Feasibility of prevention of type 2 diabetes in low- and middle-income countries.

Type 2 diabetes is a leading cause of global mortality and morbidity. Nearly 80% of individuals with diabetes live in low- and middle-income countries (LMICs), where nearly half of those with the condition remain undiagnosed. The majority of known cases have sub-optimal clinical outcomes. Moreover, large populations with impaired glucose tolerance and/or impaired fasting glucose contribute to the rapid increase in type 2 diabetes. Globally, priority should be given to limit the population with diabetes, especially in LMICs, alongside actions to optimise the care of people diagnosed with diabetes. Primary prevention studies in LMICs have generated evidence to show the efficacy and scalability of strategies to fully prevent or delay the development of diabetes in high-risk groups. However, these are mainly limited to certain countries in Asia, particularly China and India. The studies have indicated that prevention policies are effective in populations with a high risk of type 2 diabetes, and they also have long-term benefits, not only for the risk of type 2 diabetes but also for the risk of associated metabolic disorders, such as CVDs. For the effective conduct of national programmes, innovative mechanisms must be implemented, such as the use of information technology, joint efforts of multiple teams implementing similar programmes, and involvement of governmental and non-governmental partnerships. Continuous monitoring and long-term studies are required to assess the utility of these programmes. The effectiveness of such programmes in LMICs has not been proven over the longer term, except in China. Despite the available evidence, the feasibility of prevention strategies for type 2 diabetes in LMICs at population level remains an enigma. There remain challenges in the form of cultural, societal and economic constraints; insufficient infrastructure and healthcare capacity; and the non-fully elucidated natural history and determinants of type 2 diabetes in LMICs.

A systematic review assessing the association of inflammatory markers with kidney dysfunction in people living with HIV on highly active antiretroviral therapy.

Monitoring chronic diseases, particularly kidney disorders, in people living with HIV (PLWH) is of paramount importance. Here, a systematic search was conducted across electronic search engine and databases like PubMed, Scopus, and Google Scholar, from date of inception until December 2023, to identify pertinent studies reporting on any association between inflammation and kidney function in PLWH. Only six clinical studies in peer-reviewed journals met the inclusion criteria, involving 1467 participants aged 37 to 51, with approximately 17% being females. The report emphasizes the potential impact of highly active antiretroviral therapy (HAART) on kidney function in PLWH, highlighting the significance of monitoring inflammation markers as indicators of kidney function, even when HAART is effective. Acknowledging study limitations, particularly the scarcity of relevant research, the findings highlight a need for more research to inform on clinical guidance to optimize HIV management, particularly regarding kidney health and HAART regimens. Although very limited studies were evaluated, the study lays an important foundation for future research to uncover the complex relationship between HAART, inflammation markers, and kidney health in PLWH.

High-sensitivity C-reactive protein among people living with HIV on highly active antiretroviral therapy: a systemic review and meta-analysis.

The pathological consequences of inflammation persist in people living with the human immunodeficiency virus (PLWH), regardless of the positive outcomes of highly active antiretroviral therapy (HAART). The current systematic review and meta-analysis aims to understand and explore the levels of high-sensitivity C-reactive protein (hs-CRP) and other cardiovascular disease (CVD)-risk factors including lipid profiles among PLWH on HAART. Major electronic databases including PubMed, Scopus, and Web of Science were searched to retrieve relevant global literature reporting on hs-CRP levels in PLWH on HAART. A total of twenty-two studies with an average participant age of 40 years were eligible for this systematic review and meta-analysis. Majority of the included studies were from Africa (n = 11), the United States (n = 6), and Europe (n = 5). Our systemic review showed that most studies reported increased levels of hs-CRP among PLWH on HAART when compared to controls (PLWH not on HAART or those without HIV), especially in studies from Africa. This was supported by a meta-analysis showing significantly elevated levels of hs-CRP in PLWH on HAART when compared to PLWH not on HAART (standardised mean difference [SMD] = 0.56; 95% CI = 0.10­1.01, z = 2.41; p = 0.02) or those without HIV (SMD = 1.19; 95% CI = 0.76­1.63, z = 5.35; p < 0.001). Where lipid profiles, as a major predictor for CVD risk, were also impaired in PLWH on HAART when compared to PLWH not on HAART and HIV-negative participants. In conclusion, elevated levels of hs-CRP and lipid levels are prevalent in PLWH on HAART, this may increase the risk of CVD complications, especially for those people living in Africa. However, more evidence in larger population studies is required to confirm these outcomes and unveil any possible clinical implications of HAART-induced modulation of hs-CRP levels in PLWH.

