搜索结果：African journal of laboratory medicine

African swine fever (ASF) is a highly contagious and fatal hemorrhagic disease of swine. While vaccines have been licensed in Vietnam and the Philippines, their global application remains constrained by insufficient large-scale validation of safety and efficacy, rendering rapid and reliable diagnostic assays crucial for effective prevention and control. In this study, a multi-epitope antigen (MEA) was rationally designed by utilizing informatics to predict and select 15 conserved B-cell epitopes from four major African swine fever virus (ASFV) structural proteins: p30, p54, p72, and pA104R. The recombinant MEA was expressed in Escherichia coli, and its immunogenicity was validated by Western blot and indirect immunofluorescence assays. This antigen was subsequently utilized as the basis for an indirect enzyme-linked immunosorbent assay (iELISA) whose reaction conditions were systematically optimized. The optimal cutoff value for the iELISA was determined to be 0.315 from the analysis of 100 known ASFV-negative serum samples. The assay demonstrated excellent reproducibility, with intra- and inter-assay coefficients of variation below 10%, and exhibited high specificity, with no cross-reactivity against sera positive for other common swine viruses. Notably, the developed assay exhibited high sensitivity, capable of detecting ASFV antibodies in serum samples at dilutions up to 1:6,400. Furthermore, it demonstrated superior sensitivity compared to two commercial ELISA kits in validating clinical samples from regions with circulating Genotype II strains. These findings highlight the successful development of a sensitive and specific iELISA for ASFV antibody detection, representing a valuable new tool for large-scale epidemiological surveillance and the implementation of robust control strategies for ASF.IMPORTANCEAfrican swine fever (ASF) is a devastating viral disease of swine causing substantial economic losses globally. Although vaccines have recently been licensed in countries such as Vietnam and the Philippines, the global availability of a universally standardized and safe vaccine remains a significant challenge. Control efforts continue to rely heavily on rapid and accurate diagnosis. A significant limitation of current serological assays is their variable sensitivity, which can lead to missed detections and compromise surveillance programs. This study addresses this deficiency through a rational, epitope-based engineering approach. We designed a single, chimeric antigen by genetically fusing 15 conserved, immunodominant B-cell epitopes from four major African swine fever virus proteins. The resulting indirect enzyme-linked immunosorbent assay demonstrated high specificity, excellent reproducibility, and, critically, superior diagnostic sensitivity compared to two commercial kits. This work reports the development of a significantly improved serodiagnostic tool, offering enhanced reliability for large-scale epidemiological surveillance and supporting more robust control strategies against ASF.

The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.

Assessing and understanding communicative health literacy (COM-HL) in healthcare settings is essential, as it constitutes a fundamental tool of public health and health promotion. Despite its importance, COM-HL remains an underinvestigated topic in Africa. Consequently, the development and validation of a Portuguese COM-HL scale could be regarded as a significant contribution to the assessment of the COM-HL in Portuguese-speaking African countries. Therefore, the aims of this study were to assess the psychometric properties of the Portuguese COM-HL instruments, to describe the COM-HL of Angolan adults and investigate its determinants. Cross-sectional survey. Purposively selected recruitment sites within the municipality/district in seven provinces of Angola across the North, South and East regions. 1839 Angolan adults from 3041 invited persons, predominantly females (53.6%). Quota sampling was used to ensure representation across key sociodemographic strata. Within each quota, recruitment sites, data collection time points and participants were randomly selected. The inclusion criteria were age 18 years or above, Angolan nationality, permanent residence in Angola, the ability to speak the language of the questionnaire and the absence of mental disabilities or any other incapacity to perform the interview. Measurement properties of the six-item and 11-item versions of the COM-HL instrument assessed through Cronbach's alpha and Spearman-Brown coefficient, construct validity of the questionnaire investigated by principal component analysis (PCA), the relationship between COM-HL and independent variables measured with linear regression analyses. The Cronbach's alpha of the 11-item COM-HL scale was 0.92, and the Spearman-Brown correlation was 0.89. The items belonged to one factor, and 56.7% of the total variance was explained by this factor based on the PCA. The mean score was 52.4 (95% CI 51.42 to 53.45). For the six-item version, the Cronbach's alpha was 0.86, and the Spearman-Brown correlation was 0.83. The items belonged to one factor, and 58.1% of the total variance was explained by this factor based on the PCA. The mean score was 49.9 (95% CI 48.83 to 50.97). In both versions of the scale, getting enough time in the consultation with your doctor was rated as the most difficult task. The absence of financial deprivation (p<0.001), the location of residence within an urban area (p<0.001) and the possession of at least a fair health status (p<0.02) were identified as positive determinants of COM-HL. The questionnaires can be characterised by good internal consistency and seem to be an appropriate tool to assess COM-HL in Portuguese-speaking countries. Angolan adults scored relatively low for COM-HL. People found it difficult to get enough time during consultations. Therefore, it is recommended to improve the communication skills of physicians and facilitate communication among healthcare users.

