The Lancet Regional Health - Americas

BackgroundThe Toto Bora trial tested whether a course of azithromycin reduced rates of re-hospitalization or death in the 6 months following hospitalization among Kenyan children. We hypothesized that azithromycin would reduce enteric bacteria and increase carriage of macrolide resistance in the subsequent 3 months. MethodsKenyan children (1-59 months) hospitalized and subsequently discharged for non-traumatic conditions provided fecal samples before and 3 months after randomization to a 5-day course of azithromycin or placebo. Quantitative PCR identified enteropathogens and AMR-conferring genes in fecal samples. Generalized estimating equations assessed the impact of the randomization arm on pathogen and resistance gene detection, accounting for baseline presence and site. ResultsAmong 1,393 baseline stools, 12.4% had at least one bacterial enteropathogen, 94.7% had at least one macrolide-resistance gene, and 92.6% had at least one beta-lactamase-resistance gene identified. At month 3, children randomized to azithromycin had a 6.1% higher likelihood of carrying a macrolide resistance gene compared to placebo (adjusted prevalence ratio [aPR], 1.06; 95% CI, 1.04-1.08; P<0.001). Specifically, azithromycin randomization was associated with a higher relative prevalence of erm(B) (aPR, 1.09 [95% CI, 1.04-1.15]; P=0.001), erm(C) (aPR, 1.23 [95% CI, 1.14-1.31]; P<0.001), msr(A) (aPR, 1.14 [95% CI, 1.04-1.25]; P=0.007), and msr(D) (aPR, 1.07 [95% CI, 1.03-1.11]; P=0.001). There was no difference in overall bacterial pathogen prevalence (18.9% vs 17.3%) between randomization arms, but a slightly lower proportion of children had Shigella after randomization in the azithromycin arm (3% vs. 5%, aPR, 0.79 [95% CI, 0.62, 1.01]; P=0.063). InterpretationAzithromycin at hospital discharge was associated with higher carriage of macrolide-resistance-conferring genes in the post-discharge period compared with placebo, without significant declines in enteric pathogen carriage other than modest changes to Shigella. The potential benefits and risks of empiric azithromycin need to be considered, as children are increasingly exposed to this broad-spectrum antibiotic.

Globally, respiratory tract infections (RTI) are the main cause of morbidity, and in Low-middle-income countries (LMICs) RTI including pneumonia are a leading cause of morbidity and mortality in children <5 years. Diarrheal illness increases RTI risk in young children through micronutrient depletion, and immune stress, yet data on post-diarrhea RTI burden in LMICs are limited. We determined the prevalence and risk factors of RTI within three months following medically-attended diarrhea (MAD) in children aged 6-35 months enrolled in seven EFGH country sites in Asia, Africa and South America. The EFGH study prospectively enrolled children aged 6-35 months with MAD in selected health facilities during a 24-month period from 2022 to 2024 and followed them for three months. RTI was defined as cough or difficulty breathing and the presence of one of the following symptoms at any scheduled or unscheduled visit during follow-up: stridor; fast-breathing; oxygen saturation <90%; or chest indrawing. The period prevalence and 95% confidence intervals of RTI were calculated, and correlates of RTI were assessed using modified-Poisson regression. From June 2022 to August 2024, 9,476 children aged 6-35 months presenting with MAD in the EFGH study sites were screened: 9,116 (96.2%) included in the current study. Nearly half were female (46.7%), and median age was 15 months. Overall, 48.5% received all age-appropriate vaccines, and 87.6% received the pneumococcal vaccine, with significant variation across countries. Nearly one-quarter of children were stunted, 17.2% wasted, and 21.9% underweight. RTI occurred in 3.8% of children during the three-month follow-up, mostly within the first month. Higher prevalence of RTI occurred among children aged 12-23 months (8.7%), those undernourished (16.1%), unvaccinated (4.0%) or living in poor sanitation settings (4.1%). While children who received all age-appropriate or pneumococcal vaccinations had a lower crude prevalence of RTI, these associations were not statistically significant after adjusting for age, sex and study site. RTI was infrequently observed in the three months following MAD presentation, with significant variability by site and with the highest prevalence in Malawi. RTI risk was highest in 12-23-month-olds and among children with undernutrition, and those living in poor sanitation conditions.

