Epidemiology and antimicrobial resistance of Mycobacterium spp. in the United Arab Emirates: a retrospective analysis of 12 years of national antimicrobial resistance surveillance data.

Introduction: The Eastern Mediterranean Regional Office (EMRO) region accounts for almost 8% of all global Mycobacterium tuberculosis (TB) cases, with TB incidence rates ranging from 1 per 100,000 per year in the United Arab Emirates (UAE) to 204 per 100,000 in Djibouti. The national surveillance data from the Middle East and North Africa (MENA) region on the epidemiology and antimicrobial resistance trends of TB, including MDR-TB remains scarce. Methods: A retrospective 12-year analysis of N = 8,086 non-duplicate diagnostic Mycobacterium tuberculosis complex (MTB complex) isolates from the UAE was conducted. Data were generated through routine patient care during the 2010-2021 years, collected by trained personnel and reported by participating surveillance sites to the UAE National Antimicrobial Resistance (AMR) Surveillance program. Data analysis was conducted with WHONET, a windows-based microbiology laboratory database management software developed by the World Health Organization Collaborating Center for Surveillance of Antimicrobial Resistance, Boston, United States (https://whonet.org/). Results: A total of 8,086 MTB-complex isolates were analyzed. MTB-complex was primarily isolated from respiratory samples (sputum 80.1%, broncho-alveolar lavage 4.6%, pleural fluid 4.1%). Inpatients accounted for 63.2%, including 1.3% from ICU. Nationality was known for 84.3% of patients, including 3.8% Emiratis. Of UAE non-nationals, 80.5% were from 110 countries, most of which were Asian countries. India accounted for 20.8%, Pakistan 13.6%, Philippines 12.7%, and Bangladesh 7.8%. Rifampicin-resistant MTB-complex isolates (RR-TB) were found in 2.8% of the isolates, resistance to isoniazid, streptomycin, pyrazinamide, and ethambutol, was 8.9, 6.9, 3.4 and 0.4%, respectively. A slightly increasing trend of resistance among MTB-complex was observed for rifampicin from 2.5% (2010) to 2.8% (2021). Conclusion: Infections due to MTB-complex are relatively uncommon in the United Arab Emirates compared to other countries in the MENA region. Most TB patients in the UAE are of Asian origin, mainly from countries with a high prevalence of TB. Resistance to first line anti-tuberculous drugs is generally low, however increasing trends for MDR-TB mainly rifampicin linked resistance is a major concern. MDR-TB was not associated with a higher mortality, admission to ICU, or increased length of hospitalization as compared to non-MDR-TB.

Multidrug-resistant tuberculosis: latest opinions on epidemiology, rapid diagnosis and management.

PURPOSE OF REVIEW: This review addresses the escalating global challenge of multidrug-resistant tuberculosis (MDR-TB) in Sub-Saharan Africa, with a focus on its complex comorbidity with HIV/AIDS. Emphasizing the urgency of the issue, the review aims to shed light on the unique healthcare landscape shaped by the convergence of high prevalence rates and intersecting complexities with HIV/AIDS in the region. RECENT FINDINGS: A notable increase in MDR-TB cases across Sub-Saharan Africa is attributed to challenges in timely diagnoses, treatment initiation, and patient treatment defaulting. The literature underscores the critical need for proactive measures to address diagnostic and treatment gaps associated with MDR-TB, particularly concerning its comorbidity with HIV/AIDS. SUMMARY: To effectively manage MDR-TB and its co-morbidity with HIV/AIDS, proactive screening programs are imperative. The review highlights the necessity of active follow-up strategies to ensure treatment adherence and reduce default rates, offering evidence-based insights for improved disease management in the region.

Perspectives on development and advancement of new tuberculosis vaccines.

Tuberculosis (TB) remains a leading cause of death worldwide and is estimated to have caused 1.3 million deaths worldwide in 2022. Approximately one quarter of the world's population are infected with Mycobacterium tuberculosis, of whom up to 10% will progress to developing active TB disease. Achieving the World Health Organization End TB Strategy targets of a 95% reduction in TB mortality and a 90% reduction in TB incidence worldwide by 2035 remains a daunting task. The continuing spread of multidrug-resistant TB adds another obstacle to achieving global TB control. Larger funding pledges coupled with technological advances have recently enabled the enhancement of TB vaccine development efforts. These are yielding a pipeline of over 17 products currently in different stages of clinical trials. Emerging promising phase I and II trial results and advancement to phase III trials have necessitated "vaccine preparedness" in parallel so that a smooth transition from any positive clinical trial result to phase IV evaluation and implementation into policy and practice can follow. Promotion of a human rights-based approach, which recognizes and upholds the fundamental rights of all affected by the disease, is essential to ensure universal access to quality TB vaccines, regardless of their background or personal circumstances.

