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BACKGROUND: Despite growing efforts to improve access to vaccination, millions of children, especially in developing countries, have not received a single dose of diphtheria, tetanus, and pertussis (DTP) vaccine. Consequently, they are often called zero-dose children (ZDC). With limited health resources, prioritising communities for rapid and mass zero-dose catch-up vaccination in missed communities to avert epidemic outbreaks is complicated by unreliable denominators used to compute vaccination coverages. Incorporating other indicators of access and utilisation of vaccination services can help with identifying and ranking missed communities based on the likelihood of finding ZDC. We described the process of generating a scoring method to rank health areas in Cameroon based on their likelihood of containing ZDC. METHODS: We used geospatial analysis to compute and aggregate health area characteristics, including hard-to-reach (HTR) areas (defined as areas of settlement above a one- (for urban areas) or 15-kilometre radius (for rural areas) beyond a vaccinating health facility), amount of area covered by slums and new area settlement, and percentage of children unvaccinated for DTP-1. We attributed a weight based on the ability to limit accessibility or utilisation of vaccination services to each characteristic and computed the score as a weighted average of health area characteristics. The health area score ranged from 0 to 1, with higher scores representing a higher likelihood of containing ZDC. We stratified the analysis by rural and urban health areas. RESULTS: We observed substantial district and regional variations in health area scores, with hotspots health areas (administrative level 4) observed in the Far North (0.83), North (0.81), Adamawa (0.80), East (0.75), and South West (0.67) regions. The Adamawa region had the highest percentage of health areas with the highest score (78%), followed by the East (50%), West (48%), and North (46%) regions. For most regions (Far North, South, South West, Littoral, West, and North West), DTP-1 contributed the most to the score. However, HTR settlement areas within a health area contributed substantially to the overall score in the East, North, and Adamawa regions. CONCLUSIONS: We found substantial variations in health area scores with hotspots in the Far North, North, Adamawa, East, and South West regions. Although DTP-1 could be used as an indicator to identify health areas with ZDC for most communities, HTR settlement area was a valuable indicator in ranking priority health areas in the East, North, and Adamawa regions, further emphasising the need to consider other indicators before prioritisation.
\n \n\n \n \nBACKGROUND: Immunization is regarded as one of the most cost-effective public health interventions in global health. However, its cost-effectiveness depends greatly on the knowledge and skills of vaccinators. With the growing complexity of immunization programs, the need for a well-trained vaccination workforce cannot be overemphasized. In this study, we assessed the knowledge, attitudes, and practices among vaccination staff in Cameroon. METHODS: Through a descriptive cross-sectional design, we used structured questionnaires and observation guides to collect data from vaccination staff in health facilities that were selected by a multistage sampling method. Data were analyzed using STATA 13 software. RESULTS: Overall, we collected data from Expanded Program on Immunization focal staff in 265 health facilities across 68 health districts. Over half (53%) of the surveyed facilities were found in rural areas. Nearly two-thirds of health facilities had immunization focal staff with knowledge gaps for each of the four basic immunization indicators assessed. In other words, only 37% of staff knew how to estimate coverages, 36% knew how to\u00a0inteprete the EPI monitoring curve, 35% knew how to prepare vaccine orders, and 37% knew how to estimate vaccine wastage. In terms of practices, staff waited for more than ten children to be present before opening a 20-dose vaccine vial in 63% of health facilities, and more than five children to be present before opening a 10-dose vaccine vial in 80% of surveyed facilities. Provision of vaccine-specific information (informing caregiver about vaccine received, explanation of benefits and potential side effects) during immunization sessions was suboptimal for the most part. CONCLUSION: This study suggests marked deficits in immunization knowledge among vaccination staff and exposes common attitudes and practices that could contribute to missed opportunities for vaccination and hinder vaccination coverage and equity in Cameroon. Our findings highlight the urgent need to invest in comprehensive capacity building of vaccination staff in Cameroon, especially now that the\u00a0immunization program is becoming increasingly complex.
