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Purpose: As countries work toward 90:90:90 targets, early identification of patients with inadequate response to antiretroviral therapy (ART) is critical for achieving optimal HIV treatment outcomes. We developed and evaluated a clinical prediction score (CPS) to identify HIV-positive patients at risk of poor viral load suppression at 6 months on ART. Patients and methods: We conducted a prospective cohort study of HIV-positive ART naïve adults (≥18 years) initiating standard first-line ART between February 2012 and April 2014 at Themba Lethu Clinic in Johannesburg, South Africa. We used Modified Poisson regression to estimate the association between patient characteristics and poor viral load suppression, defined as a viral load ≥400 copies/mL at 6 months on ART. We developed a CPS following the Spiegel Halter and Knill-Jones approach and determined the diagnostic accuracy compared to viral load as the "gold standard". We identified the optimal cutoff at which the CPS would identify those at risk of poor viral load suppression. Results: Among 353 patients, 67.7% had a viral load measurement at 6 months on ART and 30.1% of these were viremic (≥400 copies/mL). Male gender, platelet count <150 cells/mm 3 , ≥7 days late for ≥2 ARV visits, visual analog scale (VAS) <90% and <14.5 fL increase in mean cell volume from baseline to 6 months were included in the CPS. The optimal cutoff was 5 (≥5 vs <5; sensitivity [Se] 65.3%, specificity [Sp] 46.7%) and the CPS performed better than standard measures of adherence (eg, VAS Se 24.5%; Simplified Medication Adherence Questionnaire Se 26.5%). Conclusion: Our findings suggest a 6-month CPS may have the potential to identify patients at risk of poor viral load suppression. The CPS may be used to target patients who need intensive adherence support, with the caveat that there may be a three- to four-fold increase in the pool of patients identified for adherence counseling., Competing Interests: DE reports grants from Health Economics and Epidemiology Research Office during the conduct of the study. The authors report no other conflicts of interest in this work.

Objectives: The expanding burden of non-communicable diseases (NCDs) globally will require novel public health strategies. Community-based screening has been promoted to augment efficiency of diagnostic services, but few data are available on the downstream impact of such programmes. We sought to assess the impact of a home-based blood pressure screening programme on linkage to hypertension care in rural South Africa., Setting: We conducted home-based blood pressure screening withinin a population cohort in rural KwaZulu-Natal, using the WHO Stepwise Approach to Surveillance (STEPS) protocol., Participants: Individuals meeting criteria for raised blood pressure (≥140 systolic or ≥90 diastolic averaged over two readings) were referred to local health clinics and included in this analysis. We defined linkage to care based on self-report of presentation to clinic for hypertension during the next 2 years of cohort observation. We estimated the population proportion of successful linkage to care with inverse probability sampling weights, and fit multivariable logistic regression models to identify predictors of linkage following a positive hypertension screen., Results: Of 11 694 individuals screened, 14.6% (n=1706) were newly diagnosed with elevated pressure. 26.9% (95% CI 24.5% to 29.4%) of those sought hypertension care in the following 2 years, and 38.1% (95% CI 35.6% to 40.7%) did so within 5 years. Women (adjusted OR (aOR) 2.41, 95% CI 1.68 to 3.45), those of older age (aOR 11.49, 95% CI 5.87 to 22.46, for 45-59 years vs <30) and those unemployed (aOR 1.71, 95% CI 1.10 to 2.65) were more likely to have linked to care., Conclusions: Linkage to care after home-based identification of elevated blood pressure was rare in rural South Africa, particularly among younger individuals, men and the employed. Improved understanding of barriers and facilitators to NCD care is needed to enhance the effectiveness of blood pressure screening in the region., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.)