BackgroundLynch syndrome (LS) is a cancer susceptibility syndrome caused by germline pathogenic variants in DNA mismatch repair (MMR) genes. Due to increased risk of colorectal cancer (CRC), enhanced colonoscopic surveillance is recommended for heterozygote MMR-carriers. ObjectiveUsing a registry of English LS patients linked to digital National Health Service records, we aimed to assess adherence of MMR-carriers to national surveillance guidelines, and to determine the impact of surveillance on CRC incidence and mortality. DesignWe described the frequency of colonoscopies in 4,732 MMR-carriers and used logistic regression to determine predictors of surveillance adherence. For MMR-carriers with a record of surveillance and those without, we: estimated age-specific annual CRC incidence rates (AS-AIRs) and cumulative lifetime risks, assessed for stage-shift by comparing CRC stage distributions and stage-specific AS-AIRs, and estimated risks of death from CRC and any cause using Kaplan-Meier methods and Cox Proportional Hazards regression. ResultsSurveillance at a mean interval of [&le;] 3 years (n=3028) was associated with a decrease in CRC-specific and all-cause mortality, without an associated change in total CRC incidence, even after multivariate adjustment. No strong evidence of stage-shift was observed. Colonoscopic surveillance at a mean interval of [&le;] 2 years (n=1569) was associated with an increase in total CRC incidence. Incidence of early-stage cancers was also higher, with no corresponding decrease in late-stage cancers, which may reflect the short follow-up period or the impact of overdiagnosis. ConclusionThe observed reduction in all-cause mortality amongst regularly-surveilled MMR-carriers may indicate an impact of surveillance on CRC-specific mortality, though in the context of a non-randomised study likely reflects the influence of selection bias. KEY MESSAGES OF ARTICLEO_ST_ABSWhat is already known on this topicC_ST_ABSRegular surveillance colonoscopy is recommended in Lynch syndrome, though evidence to support this remains mixed. We searched PubMed for articles published from inception to 01/05/2024 using the terms "Lynch syndrome", "HNPCC", "colonoscopy", "sigmoidoscopy", "surveillance", and "screening". We found one controlled trial and several small analytical studies dating from the early 2000s which compared surveilled and non-surveilled populations and found surveillance to be associated with reduced colorectal cancer (CRC) incidence and improved survival. More recent longitudinal observational studies, most without comparator groups, found a high incidence of CRC in LS populations despite being resident in countries where surveillance was recommended. A small number of studies directly assessed time since last colonoscopy against CRC incidence and stage with mixed findings. Finally, cross-sectional comparisons between countries of CRC incidence rates and surveillance interval recommendations found no relationship between the two1,2. What this study addsHere, we conduct an observational cohort study on a large national cohort of MMR germline pathogenic variant (GPV) carriers (MMR-carriers) in England (n=4,732), comparing CRC incidence and mortality in individuals with a record of regular surveillance to those without. Through linkage of the English National Lynch Syndrome Registry to Hospital Episodes Statistics data, we are uniquely able to study a comprehensive national population of MMR-carriers and identify the dates on which colonoscopies were undertaken over time, allowing assessment of adherence to national surveillance guidelines and the impact this has on CRC outcomes. Notably, receipt of regular colonoscopy was strongly associated with deprivation as well as ethnicity. The results show that regular surveillance at an average interval of 3 years (or less) is not associated with a reduction in CRC incidence when compared to less frequent surveillance, but an apparent decrease in both CRC-specific and overall mortality is observed, even after adjustment for confounding variables. Conversely, regular surveillance at an average interval of 2 years (or less) is associated with an increase in CRC incidence when compared to less frequent surveillance, which may suggest increased diagnosis of early-stage cancers or, due to the absence of a reduction in late-stage cancers, overdiagnosis. The observed impact of surveillance on overall mortality may demonstrate the impact of surveillance on CRC-specific mortality, or, in the context of an observational (non-randomised) study, indicate that the results are subject to selection bias. How this study might affect research, practice, or policyEvidence for the benefit of surveillance colonoscopy remains mixed. Whilst polypectomy would be anticipated to prevent CRC development (thus reducing CRC incidence), several studies have observed increased frequency of CRCs in MMR-carriers undergoing frequent surveillance colonoscopy, which may reflect overdiagnosis. The selection bias inherent to observational studies of surveillance renders mortality outcomes challenging to interpret. Randomised controlled trials of colonoscopic surveillance in MMR-carriers are required for effectiveness of this intervention to be accurately assessed. Given ethical and feasibility challenges, randomised controlled trials might be complemented by quasi-experimental designs using advanced observational methods for assessing effectiveness.

Drug overdose deaths in the United States reached record levels during the fentanyl era before recently declining. A plausible hypothesis is that a sudden drop in fentanyl purity beginning in 2023 caused the downturn in overdose mortality. We evaluated this hypothesis by replicating a published analysis with regional overdose data, using models that account for time trends and autocorrelation, and negative control indicators to test for spurious correlation. When fentanyl purity was rising, the national purity series did not track overdose increases in most regions and showed only a modest association in the West. When both purity and mortality later declined, the observed associations were also seen with unrelated macroeconomic indicators that shared the same time pattern. National fentanyl purity alone does not provide a sufficient explanation for recent overdose declines.