\n \n\n \n \nThe Covid-19 pandemic is a unique event in the modern history of humanity, which has generated great challenges and, at the same time, valuable opportunities for public health. A number of examples of them are found in the more than three hundred pages of this book. In each chapter it is possible to understand how a vaccine for Covid-19 was developed in record time - due to the urgency of an antidote that would allow us to deal with this terrible disease - through the acceleration, compliance and improvement of all labor criteria, production, evaluation, timely release, and security. This entire process of developing the first vaccine produced by Brazil was described in a very creative way, allowing the reader to dive into a technical-scientific content of the highest level. The book presents an overview that goes through the origin of the virus, the transmission mechanisms of SARS-CoV-2, the vaccine development process and the regulatory and legal instruments to guarantee access to vaccination - starting with the most vulnerable populations. It also describes the trials and phases of clinical study development that ensured the vaccine's safety and efficacy. It also covers the logistics of distribution and pharmacovigilance for monitoring the product in the user population until the detailing of the technological prospection, as well as showing the necessary steps to carry out a process of technology transfer of the vaccine from the viral vector. Among the various innovations, it is worth highlighting: preparation of a technological order through ETEC; use of continuous submission to the National Health Surveillance Agency (ANVISA); and emergency use authorization. This effort made it possible to meet the expressive demand for Covid-19 vaccines in Brazil in a timely manner and on an unprecedented scale. For the Pan American Health Organization (PAHO), which turns 120 on December 2, 2022, it is an honor to have Bio-Manguinhos/Fiocruz as part of our history. Due to its outstanding performance on the international scene, this institute is a true heritage of humanity. And now, with the first Brazilian vaccine for Covid-19, Bio-Manguinhos/Fiocruz consolidates Brazil's leadership in the production of immunobiologicals in Latin America and the Caribbean, ensuring greater self-sufficiency and sustainability of basic health supplies not only for the country, but for the entire region of the Americas.
\n \n\n \n \nBackground: Breastfeeding has long-term benefits, such as reducing obesity, allergies, asthma, wheezing, inflammatory bowel disease, diabetes, cardiovascular disease and effecting on brain development. This study aimed to investigate the relationship between exclusive breastfeeding and mental concentration in first and second grade primary school children. Methods: In this cross-sectional study, 90 students (7-8 years old) were studied in Mashhad, Iran. The history and duration of breastfeeding were asked from children\u2019s mothers, and their mental concentration and short term memory were measured by Toulouse Pieron and Digit learning tests, respectively. Results: The mean of the breastfeeding period was 5.72 \u00b1 6.89 month and the mean of total scores was 51.2 \u00b1 32.44 for Toulouse Pieron test and 8.57 \u00b1 6.52 for Digit learning test in all participants. The correlation between the Toulouse Pieron and Digit learning test, and breastfeeding history indicated that exclusive breast-fed children showed higher test results and therefore, better mental concentration and short term memory (P < 0.001). Conclusion: Based on the findings, exclusive breastfeeding has a positive effect on mental concentration and short term memory with respect to its duration.
\n \n\n \n \nBackground: We were conducted this study to assess the prevalence of food insecurity in heart failure patients households and the relationship between food security and some variables in this households. Methods: In this cross sectional study, a total of 300 heart failure patients' households were studied in Imam Reza hospital of Mashhad. The Iranian version of household food insecurity access scale was used to measure food security. Results: Among the participants in this study, 129 patients (43%) were secure, 42 patients (14%), 82 patients (27.3%) and 47 patients (15.7%) were mild, moderate and sever insecure, respectively. Chi-square test results show that there is a strong association between diabetes, hypertension, body mass index (BMI), and food security distribution (P < 0.01). Conclusions: Based on our findings, food insecurity is mild to severe prevalent in heart failure patients households, meanwhile there is a strong relationship between diabetes, hypertension, BMI and food security status, so it is important to assess their food status and prevent from worsening their nutritional status.