The 2017 Lancet Commission on Pollution and Health identified soil as an important, daily route of public exposure to a variety of pollutants. Lead and arsenic are two potential soil contaminants associated with serious health effects including reductions in intelligence, behavioral effects and aggressive or violent behavior (lead), as well as skin changes, cancer of the skin, bladder, liver and lungs and developmental delays (arsenic). In this study soil samples were collected, using US EPA methods, from gardens in four Johannesburg neighborhoods, and analyzed for lead and arsenic content using a portable X-ray fluorescence spectrometer. The results showed widely varied concentrations of arsenic and lead in soil collected across the four neighborhoods. Concentrations of lead (range: 0.1-2141.0 mg/kg; mean: 241.7 mg/kg (SD 282.8); median 158.1 mg/kg) exceeding local and international reference levels were found in an inner city suburb, while raised arsenic concentrations (range: 0.1-65.3 mg/kg; mean: 18.3 mg/kg (SD 11.7); median: 19.1) were found in the gardens of a suburb located very close to a mine tailings facility. This study confirms the potential for high levels of exposure to toxic metals in residential gardens in an urban African setting. There is a pressing need for scaled up attention to the public health implications of exposure to soil pollution in developing countries., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Age cohort differences in haemoglobin concentrations and associations with physical and cognitive performance among populations of lower income and middle-income countries have not previously been described. We examined the association between these factors among older men and women in rural South Africa., Methods: We analysed cross-sectional data from a population-based study of rural South African men and women aged 40 and over (n=4499), with data drawn from questionnaire responses, a cognitive battery, objective physical function tests and blood tests. Anaemia was defined as a haemoglobin concentration <12 g/dL for women and <13 g/dL for men. We related haemoglobin concentrations to each of age, grip strength, walk speed and a latent cognitive function z-score for men and women separately. We used unadjusted correlations and linear models to adjust for comorbidities and inflammation., Results: In total, 1042 (43.0%) women and 833 (40.1%) men were anaemic. Haemoglobin concentrations were inversely correlated with age for men but not for women; in adjusted analyses, haemoglobin was 0.3 g/dL lower per decade older for men (95% CI 0.2 to 0.4 g/dL). In adjusted analyses, haemoglobin concentration was independently associated with grip strength in women (B=0.391, 95% CI 0.177 to 0.605), but this did not reach significance in men (B=0.266, 95% CI -0.019 to 0.552); no associations were observed between haemoglobin levels and walk speed or cognitive score., Conclusions: Anaemia was prevalent in this study population of middle-aged and older, rural South African adults, but in contrast to high-income countries, it was not associated with poor physical or cognitive function. Our findings need to be replicated in other populations., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: Community mobilization (CM) is increasingly recognized as critical to generating changes in social norms and behaviours needed to achieve reductions in HIV. We conducted a CM intervention to modify negative gender norms, particularly among men, in order to reduce associated HIV risk., Methods: Twenty two villages in the Agincourt Health and Socio-Demographic Surveillance Site in rural Mpumalanga, South Africa were randomized to either a theory-based, gender transformative, CM intervention or no intervention. Two cross-sectional, population-based surveys were conducted in 2012 (pre-intervention, n = 600 women; n = 581 men) and 2014 (post-intervention, n = 600 women; n = 575 men) among adults ages 18 to 35 years. We used an intent-to-treat (ITT) approach using survey regression cluster-adjusted standard errors to determine the intervention effect by trial arm on gender norms, measured using the Gender Equitable Mens Scale (GEMS), and secondary behavioural outcomes., Results: Among men, there was a significant 2.7 point increase (Beta Coefficient 95% CI: 0.62, 4.78, p = 0.01) in GEMS between those in intervention compared to control communities. We did not observe a significant difference in GEMS scores for women by trial arm. Among men and women in intervention communities, we did not observe significant differences in perpetration of intimate partner violence (IPV), condom use at last sex or hazardous drinking compared to control communities. The number of sex partners in the past 12 months (AOR 0.29, 95% CI 0.11 to 0.77) were significantly lower in women in intervention communities compared to control communities and IPV victimization was lower among women in intervention communities, but the reduction was not statistically significant (AOR 0.53, 95% CI 0.24 to 1.16)., Conclusion: Community mobilization can reduce negative gender norms among men and has the potential to create environments that are more supportive of preventing IPV and reducing HIV risk behaviour. Nevertheless, we did not observe that changes in attitudes towards gender norms resulted in desired changes in risk behaviours suggesting that more time may be necessary to change behaviour or that the intervention may need to address behaviours more directly., Clinical Trials Number: ClinicalTrials.gov NCT02129530., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.)