Exome sequencing (ES) has become a valuable approach for diagnosing developmental disorders (DD), improving the diagnostic yield to up to 40%, and offering a potential end to the diagnostic odyssey experienced by many families. However, there remains a scarcity of studies assessing the lived experiences of parents and caregivers of individuals with DD, particularly within an African context. From the Deciphering Developmental Disorders in Africa (DDD-Africa) study, 101 parents from 97 families who received ES results for their child with a previously undiagnosed DD participated in this sub-study, which aimed to explore parents' expected utility of ES results and the psychological, social, and emotional impacts of receiving such results. Before result feedback consultations, researcher-administered pre-result feedback questionnaires were completed to determine parents' expectations of ES results and their motivations for seeking a confirmed diagnosis. Consultation summary notes were analyzed using a deductive, literature-informed quantitative content analysis to identify psychological aspects that arose immediately after receiving results. The vast majority of parents, 98 of 101 (97.0%), expressed that they expected results to help them gain knowledge and understanding of their child's condition, and many ranked gaining a better understanding of their child's condition and potential future health problems as their primary motivator for seeking a confirmed diagnosis. Receiving a confirmed diagnosis was overwhelming and emotional for 39 of 97 (40.2%) families and elicited complex emotional responses. Results brought relief and/or a sense of resolution to 42 of 97 (43.3%) families, while 32 of 97 (34.5%) were accepting of their child's condition before receiving a result and 20 of 97 (20.6%) families experienced grief or a loss of hope. This study accentuates the importance of confirming a genetic diagnosis in individuals with DD, with parents expecting results to enhance their understanding of their child's condition, its cause, and any future health problems, illustrating the importance of genetic counseling in preparing and supporting families for ES result feedback.

Human African trypanosomiasis (HAT) is a fatal vector-borne disease caused by Trypanosoma brucei. Although HAT incidence has declined, meeting WHO's elimination targets remain difficult, particularly due to limited diagnostic sensitivity for low-parasite load-infections. Arboviruses such as dengue (DENV 1-4), chikungunya (CHIKV), and yellow fever (YFV) virus, present with nonspecific febrile symptoms similar to HAT and are underdiagnosed in Sub-Saharan Africa. Due to this overlap in symptoms and a suspected geographical overlap of vectors and pathogens in the Democratic Republic of the Congo (DRC) the pathogens were combined in a multiplex-PCR panel. Sample-to-result platforms (S2R) can reduce hands-on time and infrastructure requirements, making them ideal for peripheral laboratories. We developed a multiplex real-time RT-PCR assay on the ARIES&#xae; platform, for simultaneous detection of HAT, DENV, CHIKV and YFV, showing how automated, closed-cartridge PCR can simplify testing. A technical validation and retrospective sample testing (n&#x2009;=&#x2009;242) were performed at the Institute of Tropical Medicine (ITM). Field validation took place in the DRC with retrospective samples from a CHIKV outbreak (n&#x2009;=&#x2009;121) in Institut National pour la Recherche Biom&#xe9;dicale (INRB) Kinshasa and 52 prospective whole blood samples from acute febrile patients in Centre de Recherche en Sant&#xe9; de Kimpese (CRSK) in Kimpese. The assay showed a slight loss of sensitivity, evidenced in the technical validation, and the non-detection of some T.b.gambiense and retrospective arboviral samples at ITM with low pathogen loads. CHIKV samples tested in Kinshasa showed a sensitivity of 89.4%. Although all samples tested in Kimpese were negative for the pathogens, it demonstrated how just a few days of training and the simplified workflows of a S2R-platform can enable robust diagnostics under challenging conditions. Ensuring rapid, sensitive molecular diagnostics in resource-limited settings is critical for eliminating HAT and strengthening surveillance of emerging arboviruses. Despite the recent discontinuation of ARIES&#xae;, our findings confirm the feasibility and reliability of detecting diverse pathogens with minimal laboratory resources. The assay aligns with WHO and FIND target-product profiles, highlighting its relevance for neglected diseases in low-resource settings. These results emphasize the ongoing need for open, flexible S2R platforms to support disease surveillance and outbreak preparedness. Clinicaltrials.gov NCT04760678, registered on February 17th, 2021.