\n \n\n \n \nThe heritability of susceptibility to tuberculosis (TB) disease has been well recognized. Over 100 genes have been studied as candidates for TB susceptibility, and several variants were identified by genome-wide association studies (GWAS), but few replicate. We established the International Tuberculosis Host Genetics Consortium to perform a multi-ancestry meta-analysis of GWAS, including 14,153 cases and 19,536 controls of African, Asian, and European ancestry. Our analyses demonstrate a substantial degree of heritability (pooled polygenic h2 = 26.3%, 95% CI 23.7-29.0%) for susceptibility to TB that is shared across ancestries, highlighting an important host genetic influence on disease. We identified one global host genetic correlate for TB at genome-wide significance (p<5 \u00d7 10-8) in the human leukocyte antigen (HLA)-II region (rs28383206, p-value=5.2 \u00d7 10-9) but failed to replicate variants previously associated with TB susceptibility. These data demonstrate the complex shared genetic architecture of susceptibility to TB and the importance of large-scale GWAS analysis across multiple ancestries experiencing different levels of infection pressure.
\n \n\n \n \nBackground: As well as suffering a high burden of pneumococcal disease people living with HIV (PLHIV) may contribute to community transmission in sub-Saharan African (sSA) settings. Pneumococcal vaccination is not currently offered to PLHIV in sSA but may prevent disease and reduce transmission. More evidence of vaccine effectiveness against carriage in PLHIV is needed. An Experimental Human Pneumococcal Carriage model (EHPC) has been safely and acceptably used in healthy adults in Malawi to evaluate pneumococcal vaccines against carriage and to identify immune correlates of protection from carriage. This study will establish the same model in PLHIV and will be the first controlled human infection model (CHIM) in this key population. Methods: Healthy participants with and without HIV will be inoculated intranasally with Streptococcus pneumoniae serotype 6B. Sequential cohorts will be challenged with increasing doses to determine the optimal safe challenge dose to establish experimental carriage. Nasal fluid, nasal mucosal, and blood samples will be taken before inoculation and on days 2, 7, 14, and 21 following inoculation to measure pneumococcal carriage density and identify immune correlates of protection from carriage. The vast majority of natural pneumococcal carriage events in PLHIV do not result in invasive disease and no invasive disease is expected in this study. However, robust participant safety monitoring is designed to identify signs of invasive disease early should they develop, and to implement treatment immediately. Participants will complete a Likert-style questionnaire at study-end to establish acceptability. Interpretations: We expect the EHPC model to be safely and acceptably implemented in PLHIV. The CHIM can then be used to accelerate pneumococcal vaccine evaluations in this population, and an evidence-based pneumococcal vaccination policy for PLHIV in sSA.
\n \n\n \n \nBACKGROUND: High-quality systematic data on antimicrobial use in UK inpatient paediatric haematology-oncology services are lacking, despite this population being at high risk from antimicrobial exposure and resistance. OBJECTIVES: We conducted a retrospective study to demonstrate how routinely collected electronic prescribing data can address this issue. PATIENTS AND METHODS: This retrospective study describes and compares IV antibiotic consumption between two UK paediatric haematology-oncology inpatient units, between 2018 and 2022. Both sites provide similar services and receive proactive antimicrobial stewardship input. Data were extracted from each site's antimicrobial surveillance system, which report monthly days of therapy (DOT) per 100\u2005patient-days (PD). Consumption was reported for specific and total antibiotics. Trends were modelled using linear regression and autoregressive moving average models. RESULTS: Total IV antibiotic consumption at each site was similar. Median monthly DOT per 100\u2005PD were 25.9 (IQR: 22.1-34.0) and 29.4 (24.2-34.9). Total antibiotic use declined at both sites, with estimated annual yearly reductions of 3.52\u2005DOT per 100\u2005PD (95% CI: 0.46-6.59) and 2.57 (1.30-3.85). Absolute consumption was similar for carbapenems, piperacillin/tazobactam and aminoglycosides, whilst ceftriaxone and teicoplanin demonstrated approximately 3-fold relative differences in median monthly consumption. Meropenem, piperacillin/tazobactam, teicoplanin, vancomycin and gentamicin all demonstrated statistically significant reductions in use over time at either one or both sites, although this was most marked for piperacillin/tazobactam and vancomycin. CONCLUSIONS: Routinely collected electronic prescribing data can aid benchmarking of antibiotic use in paediatric haematology-oncology inpatients, highlighting areas to target stewardship strategies, and evaluating their impact. This approach should be rolled out nationally, and to other high-risk groups.