Background: The 2024-25 influenza season was the most severe in the United States (US) since 2017-18, with co-circulation of both influenza A virus subtypes (H1N1 and H3N2). Influenza vaccine effectiveness (VE) has varied by season, setting, and patient characteristics. Methods: Using electronic healthcare encounter data from eight US states, we evaluated influenza vaccine effectiveness (VE) against influenza-associated hospitalizations and emergency department or urgent care (ED/UC) encounters from October 2024-April 2025 among children aged 6 months-17 years and adults aged 18+ years. Using a test-negative, case-control design, we compared the odds of influenza vaccination between acute respiratory illness (ARI) encounters with a positive (cases) versus negative (controls) test for influenza by molecular assay, adjusting for confounders. Results: Analyses included 108,618 encounters (5,764 hospitalizations and 102,854 ED/UC encounters) among children and 309,483 encounters (76,072 hospitalizations and 233,411 ED/UC encounters) among adults. Among children across care settings, 17.0% (6,097/35,765) of cases versus 29.4% (21,449/72,853) of controls were vaccinated. Among adults, 28.2% (21,832/77,477) of cases versus 44.2% (102,560/232,006) of controls were vaccinated. VE was 51% (95% confidence interval [95% CI]: 41-60%) against influenza-associated hospitalizations and 54% (95% CI: 52-55%) against influenza-associated ED/UC encounters among children. VE was 43% (95% CI: 41-46%) against influenza-associated hospitalizations and 49% (95% CI: 47-50%) against influenza-associated ED/UC encounters among adults. Conclusions: Influenza vaccination provided protection against influenza-associated hospitalizations and ED/UC encounters among children and adults in the US during the severe 2024-25 influenza season. These findings support influenza vaccination as an important tool to reduce influenza-associated disease.

In a confirmatory study, we evaluated the immunogenicity and protective efficacy of a heterologous prime-boost vaccination strategy against respiratory syncytial virus (RSV) in non-human primates. Building on prior evidence of protective mucosal immunity induced by intramuscular DNA priming followed by an oropharyngeal adenoviral boost, we conducted a randomized, blinded, dual-centre study across two European primate research facilities. Rhesus macaques received a codon-optimized RSV-F DNA vaccine via electroporation, followed by two mucosal administrations of a recombinant adenovirus serotype 5 vector encoding the same antigen. Control groups included animals vaccinated with irrelevant influenza antigens and a comparator group mimicking natural immunity induced by primary RSV infection. Systemic and mucosal immune responses, including RSV-F-specific antibodies and tissue-resident memory T cells, were monitored longitudinally. Here, we detected robust immune responses, but with some variability between the two centres. However, following experimental RSV challenge performed 22 weeks after the final immunization, RSV-vaccinated animals demonstrated markedly reduced viral replication in both upper and lower respiratory tracts. However, unexpected RSV-specific immunity in the control group at one single study site prevented confirmation of the predefined primary endpoint. Overall, these results support the potential of mucosal adenoviral boosting following DNA priming to induce protective immunity against RSV, while highlighting challenges associated with multi-centre preclinical vaccine studies.

Background Childhood sensory and intellectual disabilities represent significant yet under-recognized barriers to learning and human capital development. This study analyzes prevalence and severity of these conditions among 149.3 million children aged 5-19 years across 25 countries in Latin America and the Caribbean (LAC) using Global Burden of Disease 2023 data. Methods We extracted GBD 2023 estimates for vision loss, hearing loss, and intellectual disability across 25 LAC countries, stratified by age, sex, and severity. Regional estimates were calculated using population-weighted averages. Severity distributions were compared with OECD countries to contextualize regional patterns. Results: These conditions are estimated to affected 9,282,921 children (6.22%; 95% UI: 5.89-6.54%). Hearing loss was predominant, affecting an estimated 5.42 million (3.63%, 3.41-3.86), with 87.6% mild-to-moderate. Intellectual disability estimated to affected 2.56 million (1.71%, 1.58-1.85), with 61.7% borderline-to-mild. Vision loss estimated to affected 1.30 million (0.87%, 0.79-0.96), with 89% that can be effectively addressed with spectacles. Prevalence increased with age across all conditions. Male predominance was consistent for intellectual disability (2.00% vs 1.42%). Annual economic cost totaled US$19.3-29.0 billion, while comprehensive interventions would require US$9.45-14.23 billion with benefit-cost ratios of 2:1 to 15:1. Conclusions The distribution of children across milder levels of difficulty underscores the opportunity for education and public health systems to provide timely and accessible support. With approximately 88% of sensory impairments addressable through established technologies, investments in inclusive services can yield strong social and economic returns.