HbA1c comparable to fasting glucose in the external validation of the African Diabetes Risk Score and other established risk prediction models in Black South Africans.

BACKGROUND: The use of non-invasive risk scores to detect undiagnosed type 2 diabetes (T2D) ensures the restriction of invasive and costly blood tests to those most likely to be diagnosed with the disease. This study assessed and compared the performance of the African Diabetes Risk Score (ADRS) with three other diabetes risk prediction models for identifying screen-detected diabetes based on fasting plasma glucose (FPG) or glycated haemoglobin (HBA1c). METHODS: Age, sex, waist circumference, body mass index, blood pressure, history of diabetes and physical activity levels from the SA-NW-PURE study were used to externally validate the ADRS and other established risk prediction models. Discrimination was assessed and compared using C-statistics and nonparametric methods. Calibration was assessed using calibration plots, before and after recalibration. RESULTS: Nine hundred and thirty-seven participants were included; 14% had prevalent undiagnosed T2D according to FPG and 26% according to HbA1c. Discrimination was acceptable and was mostly similar between models for both diagnostic measures. The C-statistics for diagnosis by FPG ranged from 0.69 for the Simplified FINDRISC model to 0.77 for the ADRS model and 0.77 for the Simplified FINDRISC model to 0.79 for the ADRS model for diagnosis by HbA1c. Calibration ranged from acceptable to good, though over- and underestimation were present. All models improved significantly following recalibration. CONCLUSIONS: The models performed comparably, with the ADRS offering a non-invasive way to identify up to 79% of cases. Based on its ease of use and performance, the ADRS is recommended for screening for T2D in certain Black population groups in South Africa. HbA1c as a means of diagnosis also showed comparable performance with FPG. Therefore, further validation studies can potentially use HbA1c as the standard to compare to.

Clinical utility of novel anthropometric indices in identifying type 2 diabetes mellitus among South African adult females.

AIM: To assess the clinical utility of novel anthropometric indices and other traditional anthropometric indices in identifying the risk of type 2 diabetes mellitus (T2D) among South African adult females. METHODS: In the first South African National Health and Nutrition Examination Survey (SANHANES-1), traditional [body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR)] and novel [a-body shape index (ABSI), abdominal volume index (AVI), body adiposity index (BAI), body roundness index (BRI), conicity index (CI), and Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE)] anthropometric indices were assessed. T2D was diagnosed using glycated haemoglobin (HbA1c) ≥ 6.5% among participants without known T2D. Basic statistics and multiple regression analyses were explored the association between anthropometric indices and newly diagnosed T2D. Receiver operating characteristic (ROC) curve analysis was used to measure the predictive ability of both traditional and novel indices. RESULTS: Among 2 623 participants, 384 (14.6%) had newly diagnosed T2D. All anthropometric indices mean values were significantly higher among participants with T2D (most p < 0.001). Higher mean values increased T2D odds e.g., in the model adjusted for age, employment, residence, and population group, odds ratio (OR) and 95% confidence interval (CI) for T2D with some of anthropometric indices were: 1.86 (1.60-2.15) for WC, 1.84 (1.59-2.13) for WHtR, 1.73 (1.51-1.99) for AVI, 1.71 (1.49-1.96) for BRI and 1.86 (1.57-2.20) for CUN-BAE. The top quartile for all indices had the highest T2D odds (p < 0.05). These outcomes were the highest for WC, AVI, and CUN-BAE and remained so even after removing the confounding effects of age, employment, population group, and residence. Based on the ROC analysis, none of the anthropometrical indices performed excellently (i.e., had an area under the curve [AUC] > 0.80). The WC, WHtR, AVI, BRI, and CUN-BAE, however, performed acceptably (AUCs 0.70-0.79), while also exhibiting corresponding cutoff values of 86.65 cm, 0.57, 15.52, 3.83, and 38.35, respectively. CONCLUSIONS: The data shows that traditional and novel anthropometric indices similarly identifying newly diagnosed T2D among adult South African females. We recommend the continuing the use of traditional indices, as they are affordable and easy to use in our setting.

Evaluation of the relationship between occupational-specific task performance and measures of physical fitness, cardiovascular and musculoskeletal health in firefighters.