\n \n\n \n \nHIC-Vac is an international network of researchers dedicated to developing human infection challenge studies to accelerate vaccine development against pathogens of high global impact. The HIC-Vac Annual Meeting (3rd and 4th November 2022) brought together stakeholders including researchers, ethicists, volunteers, policymakers, industry partners, and funders with a strong representation from low- and middle-income countries. The network enables sharing of research findings, especially in endemic regions. Discussions included pandemic preparedness and the role of human challenge to accelerate vaccine development during outbreak, with industry speakers emphasising the great utility of human challenge in vaccine development. Public consent, engagement, and participation in human challenge studies were addressed, along with the role of embedded social science and empirical studies to uncover social, ethical, and regulatory issues around human infection challenge studies. Study volunteers shared their experiences and motivations for participating in studies. This report summarises completed and ongoing human challenge studies across a variety of pathogens and demographics, and addresses other key issues discussed at the meeting.
\n \n\n \n \nWith the continued emergence of variants of concern, the global threat of COVID-19 persists, particularly in low- and middle-income countries with limited vaccine access. Protein-based vaccines, such as SCB-2019, can be produced on a large scale at a low cost while antigen design and adjuvant use can modulate efficacy and safety. While effective humoral immunity against SARS-CoV-2 variants has been shown to depend on both neutralization and Fc-mediated immunity, data on the effectiveness of protein-based vaccines with enhanced Fc-mediated immunity is limited. Here, we assess the humoral profile, including antibody isotypes, subclasses, and Fc receptor binding generated by a boosting with a recombinant trimer-tag protein vaccine SCB-2019. Individuals who were primed with 2 doses of the ChAdOx1 vaccine were equally divided into 4 groups and boosted with following formulations: Group 1: 9\u2009\u03bcg SCB-2019 and Alhydrogel; Group 2: 9\u2009\u03bcg SCB-2019, CpG 1018, and Alhydrogel; Group 3: 30\u2009\u03bcg SCB-2019, CpG 1018, and Alhydrogel; Group 4: ChAdOx1. Group 3 showed enhanced antibody Fc\u03b3R binding against wild-type and variants compared to Groups 1 and 2, showing a dose-dependent enhancement of immunity conferred by the SCB-2019 vaccine. Moreover, from day 15 after vaccination, Group 3 exhibited higher IgG3 and Fc\u03b3R binding across variants of concerns, including Omicron and its subvariants, compared to the ChAdOx1-boosted individuals. Overall, this highlights the potential of SCB-2019 as a cost-efficient boosting regimen effective across variants of concerns.