Barriers and enablers for implementation of digital-linked diagnostics models at point-of-care in South Africa: stakeholder engagement.

The integration of digital technologies holds significant promise in enhancing accessibility to disease diagnosis and treatment at point-of-care (POC) settings. Effective implementation of such interventions necessitates comprehensive stakeholder engagements. This study presents the outcomes of a workshop conducted with key stakeholders, aiming to discern barriers and enablers in implementing digital-connected POC diagnostic models in South Africa. The workshop, a component of the 2022 REASSURED Diagnostics symposium, employed the nominal group technique (NGT) and comprised two phases: Phase 1 focused on identifying barriers, while Phase 2 centered on enablers for the implementation of digital-linked POC diagnostic models. Stakeholders identified limited connectivity, restricted offline functionality, and challenges related to load shedding or rolling electricity blackouts as primary barriers. Conversely, ease of use, subsidies provided by the National Health Insurance, and 24-h assistance emerged as crucial enablers for the implementation of digital-linked POC diagnostic models. The NGT workshop proved to be an effective platform for elucidating key barriers and enablers in implementing digital-linked POC diagnostic models. Subsequent research endeavors should concentrate on identifying optimal strategies for implementing these advanced diagnostic models in underserved populations.

Epidemiology, clinical profiles, and prognostic value of COVID-19-related cutaneous manifestations in African populations: a rapid narrative review.

BACKGROUND: Skin manifestations' true prognostic value, and clinical and epidemiological pictures in SARS-CoV-2 infection in African populations are poorly described and understudied. More familiarity with COVID-19 cutaneous manifestations may aid in early clinical diagnosis or guide prognosis. METHODS: In this literature review, we looked for potential studies published from December 2019 to March 2023 on COVID-19 cutaneous lesions in African populations. Our key questions were focused on the prognostic values of cutaneous manifestations related to COVID-19. RESULTS: Our findings show that cutaneous manifestations of COVID-19 vary by country and severity of COVID-19, primarily multisystem inflammatory syndrome (MIS). Significant differences were also found between various dermatological lesions, primarily MIS, erythema multiforme-like, livedoid, vesicular, or varicella-like rashes, urticarial, maculopapular or morbilliform rashes, and chilblain-like or pernio-like rashes. There were 47.5% (115/242) of MIS cases reported in nine published African studies. Our findings also revealed that MIS may be diagnosed in 2-7 days due to early onset rash. Advanced age, obesity, diabetes, cardiovascular disease, HIV, tuberculosis, asthma, atopic disease, underweight, malnutrition, and malignancy were found to be associated with COVID-19 cutaneous manifestations in African populations. CONCLUSIONS: COVID-19-related skin manifestations in African populations are important as a driving force in COVID-19 prognosis.

Detecting the most critical clinical variables of COVID-19 breakthrough infection in vaccinated persons using machine learning.

Background: COVID-19 vaccines offer different levels of immune protection but do not provide 100% protection. Vaccinated persons with pre-existing comorbidities may be at an increased risk of SARS-CoV-2 breakthrough infection or reinfection. The aim of this study is to identify the critical variables associated with a higher probability of SARS-CoV-2 breakthrough infection using machine learning. Methods: A dataset comprising symptoms and feedback from 257 persons, of whom 203 were vaccinated and 54 unvaccinated, was used for the investigation. Three machine learning algorithms - Deep Multilayer Perceptron (Deep MLP), XGBoost, and Logistic Regression - were trained with the original (imbalanced) dataset and the balanced dataset created by using the Random Oversampling Technique (ROT), and the Synthetic Minority Oversampling Technique (SMOTE). We compared the performance of the classification algorithms when the features highly correlated with breakthrough infection were used and when all features in the dataset were used. Result: The results show that when highly correlated features were considered as predictors, with Random Oversampling to address data imbalance, the XGBoost classifier has the best performance (F1 = 0.96; accuracy = 0.96; AUC = 0.98; G-Mean = 0.98; MCC = 0.88). The Deep MLP had the second best performance (F1 = 0.94; accuracy = 0.94; AUC = 0.92; G-Mean = 0.70; MCC = 0.42), while Logistic Regression had less accurate performance (F1 = 0.89; accuracy = 0.88; AUC = 0.89; G-Mean = 0.89; MCC = 0.68). We also used Shapley Additive Explanations (SHAP) to investigate the interpretability of the models. We found that body temperature, total cholesterol, glucose level, blood pressure, waist circumference, body weight, body mass index (BMI), haemoglobin level, and physical activity per week are the most critical variables indicating a higher risk of breakthrough infection. Conclusion: These results, evident from our unique data source derived from apparently healthy volunteers with cardiovascular risk factors, follow the expected pattern of positive or negative correlations previously reported in the literature. This information strengthens the body of knowledge currently applied in public health guidelines and may also be used by medical practitioners in the future to reduce the risk of SARS-CoV-2 breakthrough infection.