INTRODUCTION: Firefighters are required to perform physically strenuous tasks such as hose drags, victim rescues, forcible entries and stair climbs to complete their public safety mission. Occupational-specific tasks are often used to evaluate the ability of firefighters to adequately/safely perform their duties. Depending on the regions, occupational-specific tasks include six to eight individual tasks, which emphasize distinct aspects of their physical fitness, while also requiring different levels of cardiovascular (CVH) and musculoskeletal health (MSH). Therefore, the aim of this study was to evaluate the relationship between specific occupational task performance and measures of physical fitness, cardiovascular and musculoskeletal health. METHODS: Using a cross-sectional design, 282 full-time male and female firefighters were recruited. A researcher-generated questionnaire and physical measures were used to collect data on sociodemographic characteristics, CVH, MSH and weekly physical activity habits. Physical measures were used to collect data on physical fitness and occupational-specific task performance. RESULTS: Absolute cardiorespiratory fitness (abV̇O2max), grip strength, leg strength, push-ups, sit-ups and lean body mass (all p < 0.001) had an inverse association with completion times on all occupational-specific tasks. Age was positively related to the performance of all tasks (all p < 0.05). Higher heart rate variability (HRV) was associated with better performance on all tasks (all p < 0.05). Bodyfat percentage (BF%) and diastolic blood pressure were positively associated with the step-up task (p < 0.05). Lower back musculoskeletal injury (LoBMSI), musculoskeletal discomfort (MSD), and lower limb MSD were associated with a decreased odds of passing the step-up. Upper body MSIs (UBMSI), LoBMSIs and Lower back MSD were associated with decreased odds of passing the rescue drag. CONCLUSION: Firefighters that were taller, leaner, stronger and fitter with a more favourable CVH profile, higher HRV and less musculoskeletal discomfort performed best on all occupational-specific tasks.

A study protocol for a cluster randomized controlled trial to test the applicability of the South African diabetes prevention program in the Eastern Cape Province of South Africa.

BACKGROUND: Convincing evidence supports the effectiveness of lifestyle interventions in preventing the occurrence of diabetes in high-income countries, however little is known about appropriate interventions for use in African countries, where there are higher relative increases in diabetes prevalence. The South African Diabetes Prevention Programme (SA-DPP) was initiated with the aim of preventing or delaying the occurrence of diabetes among South Africans (SAs), through interventions, targeting lifestyle changes related to diet and physical activity. The purpose of the current project is to implement and evaluate the suitability and applicability of the SA-DPP developed and tailored in urban populations in the Western Cape Province, in peri-urban populations in the Eastern Cape Province of SA. METHODS: The SA-DPP, which is an cluster randomized control trial, will be implemented in adults aged 30-65 years residing in the OR Tambo district, Eastern Cape, SA. Participants will be recruited using self-selected sampling techniques and 24 clusters across peri-urban communities will be randomly allocated to participate in the lifestyle intervention, facilitated by non-professional health workers (NPHW). The diabetes risk screening will follow a two-staged approach, including the community-based screening, using the African diabetes risk score (ADRS), followed by a clinic-based risk status assessment by an oral glucose tolerance test (OGTT) to exclude unknown diabetes. The lifestyle-change objectives of the current programme relate to, 1) < 30% of total energy intake from fat; 2) < 10% of total energy intake from saturated fat; 3) > 15 g of fibre/1000 kcal; 4) > 4 h/week moderate level of physical activity; and 5) > 2% body mass index (BMI) reduction. DISCUSSION: The SA-DPP could represent a successful model for the prevention of diabetes and potentially other lifestyle-related diseases in SA and other countries in the region that are confronted with similar challenges. TRIAL REGISTRATION: PACTR202205591282906.

Task shifting roles, interventions and outcomes for kidney and cardiovascular health service delivery among African populations: a scoping review.