\n \n\n \n \nINTRODUCTION: Invasive non-typhoidal Salmonella (iNTS) serovars are a major cause of community-acquired bloodstream infections in sub-Saharan Africa (SSA). In this setting, Salmonella enterica serovar Typhimurium accounts for two-thirds of infections and is associated with an estimated case fatality rate of 15%-20%. Several iNTS vaccine candidates are in early-stage assessment which-if found effective-would provide a valuable public health tool to reduce iNTS disease burden. The CHANTS study aims to develop a first-in-human Salmonella Typhimurium controlled human infection model, which can act as a platform for future vaccine evaluation, in addition to providing novel insights into iNTS disease pathogenesis. METHODS AND ANALYSIS: This double-blind, safety and dose-escalation study will randomise 40-80 healthy UK participants aged 18-50 to receive oral challenge with one of two strains of S. Typhimurium belonging to the ST19 (strain 4/74) or ST313 (strain D23580) lineages. 4/74 is a global strain often associated with diarrhoeal illness predominantly in high-income settings, while D23580 is an archetypal strain representing invasive disease-causing isolates found in SSA. The primary objective is to determine the minimum infectious dose (colony-forming unit) required for 60%-75% of participants to develop clinical or microbiological features of systemic salmonellosis. Secondary endpoints are to describe and compare the clinical, microbiological and immunological responses following challenge. Dose escalation or de-escalation will be undertaken by continual-reassessment methodology and limited within prespecified safety thresholds. Exploratory objectives are to describe mechanisms of iNTS virulence, identify putative immune correlates of protection and describe host-pathogen interactions in response to infection. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the NHS Health Research Authority (London-Fulham Research Ethics Committee 21/PR/0051; IRAS Project ID 301659). The study findings will be disseminated in international peer-reviewed journals and presented at national/international stakeholder meetings. Study outcome summaries will be provided to both funders and participants. TRIAL REGISTRATION NUMBER: NCT05870150.
\n \n\n \n \nSARS-CoV-2 infections in children are generally asymptomatic or mild and rarely progress to severe disease and hospitalization. Why this is so remains unclear. Here we explore the potential for protection due to pre-existing cross-reactive seasonal coronavirus antibodies and compare the rate of antibody decline for nucleocapsid and spike protein in serum and oral fluid against SARS-CoV-2 within the pediatric population. No differences in seasonal coronaviruses antibody concentrations were found at baseline between cases and controls, suggesting no protective effect from pre-existing immunity against seasonal coronaviruses. Antibodies against seasonal betacoronaviruses were boosted in response to SARS-CoV-2 infection. In serum, anti-nucleocapsid antibodies fell below the threshold of positivity more quickly than anti-spike protein antibodies. These findings add to our understanding of protection against infection with SARS-CoV-2 within the pediatric population, which is important when considering pediatric SARS-CoV-2 immunization policies.
\n \n\n \n \nOBJECTIVE: To investigate whether intravenous immunoglobulin (IVIG) improves neurological outcomes in children with encephalitis when administered early in the illness. DESIGN: Phase 3b multicentre, double-blind, randomised placebo-controlled trial. SETTING: Twenty-one hospitals in the UK. PARTICIPANTS: Children aged 6 months to 16 years with a diagnosis of acute or subacute encephalitis, with a planned sample size of 308. INTERVENTION: Two doses (1\u2009g/kg/dose) of either IVIG or matching placebo given 24-36\u2009hours apart, in addition to standard treatment. MAIN OUTCOME MEASURE: The primary outcome was a 'good recovery' at 12 months after randomisation, defined as a score of\u22642 on the Paediatric Glasgow Outcome Score Extended. SECONDARY OUTCOME MEASURES: The secondary outcomes were clinical, neurological, neuroimaging and neuropsychological results, identification of the proportion of children with immune-mediated encephalitis, and IVIG safety data. RESULTS: 18 participants were recruited from 12 hospitals and randomised to receive either IVIG (n=10) or placebo (n=8) between 23 December 2015 and 26 September 2017. The study was terminated early following withdrawal of funding due to slower than anticipated recruitment, and therefore did not reach the predetermined sample size required to achieve the primary study objective; thus, the results are descriptive. At 12 months after randomisation, 9 of the 18 participants (IVIG n=5/10 (50%), placebo n=4/8 (50%)) made a good recovery and 5 participants (IVIG n=3/10 (30%), placebo n=2/8 (25%)) made a poor recovery. Three participants (IVIG n=1/10 (10%), placebo n=2/8 (25%)) had a new diagnosis of epilepsy during the study period. Two participants were found to have specific autoantibodies associated with autoimmune encephalitis. No serious adverse events were reported in participants receiving IVIG. CONCLUSIONS: The IgNiTE (ImmunoglobuliN in the Treatment of Encephalitis) study findings support existing evidence of poor neurological outcomes in children with encephalitis. However, the study was halted prematurely and was therefore underpowered to evaluate the effect of early IVIG treatment compared with placebo in childhood encephalitis. TRIAL REGISTRATION NUMBER: Clinical Trials.gov NCT02308982; ICRCTN registry ISRCTN15791925.
