mg/kg(1000mg/1250mg) or 20mg/kg(1250mg/1500mg) alongside a multidrug regimen. The primary efficacy outcome was time to sputum culture conversion and the primary safety outcome was grade 3 or higher adverse events. FINDINGS: 111 participants were randomized from three sites in South Africa and Peru. 83(75%) had cavities on chest x-ray, 55(50%) had a smear grading of 3+, median BMI was 20.4 kg/m(2). Median levofloxacin AUC/MIC was 573, 633, 918 and 1343 across the four treatment arms. There was no difference in time to culture conversion on solid or liquid media by treatment arm (stratified log-rank p=0.282), by tertile of AUC/MIC (p=0.350), or by dose received (p=0.723); 69.3%, 74.8%, 70.6% and 78.3% achieved culture conversion after 8 weeks on solid media respectively across the treatment arms; 64.6%, 69.5%, 52.6% and 69.6% in liquid culture. More participants experienced a grade 3-5 adverse event by dose (37.0% and 16.0% in the highest and lowest dose groups respectively, p=0.042, Cochran-Armitage test for trend) and by tertile of AUC (p=0.011). INTERPRETATION: As part of a multidrug regimen, doses of levofloxacin above 1000mg resulted in greater exposures and increased frequency of adverse events but did not result in faster time to sputum culture conversion. A dose of 1000mg daily can achieve the target exposure in nearly all adults and was well tolerated. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT01918397.

BACKGROUND: We estimate annual viral influenza-associated mild-to-moderate illness, hospitalizations, and deaths in 6 South American countries (Argentina, Brazil, Chile, Ecuador, Paraguay, and Uruguay) during the 2015-2019 influenza seasons as a first step in evaluating the full value of influenza vaccination in the subregion. METHODS: We applied a multiplier method using monthly hospital discharge and vital statistics death records, influenza surveillance data, and population projections to estimate mild-to-moderate influenza-associated illness, hospitalizations, and deaths. We estimated the uncertainty bounds based on the 2.5th and 97.5th percentiles of the Monte Carlo simulated distributions for the number of cases and obtained the ranges from the minimum value of the 2.5th and the maximum value of the 97.5th percentile. RESULTS: In selected countries with a total population of 307 million people, the yearly influenza-associated burden of disease ranged between 51 and 78 million mild-to-moderate influenza illnesses, between 323 379 and 490 049 hospitalizations, and between 22 662 and 46 971 deaths during the 2015-2019 influenza seasons. CONCLUSIONS: Each year, influenza is associated with millions of illnesses, hundreds of thousands of hospitalizations, and tens of thousands of deaths in 6 South American countries, affecting a significant portion of the population. Such findings can be used to estimate the number of illnesses averted through vaccination programs and the cost-benefit of influenza vaccines.

BACKGROUND: Clusters of rapid HIV transmission indicate larger underlying networks that are not effectively reached by HIV prevention, testing, and care services. Starting in 2018, the Centers for Disease Control and Prevention (CDC) funded 59 U.S. health departments (HDs) to detect and respond to HIV clusters; HDs began reporting clusters to CDC in January 2020. METHODS: For clusters reported to CDC, we described cluster characteristics at detection, including detection method; size; HIV transmission category, defined as that of >50% of cluster members; and HD investigation and response activities. RESULTS: During 2020-2022, 45 HDs reported 322 HIV clusters, with most detected by molecular analysis of HIV sequences (75%). Most were detected in the South (46%) and three-quarters were predominant sexual transmission. Median cluster size at detection for molecular clusters was 10 persons (interquartile range 7-18). Among 205 clusters with follow-up data, investigation and response activities were conducted for 95%, including direct outreach to persons in clusters for partner services (64%), medical chart reviews (42%), and focused testing events (13%). Limited data on named partners tested showed that 11% received new HIV diagnoses. CONCLUSIONS: HD HIV cluster detection activities detected many clusters. Response activities were tailored for different clusters and intervened in networks with rapid transmission and high undiagnosed infection, as indicated by high positivity among partners. Cluster detection and response is an important tool to identify and address gaps in HIV prevention, testing, and care that facilitate rapid transmission.