BACKGROUND: Human resources for health (HRH) shortages are a major limitation to equitable access to healthcare. African countries have the most severe shortage of HRH in the world despite rising communicable and non-communicable disease (NCD) burden. Task shifting provides an opportunity to fill the gaps in HRH shortage in Africa. The aim of this scoping review is to evaluate task shifting roles, interventions and outcomes for addressing kidney and cardiovascular (CV) health problems in African populations. METHODS: We conducted this scoping review to answer the question: "what are the roles, interventions and outcomes of task shifting strategies for CV and kidney health in Africa?" Eligible studies were selected after searching MEDLINE (Ovid), Embase (Ovid), CINAHL, ISI Web of Science, and Africa journal online (AJOL). We analyzed the data descriptively. RESULTS: Thirty-three studies, conducted in 10 African countries (South Africa, Nigeria, Ghana, Kenya, Cameroon, Democratic Republic of Congo, Ethiopia, Malawi, Rwanda, and Uganda) were eligible for inclusion. There were few randomized controlled trials (n = 6; 18.2%), and tasks were mostly shifted for hypertension (n = 27; 81.8%) than for diabetes (n = 16; 48.5%). More tasks were shifted to nurses (n = 19; 57.6%) than pharmacists (n = 6; 18.2%) or community health workers (n = 5; 15.2%). Across all studies, the most common role played by HRH in task shifting was for treatment and adherence (n = 28; 84.9%) followed by screening and detection (n = 24; 72.7%), education and counselling (n = 24; 72.7%), and triage (n = 13; 39.4%). Improved blood pressure levels were reported in 78.6%, 66.7%, and 80.0% for hypertension-related task shifting roles to nurses, pharmacists, and CHWs, respectively. Improved glycaemic indices were reported as 66.7%, 50.0%, and 66.7% for diabetes-related task shifting roles to nurses, pharmacists, and CHWs, respectively. CONCLUSION: Despite the numerus HRH challenges that are present in Africa for CV and kidney health, this study suggests that task shifting initiatives can improve process of care measures (access and efficiency) as well as identification, awareness and treatment of CV and kidney disease in the region. The impact of task shifting on long-term outcomes of kidney and CV diseases and the sustainability of NCD programs based on task shifting remains to be determined.

MicroRNAs Associated with Chronic Kidney Disease in the General Population and High-Risk Subgroups-A Systematic Review.

The potential utility of microRNAs (miRNAs) as diagnostic or prognostic biomarkers, as well as therapeutic targets, for chronic kidney disease (CKD) has been advocated. However, studies evaluating the expression profile of the same miRNA signatures in CKD report contradictory findings. This review aimed to characterize miRNAs associated with CKD and/or measures of kidney function and kidney damage in the general population, and also in high-risk subgroups, including people with hypertension (HTN), diabetes mellitus (DM) and human immunodeficiency virus (HIV) infection. Medline via PubMed, Scopus, Web of Science, and EBSCOhost databases were searched to identify relevant studies published in English or French languages on or before 30 September 2022. A total of 75 studies fulfilled the eligibility criteria: CKD (n = 18), diabetic kidney disease (DKD) (n = 51) and HTN-associated CKD (n = 6), with no study reporting on miRNA profiles in people with HIV-associated nephropathy. In individuals with CKD, miR-126 and miR-223 were consistently downregulated, whilst in DKD, miR-21 and miR-29b were consistently upregulated and miR-30e and let-7a were consistently downregulated in at least three studies. These findings suggest that these miRNAs may be involved in the pathogenesis of CKD and therefore invites further research to explore their clinical utility for CKD prevention and control.

The need for screening, early diagnosis, and prediction of chronic kidney disease in people with diabetes in low- and middle-income countries-a review of the current literature.

Chronic kidney disease (CKD) in people with diabetes is becoming an increasing major public health concern, disproportionately burdening low- and middle-income countries (LMICs). This rising burden is due to various factors, including the lack of disease awareness that results in late referral and the cost of screening and consequent treatment of the comorbid conditions, as well as other factors endemic to LMICs relating to inadequate management of risk factors. We critically assessed the extant literature, by performing searches of Medline via PubMed, EBSCOhost, Scopus, and Web of Science, for studies pertaining to screening, diagnosis, and prediction of CKD amongst adults with diabetes in LMICs, using relevant key terms. The relevant studies were summarized through key themes derived from the Wilson and Jungner criteria. We found that screening for CKD in people with diabetes is generally infrequent in LMICs. Also, LMICs are ill-equipped to appropriately manage diabetes-associated CKD, especially its late stages, in which supportive care and kidney replacement therapy (KRT) might be required. There are acceptable and relatively simple tools that can aid diabetes-associated CKD screening in these countries; however, these tools come with limitations. Thus, effective implementation of diabetes-associated CKD screening in LMICs remains a challenge, and the cost-effectiveness of such an undertaking largely remains to be explored. In conclusion, for many compelling reasons, screening for CKD in people with diabetes should be a high policy priority in LMICs, as the huge cost associated with higher mortality and morbidity in this group and the cost of KRT offers a compelling economic incentive for improving early detection of diabetes in CKD.

The role of adiposity, diet and inflammation on the discordance between LDL-C and apolipoprotein B.