BackgroundAn upsurge in Streptococcus pyogenes infections 2022-2023 highlighted potential benefits of point-of-care tests (POCT) to support clinical pathways, prevent outbreaks, and optimise antibiotic use. ObjectivesWe conducted a pilot research study in a west London paediatric emergency department (ED) to determine whether a molecular POCT had potential to alter management in children who were also having a conventional throat swab taken for culture. MethodsChildren <16 years presenting to ED who had a throat swab requested by a clinician were invited to have a second swab taken for research purposes only. Clinical management was unaffected by the research swab result, which was processed using a molecular POCT that was not approved for use in the host NHS Trust. ResultsPrevalence of streptococcal infection was low during the study (May 2023-June 2025); swab positivity in symptomatic children was 12.8% (6/47). Overall, 38/49 (77.6%) participants who had throat swabs received antibiotics. Of those children recommended to receive antibiotics, 29/38 (76.3%) had a negative POCT. Mean time to reporting of positive throat swab culture results was 3.67 days (range 3-5 days) leading to occasional delay in treatment, although POCT identified positive results within minutes. ConclusionAntibiotic use was frequent and could be avoided or stopped by use of a rule out POCT in over three-quarters of children in the ED, if suspicion of S. pyogenes is the main driver for prescribing. POCT were easy to process and produced immediate results compared with culture, in theory enabling timely decision-making and avoiding treatment delay.

BackgroundAccess to safe, equitable, and affordable surgical and anesthesia care is critical to reducing the burden of surgical diseases in Africa. To understand the state of access in South Sudan, we conducted a baseline assessment of surgical services in Central Equatoria State (CES) in May 2024. ObjectivesThis study aimed to survey public healthcare facilities in CES capable of providing essential surgical services. We used the capacity to perform cesarean section, laparotomy, and open fracture management--Bellwether procedures--as a proxy for assessing workforce, infrastructure, financing, information management, and service delivery. MethodsWe used a validated and contextualized Surgical Assessment Tool developed by the Harvard Program on Global Surgery and Social Change and the World Health Organization. Data were collected at the facility level and summarized descriptively using percentages, means (standard deviations), medians (minimum, maximum), and visualized in graphs, charts, and tables. ResultsAll three public health facilities assessed could perform Bellwether procedures for their catchment populations. However, workforce availability, financing, and surgical infrastructure were major constraints. The surgical workforce density was 2.27 surgical, anesthesia, and obstetric specialists per 100,000 population. Specialized procedures--such as repair of cleft lip and palate, clubfoot, and hydrocephalus shunt--were unavailable at all sites. None had magnetic resonance imaging (MRI) machines. The total average annual facility budget was $918,850, ranging from $3,960 to $800,000 at the teaching hospital--insufficient for proper operations. ConclusionWhile Bellwether procedures are routinely performed, access to quality and affordable care is compromised by deficits in workforce, financing, and infrastructure. We recommend that the Ministry of Health scale this survey nationally and develop a surgical policy and strategic plan focused on improving infrastructure, workforce, and financing for surgical and anesthesia care in South Sudan.

ObjectivesTo estimate current, and 5- and 10-year projected, number of cases of cancer per year in transgender and gender diverse (TGD) people in England, overall and by tumour type, accounting for uptake of gender affirming care (GAC). DesignPopulation-based epidemiological modelling study using an age-stratified Monte Carlo simulations approach and the NORDPRED method for predictions. SettingModels estimating cancer case numbers for TGD people in England based on publicly available 2023 cancer surveillance data and survey-based 2025 GAC access, and predicted at 5 and 10 years hence. ParticipantsTGD people aged 15 years and above. Main outcome measuresPrimary cancer cases per year overall, by gender, age group, tumour type, and current and planned GAC. ResultsThe estimated TGD population size in England is 441547 (95% uncertainty interval (UI) 429207- 452890). Total cases per year of cancer in TGD people is expected to be 966 (95% UI 882-1069) excluding non-melanoma skin. Most cases are expected to occur in people aged 60-64. The top 5 expected cancers in TGD people are breast (19%, n = 187, 95% UI 149-241), colorectal (12%, n = 117, 95% UI 106-129), lung (11%, n = 108, 95% UI 96-122), melanoma (7.1%, n = 69, 95% UI 64-74) and urinary (6.2%, n = 60, 95% UI 54-67). Total cases of cancer in TGD people are estimated to be 1740 (95% UI 1584-1934) in 5 years and 2258 (95% UI 2066-2507) in 10 years (excluding non-melanoma skin). If TGD people were able to access their planned level of GAC, this would reduce these figures to 1555 (95% CI 1386-1766) and 2012 (95% CI 1797-2282) respectively. ConclusionsThis study provides prediction of cancer cases in TGD people in England, supporting the planning of service provision and training. This is vital, as with increasing disclosure, and long wait times for GAC, cancer cases in TGD people are predicted to increase. Summary BoxesO_ST_ABSWhat is already known on this topicC_ST_ABSThe annual number of cases of cancer in transgender and gender diverse (TGD) people in England is currently unknown as gender incongruence is not collected as part of the National Cancer Registration and Analysis Service. Some gender-affirming care (GAC) interventions are known to modulate cancer risk. Use of testosterone and chest reconstruction for transmasculine people is known to reduce their incidence of breast cancer compared to cisgender women. Use of oestradiol alongside medical or surgical androgen suppression has been shown to reduce the incidence of prostate cancer in transfeminine people while increasing their risk of breast cancer, compared to cisgender men. What this study addsThis study found that there are likely to be approximately 966 cases of cancer (excluding non-melanoma skin) in TGD people per year in the UK. Though total annual cases of cancer in TGD people are expected to be 2258 in 10 years, improved access to gender-affirming care could reduce total cases to 2012 (a 11% reduction). These figures provide additional justification for funding to improve access to GAC via the National Health Service (NHS), as well as for training on the oncological needs of this population.