Antimicrobial resistance (AMR) is an urgent threat to public health, but gaps in surveillance limit the detection of emergent novel threats and knowledge about the global distribution of AMR genes. International travelers frequently acquire AMR organisms, and thus may provide a window into AMR dynamics in otherwise poorly monitored regions and environments. To assess the utility of travelers as global AMR sentinels, we collected pre- and post-travel stool samples from 608 travelers, which were screened for the presence of extended-spectrum beta-lactamase producing Enterobacterales, carbapenem-resistant Enterobacterales, and mcr-mediated colistin-resistant Enterobacterales. A total of 307 distinct AMR organisms were sequenced in order to determine genotypic patterns and their association with travel region and behavior. Travel-associated AMR organisms were overwhelmingly E. coli, which exhibited considerable phylogenetic diversity regardless of travel region. However, the prevalence of resistance genes varied by region, with bla (CTX-M-55) and bla (CTX-M-27) significantly more common in travelers returning from South America and South-Eastern Asia, respectively. Hybrid assembly and plasmid reconstruction revealed the genomic neighborhood of bla (CTX-M-55) frequently matched a motif previously linked to animal populations. Contact with animals was also associated with virulence factors in acquired AMR organisms, including carriage of the ColV plasmid, a driver of avian pathogenic E. coli. We identified novel variants of the mcr-1 gene in strains acquired from Western Africa, highlighting the potential for traveler surveillance to detect emerging clinical threats. Ongoing efforts to track travel-acquired organisms could complement existing global AMR surveillance frameworks.

BACKGROUND: Approaches for determining whether influenza vaccination prevents infection, attenuates illness, or both are important for developing improved vaccines. We estimated influenza infection incidence and evaluated symptom ascertainment methodologies in children to inform future vaccine trial design. METHODS: We conducted a prospective cohort study among children aged 6 to 23 months from May to October 2022. Study nurses collected symptom and temperature data and midturbinate nasal swabs twice weekly irrespective of symptoms; caregivers entered symptom data daily and collected nasal swabs weekly. Samples were tested for influenza with polymerase chain reaction. RESULTS: Of 230 healthy screened children, 93 were enrolled, of whom 87 (94%) completed 6-month follow-up. In total, 95% (4245/4476) of scheduled nurses, 90% (2045/2276) of caregiver swabs, 99% (92/93) of baseline blood collections, and 67% (9245/13 768) of scheduled symptom diaries were completed. Polymerase chain reaction-confirmed influenza incidence was 65% (60/93) for ≥1 infection; 11 (18%) individuals had 2 episodes and 1 (2%) had 3. Of 73 episodes, 55 (75%) had ≥1 symptom and 37 (51%) had fever (measured and/or reported). Median infection duration was 7 days (IQR, 4-9). Human RNase P gene was detected in 99% (2032/2045) of caregiver-collected swabs, through which 5 additional episodes were identified. Per episode, caregivers' diaries of reported and measured fever were 19% (25/73, 34%) and 11% (15/73, 21%) higher than nurse-reported (11/73, 15%) and nurse-measured (7/73, 10%) fever, respectively. CONCLUSIONS: The incidence of influenza infection was high and mainly symptomatic, suggesting that this platform could be suitable for future trials of vaccine efficacy and correlates of protection against infection and illness in children.

OBJECTIVES: To evaluate how postmortem anthropometric malnutrition (PAM) measures align with expert panel attribution of malnutrition as a causal or significant condition in under-5 mortality (U5M). DESIGN: Cohort study using data from the Child Health and Mortality Prevention Surveillance network, incorporating clinical records, postmortem anthropometrics, minimally invasive tissue sampling, clinical abstraction and verbal autopsy to determine multiple causes of death. SETTING/PARTICIPANTS: 1405 deaths of children aged 1-59 months from six African countries between 2016 and 2023. PRIMARY AND SECONDARY OUTCOME MEASURES: PAM was determined using z-scores from the WHO Child Growth Standards: underweight (weight-for-age<(-2)), wasting (arm circumference-for-age or weight-for-length<(-2)) and stunting (length-for-age <(-2)). Performance metrics (sensitivity (SE), specificity (SP) and positive predictive values (PPV)) were calculated to determine the alignment between PAM and expert panel attribution of malnutrition as a causal or significant condition to death. RESULTS: Nearly 75% of cases demonstrated moderate-to-severe malnutrition by PAM, while expert panels attributed malnutrition in 41% of cases. Performance metrics varied across anthropometric indices: underweight exhibited the highest SE (89.7%), while wasting based on arm circumference had the highest SP (81.9%) and PPV (76.8%). Discrepancies between PAM classification and expert panel attribution differed significantly by site, age, location of death and preventability of death (p<0.05). Adjusted multivariate regression showed that expert panel attribution was more likely with increasing severity of PAM. CONCLUSIONS: The proportion of U5M attributable to malnutrition ranged between 41% (expert panel attribution) and 74% (PAM). Variability in classification underscores the need for monitoring and quality improvement measures to address discrepancies. Improved alignment between PAM and panel assessments is essential for accurately identifying malnutrition-related deaths and designing effective interventions to reduce U5M.