Machine learning algorithms for predicting determinants of COVID-19 mortality in South Africa.

Background: COVID-19 has strained healthcare resources, necessitating efficient prognostication to triage patients effectively. This study quantified COVID-19 risk factors and predicted COVID-19 intensive care unit (ICU) mortality in South Africa based on machine learning algorithms. Methods: Data for this study were obtained from 392 COVID-19 ICU patients enrolled between 26 March 2020 and 10 February 2021. We used an artificial neural network (ANN) and random forest (RF) to predict mortality among ICU patients and a semi-parametric logistic regression with nine covariates, including a grouping variable based on K-means clustering. Further evaluation of the algorithms was performed using sensitivity, accuracy, specificity, and Cohen's K statistics. Results: From the semi-parametric logistic regression and ANN variable importance, age, gender, cluster, presence of severe symptoms, being on the ventilator, and comorbidities of asthma significantly contributed to ICU death. In particular, the odds of mortality were six times higher among asthmatic patients than non-asthmatic patients. In univariable and multivariate regression, advanced age, PF1 and 2, FiO2, severe symptoms, asthma, oxygen saturation, and cluster 4 were strongly predictive of mortality. The RF model revealed that intubation status, age, cluster, diabetes, and hypertension were the top five significant predictors of mortality. The ANN performed well with an accuracy of 71%, a precision of 83%, an F1 score of 100%, Matthew's correlation coefficient (MCC) score of 100%, and a recall of 88%. In addition, Cohen's k-value of 0.75 verified the most extreme discriminative power of the ANN. In comparison, the RF model provided a 76% recall, an 87% precision, and a 65% MCC. Conclusion: Based on the findings, we can conclude that both ANN and RF can predict COVID-19 mortality in the ICU with accuracy. The proposed models accurately predict the prognosis of COVID-19 patients after diagnosis. The models can be used to prioritize COVID-19 patients with a high mortality risk in resource-constrained ICUs.

Understanding health outcome drivers among adherence club patients in clinics of Gauteng, South Africa: a structural equation modelling (SEM) approach.

BACKGROUND: There has been growing interest in understanding the drivers of health outcomes, both in developed and developing countries. The drivers of health outcomes, on the other hand, are the factors that influence the likelihood of experiencing positive or negative health outcomes. Human Immunodeficiency Virus (HIV) continues to be a significant global public health challenge, with an estimated 38 million people living with the aim of this study was therefore to develop and empirically test a conceptual research model using SEM, aimed at explaining the magnitude of various factors influencing HIV and other health outcomes among patients attending Adherence Clubs. METHOD: This was a cross sectional survey study design conducted in 16 health facilities in the City of Ekurhuleni in Gauteng Province, South Africa. A total of 730 adherence club patients were systematically sampled to participate in a closed ended questionnaire survey. The questionnaire was assessed by Cronbach's alpha coefficient for internal consistency. The proposed model was tested using structural equation modelling (AMOS software: ADC, Chicago, IL, USA). RESULTS: A total of 730 adherence club members participated in the study. Of these, 425 (58.2%) were female and 305 (41.8%) were male. The overall results indicated a good reliability of all the scale involved in this study as Cronbach alphas ranged from 0.706 to 0.874, and composite reliability from 0.735 to 0.874. The structural model showed that the constructs health seeking behavior (ß = 0.267, p = 0.000), health care services (ß = 0.416, p = 0.000), stigma and discrimination (ß = 0.135, p = 0.022) significantly predicted health outcomes and explained 45% of its variance. The construct healthcare service was the highest predictor of health outcomes among patients in adherence clubs. CONCLUSION: Patient health seeking behaviour, healthcare services, stigma and discrimination were associated with perceived health outcomes. Since adherence clubs have been found to have a significant impact in improving patient outcomes and quality of life, there is a need to ensure replication of this model.