Urinary tract infections (UTIs) are among the most common infectious diseases worldwide, with Escherichia coli being the predominant uropathogen. The increasing prevalence of extended-spectrum beta-lactamase (ESBL)-producing strains and their association with fluoroquinolone resistance pose a significant challenge to empirical therapy, particularly in community settings. The aim of this study was to determine the epidemiology and predictive factors associated with ESBL-producing E. coli and its concomitant fluoroquinolone resistance in community-acquired clinical isolates. A retrospective cross-sectional study was conducted analyzing 244 clinical E. coli isolates. Demographic and microbiological data were collected, including age, sex, sample type, and antibiotic susceptibility. Associations between variables and ESBL production were assessed using Pearsons chi-squared test, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Of the isolates, 165 (68%) were ESBL-producing. A significant association was observed between age group and ESBL production (p < 0.001), with the highest frequency in the 20-39 age group. Most ESBL-positive isolates were obtained from women (73%), although odds ratio (OR) analysis suggested a non-significant trend toward a higher probability in men (OR = 1.29; 95% CI: 0.72-2.31). High rates of fluoroquinolone resistance were identified among the ESBL-producing isolates, with 30% resistance to levofloxacin and 35% to ciprofloxacin (p < 0.001). Urine samples showed the highest concentration of ESBL-positive isolates, with a significant association between sample type and resistance (p < 0.001). The high prevalence of ESBL-producing E. coli and its concomitant resistance to fluoroquinolones highlight a critical challenge for the empirical treatment of urinary tract infections in Mexico, underscoring the need to strengthen antimicrobial use management and local surveillance strategies.

BackgroundInvasive lobular breast cancer (ILC) is the most commonly diagnosed special histological subtype of breast cancer (BC). Metastatic ILC (mILC) is less sensitive to FDG-PET imaging and often metastasizes to unusual sites --peritoneum, gastrointestinal (GI) tract, ovaries, urinary tract, and orbit--which may go unrecognized after a long disease-free interval. Some metastatic sites cause nonspecific symptoms, like abdominal/epigastric pain, with numerous published case reports of mILC misdiagnosed as gastric cancer. These atypical BC metastatic sites may lead to late and/or misdiagnosis, thereby delaying effective treatments. ObjectiveWe developed a patient survey to investigate the patient-reported prevalence of delayed diagnosis or misdiagnosis of mILC and their potential impact upon treatment outcomes. MethodsA 45-question survey was developed and piloted with breast cancer researchers, clinical oncologists, and patient advocates. This IRB-approved survey was then distributed to patients with ILC. Analyses including data QC and visualization were conducted in R using descriptive statistics. Incomplete or inconsistent responses were excluded, and summary statistics were stratified by four common mILC sites to highlight subgroup differences. Results525 patient surveys were completed, with 450 patients diagnosed with ILC, and of those 321 diagnosed with mILC. For those with mILC, 33.3% (n=107) were diagnosed with de novo mILC at initial presentation. Of the patients diagnosed with mILC, 32.1% (n=103) presented with other medical conditions at diagnosis. Misdiagnosis was reported by 26.2% (n=84) of patients with mILC, and of these cases, 31% (n=26) had [&ge;]2 misdiagnoses. The top 5 misdiagnoses were bone-related condition (24.7%), benign breast condition (23.4%), another type of BC (7.8%), diagnostic delay (7.8%), and menopause related (5.2%). 44.5% of patients waited [&ge;]1 year for an accurate diagnosis. 49 patients were treated for their misdiagnosis, and 6 received incorrect cancer treatments. The most frequently reported contributors to delayed or misdiagnosis were inconclusive imaging, providers lack of ILC knowledge, and initial misdiagnosis. Of the 321 patients with mILC, 138 (42.9%) reported symptoms before diagnosis; the most common were back pain (16.5%), fatigue/malaise (14.9%), GI symptoms (11.8%), bloating (8.4%), and weight loss (8.1%). Although 40% of patients reported having a mammogram at the time of their initial misdiagnosis, ILC was detected in only 20.5% (24/116) of these cases, and mammography detected only 5 (25%) of the 20 de novo mILC cases. Patients reported additional diagnostic testing within 1-3 months of their initial mammogram, includingbiopsy, ultrasound (US), and MRI. 47.9% of patients were in active BC surveillance after curative intent therapy at the time of their mILC diagnosis; however, no statistical difference was seen in time to diagnosis versus those patients not under surveillance. ConclusionOur survey results underscore the urgent need to improve diagnostic strategies for mILC. Addressing delays and diagnostic errors in mILC is critical to optimizing treatment strategies and improving patient outcomes.