Background: Frailty is a key predictor of death and dependency, yet little is known about frailty in sub-Saharan Africa despite rapid population ageing. We describe the prevalence and correlates of phenotypic frailty using data from the Health and Aging in Africa: Longitudinal Studies of an INDEPTH Community cohort., Methods: We analysed data from rural South Africans aged 40 and over. We used low grip strength, slow gait speed, low body mass index, and combinations of self-reported exhaustion, decline in health, low physical activity and high self-reported sedentariness to derive nine variants of a phenotypic frailty score. Each frailty category was compared with self-reported health, subjective wellbeing, impairment in activities of daily living and the presence of multimorbidity. Cox regression analyses were used to compare subsequent all-cause mortality for non-frail (score 0), pre-frail (score 1-2) and frail participants (score 3+)., Results: Five thousand fifty nine individuals (mean age 61.7 years, 2714 female) were included in the analyses. The nine frailty score variants yielded a range of frailty prevalences (5.4% to 13.2%). For all variants, rates were higher in women than in men, and rose steeply with age. Frailty was associated with worse subjective wellbeing, and worse self-reported health. Both prefrailty and frailty were associated with a higher risk of death during a mean 17 month follow up for all score variants (hazard ratios 1.29 to 2.41 for pre-frail vs non-frail; hazard ratios 2.65 to 8.91 for frail vs non-frail)., Conclusions: Phenotypic frailty could be measured in this older South African population, and was associated with worse health, wellbeing and earlier death.

Background: Tuberculosis (TB) continues to be a major global health problem. While progress has been made to improve TB cure rates, South Africa's 76 % smear-positive pulmonary TB (PTB) case cure rate remains below the WHO target of 85 %. We report on the trends of TB smear non-conversion and their predictors at the end of an intensive phase of treatment, and how this impacted on treatment outcomes of smear-positive PTB cases in Eden District, Western Cape Province, South Africa., Methods: Routinely collected, retrospective data of smear-positive PTB cases from the electronic TB register in Eden District between 2007 and 2013 was extracted. Non-conversion was defined as persistent sputum smear-positive PTB cases at the end of the two or three month intensive phase of treatment. Chi-square test for linear trend and simple linear regression analysis were used to analyse the change in percentages and slope of TB smear non-conversion rates over time. Risk factors for TB non-conversion, and their impact on treatment outcomes, were evaluated using logistic regression models., Results: Of 12,742 total smear-positive PTB cases included in our study, 12.8 % (n = 1627) did not sputum smear convert; 13.3 % (1411 of 10,574) of new cases and 9.9 % (216 of 2168) of re-treatment cases. Although not statistically significant in either new or re-treatment cases, between 2007 and 2013, smear non-conversion decreased from 16.4 to 12.7 % (slope = -0.60; 95 % CI: -1.49 to 0.29; p = 0.142) in new cases, and from 11.3 to 10.8 % in re-treatment cases (slope = -0.29; 95 % CI: -1.06 to 0.48; p = 0.376). Male gender, HIV co-infection and a >2+ acid fast bacilli (AFB) smear grading at the start of TB treatment were independent risk factors for non-conversion (p < 0.001). Age was a risk factor for non-conversion in new cases, but not for re-treatment cases. Non-conversion was also associated with unsuccessful treatment outcomes (p < 0.01), including treatment default and treatment failure., Conclusions: Smear-positive PTB cases, especially men and those with identified risk factors for non-conversion, should be closely monitored throughout their treatment period. The South African TB control program should invest in patient adherence counselling and education to mitigate TB non-conversion risk factors, and to improve conversion and TB cure rates.