BACKGROUND AND AIMS: While low-density lipoprotein cholesterol (LDL-C) is a good predictor of atherosclerotic cardiovascular disease, apolipoprotein B (ApoB) is superior when the two markers are discordant. We aimed to determine the impact of adiposity, diet and inflammation upon ApoB and LDL-C discordance. METHODS AND RESULTS: Machine learning (ML) and structural equation models (SEMs) were applied to the National Health and Nutrition Examination Survey to investigate cardiometabolic and dietary factors when LDL-C and ApoB are concordant/discordant. Mendelian randomisation (MR) determined whether adiposity and inflammation exposures were causal of elevated/decreased LDL-C and/or ApoB. ML showed body mass index (BMI), dietary saturated fatty acids (SFA), dietary fibre, serum C-reactive protein (CRP) and uric acid were the most strongly associated variables (R2 = 0.70) in those with low LDL-C and high ApoB. SEMs revealed that fibre (b = -0.42, p = 0.001) and SFA (b = 0.28, p = 0.014) had a significant association with our outcome (joined effect of ApoB and LDL-C). BMI (b = 0.65, p = 0.001), fibre (b = -0.24, p = 0.014) and SFA (b = 0.26, p = 0.032) had significant associations with CRP. MR analysis showed genetically higher body fat percentage had a significant causal effect on ApoB (Inverse variance weighted (IVW) = Beta: 0.172, p = 0.0001) but not LDL-C (IVW = Beta: 0.006, p = 0.845). CONCLUSION: Our data show increased discordance between ApoB and LDL-C is associated with cardiometabolic, clinical and dietary abnormalities and that body fat percentage is causal of elevated ApoB.

Assessment of the association between plant-based dietary exposures and cardiovascular disease risk profile in sub-Saharan Africa: a systematic review.

BACKGROUND: Studies have investigated dietary attributes associated with cardiovascular disease (CVD) risk in Africa. However, there has been no effort to critically assess the existing evidence. This systematic review examined available evidence on the association between plant-based dietary exposures and CVD risk profile in Africa. PROSPERO registration number: CRD42020159862. METHODS: We conducted a literature search for observational studies reporting on plant-based dietary exposures in relation to CVD risk profile in African populations. PubMed-Medline, Scopus, EBSCOhost, and African Journals Online platforms were searched up to 19 March 2021. Titles and abstracts of the identified records were screened independently by two investigators. The quality of the studies was also assessed independently. RESULTS: Of 458 entries identified, 15 studies published between 2002 and 2020 were included in this review. These studies originated from 12 sub-Saharan Africa (SSA) countries. Sample sizes ranged from 110 to 2362, age from 18 to 80 years; and majority of participants were females (66.0%). In all, four plant-based dietary exposures were identified across SSA. Sixty percent of the studies reported a significant association between a plant-based dietary exposure with at least one CVD risk factor such as hypertension, diabetes mellitus, dyslipidaemia, overweight/obesity, and metabolic syndrome. CONCLUSIONS: The few available studies suggest that there may be a protective effect of plant-based dietary exposures on CVD risk profile in the African setting. Nonetheless, more elaborated studies are still needed to address plant-based diet (PBD) adherence in relation with CVD risk in African populations.

Two novel microRNAs and their association with absolute blood pressure parameters in an urban South African community.

MicroRNAs are important in development of disease, and description of novel microRNAs adds to the pool of microRNAs that can be targeted for diagnostic and therapeutic purposes in disease. Herein, we aimed to describe novel microRNAs in a normotensive and hypertensive African population and relate their expression to blood pressure parameters and hypertension status. Previous work using next-generation sequencing showed differential expression of two novel microRNAs in the blood of normotensives and hypertensives. Herein, we have investigated these novel microRNAs by quantitative reverse transcription polymerase chain reaction in a cohort of 881 participants in this study. The relationship between the novel microRNAs and systolic and diastolic blood pressure as well as mean arterial pressure was also investigated. Age and sex-adjusted Spearman's correlations were used to assess the relationship between microRNAs and cardiovascular risk profile variables whilst multivariable logistic regression models were used to assess the association of microRNAs with screen-detected and known hypertension. The novel microRNAs (miR-novel-chr1_36178 and miR-novel-chr15_18383) were significantly dysregulated by hypertension status. The expression of miR-novel-chr1_36178 differed according to sex, correlated with mean arterial pressure and systolic and diastolic blood pressure at higher levels of expression and was associated with screen-detected hypertension. The association of miR-novel-chr1_36178 expression with mean arterial pressure and systolic and diastolic blood pressure, as well as its dysregulation according to hypertension status suggests its possible utility as a biomarker target for hypertension diagnosis and/or therapeutics. Furthermore, its association with screen detected hypertension and dose-response relationship with blood pressure suggests it may be used to identify and monitor individuals at risk of hypertension.