Despite widespread implementation of vertical transmission prevention and paediatric HIV programmes, HIV remains a leading cause of child mortality. We analysed HIV-attributed deaths in the Child Health and Mortality Prevention Surveillance (CHAMPS) network, focusing on comorbidities, co-infections, and care gaps. We conducted a prospective, descriptive analysis of deaths in children younger than 5 years (under-5) recorded from Dec 3, 2016, to Dec 31, 2024, across seven CHAMPS sites in Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, South Africa, and Bangladesh. Causes of death were determined through standardised post-mortem investigations using minimally invasive tissue sampling, histopathology, molecular testing, clinical record abstraction, and verbal autopsy. Multidisciplinary panels adjudicated causes of death, and descriptive statistics were used to summarise demographic, clinical, and laboratory findings. Of 5200 under-5 deaths with an assigned cause, 164 (3&#xb7;2%) had HIV in the causal chain-two neonatal and 162 infant or child deaths. 31 additional infants and children with HIV had HIV listed as a contributing condition only. Among infants and children, HIV-attributed mortality was highest in Mozambique (38 [13%] of 296), Kenya (41 [8%] of 499), Sierra Leone (39 [8%] of 500), Mali (13 [8%] of 168), and South Africa (30 [8%] of 399), and was rare in Ethiopia (one [1%] of 140) and absent in Bangladesh (none of 15). Only 94 (58%) of 162 HIV-attributed cases had documented antemortem diagnoses; of those, 63 (67%) had received antiretroviral therapy. Comorbidities included lower respiratory infections (84 [52%] of 162), sepsis (70 [43%]), malaria (27 [17%]), diarrhoeal diseases (26 [16%]), anaemia (22 [14%]), other infections (22 [14%]), and meningitis or encephalitis (15 [9%]). Wasting syndrome was present in 89 (55%) of 162, and 144 (89%) of 162 had other infections in the causal chain, including cytomegalovirus (48 [30%] of 162), Klebsiella pneumoniae (48 [30%]), Streptococcus pneumoniae (30 [19%]), and Pneumocystis jirovecii (24 [15%]). Paediatric HIV remains a major contributor to under-5 mortality in high-burden settings, often alongside co-infections and malnutrition. Low diagnosis and treatment rates reflect missed care opportunities. Strengthening early detection, treatment, and maternal-child health services is essential to reducing deaths and achieving global HIV targets. Bill & Melinda Gates Foundation.

Objective: This exploratory post hoc analysis examined the safety/efficacy of the aripiprazole once-monthly 400 mg (AOM 400) long-acting injectable (LAI) in Black/African American patients diagnosed with bipolar I disorder (BP-I). Methods: Data were from a 52-week, open-label trial of AOM 400 maintenance treatment in patients diagnosed with DSM-IV-TR-defined BP-I. Outcomes included treatment-emergent adverse events (TEAEs), clinician-rated extrapyramidal symptoms (EPS), patient stability, Young Mania Rating Scale (YMRS), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impression-Bipolar Version-Severity (CGI-BP-S) scores, functioning, and quality of life (QoL). Data analyses comprised descriptive statistics and a mixed model for repeated measures. Results: Outcomes were analyzed in 464 patients (Black/African American, n=104; White, n=255; Asian, n=94; other racial groups, n=11). No notable increase in TEAEs, serious TEAEs, or TEAEs leading to discontinuation were observed in Black/African American patients vs those in other racial groups. Rates of akathisia, tremor, increased weight, or hypertension were lower/similar in Black/African American patients vs other racial groups; changes in EPS scores were minimal in all groups. At last visit, 90.1% of Black/African American patients were stable, similar to other racial groups. Small changes in YMRS total score occurred in all groups, with MADRS total score and CGI-BP-S scores largely unchanged. Functioning and QoL improved in Black/African American patients, to a similar/greater degree than other racial groups. Limitations include the open-label design, prior aripiprazole stabilization, and sparse metabolic laboratory data, constraining causal inference and metabolic conclusions. Conclusion: The safety and efficacy of AOM 400 is comparable between Black/African American and non-Black/African American patients with BP-I. The data provide valuable evidence supporting second-generation LAI antipsychotic use in these patients. Trial Registration: ClinicalTrials.gov identifier: NCT01710709.