Background: Epilepsy is a common neurological disorder, with over 80 % of cases found in low- and middle-income countries (LMICs). Studies from high-income countries find a significant economic burden associated with epilepsy, yet few studies from LMICs, where out-of-pocket costs for general healthcare can be substantial, have assessed out-of-pocket costs and health care utilization for outpatient epilepsy care., Methods: Within an established health and socio-demographic surveillance system in rural South Africa, a questionnaire to assess self-reported health care utilization and time spent traveling to and waiting to be seen at health facilities was administered to 250 individuals, previously diagnosed with active convulsive epilepsy. Epilepsy patients' out-of-pocket, medical and non-medical costs and frequency of outpatient care visits during the previous 12-months were determined., Results: Within the last year, 132 (53 %) individuals reported consulting at a clinic, 162 (65 %) at a hospital and 34 (14 %) with traditional healers for epilepsy care. Sixty-seven percent of individuals reported previously consulting with both biomedical caregivers and traditional healers. Direct outpatient, median costs per visit varied significantly (p < 0.001) between hospital (2010 International dollar ($) 9.08; IQR: $6.41-$12.83) and clinic consultations ($1.74; IQR: $0-$5.58). Traditional healer fees per visit were found to cost $52.36 (IQR: $34.90-$87.26) per visit. Average annual outpatient, clinic and hospital out-of-pocket costs totaled $58.41. Traveling to and from and waiting to be seen by the caregiver at the hospital took significantly longer than at the clinic., Conclusions: Rural South Africans with epilepsy consult with both biomedical caregivers and traditional healers for both epilepsy and non-epilepsy care. Traditional healers were the most expensive mode of care, though utilized less often. While higher out-of-pocket costs were incurred at hospital visits, more people with ACE visited hospitals than clinics for epilepsy care. Promoting increased use and effective care at clinics and reducing travel and waiting times could substantially reduce the out-of-pocket costs of outpatient epilepsy care.

Background: Despite the widely documented success of antiretroviral therapy (ART), stakeholders continue to face the challenges of poor HIV treatment outcomes. While many studies have investigated patient-level causes of poor treatment outcomes, data on the effect of health systems on ART outcomes are scarce., Objective: We compare treatment outcomes among patients receiving HIV care and treatment at a public and private HIV clinic in Johannesburg, South Africa., Patients and Methods: This was a retrospective cohort analysis of ART naïve adults (≥18.0 years), initiating ART at a public or private clinic in Johannesburg between July 01, 2007 and December 31, 2012. Cox proportional-hazards regression was used to identify baseline predictors of mortality and loss to follow-up (>3 months late for the last scheduled visit). Generalized estimating equations were used to determine predictors of failure to suppress viral load (≥400 copies/mL) while the Wilcoxon rank-sum test was used to compare the median absolute change in CD4 count from baseline to 12 months post-ART initiation., Results: 12,865 patients initiated ART at the public clinic compared to 610 at the private clinic. The patients were similar in terms of sex and age at initiation. Compared to public clinic patients, private clinic patients initiated ART at higher median CD4 counts (159 vs 113 cells/mm(3)) and World Health Organization stage I/II (76.1% vs 58.5%). Adjusted hazard models showed that compared to public clinic patients, private clinic patients were less likely to die (adjusted hazard ratio [aHR] 0.50; 95% confidence interval [CI] 0.35-0.70) but were at increased risk of loss to follow-up (aHR 1.80; 95% CI 1.59-2.03). By 12 months post-ART initiation, private clinic patients were less likely to have a detectable viral load (adjusted relative risk 0.65; 95% CI 0.49-0.88) and recorded higher median CD4 change from baseline (184 cells/mm(3) interquartile range 101-300 vs 158 cells/mm(3) interquartile range 91-244), when compared to public clinic patients., Conclusion: We identified differences in treatment outcomes between the two HIV clinics. Findings suggest that the type of clinic at which ART patients initiate and receive treatment can have an impact on treatment outcomes. Further research is necessary to provide more conclusive results.