Burden and risk factors of chronic obstructive pulmonary disease in Sub-Saharan African countries, 1990-2019: a systematic analysis for the Global Burden of disease study 2019.

Background: Sub-Saharan Africa (SSA) has experienced a surge of non-communicable diseases (NCDs) including chronic obstructive pulmonary disease (COPD) over the past two decades. Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), in this study we have estimated the burden and attributable risk factors of COPD across SSA countries between 1990 and 2019. Methods: COPD burden and its attributable risk factors were estimated using data from the 2019 GBD. Percentage change was estimated to show the trend of COPD estimates from 1990 to 2019. COPD estimates attributable by risk factors were also reported to ascertain the risk factor that brings the greatest burden by sex and locations (at country and regions level). Findings: In 2019, all-age prevalent cases of COPD in SSA were estimated to be 10.3 million (95% Uncertainty Intervals (UI) 9.7 million to 10.9 million) showing an increase of 117% compared with the number of all-age COPD cases in 1990. From 1990 to 2019, SSA underwent an increased percentage change in all-age YLDs due to COPD ranging from 41% in Lesotho to 203% in Equatorial Guinea. The largest premature mortality due to COPD was reported from Central SSA accounting for 729 subjects (95% UI, 509-1078). The highest rate of DALYs attributable to COPD was observed in Lesotho. Household air pollution from solid fuel was the primary contributor of the age standardized YLDs, death rate, and DALYs rate per 100,000 population. Interpretation: The prevalence of COPD in SSA has had a steady increase over the past three decades and has progressively become a major public health burden across the region. Household air pollution from solid fuel is the primary contributor to COPD related burden, and its percentage contribution showed a similar trend to the reduction of COPD attributed age-standardized DALY rate. The methodological limitations of surveys and datapoints included in the GBD need to be considered when interpreting these associations. Funding: There are no specific fundings received for this study. The Global Burden of Disease study was supported by funding from the Bill & Melinda Gates Foundation.

The interface between SARS-CoV-2 and non-communicable diseases (NCDs) in a high HIV/TB burden district level hospital setting, Cape Town, South Africa.

BACKGROUND: COVID-19 experiences on noncommunicable diseases (NCDs) from district-level hospital settings during waves I and II are scarcely documented. The aim of this study is to investigate the NCDs associated with COVID-19 severity and mortality in a district-level hospital with a high HIV/TB burden. METHODS: This was a retrospective observational study that compared COVID-19 waves I and II at Khayelitsha District Hospital in Cape Town, South Africa. COVID-19 adult patients with a confirmed SARS-CoV-2 polymerase chain reaction (PCR) or positive antigen test were included. In order to compare the inter wave period, clinical and laboratory parameters on hospital admission of noncommunicable diseases, the Student t-test or Mann-Whitney U for continuous data and the X2 test or Fishers' Exact test for categorical data were used. The role of the NCD subpopulation on COVID-19 mortality was determined using latent class analysis (LCA). FINDINGS: Among 560 patients admitted with COVID-19, patients admitted during wave II were significantly older than those admitted during wave I. The most prevalent comorbidity patterns were hypertension (87%), diabetes mellitus (65%), HIV/AIDS (30%), obesity (19%), Chronic Kidney Disease (CKD) (13%), Congestive Cardiac Failure (CCF) (8.8%), Chronic Obstructive Pulmonary Disease (COPD) (3%), cerebrovascular accidents (CVA)/stroke (3%), with similar prevalence in both waves except HIV status [(23% vs 34% waves II and I, respectively), p = 0.022], obesity [(52% vs 2.5%, waves II and I, respectively), p <0.001], previous stroke [(1% vs 4.1%, waves II and I, respectively), p = 0.046]. In terms of clinical and laboratory findings, our study found that wave I patients had higher haemoglobin and HIV viral loads. Wave II, on the other hand, had statistically significant higher chest radiography abnormalities, fraction of inspired oxygen (FiO2), and uraemia. The adjusted odds ratio for death vs discharge between waves I and II was similar (0.94, 95%CI: 0.84-1.05). Wave I had a longer average survival time (8.0 vs 6.1 days) and a shorter average length of stay among patients discharged alive (9.2 vs 10.7 days). LCA revealed that the cardiovascular phenotype had the highest mortality, followed by diabetes and CKD phenotypes. Only Diabetes and hypertension phenotypes had the lowest mortality. CONCLUSION: Even though clinical and laboratory characteristics differed significantly between the two waves, mortality remained constant. According to LCA, the cardiovascular, diabetes, and CKD phenotypes had the highest death probability.