Anemia is an important cause of child morbidity and mortality. Postmortem point-of-care hemoglobin testing is a potential method for assessing anemia at death, but its reliability has not been extensively studied. We aimed to assess the feasibility and validity of postmortem point-of-care hemoglobin assessment using HemoCue in the setting of a child mortality surveillance program in South Africa.In a pilot cohort study, 44 children under five years of age who died in an academic hospital in South Africa were enrolled. Hemoglobin levels were measured from venous blood antemortem using standard hematology analyzers and postmortem using the HemoCue 201 from blood collected within 72 hours of death (either by needle aspiration or from whole blood collected in an EDTA tube). Updated World Health Organization hemoglobin cutoffs to define anemia were used. Wilcoxon signed-rank tests, equivalence tests, and regression models assessed the concordance between antemortem and postmortem hemoglobin concentrations. Postmortem testing showed a significant decrease in hemoglobin concentrations compared to antemortem levels. However, no significant differences were found between hemoglobin measurements from needle aspiration and those from EDTA tubes postmortem. The prevalence of anemia increased from 52% antemortem to 73-77% postmortem, with the most notable rises in moderate and severe anemia. Bland-Altman analysis confirmed a systematic, not random, decrease in postmortem hemoglobin measurements. Upon applying a fixed adjustment of 2.5 g/dL, the sensitivity and specificity of postmortem hemoglobin testing to diagnose anemia were 69.6% and 61.9%, respectively. Postmortem point-of-care hemoglobin testing using HemoCue is feasible and offers a potentially valid reflection of antemortem anemia status in deceased children, despite consistently lower measured values postmortem. These findings support the utility of postmortem hemoglobin assessments in determining the presence and severity of anemia at the time of death.

OBJECTIVE: This pilot study explores the feasibility and acceptability of using telephonic verbal autopsies (teleVAs) in South Africa to collect information on causes of death. DESIGN: Quantitative and qualitative data collection methods were used to evaluate the feasibility and acceptability of these telephonic interviews. SETTING: The teleVA pilot was conducted in South Africa's Western Cape province. The qualitative component also included two rural South African Population Research Infrastructure Network nodes (Africa Health Research Institute in KwaZulu-Natal and Agincourt in Mpumalanga), which had transitioned to teleVAs during COVID-19, allowing exploration of teleVA's feasibility in both urban and rural settings. PARTICIPANTS: We recruited 229 respondents to participate in a pilot teleVA. After each VA, VA interviewers filled in a survey to assess their perceptions and discern if they experienced any technical challenges. We also conducted 18 in-depth interviews with both interviewers (n=6) and respondents (n=12) to explore their views on the acceptability of the teleVA. We conducted a thematic analysis of these interviews. INTERVENTIONS: VA was piloted over the phone, instead of face-to-face. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes focused on the feasibility and acceptability of phone VAs among both interviewers and respondents. Secondary outcomes evaluated the quality of teleVAs. RESULTS: Participants expressed willingness to participate in teleVAs, considering them valuable for public health planning and decision-making. The feasibility of collecting next-of-kin information proved challenging, with incomplete or incorrect contact details posing future logistic issues. Only one question out of 76, showed a statistically significant difference in the proportions of non-informative teleVA compared with face-to-face VA. CONCLUSIONS: The study offers valuable insights into using teleVAs to gather cause of death information in resource-limited settings. It highlights the feasibility and acceptability of teleVAs while emphasising the need for comprehensive planning, integration with the civil registration and vital statistics system and community participation enhancement.

Transgender youth are disproportionately affected by HIV, particularly minoritized youth in the US south. To understand HIV service use among transgender youth, we interviewed 25 young racial and ethnic minority clients of four southern community-based HIV service organizations (CBOs), and CBO staff (n = 12), about service access and use. Participants were assigned male at birth and identified as female (n = 8), transgender (n = 11) or gender-fluid or nonbinary (n = 6). The majority were Black/African American or mixed race; four were Hispanic or Latino/a. Most were unemployed; nearly half were unstably housed or homeless during the prior year. Four service types were each used by approximately two-thirds of participants: counseling/support, HIV/STD testing/education, pre-exposure prophylaxis education/prescriptions, and transgender-related medical services (primarily hormone provision). Just over a quarter used social services (e.g., housing, employment). Key facilitators to service use included a non-stigmatizing CBO atmosphere, and easy and convenient access. Poor access (e.g., inconvenient hours, location), lack of transportation or parking, social service needs, and lack of money were barriers. Qualitative reports highlighted unmet social service needs, particularly housing, especially for those without HIV. To reduce disparities, HIV prevention for racial and ethnic minoritized transgender youth should simultaneously address hormone provision, HIV risk reduction and social service needs.

BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are estimated to be of the most prevalent infectious diseases in correctional settings worldwide. However, viral hepatitis services have not been routinely integrated into South African correctional facilities. We aimed to assess prevalence of HBV infection and HCV infection among people accessing HIV services and assess the feasibility of viral hepatitis service integration in a South African correctional centre. METHODS: Voluntarily participating people in a correctional services facility were offered free hepatitis B surface antigen (HBsAg) and anti-HCV point-of-care testing in addition to routine HIV testing and treatment services on a first-come, first-served basis during June 2021-March 2022. Off-site laboratory testing (HBV and HCV molecular testing and non-invasive liver fibrosis staging) and screening for hepatocellular carcinoma informed further management. A general practitioner at the facility managed participants, with virtual support from hepatologists. Data on age and history of injecting was collected and point-of-care and laboratory results were recorded. Data were analysed using descriptive statistics. RESULTS: The median age of the 765 people who participated was 32.5 years (IQR 27.5 - 38.2), with 2.2% (17/765) reporting having ever injected a drug. The sample prevalence was 3.9% (30/765) for HBV infection, 0.5% (3/665) for HCV infection, and 1.2% (9/765) for HIV-HBV coinfection. Thirty people had reactive HBsAg point-of-care tests. Among those with reactive HBsAg point-of-care tests 90.0% (27/30) received work-up, among whom 48.1% (13/27) were monitored, 44.4% (12/27) were placed on treatment and two people were released before a management plan could be finalised. Of those treated 33.3% (4/12) started tenofovir/emtricitabine and 66.7% (8/12) antiretroviral therapy. Of the eligible participants, 27.3% (201/735) received at least one hepatitis B vaccine dose and 26.9% (54/201) received three doses. All three participants who had confirmed HCV infection were started on direct-acting antivirals. Of the two completing treatment one achieved sustained virological response at 12 weeks (SVR12), one person was released before SVR12 was done. One person was lost to follow-up. No clinical adverse events were reported. CONCLUSION: There was a notable viral hepatitis burden among people in this correctional centre and integration of viral hepatitis services into the existing HIV services was acceptable and feasible. Further efforts to sustain and expand access to viral hepatitis services in South African correctional centres could catalyse national viral hepatitis elimination efforts.

Background: The World Health Organization (WHO) has developed guidance for community health workers (CHWs) in identifying sick young infants based on clinical signs. We conducted a prospective, observational cohort study to characterise mortality risk of young infants based on their clinical signs. Methods: We conducted a population-based, prospective observational cohort study at five sites in Bangladesh (Sylhet, November 01, 2011–December 31, 2013), India (Vellore and Odisha, September 01, 2013–February 28, 2015), and Pakistan (Karachi, January 01, 2012–December 31, 2013; Matiari, March 01, 2012–December 31, 2013) to identify newborn infants who were followed-up by CHWs through 10 scheduled home visits over the first 60 completed days after birth to identify signs of possible serious bacterial infection (PSBI). We determined the frequency of signs and conducted Cox regression to investigate the association of signs with mortality risk within 7 days of identification of the signs. Findings: CHWs made 522,309 visits to assess 63,017 young infants and found ≥1 sign(s) of PSBI at 14,245 visits (2.7%), including 5.8% (5568 of 96,390) and 1.8% (6635 of 365,769) of visits of infants 0–<3 and 7–<60 days of age, respectively. Each of the seven signs of PSBI when found alone was associated with significantly (p < 0.0001) increased risk for mortality, which increased further if any other additional sign of PSBI was found concurrently. Over the young infant period (days 0–<60) CHW identification of no movement or movement only on stimulation was associated with the highest risk for mortality [adjusted hazard ratio (aHR) 73.0, 95% confidence interval (CI) 44.4–119.9] followed by poor feeding (aHR 31.9, 95% CI 24.1–42.3) and hypothermia (<35.5 °C) (aHR 31.4, 95% CI 23.5–41.9). Hypothermia had particularly high risk for mortality during days 7–<60 (HR 45.1, 95% CI 27.6–73.4). Interpretation: WHO reconsideration of hypothermia as a sign of critical illness is warranted. Implementation research is urgently needed to reduce infant mortality by ensuring immediate referrals and interventions for children identified early by CHWs with no movement or movement only on stimulation, hypothermia, or poor feeding, especially in resource-poor settings. Funding: Bill and Melinda Gates Foundation, New Venture Fund for Global Policy and Advocacy. © 2025 The Author(s)