Although radiotherapy is an essential part of comprehensive cancer care, access is heavily limited in most sub-Saharan African (SSA) countries. Patients' barriers to care can be grouped as availability, accessibility, accommodation, affordability, and acceptability. We aimed to assess cancer patient- and caregiver-reported barriers in nine SSAn countries (Republic of the Congo, Ethiopia, Gabon, Kenya, Mali, Nigeria, Tanzania, Uganda, and Zimbabwe). We conducted a telephone-based survey among 553 randomly selected patients with breast, cervical, colorectal, and prostate cancer, Kaposi sarcoma and non-Hodgkin lymphoma diagnosed between 2018 and 2019 registered in population-based registries of the African Cancer Registry Network. We inquired about receipt of radiotherapy and barriers irrespective of recalling a recommendation. Among all categories, 21.6% (Use of alternative medicine) to 39.6% (Cost of treatment) of patients reported severe barriers. Most common was problematic Cost of treatment (69.0% overall). A high share of patients from Congo, Kenya, Nigeria, and Tanzania reported barriers. Higher education and wealth were associated with reduced problems in all categories except increased problems with Fear and Use of alternative medicine. Receipt of radiotherapy was associated with fewer problems with Availability of transport (odds ratio [OR]: 0.34; 95% confidence interval [CI], 0.13-0.88) and Trust in healthcare workers (OR: 0.44; 95% CI, 0.24-0.8), and increased Fear (OR: 2.33; 95% CI, 1.33-4.05). Seeing that one-third of the patients reported severe problems in all dimensions, shortage of radiotherapy units is not the only problematic aspect of access to radiotherapy. Improvements in affordability, patient-healthcare worker communication, and psychosocial support are needed.

Blood-based biomarkers offer a widely available, scalable, and noninvasive method to study neurodegeneration. However, the association between blood-based biomarkers of neurodegeneration and long-term risk of mortality, as well as dementia-specific mortality in a racially diverse cohort, remains understudied. The goal of this study was to determine whether baseline biomarkers of neurodegeneration are associated with long-term risk of all-cause and dementia-specific mortality in a biracial cohort. The REasons for Geographic and Racial Differences in Stroke cohort study enrolled 30,239 Black and White participants across the continental United States from 2003 to 2007, with ongoing follow-up. Plasma neurofilament light chain (NfL), total tau, glial fibrillary acidic protein (GFAP), and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) were measured in baseline plasma from a random sample of participants. All-cause mortality, dementia-specific mortality, cardiovascular-specific mortality, and other causes of death were adjudicated and classified using medical records, the Social Security Death Index, and the National Death Index. Cause-specific Cox regression models accounting for competing risks were used to calculate hazard ratios (HRs) of outcomes for each biomarker separately. A total of 917 participants had a mean baseline age of 67.4 years (SD 12.1), 49.4% were female, and 48.6% self-identified as Black. With a mean follow-up of 11.1 (SD 5.7) years, 51.0% (477/935) of participants died and 9.2% experienced dementia-specific mortality (86/935). No associations were observed for total tau. In fully adjusted models for other biomarkers, HRs of all-cause mortality per standard deviation increments were 1.93 (95% CI 1.48-2.52) for GFAP, 1.90 (95% CI 1.55-2.32) for NfL, and 1.23 (95% CI 1.09-1.37) for UCH-L1. Furthermore, GFAP (HR 5.66, 95% CI 2.91-11.00) and NfL (HR 2.72, 95% CI 1.57-4.71) were associated with dementia-specific mortality in fully adjusted models. GFAP (HR 2.06, 95% CI 1.22-3.49) and NfL (HR 2.16, 95% CI 1.66-2.81) were also associated with cardiovascular-specific mortality in fully adjusted models. Plasma biomarkers of neurodegeneration, particularly GFAP and NfL, were associated with increased risk of all-cause, dementia-specific, and cardiovascular-specific mortality in a biracial cohort. These associations should be considered when assessing links between these biomarkers and other outcomes, as well as when used in clinical practice.