Burden, causation, and particularities of Long COVID in African populations: A rapid systematic review.

Objectives: To determine the prevalence of long COVID, its most common symptoms, comorbidities, and pathophysiological mechanisms in African populations. Methods: A systematic review of long COVID in African populations was conducted. The random effects model was used to calculate the pooled prevalence rates (95% CI). A narrative synthesis was also performed. Results: We included 14 studies from seven African countries, totaling 6030 previously SARS-CoV-2 infected participants and 2954 long COVID patients. Long COVID had a pooled prevalence of 41% (26-56%). Fatigue, dyspnea, and confusion or lack of concentration were the most common symptoms, with prevalence rates (95% CI) of 41% (26-56%), 25% (12-38%), and 40% (12-68%), respectively. Long COVID was mainly associated with advanced age, being female, more than three long COVID symptoms in the acute phase, initial fatigue and dyspnea, COVID-19 severity, pre-existing obesity, hypertension, diabetes mellitus, and the presence of any chronic illness (P ≤0.05). High microclot and platelet-poor plasma viscosity explained the pathophysiology of long COVID. Conclusion: Long COVID prevalence in Africa was comparable to the global prevalence. The most common symptoms were higher in Africa. Comorbidities associated with long COVID may lead to additional complications in African populations due to hypercoagulation and thrombosis.Systematic review registration: PROSPERO CRD42023430024.

A Scoping Review Evaluating the Current State of Gut Microbiota Research in Africa.

The gut microbiota has emerged as a key human health and disease determinant. However, there is a significant knowledge gap regarding the composition, diversity, and function of the gut microbiota, specifically in the African population. This scoping review aims to examine the existing literature on gut microbiota research conducted in Africa, providing an overview of the current knowledge and identifying research gaps. A comprehensive search strategy was employed to identify relevant studies. Databases including MEDLINE (PubMed), African Index Medicus (AIM), CINAHL (EBSCOhost), Science Citation index (Web of Science), Embase (Ovid), Scopus (Elsevier), WHO International Clinical Trials Registry Platform (ICTRP), and Google Scholar were searched for relevant articles. Studies investigating the gut microbiota in African populations of all age groups were included. The initial screening included a total of 2136 articles, of which 154 were included in this scoping review. The current scoping review revealed a limited number of studies investigating diseases of public health significance in relation to the gut microbiota. Among these studies, HIV (14.3%), colorectal cancer (5.2%), and diabetes mellitus (3.9%) received the most attention. The top five countries that contributed to gut microbiota research were South Africa (16.2%), Malawi (10.4%), Egypt (9.7%), Kenya (7.1%), and Nigeria (6.5%). The high number (n = 66) of studies that did not study any specific disease in relation to the gut microbiota remains a gap that needs to be filled. This scoping review brings attention to the prevalent utilization of observational study types (38.3%) in the studies analysed and emphasizes the importance of conducting more experimental studies. Furthermore, the findings reflect the need for more disease-focused, comprehensive, and population-specific gut microbiota studies across diverse African regions and ethnic groups to better understand the factors shaping gut microbiota composition and its implications for health and disease. Such knowledge has the potential to inform targeted interventions and personalized approaches for improving health outcomes in African populations.

Prevalence and trends of advanced HIV disease among antiretroviral therapy-naïve and antiretroviral therapy-experienced patients in South Africa between 2010-2021: a systematic review and meta-analysis.

BACKGROUND: Despite the significant progress made in South Africa in getting millions of individuals living with HIV into care, many patients still present or re-enter care with Advanced HIV Disease (AHD). We aimed to estimate the prevalence of AHD among ART-naive and ART-experienced patients in South Africa using studies published between January 2010 and May 2022. METHODS: We searched for relevant data on PubMed, CINAHL, Scopus and other sources, with a geographical filters limited to South Africa, up to May 31, 2022. Two reviewers conducted all screening, eligibility assessment, data extraction, and critical appraisal. We synthesized the data using the inverse-variance heterogeneity model and Freeman-Tukey transformation. We assessed heterogeneity using the I2 statistic and publication bias using the Egger and Begg's test. RESULTS: We identified 2,496 records, of which 53 met the eligibility criteria, involving 11,545,460 individuals. The pooled prevalence of AHD among ART-naive and ART-experienced patients was 43.45% (95% CI 40.1-46.8%, n = 53 studies) and 58.6% (95% CI 55.7 to 61.5%, n = 2) respectively. The time trend analysis showed a decline of 2% in the prevalence of AHD among ART-naive patients per year. However, given the high heterogeneity between studies, the pooled prevalence should be interpreted with caution. CONCLUSION: Despite HIV's evolution to a chronic disease, our findings show that the burden of AHD remains high among both ART-naive and ART-experienced patients in South Africa. This emphasizes the importance of regular measurement of CD4 cell count as an essential component of HIV care. In addition, providing innovative adherence support and interventions to retain ART patients in effective care is a crucial priority for those on ART.