Objective: We determined the performance of the Framingham score and the Systematic COronary Risk Evaluation (SCORE) in assessing high-risk atherosclerosis in patients with rheumatoid arthritis (RA)., Methods: We assembled 330 cases without established cardiovascular disease (CVD), diabetes, and moderate or severe chronic kidney disease among 451 consecutive Spanish patients who underwent CVD risk screening and carotid ultrasound-determined plaque assessment. The findings were validated in 90 black and 97 white African patients., Results: When sensitivity for the Framingham score was set at 80% in receiver-operator curve analysis [area under the curve (AUC) = 0.799], the corresponding cutoff value and specificity were 7.3% and 63%, respectively. At a specificity of 80%, the cutoff value and sensitivity were 10.8% and 65%, respectively. When sensitivity for SCORE (AUC = 0.747) was set at 80%, the cutoff value and specificity were 0.5% and 58%, respectively. At a specificity of 80%, the cutoff value and sensitivity were 1.5% and 50%, respectively. Upon applying a cutoff value of 7.3% for the Framingham and 0.5% for SCORE in African white patients with RA, the corresponding sensitivities and specificities were 67% and 72%, and 67% and 55%, respectively. CVD risk equations did not discriminate between black African patients with and without plaque (AUC = 0.544 and 0.549 for Framingham score and SCORE, respectively)., Conclusion: The Framingham score and SCORE at markedly low cutoff values of 7.3% to 10.8% and 0.5% to 1.5%, respectively, can usefully estimate plaque presence in RA. Effective population-specific CVD risk assessment strategies are needed in black African patients with RA.

Objective: We investigated the prevalence and pattern of electroencephalographic (EEG) features of epilepsy and the associated factors in Africans with active convulsive epilepsy (ACE)., Methods: We characterized electroencephalographic features and determined associated factors in a sample of people with ACE in five African sites. Mixed-effects modified Poisson regression model was used to determine factors associated with abnormal EEGs., Results: Recordings were performed on 1426 people of whom 751 (53%) had abnormal EEGs, being an adjusted prevalence of 2.7 (95% confidence interval (95% CI), 2.5-2.9) per 1000. 52% of the abnormal EEG had focal features (75% with temporal lobe involvement). The frequency and pattern of changes differed with site. Abnormal EEGs were associated with adverse perinatal events (risk ratio (RR)=1.19 (95% CI, 1.07-1.33)), cognitive impairments (RR=1.50 (95% CI, 1.30-1.73)), use of anti-epileptic drugs (RR=1.25 (95% CI, 1.05-1.49)), focal seizures (RR=1.09 (95% CI, 1.00-1.19)) and seizure frequency (RR=1.18 (95% CI, 1.10-1.26) for daily seizures; RR=1.22 (95% CI, 1.10-1.35) for weekly seizures and RR=1.15 (95% CI, 1.03-1.28) for monthly seizures))., Conclusions: EEG abnormalities are common in Africans with epilepsy and are associated with preventable risk factors., Significance: EEG is helpful in identifying focal epilepsy in Africa, where timing of focal aetiologies is problematic and there is a lack of neuroimaging services., (Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Introduction: Low and middle income countries bear the majority burden of self-harm, yet there is a paucity of evidence detailing risk-factors for self-harm in these populations. This study aims to identify environmental, socio-economic and demographic household-level risk factors for self-harm in five impoverished urban communities in Johannesburg, South Africa., Methods: Annual serial cross-sectional surveys were undertaken in five impoverished urban communities in Johannesburg for the Health, Environment and Development (HEAD) study. Logistic regression analysis using the HEAD study data (2006-2011) was conducted to identify household-level risk factors associated with self-harm (defined as a self-reported case of a fatal or non-fatal suicide attempt) within the household during the preceding year. Stepwise multivariate logistic regression analysis was employed to identify factors associated with self-harm., Results: A total of 2 795 household interviews were conducted from 2006 to 2011. There was no significant trend in self-harm over time. Results from the final model showed that self-harm was significantly associated with households exposed to a violent crime during the past year (Adjusted Odds Ratio (AOR) 5.72; 95% CI 1.64-19.97); that have a member suffering from a chronic medical condition (AOR 8.95; 95% 2.39-33.56) and households exposed to indoor smoking (AOR 4.39; CI 95% 1.14-16.47)., Conclusion: This study provides evidence on household risk factors of self-harm in settings of urban poverty and has highlighted the potential for a more cost-effective approach to identifying those at risk of self-harm based on household level factors.