Female Genital mutilation (FGM) has been associated with numerous negative health effects like sexual dysfunction, chronic pain, infections, infertility, and an increased risk of maternal mortality. To date, no recognized studies in sub-Saharan Africa (SSA) have combined machine learning (ML) models with nationally representative Demographic and Health Survey (DHS) data to classify FGM. Therefore, this study aims to identify the most effective ML model for classifying FGM in SSA. ML offers the significant advantage of handling extremely large and complex datasets with numerous variables and interactions, providing more accurate classifications than conventional statistical methods. This study used secondary data from the DHS collected between 2015 and 2023 in 11 SSA countries. The DHS employs a cross-sectional study design. A total of 62,249 women who had at least one daughter were included in the analysis. Seven classification algorithms, including Logistic Regression, Decision Tree, Random Forest (RF), Support Vector Machine (SVM), K-Nearest Neighbors (KNN), XGBoost (XGB), and Naive Bayes (NB), were used to classify FGM. The RF classifier yielded the highest performance, achieving 0.85 accuracy, 0.83 precision, 0.88 recall, 0.85 F1 score, and 0.93 AUC. Random Forest (Brier score&#x2009;=&#x2009;0.1319) and Decision Tree (0.1328) showed best calibration. The SHAP plots provide a comprehensive interpretation of the features influencing the model's classification of whether a mother reports that at least one daughter has undergone FGM. The bar plot shows the global importance of each feature, with opinion on FGM (+&#x2009;0.14), country of residence (+&#x2009;0.13), respondent's circumcision status (+&#x2009;0.11), and religious justification for FGM (+&#x2009;0.07) contributing the most on average to the classification of FGM. This study applied seven machine ML techniques to classify FGM in SSA, with the Random Forest classifier demonstrating the best performance. SHAP interpretability findings indicated that maternal opinion on FGM, country of residence, religious justifications for FGM, and the respondent's circumcision status contributed most, on average, to the classification of FGM. These results suggest that education and advocacy efforts aimed at mothers particularly those who have had FGM themselves or who believe that the practice is justified by religion should be given top priority in interventions. Implementing community engagement initiatives that challenge accepted conventions and ideas around FGM may be particularly beneficial, especially when these practices are rooted in religious or cultural justifications.

Breast cancer is a leading cause of mortality and morbidity among females worldwide. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we provided an updated comprehensive assessment of the epidemiological trends, disease burden, and risk factors associated with breast cancer globally, regionally, and nationally from 1990 to 2023. Breast cancer incidence, mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) were estimated by age and sex for 204 countries and territories from 1990 to 2023. Mortality estimates were generated using GBD Cause of Death Ensemble models, leveraging data from population-based cancer registration systems, vital registration systems, and verbal autopsies. Mortality-to-incidence ratios were calculated to derive both mortality and incidence estimates. Prevalence was calculated by combining incidence and modelled survival estimates. YLLs were established by multiplying age-specific deaths with the GBD standard life expectancy at the age of death. YLDs were estimated by applying disability weights to prevalence estimates. The sum of YLLs and YLDs equalled the number of DALYs. Breast cancer burden attributable to seven risk factors was examined through the comparative risk assessment framework. The GBD forecasting framework was used to forecast breast cancer incidence and mortality from 2024 to 2050. Age-standardised rates were calculated for each metric using the GBD 2023 world standard population. In 2023, there were an estimated 2&#xb7;30 million (95% uncertainty interval [UI] 2&#xb7;01 to 2&#xb7;61) breast cancer incident cases, 764&#x2008;000 deaths (672&#x2008;000 to 854&#x2008;000), and 24&#xb7;1 million (21&#xb7;3 to 27&#xb7;5) DALYs among females globally. In the World Bank low-income group, where a low age-standardised incidence rate (ASIR) was estimated (44&#xb7;2 per 100&#x2008;000 person-years [31&#xb7;2 to 58&#xb7;4]), the age-standardised mortality rate (ASMR) was the highest (24&#xb7;1 per 100&#x2008;000 [16&#xb7;8 to 31&#xb7;9]). The highest ASIR was in the high-income group (75&#xb7;7 per 100&#x2008;000 [67&#xb7;1 to 84&#xb7;0]), and the lowest ASMR was in the upper-middle-income group (11&#xb7;2 per 100&#x2008;000 [10&#xb7;2 to 12&#xb7;3]). Between 1990 and 2023, the ASIR in the low-income group increased by 147&#xb7;2% (38&#xb7;1 to 271&#xb7;7), compared with a 1&#xb7;2% (-11&#xb7;5 to 17&#xb7;2) change in the high-income group. The ASMR decreased in the high-income group, changing by -29&#xb7;9% (-33&#xb7;6 to -25&#xb7;9), but increased by 99&#xb7;3% (12&#xb7;5 to 202&#xb7;9) in the low-income group. The increase in age-standardised DALY rates followed that of ASMRs. Risk factors such as dietary risks, tobacco use, and high fasting plasma glucose contributed to 28&#xb7;3% (16&#xb7;6 to 38&#xb7;9) of breast cancer DALYs in 2023. The risk factors with a decrease in attributable DALYs between 1990 and 2023 were high alcohol use and tobacco. By 2050, the global incident cases of breast cancer among females were forecast to reach 3&#xb7;56 million (2&#xb7;29 to 4&#xb7;83), with 1&#xb7;37 million (0&#xb7;841 to 2&#xb7;02) deaths. The stable incidence and declining mortality rates of female breast cancer in high-income nations reflect success in screening, diagnosis, and treatment. In contrast, the concurrent rise in incidence and mortality in other regions signals health system deficits. Without effective interventions, many countries will fall short of the WHO Global Breast Cancer Initiative's ambitious target of achieving an annual reduction of 2&#xb7;5% in age-standardised mortality rates by 2040. The mounting breast cancer burden, disproportionately affecting some of the world's most vulnerable populations, will further exacerbate health inequalities across the globe without decisive immediate action. Gates Foundation, St Jude Children's Research Hospital.