Utilization of Pneumococcal Vaccine and Penicillin Prophylaxis in Sickle Cell Disease in Three African Countries: Assessment among Healthcare Providers in SickleInAfrica.

Sickle cell disease is a genetic disease with a predisposition to infections caused by encapsulated organisms, especially Streptococcus pneumoniae. Pneumococcal vaccines and prophylactic penicillin have reduced the rate of this infection and mortality in sickle cell disease. However, implementation of these interventions is limited in Africa. The objectives of the study were to assess health care providers' behaviors with the implementation of pneumococcal vaccination and penicillin prophylaxis and to identify barriers to their use. A 25-item online questionnaire was administered through SickleinAfrica: a network of researchers, and healthcare providers, in Ghana, Nigeria, and Tanzania, working to improve health outcomes of sickle cell disease in Africa. Data was collected and managed using the Research Electronic Data Capture (REDCap), tools and data analysis was done using STATA version 13 and R statistical software. Eighty-two medical practitioners responded to the questionnaire. Only 54.0 and 48.7% of respondents indicated the availability of published guidelines on sickle cell disease management and pneumococcal vaccine use, respectively, at their facilities. The majority (54.0%) perceived that the vaccines are effective but over 20.0% were uncertain of their usefulness. All respondents from Ghana and Tanzania affirmed the availability of guidelines for penicillin prophylaxis in contrast to 44.1% in Nigeria. Eighty-five percent of respondents affirmed the need for penicillin prophylaxis but 15.0% had a contrary opinion for reasons including the rarity of isolation of Streptococcus pneumoniae in African studies, and therefore, the uncertainty of its benefit. Lack of published guidelines on the management of sickle cell disease and doubts about the necessity of prophylactic measures are potential barriers to the implementation of effective interventions.

Genetic variation in toll like receptors 2, 7, 9 and interleukin-6 is associated with cytomegalovirus infection in late pregnancy.

BACKGROUND: Maternal cytomegalovirus (CMV) infection and/or reactivation in pregnancy is associated with a myriad of adverse infant outcomes. However, the role of host genetic polymorphisms in modulating maternal CMV status is inconclusive. This study investigated the possible association of single nucleotide polymorphisms in toll-like receptor (TLR) and cytokine genes with maternal plasma CMV DNA status in black Zimbabweans. METHODS: In a cross-sectional study, 110 women in late gestation who included 36 CMV infected cases and 74 CMV uninfected, age and HIV status matched controls were enrolled. Twenty single nucleotide polymorphisms in 10 genes which code for proteins involved in immunity against CMV were genotyped using Iplex GOLD SNP genotyping protocol on the Agena MassARRAY® system. Statistical analyses were performed using Stata SE and the 'Genetics' and 'SNPassoc' packages of the statistical package R. RESULTS: The TLR7 rs179008A > T (p < 0.001) polymorphism was associated while the TLR9 rs352139T > C (p = 0.049) polymorphism was on the borderline for association with CMV positive (CMV+) status. In contrast, the interleukin (IL)-6 rs10499563T > C (p < 0.001) and TLR2 rs1816702C > T (p = 0.001) polymorphisms were associated with CMV negative (CMV-) status. Furthermore, allele frequencies of SNPs in TLR2, TLR4, TLR9, TLR7, IL-6, IL-10, IL-28B, IL-1A and interferon AR1 (IFNAR1) genes are being reported here for the first time in a Zimbabwean population. The allele frequencies in the Zimbabwean population are generally comparable to other African populations but different when compared to European and Asian populations. CONCLUSIONS: Toll-like receptor and interleukin genetic polymorphisms influence CMV status in late gestation among black Zimbabweans. This is attributable to possible modulation of immune responses to CMV reactivation in a population previously exposed to CMV infection.

Association of Genetic Polymorphisms of TGF-ß1, HMOX1, and APOL1 With CKD in Nigerian Patients With and Without HIV.