\n \n\n \n \nOBJECTIVES: Whole-body magnetic resonance imaging (WB-MRI) has been demonstrated to be efficient and cost-effective for cancer staging. The study aim was to develop a machine learning (ML) algorithm to improve radiologists' sensitivity and specificity for metastasis detection and reduce reading times. MATERIALS AND METHODS: A retrospective analysis of 438 prospectively collected WB-MRI scans from multicenter Streamline studies (February 2013-September 2016) was undertaken. Disease sites were manually labeled using Streamline reference standard. Whole-body MRI scans were randomly allocated to training and testing sets. A model for malignant lesion detection was developed based on convolutional neural networks and a 2-stage training strategy. The final algorithm generated lesion probability heat maps. Using a concurrent reader paradigm, 25 radiologists (18 experienced, 7 inexperienced in WB-/MRI) were randomly allocated WB-MRI scans with or without ML support to detect malignant lesions over 2 or 3 reading rounds. Reads were undertaken in the setting of a diagnostic radiology reading room between November 2019 and March 2020. Reading times were recorded by a scribe. Prespecified analysis included sensitivity, specificity, interobserver agreement, and reading time of radiology readers to detect metastases with or without ML support. Reader performance for detection of the primary tumor was also evaluated. RESULTS: Four hundred thirty-three evaluable WB-MRI scans were allocated to algorithm training (245) or radiology testing (50 patients with metastases, from primary 117 colon [n = 117] or lung [n = 71] cancer). Among a total 562 reads by experienced radiologists over 2 reading rounds, per-patient specificity was 86.2% (ML) and 87.7% (non-ML) (-1.5% difference; 95% confidence interval [CI], -6.4%, 3.5%; P = 0.39). Sensitivity was 66.0% (ML) and 70.0% (non-ML) (-4.0% difference; 95% CI, -13.5%, 5.5%; P = 0.344). Among 161 reads by inexperienced readers, per-patient specificity in both groups was 76.3% (0% difference; 95% CI, -15.0%, 15.0%; P = 0.613), with sensitivity of 73.3% (ML) and 60.0% (non-ML) (13.3% difference; 95% CI, -7.9%, 34.5%; P = 0.313). Per-site specificity was high (>90%) for all metastatic sites and experience levels. There was high sensitivity for the detection of primary tumors (lung cancer detection rate of 98.6% with and without ML [0.0% difference; 95% CI, -2.0%, 2.0%; P = 1.00], colon cancer detection rate of 89.0% with and 90.6% without ML [-1.7% difference; 95% CI, -5.6%, 2.2%; P = 0.65]). When combining all reads from rounds 1 and 2, reading times fell by 6.2% (95% CI, -22.8%, 10.0%) when using ML. Round 2 read-times fell by 32% (95% CI, 20.8%, 42.8%) compared with round 1. Within round 2, there was a significant decrease in read-time when using ML support, estimated as 286 seconds (or 11%) quicker ( P = 0.0281), using regression analysis to account for reader experience, read round, and tumor type. Interobserver variance suggests moderate agreement, Cohen \u03ba = 0.64; 95% CI, 0.47, 0.81 (with ML), and Cohen \u03ba = 0.66; 95% CI, 0.47, 0.81 (without ML). CONCLUSIONS: There was no evidence of a significant difference in per-patient sensitivity and specificity for detecting metastases or the primary tumor using concurrent ML compared with standard WB-MRI. Radiology read-times with or without ML support fell for round 2 reads compared with round 1, suggesting that readers familiarized themselves with the study reading method. During the second reading round, there was a significant reduction in reading time when using ML support.
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