PURPOSE: To examine associations between pregnancy timing relative to the COVID-19 pandemic, maternal SARS-CoV-2 infection, and perinatal outcomes. METHODS: We conducted a retrospective cohort study of 189,097 singleton births in South Carolina (2018-2021). Pregnancy timing relative to the pandemic was classified as pre-pandemic (delivered before March 1, 2020), partial pandemic overlap (conceived before and delivered during the pandemic), or pandemic (conceived and delivered during the pandemic). We examined COVID-19 testing, severity, and timing. Modified Poisson regression models with robust variance were used. RESULTS: Compared to the pre-pandemic group, the partial overlap group had lower risks of low birthweight (LBW) (aRR=0.93, 95 % CI 0.89-0.97) and preterm birth (PTB) (aRR=0.91, 95 % CI 0.88-0.95). The pandemic group had increased risks of LBW (aRR=1.10, 95 % CI 1.06-1.14), PTB (aRR=1.10, 95 % CI 1.07-1.14), and NICU admissions (aRR=1.13, 95 % CI 1.09-1.17) but a decreased risk of breastfeeding initiation (aRR=0.98, 95 % CI 0.97-0.98). Moderate-to-severe COVID-19 symptoms increased PTB (aRR=1.34, 95 % CI 1.13-1.58). Third-trimester COVID-19 infection increased LBW (aRR=1.23, 95 % CI 1.10-1.37), PTB (aRR=1.18, 95 % CI 1.07-1.30), and NICU admissions (aRR=1.17, 95 % CI 1.05-1.30). CONCLUSIONS: Our findings highlight the importance of considering both maternal COVID-19 infection and pandemic-related factors in optimizing perinatal outcomes.

PURPOSE: Alzheimer's disease and related dementias (ADRD) are a significant public health concern characterized by memory decline that, over time, leads to loss of independence. This study reports ADRD diagnosis rates among Medicare beneficiaries aged ≥ 65 years in rural America. METHODS: We conducted a descriptive analysis of Medicare Fee-for-Service (FFS) and Medicare Advantage enrollees using administrative Medicare data from 2020. Combining data from Medicare FFS and Medicare Advantage produces a more complete and representative sample of older adults than previous studies that used FFS data alone. Nonmetropolitan counties were used to define rural. Rural ADRD diagnosis rates, stratified by age, sex, race/ethnicity, and Census region, were adjusted using the 2000 Census population standard. FINDINGS: The study population consisted of 54 million Medicare data Fee-for-Service (FFS) and Medicare Advantage enrollees aged ≥ 65; 5.3 million beneficiaries were diagnosed with ADRD, and 16.2% (n = 861,337) of beneficiaries diagnosed with ADRD resided in rural America. The age-adjusted ADRD diagnosis rate was slightly lower in rural America (9.6 per 100 beneficiaries) than in the United States (10.0 per 100 beneficiaries). The South Census region had the highest rural ADRD diagnosis rates. CONCLUSION: These findings underscore the need for targeted interventions and support mechanisms to address the growing burden of ADRD in rural communities.

BACKGROUND: Infections by Streptococcus pneumoniae and influenza viruses are vaccine-preventable diseases causing great morbidity and mortality. We evaluated pneumococcal and influenza vaccination practices during pre-international travel health consultations. METHODS: We evaluated data on pretravel visits over a 10-year period (1 July 2012 through 31 June 2022) from 31 sites in Global TravEpiNet (GTEN), a consortium of US healthcare facilities providing pretravel health consultations. Data were collected using an online structured questionnaire utilized by GTEN providers. We obtained summary statistics and performed multivariable logistic regression models to identify characteristics associated with receiving the vaccinations. RESULTS: At 116 865 pretravel visits, 28 754 (25%) travelers were eligible to receive pneumococcal vaccination and 56 150 (48%) travelers were eligible to receive influenza vaccination. A total of 19 557 (68%) pneumococcal vaccine-eligible travelers were not offered the vaccine at the pretravel visit. Among influenza vaccine-eligible travelers, 8592 (15%) were not offered the vaccine, and an additional 16 931 (30%) travelers declined the vaccine. Influenza vaccine was not available for 8014 (14%) eligible travelers. Nonadministration of the influenza vaccine was most frequent in the months of April through September. Compared to nonacademic centers or centers in the South or Midwest, travelers seen in academic centers or centers in the Northeast were more likely to receive either vaccine. CONCLUSIONS: Increasing awareness of global influenza transmission patterns and improving access to routine vaccines at the pretravel encounter may enhance vaccination for respiratory pathogens in departing US international travelers.