Background: In Burkina Faso, typhoid fever remains a major public health concern, with a high incidence among children younger than 15 years of age. To address this burden, the country introduced typhoid conjugate vaccine in January 2025 through a national vaccination campaign reaching children aged 9 months to 14 years. This study aimed to estimate the cost of typhoid conjugate vaccine delivery during the national campaign and to identify the main cost drivers across different administrative levels. Methods: We conducted a cross-sectional, retrospective costing study using a microcosting approach from the government perspective. We collected data from fifty health facilities, eight health districts, five health regions, and the national level. Financial and economic costs were estimated for each level, excluding vaccine and syringe costs. All costs were converted to 2024 USD using the official exchange rate. Findings: Vaccinators administered a total of 10.5 million typhoid conjugate vaccine doses. The average financial cost per dose was $0.47 (95% CI: $0.39-$0.51), and the economic cost was $2.16 (95% CI: $1.71-$2.56). Human resources and per diem payments were the main contributors to costs. Costs varied by geography, delivery strategy, and security context, with higher costs observed in rural and conflict-affected areas. The mobile-temporary posts strategy had the highest economic cost per dose ($2.02; 95% CI: $1.64-$2.40), while the fixed strategy had the highest financial cost per dose ($0.41; 95% CI: ($0.32-$0.49). Conclusion: The financial cost per dose remained within Gavi, the Vaccine Alliance's operational support range. The observed cost variations highlight the need for targeted funding and enhanced logistical support to ensure equitable access, particularly in rural and insecure areas. This study provides evidence to inform future vaccination campaigns and supports decision-making for typhoid conjugate vaccine introduction in other countries in the region.

IntroductionColorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide, despite advances in conventional oncological therapies. In recent years, various studies have made advances in integrative oncology, such as investigating the use of Chinese Herbal Medicine (CHM) as a complementary therapy alongside conventional oncological therapies to alleviate treatment-related adverse effects, improve quality of life, and potentially enhance therapeutic outcomes. Despite this, clinical practice in this area remains highly heterogeneous, with limited standardized guidelines on key areas of concern such as (1) optimal intervention, (2) recommended stage and duration of intervention, (3) safety considerations, and (4) possible herb-drug interactions. Hence, this study aims to establish expert consensus on the usage of CHM as a complementary therapy in the management of CRC, to support safe, consistent, and evidence-informed clinical practice. Methods and AnalysisWe will employ a modified Delphi technique to achieve consensus amongst a panel of international experts in various fields related to integrative oncology. Prior to the study, a list of questionnaire items was developed based on a systematic review of existing clinical practice guidelines on CRC. An international panel will be invited based on established international profile in integrative oncology research and clinical practice, and by peer referral. Two rounds of Delphi will be conducted using anonymous online questionnaires. Consensus will be considered reached if at least 50% of the panel strongly agree/disagree that an item should be included or excluded while strong consensus will be set at 76%. Items which achieve strong consensus after Round 1 will be removed, before being sent out for Round 2 with a summary of Round 1 responses for a final consensus. Ethics and DisseminationEthics approval has been obtained from the Institutional Review Board of Nanyang Technological University (IRB-2025-1222). Our findings will be disseminated through peer-reviewed publications and conference presentations. Strengths and limitations of this studyO_LIThis study will develop an expert consensus which aims to guide future integration of Chinese Herbal Medicine (CHM) as a complementary therapy into colorectal cancer (CRC) management. C_LIO_LIKey concerns in areas such as determining the (1) optimal intervention, (2) recommended stage and duration of intervention, (3) safety considerations, and (4) possible herb-drug interactions, thereby laying the groundwork for potential future incorporation of CHM into CRC treatment protocols alongside conventional oncology approaches has been identified, thus limiting implementation in clinical practice. C_LIO_LIDesigning a study e-guide, followed by the consensus rounds study online will facilitate participants responses and the dissemination of information from previous rounds. C_LI

Numerous factors may influence the optimal rollout of new gonococcal antibiotics. We compared eight rollout strategies using a gonorrhea transmission model and ranked strategies by the number of gonococcal infections and clinically useful antibiotic lifespan. Rankings were most sensitive to the starting ceftriaxone resistance prevalence and screening frequency.