RATIONALE & OBJECTIVE: Recent studies in the human immunodeficiency virus (HIV)-infected population have suggested that there are genetic predispositions to the development of chronic kidney disease (CKD) in this context. We investigated the association of genetic polymorphisms of the genes encoding apolipoprotein L1 (APOL1), transforming growth factor ß1 (TGF-ß1; a profibrotic cytokine), and heme oxygenase 1 (HMOX1) with prevalent CKD among adults with and without HIV infection. STUDY DESIGN: Case-control study. SETTING & PARTICIPANTS: West African adults including 217 HIV-infected patients with CKD (HIV+/CKD+ group), 595 HIV-infected patients without CKD (HIV+/CKD- group), 269 with CKD and no HIV infection (HIV-/CKD+ group), and 114 with neither CKD nor HIV (HIV-/CKD- group). EXPOSURE: The genetic polymorphisms with reference single-nucleotide polymorphism (rs) identification numbers rs1800469 (TGF-ß1), rs1800470 (TGF-ß1), rs121918282 (TGF-ß1); rs60910145 (APOL1 G1 risk allele), rs73885319 (APOL1 G1 risk allele), rs71785313 (APOL1 G2 risk allele), and rs743811 (HMOX1); HIV. OUTCOME: CKD. ANALYTICAL APPROACH: Single-nucleotide polymorphism (SNP) genotyping of rs1800469 (TGF-ß1), rs1800470 (TGF-ß1), rs121918282 (TGF-ß1); rs60910145 (APOL1), rs73885319 (APOL1), rs71785313 (APOL1), and rs743811 (HMOX1) was performed. Hardy-Weinberg equilibrium was evaluated for all SNPs, and minor allele frequencies were reported. A case-control analysis was performed, and multivariable logistic regression was used to control for potential confounders. RESULTS: Minor allele frequencies for TGF-ß1 (rs1800469, rs1800470, and rs1800471), APOL1 (rs60910145, rs73885319, and rs71785313), and HMOX1 (rs743811) were 0.25, 0.46, 0.46, 0.44, 0.45, 0.17, and 0.14, respectively. Among HIV-positive individuals, only TGF-ß1 rs1800470 (GG vs AA), APOL1 (in the recessive model), and hypertension were associated with prevalent CKD (adjusted ORs of 0.44 [95% CI, 0.20-0.97], 2.54 [95% CI, 1.44-4.51], and 2.17 [95% CI, 1.35-3.48], respectively). No SNP polymorphisms were associated with prevalent CKD among HIV-negative individuals. LIMITATIONS: The lack of histopathology data for proper categorization of the type of HIV-related nephropathy. CONCLUSIONS: APOL1 polymorphisms were highly prevalent in this population and among adult patients infected with HIV and were associated with increased CKD risk. The TGF-ß1 (rs1800470) polymorphism was associated with reduced risk, and HMOX1 polymorphisms were unassociated with CKD.

The agreement between fasting glucose and markers of chronic glycaemic exposure in individuals with and without chronic kidney disease: a cross-sectional study.

BACKGROUND: To assess whether the agreement between fasting glucose and glycated proteins is affected by chronic kidney disease (CKD) in a community-based sample of 1621 mixed-ancestry South Africans. METHODS: CKD was defined as an estimated glomerular filtration rate < 60 ml/min/1.73 m2. Fasting plasma glucose and haemoglobin A1c (HbA1c) concentrations were measured by enzymatic hexokinase method and high-performance liquid chromatography, respectively, with fructosamine and glycated albumin measured by immunoturbidimetry and enzymatic method, respectively. RESULTS: Of those with CKD (n = 96), 79, 16 and 5% where in stages 3, 4 and 5, respectively. Those with CKD had higher levels of HbA1c (6.2 vs. 5.7%; p < 0.0001), glycated albumin (15.0 vs. 13.0%; p < 0.0001) and fructosamine levels (269.7 vs. 236.4 µmol/l; p < 0.0001), compared to those without CKD. Higher fasting glucose levels were associated with higher HbA1c, glycated albumin and fructosamine, independent of age, gender, and CKD. However, the association with HbA1c and glycated albumin differed by CKD status, at the upper concentrations of the respective markers (interaction term for both: p ≤ 0.095). CONCLUSION: Our results suggest that although HbA1c and glycated albumin perform acceptably under conditions of normoglycaemia, these markers correlate less well with blood glucose levels in people with CKD who are not on dialysis.

Optimizing Tuberculosis Diagnosis in Human Immunodeficiency Virus-Infected Inpatients Meeting the Criteria of Seriously Ill in the World Health Organization Algorithm.