Background: The disability adjusted life year (DALY) is a composite measure of disease burden that includes both morbidity and mortality, and is relevant to conditions such as epilepsy that can limit productive functioning. The 2010 Global Burden of Disease (GBD) study introduced a number of new methods and definitions, including a prevalence-based approach and revised disability weights to calculate morbidity and new standard life expectancies to calculate premature mortality. We used these approaches, and local, population-based data, to estimate the burden of convulsive epilepsy in rural South Africa., Methods & Findings: Comprehensive prevalence, incidence and mortality data on convulsive epilepsy were collected within the Agincourt sub-district in rural northeastern South Africa between 2008 and 2012. We estimated DALYs using both prevalence- and incidence-based approaches for calculating years of life lived with disability. Additionally, we explored how changing the disease model by varying the disability weights influenced DALY estimates. Using the prevalence-based approach, convulsive epilepsy in Agincourt resulted in 332 DALYs (95% uncertainty interval (UI): 216-455) and 4.1 DALYs per 1,000 individuals (95%UI: 2.7-5.7) annually. Of this, 26% was due to morbidity while 74% was due to premature mortality. DALYs increased by 10% when using the incidence-based method. Varying the disability weight from 0.072 (treated epilepsy, seizure free) to 0.657 (severe epilepsy) caused years lived with disability to increase from 18 (95%UI: 16-19) to 161 (95%UI: 143-170)., Conclusions: DALY estimates are influenced by both the methods applied and population parameters used in the calculation. Irrespective of method, a significant burden of epilepsy is due to premature mortality in rural South Africa, with a lower burden than rural Kenya. Researchers and national policymakers should carefully interrogate the methods and data used to calculate DALYs as this will influence policy priorities and resource allocation.

Background: Epilepsy is one of the most common neurological conditions globally, estimated to constitute 0.75% of the global burden of disease, with the majority of this burden found in low- and middle- income countries (LMICs). Few studies from LMICs, including much of sub-Saharan Africa, have described the incidence, remission or mortality rates due to epilepsy, which are needed to quantify the burden and inform policy. This study investigates the epidemiological parameters of convulsive epilepsy within a context of high HIV prevalence and an emerging burden of cardiovascular disease., Methods: A cross-sectional population survey of 82,818 individuals, in the Agincourt Health and Socio-demographic Surveillance Site (HDSS) in rural northeast South Africa was conducted in 2008, from which 296 people were identified with active convulsive epilepsy. A follow-up survey was conducted in 2012. Incidence and mortality rates were estimated, with duration and remission rates calculated using the DISMOD II software package., Results: The crude incidence for convulsive epilepsy was 17.4/100,000 per year (95%CI: 13.1-23.0). Remission was 4.6% and 3.9% per year for males and females, respectively. The standardized mortality ratio was 2.6 (95%CI: 1.7-3.5), with 33.3% of deaths directly related to epilepsy. Mortality was higher in men than women (adjusted rate ratio (aRR) 2.6 (95%CI: 1.2-5.4)), and was significantly associated with older ages (50+ years versus those 0-5 years old (RR 4.8 (95%CI: 0.6-36.4))., Conclusions: The crude incidence was lower whilst mortality rates were similar to other African studies; however, this study found higher mortality amongst older males. Efforts aimed at further understanding what causes epilepsy in older people and developing interventions to reduce prolonged seizures are likely to reduce the overall burden of ACE in rural South Africa.

Objective: We conducted a community survey to estimate the prevalence and describe the features, risk factors, and consequences of convulsive status epilepticus (CSE) among people with active convulsive epilepsy (ACE) identified in a multisite survey in Africa., Methods: We obtained clinical histories of CSE and neurologic examination data among 1,196 people with ACE identified from a population of 379,166 people in 3 sites: Agincourt, South Africa; Iganga-Mayuge, Uganda; and Kilifi, Kenya. We performed serologic assessment for the presence of antibodies to parasitic infections and HIV and determined adherence to antiepileptic drugs. Consequences of CSE were assessed using a questionnaire. Logistic regression was used to identify risk factors., Results: The adjusted prevalence of CSE in ACE among the general population across the 3 sites was 2.3 per 1,000, and differed with site (p < 0.0001). Over half (55%) of CSE occurred in febrile illnesses and focal seizures were present in 61%. Risk factors for CSE in ACE were neurologic impairments, acute encephalopathy, previous hospitalization, and presence of antibody titers to falciparum malaria and HIV; these differed across sites. Burns (15%), lack of education (49%), being single (77%), and unemployment (78%) were common in CSE; these differed across the 3 sites. Nine percent with and 10% without CSE died., Conclusions: CSE is common in people with ACE in Africa; most occurs with febrile illnesses, is untreated, and has focal features suggesting preventable risk factors. Effective prevention and the management of infections and neurologic impairments may reduce the burden of CSE in ACE., (© 2015 American Academy of Neurology.)