BACKGROUND: TB preventive treatment (TPT) prevents the development of TB disease in individuals at risk of progression from infection to disease. However, implementation of TPT for children is poor in most high-burden settings. The long duration and pill burden of the 6-month once-daily isoniazid regimen (6H) pose significant barriers to completion. We aimed to understand children's, caregivers', and healthcare providers' experiences of the 12-week once-weekly rifapentine and isoniazid (3HP) regimen using a dispersible tablet formulation in South Africa. METHODS: Serial, in-depth qualitative interviews with 20 child-caregiver dyads, including 5 children living with HIV (CLWH) and 9 healthcare providers across two study sites implementing a pharmacokinetic and safety trial of 3HP, were analysed deductively. RESULTS: Of those with experience using both 3HP and 6H, caregivers and healthcare providers preferred 3HP, and study participants reported that the 3HP formulation was more palatable and easier to prepare and administer. Caregivers and healthcare providers were concerned about optimally integrating 3HP into routine care, primarily due to its once-weekly administration. Children with HIV preferred the once-daily 6H regimen for its ease of use with their daily antiretroviral therapy. CONCLUSIONS: 3HP reduced the administration burden for children and their caregivers. Once weekly, 3HP dosing will require education and adherence support to ensure completion.

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

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

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

BACKGROUND: Previous studies have estimated preexposure prophylaxis (PrEP) use among persons with commercial health insurance and Medicaid. However, data are lacking regarding PrEP use among those with Medicare. METHODS: Using a previously developed algorithm, we estimated the number of Medicare beneficiaries (MBs) with fee-for-service (FFS) claims who were prescribed PrEP from 2014 to 2021. The analysis was stratified by age, sex, and race/ethnicity. We also examined trends in PrEP prevalence by U.S. state and demographic characteristics during 2014-2021. RESULTS: The number of Medicare PrEP users increased 11-fold, from 388 in 2014 to 4,685 in 2021. MBs prescribed PrEP were predominantly younger men, White persons, residing in the South or West regions, living with a disability, and dually eligible for both Medicare and Medicaid. The prevalence of PrEP prescriptions among MBs increased 12-fold, from 9.7 per million in 2014 to to 120.0 per million in 2021. Black/African American persons had the highest prevalence of PrEP use, followed by Hispanic/Latino and White persons in 2021. The District of Columbia had the highest prevalence of PrEP use compared with other U.S. states in 2021. Significant increasing trends in PrEP use were observed across sex, age groups, and race/ethnicity. CONCLUSIONS: Disparities in PrEP uptake existed across MB demographic subgroups from 2014 to 2021. Public health interventions are needed to increase PrEP access and utilization, particularly among women, younger MBs, Black persons, and Hispanic persons, including those with Medicare. Strategies and policies to expand PrEP use are essential for optimal HIV prevention in the United States.

Evolving technology and the development of new devices that can aerosolize water present a risk for new sources of Legionella bacteria growth and spread within industrial settings. We investigated a cluster of legionellosis among employees of a manufacturing facility in South Carolina, USA, and found 2 unique equipment sources of Legionella bacteria. The cluster of cases took place during August-November 2022; a total of 34 cases of legionellosis, including 15 hospitalizations and 2 deaths, were reported. Legionella pneumophila was isolated from 3 devices: 2 water jet cutters and 1 floor scrubber. L. pneumophila sequence type 36 was identified in environmental isolates and 1 patient specimen, indicating that those devices were the likely source of infection. Remediation was ultimately achieved through the development and implementation of a device-specific water management program. Manufacturing facilities that use aerosol-generating devices should consider maintaining updated Legionella water management programs to prevent Legionella bacterial infections.