Background: The World Health Organization (WHO) algorithm for the diagnosis of tuberculosis in seriously ill human immunodeficiency virus (HIV)-infected patients lacks a firm evidence base. We aimed to develop a clinical prediction rule for the diagnosis of tuberculosis and to determine the diagnostic utility of the Xpert MTB/RIF assay in seriously ill HIV-infected patients. Methods: We conducted a prospective study among HIV-infected inpatients with any cough duration and WHO-defined danger signs. Culture-positive tuberculosis from any site was the reference standard. A priori selected variables were assessed for univariate associations with tuberculosis. The most predictive variables were assessed in a multivariate logistic regression model and used to establish a clinical prediction rule for diagnosing tuberculosis. Results: We enrolled 484 participants. The median age was 36 years, 65.5% were female, the median CD4 count was 89 cells/µL, and 35.3% were on antiretroviral therapy. Tuberculosis was diagnosed in 52.7% of participants. The c-statistic of our clinical prediction rule (variables: cough ≥14 days, unable to walk unaided, temperature >39°C, chest radiograph assessment, hemoglobin, and white cell count) was 0.811 (95% confidence interval, .802-.819). The classic tuberculosis symptoms (fever, night sweats, weight loss) added no discriminatory value in diagnosing tuberculosis. Xpert MTB/RIF assay sensitivity was 86.3% and specificity was 96.1%. Conclusions: Our clinical prediction rule had good diagnostic utility for tuberculosis among seriously ill HIV-infected inpatients. Xpert MTB/RIF assay, incorporated into the updated 2016 WHO algorithm, had high sensitivity and specificity in this population. Our findings could facilitate improved diagnosis of tuberculosis among seriously ill HIV-infected inpatients in resource-constrained settings.

Clinical and genetic factors are associated with pain and hospitalisation rates in sickle cell anaemia in Cameroon.

We aimed to investigate the clinical and genetic predictors of painful vaso-occlusive crises (VOC) in sickle cell disease (SCD) in Cameroon. Socio-demographics, clinical variables/events and haematological indices were acquired. Genotyping was performed for 40 variants in 17 pain-related genes, three fetal haemoglobin (HbF)-promoting loci, two kidney dysfunctions-related genes, and HBA1/HBA2 genes. Statistical models using regression frameworks were performed in R® . A total of 436 hydoxycarbamide- and opioid-naïve patients were studied; median age was 16 years. Female sex, body mass index, Hb/HbF, blood transfusions, leucocytosis and consultation or hospitalisation rates significantly correlated with VOC. Three pain-related genes variants correlated with VOC (CACNA2D3-rs6777055, P = 0·025; DRD2-rs4274224, P = 0·037; KCNS1-rs734784, P = 0·01). Five pain-related genes variants correlated with hospitalisation/consultation rates. (COMT-rs6269, P = 0·027; FAAH-rs4141964, P = 0·003; OPRM1-rs1799971, P = 0·031; ADRB2-rs1042713; P < 0·001; UGT2B7-rs7438135, P = 0·037). The 3·7 kb HBA1/HBA2 deletion correlated with increased VOC (P = 0·002). HbF-promoting loci variants correlated with decreased hospitalisation (BCL11A-rs4671393, P = 0·026; HBS1L-MYB-rs28384513, P = 0·01). APOL1 G1/G2 correlated with increased hospitalisation (P = 0·048). This first study from Africa has provided evidence supporting possible development of genetic risk model for pain in SCD.

An African perspective on the genetic risk of chronic kidney disease: a systematic review.

BACKGROUND: Individuals of African ethnicity are disproportionately burdened with chronic kidney disease (CKD). However, despite the genetic link, genetic association studies of CKD in African populations are lacking. METHODS: We conducted a systematic review to critically evaluate the existing studies on CKD genetic risk inferred by polymorphism(s) amongst African populations in Africa. The study followed the HuGE handbook and PRISMA protocol. We included studies reporting on the association of polymorphism(s) with prevalent CKD, end-stage renaldisease (ESRD) or CKD-associated traits. Given the very few studies investigating the effects of the same single nucleotide polymorphisms (SNPs) on CKD risk, a narrative synthesis of the evidence was conducted. RESULTS: A total of 30 polymorphisms in 11 genes were investigated for their association with CKD, ESRD or related traits, all using the candidate-gene approach. Of all the included genes, MYH9, AT1R and MTHFR genes failed to predict CKD or related traits, while variants in the APOL1, apoE, eNOS, XPD, XRCC1, renalase, ADIPOQ, and CCR2 genes were associated with CKD or other related traits. Two SNPs (rs73885319, rs60910145) and haplotypes (G-A-G; G1; G2) of the apolipoprotein L1 (APOL1) gene were studied in more than one population group, with similar association with prevalent CKD observed. The remaining polymorphisms were investigated in single studies. CONCLUSION: According to this systematic review, there is currently insufficient evidence of the specific polymorphisms that poses African populations at an increased risk of CKD. Large-scale genetic studies are warranted to better understand susceptibility polymorphisms, specific to African populations.