Toxoplasmosis is a parasitic zoonosis of major importance, particularly during pregnancy because of the risk of maternal-foetal transmission. The aim of the study was to estimate the seroprevalence of Toxoplasma gondii in pregnant women at the University Hospital of Cocody and to describe IgG/IgM serological profiles. We conducted a retrospective cross-sectional study from April 2022 to March 2023 at the immunology laboratory of the University Hospital of Cocody. Toxoplasma gondii-specific IgG and IgM antibodies were measured by electrochemiluminescence immunoassay and then interpreted according to serological profiles. Chi-square test was used to assess the association between IgM positivity and pregnancy trimester. Out of 200 pregnant women, previous infection was observed in 45.0% (IgG+/IgM-), current infection in 4.0% (IgG+/IgM+), recent infection in 5.5% (IgG-/IgM+), and no infection in 45.5% (IgG-/IgM-). Of the women, 83% were tested after the first trimester. The proportion of recent infections (IgM+) was higher in the first trimester (17.6%) than in the second (8.2%) and third (7.4%) trimesters, with no statistically significant difference (p = 0.22). The seroprevalence of toxoplasmosis remains high, with a non-negligible proportion of women presenting recent or current infection. Late initiation of screening highlights the need for strengthened strategies, including early screening, targeted antenatal education and better access to diagnostic tools to reduce the risk of transmission. This study provides updated data on the seroprevalence of gestational toxoplasmosis in C&#xf4;te d'Ivoire. Thus, it reinforces the need for early screening and targeted health awareness campaigns.

The prevalence of monoclonal gammopathy of undetermined significance (MGUS) increases with age, but the study of age of onset and the prevalence of MGUS in younger individuals has been limited by lack of sensitive serum protein testing methods. In addition, there is marked racial disparity in the prevalence in Black individuals compared with White individuals and it is important to determine if MGUS has an earlier age of onset in Black individuals. In this first large mass spectrometry-based population-based screening study of MGUS, we evaluated 12,378 individuals (3598 White, 4075 Black, 4147 Mexican Americans, and 558 others) aged 10-49 years of age. The study used serum samples from the National Health and Nutritional Examination Survey (NHANES) III. MGUS was identified in 177 persons (1.28%, 95% CI 0.95, 1.60). MGUS was detectable in 0.2% of individuals age 10-19 years and the prevalence increased with age to 0.88%, 1.46%, and 2.82% in individuals ages 20-29, 30-39, and 40-49, respectively. The age-adjusted prevalence of MGUS was significantly higher in Black individuals compared with White individuals, 1.49% (1.13, 1.95) versus 0.82% (0.57, 1.18), P&#x2009;=&#x2009;<&#x2009;0.01. MGUS had an earlier age of onset in Black individuals; the increased prevalence of MGUS among Black compared with White individuals was apparent at age 30-39 years, 2.94% vs 1.42%, and this disparity increased further in the age group 40-49 years to 5.2% vs 2.8%, respectively. There was no significant difference in the prevalence of MGUS between White individuals and Mexican American individuals in the overall cohort, or within any specific age group. The study using a highly sensitive mass spectrometry-based assay demonstrates onset of monoclonal gammopathy in the second decade of life, with a higher prevalence among the Black individuals with comparable prevalence among the White and Mexican individuals, a disparity that increases with advancing age.

Whole-genome sequencing (WGS) is transforming communicable disease surveillance globally. The National Institute for Communicable Diseases, South Africa, participates in national laboratory-based surveillance for human isolates of Salmonella. This study was to investigate human Salmonella isolates from South Africa, 2020-2023, using WGS analysis. WGS was performed using Illumina NextSeq Technology. Data were analysed using multiple bioinformatics tools, including those available at the Center for Genomic Epidemiology, Pathogenwatch and EnteroBase. Data analysis allowed for identification and characterisation of isolates. Core-genome multilocus sequence typing was used to investigate the phylogeny of isolates. Of the 8006 isolates of Salmonella that were analysed using WGS, 130 distinctive serovars and subspecies were identified. Salmonella enterica serovar Enteritidis (Salmonella Enteritidis) (4271/8006; 53.3%) and Salmonella Typhimurium (1430/8006; 17.9%) were the most prevalent serovars, accounting for 71.2% of all isolates. This was followed by Salmonella Typhi (482/8006; 6.0%). Sixteen per cent (1288/8006) of isolates showed the presence of antimicrobial resistance (AMR) determinants associated with &#x2265; 2 classes of antimicrobials. Salmonella Isangi (167/8006; 2.1%) showed the highest prevalence of AMR, with most isolates (159/167; 95.2%) showing AMR determinants associated with &#x2265; 7 classes of antimicrobials. Core-genome multilocus sequence typing was used to confirm several suspected clusters and outbreaks and identified additional cryptic or unreported clusters and outbreaks. Investigation of clusters and outbreaks mostly involved Salmonella Enteritidis and Salmonella Typhi. The implementation of WGS has enabled genomic surveillance of Salmonella, which allows for enhanced characterisation and AMR determination of isolates and identification of clusters and outbreaks, which informs targeted public health investigation and response. This study describes the population structure of Salmonella isolated from humans in South Africa and hugely contributes to the available Salmonella WGS data from Africa.