Objective: To determine whether kidney function independently relates to endothelial activation and ultrasound determined carotid atherosclerosis in black and white Africans with rheumatoid arthritis (RA)., Methods: We calculated the Jelliffe, 5 Cockcroft-Gault equations, Salazar-Corcoran, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (EGFR) equations in 233 (112 black) RA patients., Results: The CKD-EPI eGFR was <90 ml/min/1.73m2 in 49.1% and 30.6% of black and white patients, respectively (odds ratio (95% confidence interval) = 2.19 (1.28-3.75), p = 0.004). EGFRs were overall consistently associated with monocyte chemoattractant protein-1 and angiopoietin 2 concentrations in white patients, and with carotid intima-media thickness and plaque in black participants. Amongst black patients, plaque prevalence was 36.7% and the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was not associated with plaque presence for the MDRD equation (p = 0.3), whereas the respective relationship was significant or borderline significant (p = 0.003 to 0.08) and of similar extent (p>0.1 for comparisons of AUC (SE)) for the other 8 equations. Based on optimal eGFR cutoff values with sensitivities and specificities ranging from 42 to 60% and 70 to 91% respectively, as determined in ROC curve analysis, a low eGFR increased the odds ratio for plaque 2.2 to 4.0 fold., Conclusion: Reduced kidney function is independently associated with atherosclerosis and endothelial activation in black and white Africans with RA, respectively. CKD is highly prevalent in black Africans with RA. Apart from the MDRD, eGFR equations are useful in predicting carotid plaque presence, a coronary heart disease equivalent, amongst black African RA patients.

Background: Rheumatoid arthritis (RA) causes progressive joint damage and functional disability. Studies on factors affecting joint damage as clinical outcome are lacking in Africa. The aim of the present study was to identify predictors of joint damage in adult South Africans with established RA.Methods: A cross-sectional study of 100 black patients with RA of >5 years were assessed for joint damage using a validated clinical method, the RA articular damage (RAAD) score. Potential predictors of joint damage that were documented included socio-demographics, smoking, body mass index (BMI), disease duration, delay in disease modifying antirheumatic drug (DMARD) initiation, global disease activity as measured by the disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and autoantibody status. The predictive value of variables was assessed by univariate and stepwise multivariate regression analyses. A p value <0.05 was considered significant.Results: The mean (SD) age was 56 (9.8) years, disease duration 17.5 (8.5) years, educational level 7.5 (3.5) years and DMARD lag was 9 (8.8) years. Female to male ratio was 10:1. The mean (SD) DAS28 was 4.9 (1.5) and total RAAD score was 28.3 (12.8). The mean (SD) BMI was 27.2 kg/m2 (6.2) and 93% of patients were rheumatoid factor (RF) positive. More than 90% of patients received between 2 to 3 DMARDs. Significant univariate predictors of a poor RAAD score were increasing age (p = 0.001), lower education level (p = 0.019), longer disease duration (p < 0.001), longer DMARD lag (p = 0.014), lower BMI (p = 0.025), high RF titre (p < 0.001) and high ESR (p = 0.008). The multivariate regression analysis showed that the only independent significant predictors of a higher mean RAAD score were older age at disease onset (p = 0.04), disease duration (p < 0.001) and RF titre (p < 0.001). There was also a negative association between BMI and the mean total RAAD score (p = 0.049).Conclusions: Patients with longstanding established RA have more severe irreversible joint damage as measured by the clinical RAAD score, contrary to other studies in Africa. This is largely reflected by a delay in the initiation of early effective treatment. Independent of disease duration, older age at disease onset and a higher RF titre are strongly associated with more joint damage. The inverse association between BMI and articular damage in RA has been observed in several studies using radiographic damage scores. The mechanisms underlying this paradoxical association are still widely unknown but adipokines have recently been suggested to play a role.Disclosure statement: C.I. has received a research grant from the Connective Tissue Diseases Research Fund, University of the Witwatersrand. All other authors have declared no conflicts of interest. [ABSTRACT FROM PUBLISHER]