Objectives: To identifiy risk factors for antimicrobial resistance (AMR) in seven pathogen-antimicrobial combinations in patients with cancer and cancer survivors. Methods: Using data from patients with recent or past cancer diagnostic codes in Oxfordshire, UK, we examined associations between 22 potential risk-factors and AMR in blood culture isolates, collected between 1-April-2015 and 31-March-2025. Results: Among 5,975 bacteraemias in 4,365 adults, we analysed 3,141 (52.6%) due to Enterobacterales and 620 (10.4%) due to Enterococcus faecalis/faecium in 2,752 patients. Fourteen risk-factors for antimicrobial-resistant bacteraemia were identified, varying across pathogen-antimicrobial combinations. Compared with no previous antimicrobial susceptibility test result, prior resistance to the same antibiotic in any culture in the last year was strongly associated with AMR across all pathogen-antimicrobial combinations (all p<=0.001). Prior antibiotic exposure and younger age were also positively associated with AMR in four and five combinations, respectively. Cancer type showed modest effects; lymphoid/haematopoietic malignancies were associated with higher odds (vs colorectal cancer) of trimethoprim-sulfamethoxazole-resistant Enterobacterales (aOR=2.07 95%CI 1.40-3.06) and vancomycin-resistant Enterococcus bacteraemia (aOR=6.68, 1.21-36.91). Conclusions: Previous resistance was the greatest risk factor for bacteraemia with AMR in cancer patients and survivors, with prior antibiotic exposure and age also contributing. Lymphoid/haematopoietic malignancies increased risk of resistance to specific antimicrobials. Keywords: antimicrobial resistance, bacteraemia, cancer, risk factors

ABSTRACT Background: Malaria remains a leading public health burden in sub-Saharan Africa, disproportionately affecting children under five years. In response, Kenya introduced the RTS,S/AS01 malaria vaccine in selected regions, including Siaya County where malaria transmission is endemic. Despite this milestone, uptake has been inconsistent, with hesitancy emerging as a significant barrier. Objective: This study aimed to determine factors associated with malaria vaccine hesitancy among caregivers of children 6-59 months in Ugenya Subcounty, Siaya County. Methodology: A cross-sectional mixed methods design was employed involving 425 caregivers and 15 healthcare workers and County health officials between January to February 2025. Quantitative data were collected using structured questionnaires and analyzed in Stata version 17 through descriptive statistics, bivariate analysis at 20% significance threshold, and multivariable logistic regression at 5% level to determine key factors associated with malaria vaccine hesitancy. Qualitative data from 15 key informant interviews were transcribed verbatim and thematically analyzed using NVivo. Thematic analysis, guided by a predefined codebook, was used to identify recurring patterns and extract key themes, which were illustrated with direct quotations from participants Results: Overall, 42.9% of caregivers (n=181; 95% CI: 38.9%-47.3%) reported hesitancy. Significant predictors included caregiver age, marital status, family size, access to health facilities, and vaccine availability. Single caregivers, those from smaller households, and those facing health facility access challenges were more likely to be hesitant to malaria vaccine. Despite high levels of knowledge, misconceptions and misinformation about vaccine safety, often spread via social media persisted. Conversely, caregivers relying on healthcare workers and mainstream media showed greater acceptance of malaria vaccine. Conclusion and Recommendations: Malaria vaccine hesitancy remains significant at 42.9%, driven by demographic factors such as younger age, single status, and smaller household size. Structural barriers including limited vaccine availability and poor access to health facilities further contribute to reluctance. Although knowledge and awareness were high, misinformation, particularly from social media, persisted, while information from healthcare workers improved acceptance. Addressing these gaps through targeted community engagement, improved access, and trusted communication channels is essential to increase uptake of malaria vaccine.