BACKGROUND: Community-based management of acute malnutrition is an effective treatment model for severe acute malnutrition. However, sparse evidence exists on post-discharge outcomes and the sustainability of recovery. This study aimed to evaluate the risk and determinants of relapse following severe acute malnutrition recovery in high-burden settings. METHODS: This multi-country prospective cohort study followed children who had recovered from severe acute malnutrition and their non-malnourished peers in parallel for 6 months in Mali (nine sites), South Sudan (six sites), and Somalia (one site). Nutritional status was assessed by research staff at nutrition clinics monthly to obtain the proportion of children exposed to severe acute malnutrition who relapsed to acute malnutrition and the relative risk of developing acute malnutrition for exposed versus non-exposed (ie, previously non-malnourished) children. Exposed children were eligible if they had been discharged from community-based management of acute malnutrition programmes while aged 6-47 months. Non-exposed children were eligible if they had not had an episode of acute malnutrition in the previous year; non-exposed children were matched to exposed children by age, sex, and community. Acute malnutrition was defined as having a mid-upper arm circumference of less than 125 mm, a weight-for-height Z score of less than -2, or nutritional oedema. The primary outcome was the cumulative incidence of acute malnutrition at 6 months in the exposed and non-exposed cohorts. Relapse was defined as an episode of acute malnutrition among exposed children during the 6-month follow-up period. FINDINGS: Between April 9, 2021, and June 2, 2022, 2749 children were enrolled (1689 exposed and 1060 non-exposed). After 6 months, 30% (95% CI 25-34) of children previously exposed to severe acute malnutrition relapsed in Mali, 63% (95% CI 59-67) in South Sudan, and 22% (95% CI 19-25) in Somalia. Depending on the context, exposed children were 1·2-6·2 times more likely to have acute malnutrition compared with non-exposed children. Higher anthropometric measurements at discharge were protective against relapse; however, few other child-level or household-level factors at the time of discharge were associated with subsequent relapse. After discharge, children experiencing food insecurity or morbidity at time of follow-up were more likely to relapse than those who were not experiencing these factors. INTERPRETATION: Following severe acute malnutrition recovery, children have a significant risk of relapsing within 6 months, highlighting the particular vulnerability of this population. Although the community-based management of acute malnutrition model proves highly effective in saving lives, high relapse indicates the need for additional services during and following treatment to better sustain recovery. FUNDING: The United States Agency for International Development.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of combination nicotine replacement therapy (c-NRT) for smoking cessation among people with HIV (PWH) in South Africa. DESIGN: We conducted an open label, individually randomized clinical trial. METHODS: Using a two-armed approach, PWH who smoke were randomized to receive either 1) intensive anti-smoking behavioral counseling (BC) or 2) intensive anti-smoking BC plus c-NRT (nicotine patches augmented by nicotine gum). Self-reported smoking abstinence was biochemically validated with exhaled breath carbon monoxide (CO) and urine cotinine at six months. Recruitment, provision of trial interventions, and follow-up of participants took place March 2014 through June 2016. RESULTS: We randomly assigned 280 participants to the BC arm and 281 participants to the BC + c-NRT arm. 438 (78%) participants were male and 123 (22%) were female. For our primary outcome of biochemically verified abstinence at six months, 41 (15%) were quit in the BC + c-NRT arm versus 28 (10%) in the BC arm, resulting in a 5% (95% CI -1%, 10%) absolute difference in relative risk and an adjusted odd ratio of 1.47 (95% CI: 0.86, 2.52) comparing the BC + c-NRT to the BC arm. CONCLUSIONS: Although our results did not reach statistical significance, we found augmentation of BC with c-NRT to increase smoking abstinence at six months, which is consistent with performance in the general population. PWH in low-resource settings may benefit from the addition of c-NRT to existing tobacco cessation interventions.

Paratyphoid B fever (PTB) is caused by an invasive lineage (phylogroup 1, PG1) of Salmonella enterica serotype Paratyphi B (SPB). However, little was known about the global population structure, geographic distribution, and evolution of this pathogen. Here, we report a whole-genome analysis of 568 historical and contemporary SPB PG1 isolates, obtained globally, between 1898 and 2021. We show that this pathogen existed in the 13th century, subsequently diversifying into 11 lineages and 38 genotypes with strong phylogeographic patterns. Following its discovery in 1896, it circulated across Europe until the 1970s, after which it was mostly reimported into Europe from South America, the Middle East, South Asia, and North Africa. Antimicrobial resistance recently emerged in various genotypes of SPB PG1, mostly through mutations of the quinolone-resistance-determining regions of gyrA and gyrB. This study provides an unprecedented insight into SPB PG1 and essential genomic tools for identifying and tracking this pathogen, thereby facilitating the global genomic surveillance of PTB.

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.

During 2023, approximately 72,000, or nearly seven in 10, drug overdose deaths in the United States were estimated to involve illegally manufactured fentanyls (IMFs). Carfentanil, a fentanyl analog 100 times more potent than fentanyl, has reemerged in the U.S. drug supply. Using CDC's State Unintentional Drug Overdose Reporting System data, this report describes trends in overdose deaths during January 2021-June 2024, overall and with IMFs detected, by U.S. Census Bureau region, and in deaths with carfentanil detected, in 45 states and the District of Columbia (DC). Numbers of deaths with carfentanil detected by state during January 2023-June 2024 in 49 states and DC are also reported. The number of overdose deaths with IMFs detected declined from 2022 to 2023 in the Northeast (3.2% decline), Midwest (7.8%), and South (2.8%) regions; deaths in the West increased 33.9%. The percentage of deaths with IMFs detected was steady at approximately 70%-80% in the Northeast, Midwest, and South. In contrast, the percentage of deaths with IMFs detected in the West increased from 48.5% during January-March 2021 to 66.5% during April-June 2024. Overdose deaths with carfentanil detected increased approximately sevenfold, from 29 during January-June 2023 to 238 during January-June 2024; during January 2023-June 2024, overdose deaths with carfentanil detected were reported in 37 states. Overdose prevention efforts that address the widespread presence of IMFs, including carfentanil, and can rapidly adapt to other potent opioids in the drug supply might result in lasting reductions in overdose deaths across the entire United States.