Provision of HIV prevention and care services to farmworkers in sub-Saharan African countries.

OBJECTIVES: To summarise data on human immunodeficiency virus (HIV) services available to farmworkers in sub-Saharan Africa (SSA). METHODS: We conducted a systematic review to understand which HIV prevention and care services were accessed by farm workers in SSA. MEDLINE (PubMed), Embase, CINAHL (EBSCO Host), Cochrane library, African Index Medicus, Scopus, Google Scholar, Open Grey, and Web of Science Proceedings Citation Index were searched. Studies were eligible for inclusion if they measured or reported on the presence of HIV workplace policy frameworks, guidelines, or programmes for HIV prevention, treatment and care services, and other treatment modalities specifically targeting farmworkers. RESULTS: Nine studies published between 2005 and 2019 were included in the review. Six themes emerged from included studies, which include HIV policy, HIV prevention (awareness, education, and condom supply), voluntary counselling and testing, antiretroviral therapy (ART), linkage to care, and mobile clinic. Though availability of an HIV policy was inadequate, a significant positive impact of the HIV policy in influencing behaviour change was reported. Most of the farm workers could access HIV education and condom supply in their places of work. Access to ART, treatment support, and linkage to care was inadequate, but community outreach programmes and mobile clinics showed success in reaching a high number of workers with HIV testing and treatment. A majority of farm workers faced barriers in accessing government health facilities. CONCLUSIONS: The findings suggest that there is poor access to HIV services for farmworkers in SSA. There is a dire need to scale up HIV services and programmes, including mobile health facilities, in agricultural settings. Due to high labour migration patterns among farmworkers, we recommend cross-country HIV programmes that allow continuity of care across borders.

Immunologic and vascular biomarkers of mortality in critical COVID-19 in a South African cohort.

Introduction: Biomarkers predicting mortality among critical Coronavirus disease 2019 (COVID-19) patients provide insight into the underlying pathophysiology of fatal disease and assist with triaging of cases in overburdened settings. However, data describing these biomarkers in Sub-Saharan African populations are sparse. Methods: We collected serum samples and corresponding clinical data from 87 patients with critical COVID-19 on day 1 of admission to the intensive care unit (ICU) of a tertiary hospital in Cape Town, South Africa, during the second wave of the COVID-19 pandemic. A second sample from the same patients was collected on day 7 of ICU admission. Patients were followed up until in-hospital death or hospital discharge. A custom-designed 52 biomarker panel was performed on the Luminex® platform. Data were analyzed for any association between biomarkers and mortality based on pre-determined functional groups, and individual analytes. Results: Of 87 patients, 55 (63.2%) died and 32 (36.8%) survived. We found a dysregulated cytokine response in patients who died, with elevated levels of type-1 and type-2 cytokines, chemokines, and acute phase reactants, as well as reduced levels of regulatory T cell cytokines. Interleukin (IL)-15 and IL-18 were elevated in those who died, and levels reduced over time in those who survived. Procalcitonin (PCT), C-reactive protein, Endothelin-1 and vascular cell adhesion molecule-1 were elevated in those who died. Discussion: These results show the pattern of dysregulation in critical COVID-19 in a Sub-Saharan African cohort. They suggest that fatal COVID-19 involved excessive activation of cytotoxic cells and the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3) inflammasome. Furthermore, superinfection and endothelial dysfunction with thrombosis might have contributed to mortality. HIV infection did not affect the outcome. A clinically relevant biosignature including PCT, pH and lymphocyte percentage on differential count, had an 84.8% sensitivity for mortality, and outperformed the Luminex-derived biosignature.

An investigation of the correlation of vitamin D status and management outcomes in patients with severe COVID-19 at a South African tertiary hospital.