Typhoid fever remains a significant public health challenge in low- and middle-income countries. In 2018, The World Health Organization recommended a single dose typhoid conjugate vaccine (TCV) for routine immunization in endemic settings; however, evidence guiding booster doses remains limited. Homologous TCV booster doses have demonstrated immune boosting. This study assessed the immunogenicity and safety of a heterologous booster using a Vi capsular polysaccharide-CRM197 TCV (Vi-CRM) administered 5-6 years after primary vaccination with a Vi capsular polysaccharide tetanus toxoid TCV (Vi-TT) in children. Children previously enrolled in a Phase 2 trial were recruited. Participants who had received TCV at 9-11 or 15-23 months were given a Vi-CRM booster at 6-7 years of age (Booster-TCV group), and controls received their first TCV dose at the same age (1st-TCV group). Serum anti-Vi IgG concentrations were measured at baseline and 28 days post-vaccination. Solicited and unsolicited adverse events (AEs) and serious adverse events (SAEs) were recorded. Among 147 children enrolled, 87 received a second and 60 received a first TCV dose. Baseline anti-Vi IgG geometric mean titers (GMT) were higher in the Booster-TCV group (21.5 EU/mL; 95% CI: 17.2-26.8) than in the 1st-TCV group (5.5 EU/mL; 95% CI: 4.5-6.7). At day 28, GMTs rose markedly in both groups: 5140.0 EU/mL (95% CI: 4302.0-6141.3) in the Booster-TCV group and 2084.8 EU/mL (95% CI: 1724.4-2520.5) in the 1st-TCV group. Local reactions and systemic AEs were mild. No SAEs were observed. Vi-TT-induced immunity persisted for at least 5-6 years, and a heterologous booster triggered a strong immune response with universal seroconversion. These findings support heterologous prime-boost strategies to maintain protection in school-age children and inform optimization of TCV schedules in endemic regions.

Ambulatory Care Sensitive Conditions (ACSCs) are conditions for which effective and timely primary health care (PHC) can prevent hospitalizations. They are widely used as a proxy indicator of access to and quality of PHC. Despite their relevance, evidence from Central America remains scarce. This study aimed to quantify the burden, describe the epidemiological profile, and assess temporal trends of ACSCs hospitalizations in Honduras from 2014 to 2024. We conducted a retrospective observational study using national administrative hospital discharge data from all Ministry of Health hospitals. ACSCs were defined using a standardized list of 20 diagnostic groups based on ICD-10 codes. We estimated percentages and sex-age-standardized hospitalization rates per 10,000 inhabitants. Clinical indicators included length of stay (LOS) and in-hospital fatality rates. Temporal trends were evaluated using joinpoint regression models to estimate annual percent changes (APC). Analyses included stratification by age, sex, and disease category. A total of 4,023,944 hospitalizations were analyzed, of which 547,486 (13.6%) were classified as ACSCs. The overall sex-age-standardized rate was 54.1 per 10,000 inhabitants. ACSCs' standardized rates increased between 2014 and 2018 (APC: 2.7%; 95% CI: -2.4; 15.2), declined sharply between 2018 and 2021 (APC: -17.8%; 95% CI: -30.6; -10.3), and increased again between 2021 and 2024 (APC: 15.9%; 95% CI: 4.6; 37.6). Despite this rebound, rates remained below pre-pandemic levels. ACSCs were concentrated among children under 5 years (27.7%) and adults aged 60 years and older (29.9%). Noncommunicable diseases accounted for 56.8% of cases, with diabetes mellitus as the leading cause. Compared with non-ACSCs hospitalizations, ACSCs were associated with longer LOS (4.9 vs. 3.9 days; p <0.001) and higher in-hospital fatality rates (2.4% vs. 1.7%; p <0.001). ACSCs hospitalizations constitute a substantial burden in Honduras and reflect persistent gaps in PHC performance. Strengthening PHC resilience and capacity, particularly for chronic disease management and vulnerable populations, is essential to reduce avoidable hospitalizations and improve health system efficiency and equity.

Introduction: Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) has become less effective at preventing malaria due to rising parasite resistance. IPTp with dihydroartemisinin-piperaquine (DP) alone or in combination with SP (DP+SP) dramatically lowers the risk of malaria in pregnancy compared to SP but is associated with lower birthweight and early life wasting. We estimated the effect of IPTp-DP, DP+SP, and SP on infant growth outcomes and assessed possible treatment mechanisms through a causal mediation analysis. Methods: We used infant follow-up data (N=761) from a trial (NCT04336189) that randomized pregnant women to receive monthly IPTp-DP, SP, or DP+SP. We compared weight-for-length (WLZ) and length-for-age (LAZ) z-scores between treatment arms. We assessed possible mediation through pregnancy, birth, and infancy factors using interventional indirect effect models. Results: Compared to IPTp-SP, IPTp-DP+SP decreased mean WLZ by 0.18 [95% confidence interval (CI) -0.03, 0.39] between 1-3 months and 0.28 (95% CI 0.07, 0.49) between 4-6 months, with the largest differences among primigravidae. Lower risk of active placental malaria in IPTp-DP+SP helped reduce differences in mean WLZ vs IPTp-SP (+0.06, 95% CI 0.02, 0.10). The IPTp-DP+SP arm had up to 0.28 lower mean LAZ between 7-13 months compared to IPTp-DP, particularly among children who were wasted between 0-6 months; low birthweight had a persistent, mediating effect on linear growth. Conclusion: Adverse birth outcomes contributed to early growth faltering among children born to mothers receiving IPTp-DP+SP vs IPTp-SP, but the prevention of placental malaria partially counteracted the negative effects of IPTp-DP+SP on ponderal growth.