In South Africa, antiretroviral therapy adherence monitoring relies on self-reported adherence, which is prone to recall error, and only verified annually during blood viral load measurement. A novel urine tenofovir rapid assay (UTRA) is a low-cost point-of-care adherence support tool for people living with HIV (PLHIV). Nested in an effectiveness randomized trial, we aimed to understand the relative acceptability of adherence support experiences among PLHIV receiving the UTRA point-of-care adherence intervention versus standard of care. All trial participants (n = 199) completed a brief, repeat-measures, quantitative acceptability questionnaire at months 3, 6 and 12. We also conducted longitudinal in-depth interviews with 25 PLHIV with three interactions per participant over 52 weeks-a total of 75 interviews. Interviewed PLHIV were purposively sampled for balance by arm, diversity in age and gender, rich-case sampling, and saturation. We also conducted once-off in-depth interviews with five healthcare providers administering the UTRA intervention. Data were collected between May 2022 and June 2024. Qualitative data analysis involved descriptive summaries of key emergent themes with illustrative case examples augmented by descriptive statistics from the questionnaires. Participants in the intervention arm reported that being tested and informed about their adherence levels in real-time served as a reminder to take treatment consistently. The UTRA facilitated conversations between PLHIV and healthcare providers on how to overcome barriers to adherence. Participants in the control arm reported that they relied on relatives for adherence support and accountability because there is limited time for adherence discussions with healthcare providers. Healthcare providers reported that providing adherence counselling to PLHIV receiving standard of care was challenging because they relied on voluntary disclosure of adherence interruptions. PLHIV in the intervention arm reported more positive experiences of adherence support compared to those in the control arm, regardless of their adherence practices. A point-of-care adherence tool like the UTRA provides a much-needed platform for PLHIV and healthcare providers to discuss adherence practices and challenges. PLHIV preferred this style of adherence support compared to the standard of care.

Human papillomavirus (HPV35) is globally associated with only 2% of invasive cervical cancers (ICC) but demonstrates a disproportionately higher prevalence in sub-Saharan Africa, reaching up to 10% in previous reports. In this review, we provide updated data from multiple African countries, revealing high HPV35 prevalence rates in women with precancerous and ICC lesions. Among women with ICC, the highest prevalence of HPV35 was observed in Mozambique (30% and 19%), Kenya (26% and 22%), South Africa (17%), Burkina Faso (13.7%), Zimbabwe (11%), and Tanzania (11.2%). Similarly, in women with precancerous lesions (LSIL/HSIL/CIN1-3), the highest rates were recorded in Tanzania (26%) and Botswana (23% and 20%). These findings highlight a significant and underappreciated burden of HPV35-associated cervical disease in African populations, particularly among women with precancerous and invasive lesions. The findings call for an urgent re-evaluation of current HPV vaccination strategies to consider the inclusion of HPV35, which could profoundly enhance the effectiveness of cervical cancer prevention programs in sub-Saharan Africa.