Background: Severe COVID-19 has a poor prognosis, and biomarkers may predict disease severity. This study aimed to assess the effect of baseline Vitamin D (VitD) inadequacy on outcome of patients with severe COVID-19 admitted to intensive care unit (ICU) in a tertiary hospital in South Africa. Methods: Patients with confirmed SARS-CoV-2 were recruited during wave II of the pandemic in Cape Town. Eighty-six patients were included in the study. They were categorized into three groups "VitD deficient, VitD insufficient and VitD sufficient". We combined the VitD deficient with insufficient group to form "VitD inadequate'' group. Cox regression analysis was done to assess the association between VitD status and mortality. Factors with p< 0.05 in adjusted multivariable cox regression were considered statistically significant. Results: The proportion of VitD inadequacy was 64% (55/86), with significantly higher proportion of hypertension (66%; p 0.012). Kaplan Meir curve showed no significant difference in the probability of survival among the COVID-19 patients admitted in the ICU with or without VitD inadequacy. However, patients with elevated serum creatinine were significantly more at risk of dying (Adjusted Hazard Ratio 1.008 (1.002 - 1.030, p<0.017). Conclusion: Our study found a high prevalence of VitD inadequacy (combined deficiency and insufficiency) in COVID-19 patients admitted to the ICU. This may indicate a possible risk of severe disease. Whilst there was no statistically significant relationship between VitD status and mortality in this cohort, baseline VitD may be an important prognostic biomarker in COVID-19 patients admitted to the ICU, particularly in those with comorbidities that predispose to VitD deficiency.

A prediction risk score for HIV among adolescent girls and young women in South Africa: identifying those in need of HIV pre-exposure prophylaxis.

BACKGROUND: In sub-Saharan Africa (SSA), adolescent girls and young women (AGYW) have the highest risk of acquiring HIV. This has led to several studies aimed at identifying risk factors for HIV in AGYM. However, a combination of the purported risk variables in a multivariate risk model could be more useful in determining HIV risk in AGYW than one at a time. The purpose of this study was to develop and validate an HIV risk prediction model for AGYW. METHODS: We analyzed HIV-related HERStory survey data on 4,399 AGYW from South Africa. We identified 16 purported risk variables from the data set. The HIV acquisition risk scores were computed by combining coefficients of a multivariate logistic regression model of HIV positivity. The performance of the final model at discriminating between HIV positive and HIV negative was assessed using the area under the receiver-operating characteristic curve (AUROC). The optimal cut-point of the prediction model was determined using the Youden index. We also used other measures of discriminative abilities such as predictive values, sensitivity, and specificity. RESULTS: The estimated HIV prevalence was 12.4% (11.7% - 14.0) %. The score of the derived risk prediction model had a mean and standard deviation of 2.36 and 0.64 respectively and ranged from 0.37 to 4.59. The prediction model's sensitivity was 16. 7% and a specificity of 98.5%. The model's positive predictive value was 68.2% and a negative predictive value of 85.8%. The prediction model's optimal cut-point was 2.43 with sensitivity of 71% and specificity of 60%. Our model performed well at predicting HIV positivity with training AUC of 0.78 and a testing AUC of 0.76. CONCLUSION: A combination of the identified risk factors provided good discrimination and calibration at predicting HIV positivity in AGYW. This model could provide a simple and low-cost strategy for screening AGYW in primary healthcare clinics and community-based settings. In this way, health service providers could easily identify and link AGYW to HIV PrEP services.

Barriers and facilitators to anti-retroviral therapy adherence among adolescents aged 10 to 19 years living with HIV in sub-Saharan Africa: A mixed-methods systematic review and meta-analysis.