BACKGROUND: Population-based incidence data on young-adult-onset type 1 diabetes and type 2 diabetes are limited. We aimed to examine secular trends in the incidence of diagnosed type 1 diabetes and type 2 diabetes with an age of onset between 15 and 39 years. METHODS: In this multicountry aggregate data analysis, we assembled eight administrative datasets from high-income jurisdictions and countries (Australia, Denmark, Finland, Hungary, Japan, Scotland, South Korea, and Spain [Catalonia]) that had appropriate data available from an international diabetes consortium (GLOBODIAB) describing incidence by diabetes type among people aged 15-39 years from 2000 to 2020. We modelled type 1 diabetes and type 2 diabetes incidence rates using Poisson regression including age and calendar time by sex. FINDINGS: During the years 2000-20, there were 349 591 incident diabetes (both types) cases from 346 million person-years of follow-up among people aged 15-39 years. Over time, there was no statistically significant change in the incidence of type 1 diabetes in Hungary and Japan. The incidence of type 1 diabetes significantly increased in Australia, Denmark, Finland, Scotland, South Korea, and Spain, with annual changes ranging from 0·5% to 6·0%. The incidence of type 2 diabetes significantly increased in four of eight jurisdictions (Denmark, Finland, Japan, and South Korea), with annual increases from 2·0% to 8·5%. The magnitude of increase in incidence of type 2 diabetes was greater in Asian than non-Asian jurisdictions. There was no statistically significant change in type 2 diabetes incidence in Australia and Hungary. The incidence of type 2 diabetes significantly decreased in Scotland and Spain, with annual changes of -0·7% and -1·5%, respectively. INTERPRETATION: There is variability in the trajectory of the incidence of young-adult-onset type 2 diabetes among high-income countries or jurisdictions, with a greater evidence of increase in Asian than non-Asian countries. Evolving trends in the incidence of type 1 and type 2 diabetes in young adults call for the ongoing surveillance of diabetes incidence and a greater research focus on this population. FUNDING: US Centers for Disease Control and Prevention, Diabetes Australia Research Programme, and Victoria State Government Operational Infrastructure Support Programme.

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

Studies among men who have sex with men (MSM) in sub-Saharan Africa (SSA) focus mainly on HIV epidemiology, revealing little about the diversity within this population. We utilized data from the HIV Prevention Trials Network (HPTN) 075 study, to explore demographic and psychosexual characteristics of MSM in SSA who also have sex with women. Persons included in the analyses were aged 18-44 years and assigned male sex at birth and identified as male, reported anal sex with a man in the past 3 months, and had enrolled at one of four study sites (Kisumu, Kenya; Blantyre, Malawi; Cape Town and Soweto, South Africa). Nearly a quarter of the participants had recently engaged in sex with both men and women (MSMW). These men differed in terms of demographic and psychosexual characteristics, and sexual behavior from men who only had had sex with men (MSME). Compared to the latter, MSMW were more likely to prefer the insertive sexual role, reported more sexual partners in the past three months, and had more instances of condomless insertive anal intercourse with a man. These findings suggest that men who have sex with both men and women have specific characteristics and need tailored interventions that take their specific needs into account.

Objectives: Yellow fever (YF) remains a public health threat in Sub-Saharan Africa and South America, with an estimated 200,000 cases and 30,000 deaths annually. Although the World Health Organization considers Tanzania to be at low risk for YF because no YF cases have been reported, the country remains at alert to importation of the virus due to ecological factors and high connectivity to high-risk YF areas in other countries. This study aimed to identify points of interest with connectivity to high-risk YF areas to guide preparedness efforts in Tanzania. Methods: Using the Population Connectivity Across Borders (PopCAB) toolkit, the Nelson Mandela African Institution of Science and Technology (Department of Health and Biomedical Sciences), in collaboration with the Tanzania Ministry of Health and the Centers for Disease Control and Prevention, implemented 12 focus group discussions with participatory mapping in two high-risk borders of Mutukula and Namanga. Results: Participants identified 147 and 90 points of interest with connectivity to YF risk areas in Kenya and Uganda, respectively. The identified locations are important for trade, fishing, pastoralism, tourism, health-seeking, agriculture, mining, religious activities, education, and cross-border marriages. Conclusions: The Tanzania Ministry of Health used the results to update cross-border surveillance and risk communication strategies and vaccination guidelines to prevent the importation of YF into Tanzania. © 2024 The Authors

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