While diagnostic disparities by race and age of onset are reported in inherited retinal diseases, their impact on Stargardt disease (STGD)-a clinically and genetically heterogeneous macular dystrophy-remains unclear. We analyzed 246 STGD patients at a U.S. referral center (2003-2024) who completed genetic testing, comparing laboratory-reported results (lab-GT) with manual, phenotype-integrated reinterpretation (m-GT) of ABCA4 sequencing incorporating updated variant databases and genotype-phenotype correlation. Diagnostic yield and variant burden were assessed by race and age of onset. Positive/likely positive (P/LP) lab-GT was identified in 79% (195), with 78% (191) attributable to ABCA4 (ABCA4-positive lab-GT: 57% [141]). M-GT increased ABCA4-P/LP yield to 91% (224). Black participants had lower ABCA4-positive lab-GT than White participants (55% vs. 73%) and fewer pathogenic variants; on multivariable analysis, Black race (OR 0.34) and later age of onset (OR 0.95/year) independently predicted reduced molecular diagnosis. The disparity by race resolved with P/LP m-GT (89% vs. 90%); by age of onset, yield remained lower in late-onset cases (ABCA4-P/LP lab-GT: 86% early- [&#x2264;10&#x2009;yrs], 83% intermediate- [11-44&#x2009;yrs], 54% late-onset [&#x2265;45&#x2009;yrs], improving to 97%, 94%, and 77% after m-GT). Posttest reinterpretation improves diagnostic yield, particularly for Black and late-onset STGD patients, underscoring the value of ancestry-informed interpretation, historical reanalysis, and genotype-phenotype correlation.

Age, gender, and mutation type are key risk factors for myeloproliferative neoplasms (MPNs). Africa remains under-represented in global cancer statistics due to limited population-based genomic data. To determine the frequency and demographic associations of common MPN-related genetic abnormalities in the South African population. A retrospective cross-sectional analysis of cytogenetic results for Janus kinase-2 p.V617F (JAK-2 p.V617F), Janus kinase-2 exon 12 (JAK-2 exon 12), calreticulin (CALR), myeloproliferative leukaemia virus oncogene (MPL), and breakpoint cluster region-Abelson kinase 1 (BCR::ABL1) was conducted from 01 January 2018 to 31 May 2023. Data were retrieved from the National Health Laboratory Service and analysed for associations with age and gender using Fisher's Exact Test or Pearson's Chi-Square Test (p < 0.05). A total of 8934 patient records were analysed; 58% were male patients and 42% female patients, with a mean age of 50 &#xb1; 17 years. Among sequence variant changes, 18.2% of MPN cases were positive for BCR::ABL1, 8.5% for JAK-2 p.V617F, 0.5% for CALR, 0.04% for MPL, and none for JAK-2 exon 12. BCR::ABL1 showed equal sex distribution, while JAK-2 p.V617F increased with age and showed slight female predominance (p = 0.002). CALR and MPL frequencies were too low for meaningful association testing. BCR::ABL1 was the most frequent abnormality, especially in younger age groups, whereas JAK-2 p.V617F was linked to increasing age and female predominance. MPN genetic testing in South Africa predominantly targeted male patients (ratio 1.4:1). BCR::ABL1 was the most common abnormality, particularly in individuals aged 18 to 49 years, while JAK-2 p.V617F showed a slight female predominance (1:1.2).

Malaria is a life-threatening disease that is transmitted by the bites of infected female Anopheles mosquitoes. Women of reproductive age (WRA) are a more vulnerable group to malaria, which increases the risk of severe anemia, maternal death, and unfavorable birth outcomes. However, only limited comprehensive studies are available in the Eastern Sub-Saharan African (ESSA) region. The Global Burden of Diseases (GBD) 2023 estimates were to assess the fatal and non-fatal health outcomes of malaria among WRA in ESSA region from 1990 to 2023. The Cause of Death Ensemble Model (CODEm) modeling platform was used to estimate mortality and Years of Life Lost (YLLs) in the GBD 2023 study. Years Lived with Disability (YLDs), prevalence, and incidence of malaria disease was estimated by using Bayesian meta-regression for Disease modeling. The net change from 1990 to 2023 was evaluated by percentage change. All estimates were presented together with the 95% uncertainty intervals (95% UIs). In 2023, the highest prevalence rate of malaria among WRA was recorded in Mozambique [19627 cases per 100,000 WRA (95% UI: 12,347, 27,601)]. However, the lowest prevalence rate was estimated in Eritrea [842 (95% UI: 450, 1430)] and Rwanda [1603 (95% UI: 587, 3180)]. Mozambique had the highest incidence rate [16076 new cases per 100,000 WRA (95% UI: 11,890, 21,714)], whereas Eritrea had the lowest rate [2267 new cases per 100,000 WRA (95% UI: 962, 4539)]. The highest rates of mortality, YLLs and Disability-Adjusted Life Years (DALYs) were estimated in Mozambique, whereas the lowest rates were recorded in Ethiopia. There were substantial reductions in the rates throughout the region in 2023 compared to 1990, except in Djibouti and Ethiopia. This study has revealed that there was substantial reduction in the rates of non-fatal and fatal health outcomes of malaria among WRA in the ESSA region in 2023 compared to 1990. However, the rates remain high and heterogeneous across the region. Therefore, strengthening the health service system and sustaining strong malaria control programs across the countries are crucial to end malaria epidemics by 2030.