BACKGROUND: Human Immunodeficiency Virus (HIV) significantly affects adolescents globally, with the sub-Saharan Africa (SSA) reporting a high burden of the disease. HIV testing, treatment, and retention to care are low among adolescents. We conducted a mixed-method systematic review to assess anti-retroviral therapy (ART) adherence; barriers and facilitators to ART adherence and ART outcomes among adolescents living with HIV and on ART in sub-Saharan Africa. METHODS: We conducted searches in four scientific databases for studies conducted between 2010 and March 2022 to identify relevant primary studies. Studies were screened against inclusion criteria and assessed for quality, and data was extracted. Meta-analysis of rates and odd ratios was used to plot the quantitative studies and meta-synthesis summarized the evidence from qualitative studies. RESULTS: A total of 10 431 studies were identified and screened against the inclusion/ exclusion criteria. Sixty-six studies met the inclusion criteria (41 quantitative, 16 qualitative, and 9 mixed-methods study designs). Fifty-three thousand two hundred and seventeen (53 217) adolescents (52 319 in quantitative studies and 899 in qualitative studies) were included in the review. Thirteen support focused interventions for improved ART adherence were identified from quantitative studies. The plotted results from the meta-analysis found an ART adherence rate of 65% (95%CI 56-74), viral load suppression was 55% (95%CI 46-64), un-suppressed viral load rate of 41% (95%CI 32-50), and loss to follow up of 17% (95%CI 10-24) among adolescents. Meta-synthesis found six themes of barriers to ART (social, patient-based, economic, health system-based, therapy-based, and cultural barriers) in both the qualitative and quantitative studies, and three themes of facilitators to ART were also identified (social support, counselling, and ART education and secrecy or confidentiality) from qualitative studies. CONCLUSION: ART adherence remains low among adolescents in SSA despite multiple interventions implemented to improve ART adherence. The low adherence rate may hinder the attainment of the UNAIDS 2030 targets. Additionally, various barriers to ART adherence due to lack of support have been reported among this age group. However, interventions aimed at improving social support, educating, and counselling adolescents may improve and sustain ART adherence. TRIAL REGISTRATION: Systematic review registration: PROSPERO CRD42021284891.

Perceived readiness for diabetes and cardiovascular care delivery in Mangochi, Malawi: multicentre study from healthcare providers' perspectives.

BACKGROUND: Despite the expected prevalence rise of 98.1% for diabetes between 2010 and 2030 in sub-Saharan Africa (SSA) and the anticipated rise of both diabetes and cardiovascular diseases (CVDs) in Malawi from their current figures ( 5.6 and 8.9%; respectively), data on the readiness of health facilities to provide diabetes and cardiovascular diseases in Mangochi district is not available. Therefore, this study aimed to assess the readiness of health facilities to provide services for diabetes and cardiovascular diseases. METHODS: An exploratory study was conducted from July to early September 2021 in 34 health facilities in Mangochi, Malawi. Forty-two participants were purposefully selected. They included medical officers, clinical officers, medical assistants, and registered nurses. The study used semi-structured interviews (for qualitative data) with a checklist (for quantitative data) to provide information about the readiness of services (such as guidelines and trained staff, drugs, diagnosis capacity and equipment, essential medicines, community services, and education/counseling).The thematic content analysis and basic descriptive statistics were carried out. RESULTS: The following main theme emerged from the qualitative part: low use of diabetes-cardiovascular disease (CVD) services. This was due to: health facility factors (shortage of drugs and supplies, poor knowledge, few numbers and lack of training of providers, and absent copies of guidelines), patients factors (poor health-seeking behaviour, lack of education and counseling for many), and community factors (very limited community services for diabetes and CVDs, lack of transport policy and high transportation costs). Data from the checklists revealed low readiness scores across domains (below the 75% target) in diabetes and cardiovascular diseases: trained staff and guidelines (26.5% vs. 32.4%); diagnosis capacity and equipment (63.7% vs. 66.2%); essential medicines (33.5% vs. 41.9%), and community services, and education and counseling (37.5% vs. 42.5%). CONCLUSION: There were several noticeable shortfalls identified in the readiness of health facilities to provide diabetes and cardiovascular disease services in Mangochi health facilities. Any future intervention in diabetes-cardiovascular disease care in these areas must include these elements in its basic package.

Long-term effects of aromatase inhibitors on body mass index among postmenopausal breast cancer survivors in Africa: observational cohort study.

PURPOSE: this study was conducted to assess the impact of AIs on body mass index and high sensitivity as prognostic predictors to be incorporated into point of care technology (POCT) testing in postmenopausal breast cancer women after a 24 month follow up in Africa. An observational cohort study was conducted; including 126 female BC patients with stages ranging from 0-III initially subjected to AIs and subsequently followed up for 24 months. Multiple imputation model was conducted to predict missing data. RESULTS: Random effects model was used to monitor the changes over the time. The study revealed stronger statistically association between BMI and homocysteine (p = 0.021, 95%CI: 0.0083 to 0.1029). Weight and total body fat were strongly associated after 24 months follow up. Hs-CRP was associated with BMI (p = 0.0001), and hs-CRP was associated with other biomedical markers such as calcium (p = 0.021, 95% CI: 0.01 to 0.10), phosphate (p = 0.039, 95%CI: 0.01 to 0.10), and ferritin (p = 0.002, 95%CI: 0.02 to 0.08) and calcium. The patients subjected to AIs are likely to develop cardiovascular adverse events. POCT of care strategy which include clinical, biomedical and genetic predictor's measurement is required to improve BC survivorship.