Background: Epilepsy is common in developing countries, and it is often associated with parasitic infections. We investigated the relationship between exposure to parasitic infections, particularly multiple infections and active convulsive epilepsy (ACE), in five sites across sub-Saharan Africa., Methods and Findings: A case-control design that matched on age and location was used. Blood samples were collected from 986 prevalent cases and 1,313 age-matched community controls and tested for presence of antibodies to Onchocerca volvulus, Toxocara canis, Toxoplasma gondii, Plasmodium falciparum, Taenia solium and HIV. Exposure (seropositivity) to Onchocerca volvulus (OR = 1.98; 95%CI: 1.52-2.58, p<0.001), Toxocara canis (OR = 1.52; 95%CI: 1.23-1.87, p<0.001), Toxoplasma gondii (OR = 1.28; 95%CI: 1.04-1.56, p = 0.018) and higher antibody levels (top tertile) to Toxocara canis (OR = 1.70; 95%CI: 1.30-2.24, p<0.001) were associated with an increased prevalence of ACE. Exposure to multiple infections was common (73.8% of cases and 65.5% of controls had been exposed to two or more infections), and for T. gondii and O. volvulus co-infection, their combined effect on the prevalence of ACE, as determined by the relative excess risk due to interaction (RERI), was more than additive (T. gondii and O. volvulus, RERI = 1.19). The prevalence of T. solium antibodies was low (2.8% of cases and 2.2% of controls) and was not associated with ACE in the study areas., Conclusion: This study investigates how the degree of exposure to parasites and multiple parasitic infections are associated with ACE and may explain conflicting results obtained when only seropositivity is considered. The findings from this study should be further validated.

Objective: Osteoprotegerin (OPG) may contribute to the link between systemic inflammation and increased cardiovascular risk. We investigated the relationship of OPG concentrations with endothelial activation and carotid atherosclerosis in rheumatoid arthritis (RA)., Methods: OPG concentrations and those of endothelial activation molecules were measured by using ELISA in 34 patients who were treated with infliximab (IFX), both immediately before and after an IFX infusion. Carotid intima-media thickness (CIMT) and plaque were determined by ultrasound in 27 of the study participants., Results: Median (interquartile range) OPG concentrations decreased from 4.8 pmol/l (2.8-6.5) to 4.4 pmol/l (2.9-6.1; p = 0.04) upon IFX infusion. Baseline OPG concentrations were inversely associated with those of total and low-density lipoprotein (LDL) cholesterol (partial R = -0.50, p = 0.004, and R = -0.48, p = 0.007, respectively). Prior to IFX administration, OPG concentrations were associated with those of intercellular adhesion molecule (ICAM)-1 (partial R = 0.34, p = 0.05), CIMT (partial R = 0.51 to 0.52, p < 0.009), and plaque (OR = 1.52, 95% CI 1.01-2.29 to OR = 1.61, 95% CI 1.03-2.51; p < 0.04), independent of conventional risk factors and C-reactive protein concentrations or disease activity. Except for the OPG concentrations-plaque association (p = 0.09), these relationships remained significant subsequent to IFX administration (p < 0.05). Reductions in OPG levels related to those in vascular cell adhesion molecule (VCAM)-1 concentrations (partial R = 0.35, p = 0.04) and had borderline significance (p = 0.09) with those in ICAM-1 (partial R = 0.29) concentrations., Conclusion: OPG concentrations are independently associated with endothelial activation and carotid atherosclerosis in RA. Reductions in OPG concentrations upon IFX administration are associated with decreased endothelial activation. OPG may be involved in increased cardiovascular disease risk and may improve its stratification in patients with RA.