Eustasius Musenge

The International Classification of Function Disability and Health (ICF) in adults visiting the HIV outpatient clinic at a regional hospital in Johannesburg, South Africa

Abstract In 2005, 16.6% of South Africans between 15 and 49 years of age were HIV positive. The advent of anti-retroviral therapy has led to improved longevity, CD4 counts and clinical well-being of people living with HIV/AIDS (PLWHA). Physical impairments, activity limitations and participation restrictions of PLWHA have profound effects on the Health-related Quality of Life and functional abilities of those with the disease, and understanding thereof may assist in the formulation of rehabilitation protocols, health care interventions as well as vocational and legislative policies. The International Classification of Function, Disability and Health (ICF) is a standardised tool, endorsed by the World Health Assembly for international use, which aims to classify functioning and disability. It is structured to assess body functions and structure, functional activities and associated personal and environmental factors.This study aimed to develop a profile of the level of functional activity, using the ICF Checklist, of an urban cohort of 45 South African individuals who are HIV positive attending an outpatient clinic at the Helen Joseph Memorial Hospital, Gauteng, South Africa. The results showed a high prevalence of physical impairments, participation restrictions and selective activity limitations and that environmental factors influence their level of ability. Specific impairments where patients had problems were mental functions (69% (n=31), sensory and pain – 71% (n=32), digestive and metabolic functions 45% (n=20) and neuromuscular 27% (n=12). Activity limitations included major life areas’ 58% (n=26), interpersonal relationships 56% (n=25), mobility 40% (n=18) and general tasks and demands 38% (n=17). Limitations in mobility were significantly associated with problems of sensory functions (p=0.05), pain (p=0.006), neuromusculoskeletal and movement-related functions (p=0.006), muscle power (p=0.006) as well as energy and drive functions (p=0.001). The study identifies the level of function and ability of PLWHA, clinical markers, and how these affect the physical, psychological and social functioning of this population.

Serum matrix metalloproteinase-3 in comparison with acute phase proteins as a marker of disease activity and radiographic damage in early rheumatoid arthritis.

Matrix metalloproteinase-3 (MMP-3) is involved in the immunopathogenesis of rheumatoid arthritis (RA), but little is known about its relationship to genetic susceptibility and biomarkers of disease activity, especially acute phase reactants in early RA. MMP-3 was measured by ELISA in serum samples of 128 disease-modifying, drug-naïve patients and analysed in relation to shared epitope genotype, a range of circulating chemokines/cytokines, acute phase reactants, autoantibodies, cartilage oligomeric protein (COMP), and the simplified disease activity index (SDAI). MMP-3 was elevated >1.86 ng/ml in 56.25% of patients (P < 0.0001), correlated with several biomarkers, notably IL-8, IL-6, IFN γ, VEGF and COMP (r values = 0.22–0.33, P < 0.014–0.0001) and with CRP and SAA levels (r = 0.40 and 0.41, resp., P < 0.0000) and SDAI (r = 0.29, P < 0.0001), but not with erosions or nodulosis. However, the correlations of CRP and SAA with SDAI were stronger (respective values of 0.63 and 0.54, P < 0.001 for both). COMP correlated with smoking, RF, and MMP-3. MMP-3 is significantly associated with disease activity, inflammatory mediators and cartilage breakdown, making it a potential biomarker of disease severity, but seemingly less useful than CRP and SAA as a biomarker of disease activity in early RA.

Circulating Cytokine Profiles and Their Relationships with Autoantibodies, Acute Phase Reactants, and Disease Activity in Patients with Rheumatoid Arthritis

Our objective was to analyse the relationship between circulating cytokines, autoantibodies, acute phase reactants, and disease activity in DMARDs-naïve rheumatoid arthritis (RA) patients (n = 140). All cytokines were significantly higher in the RA cohort than in healthy controls. Moderate-to-strong positive intercorrelations were observed between Th1/Th2/macrophage/fibroblast-derived cytokines. RF correlated significantly with IL-1β, IL-2, IL-4, IL-10, IL-12, G-CSF, GM-CSF, IFN-γ, and TNF (P < .0001), and aCCP and aMCV with IL-1β, IL-2, IL-4, and IL-10 (P < .0002), while IL-6 correlated best with the acute phase reactants, CRP, and SAA (P < .0001). In patients with a DAS28 score of ≥5.1, IFN-γ, IL-1β, IL-1Ra, TNF, GM-CSF, and VEGF were significantly correlated (P < .04–.001) with high disease activity (HDA). Circulating cytokines in RA reflect a multifaceted increase in immune reactivity encompassing Th1 and Th2 cells, monocytes/macrophages, and synovial fibroblasts, underscored by strong correlations between these cytokines, as well as their relationships with RF, aCCP, and aMCV, with some cytokines showing promise as biomarkers of HDA.

Investigation into longitudinal dietary behaviours and household socio-economic indicators and their association with BMI Z-score and fat mass in South African adolescents: the Birth to Twenty (Bt20) cohort.

OBJECTIVE The present study aimed to assess the relationship between dietary habits, change in socio-economic status and BMI Z-score and fat mass in a cohort of South African adolescents. DESIGN In the longitudinal study, data were collected at ages 13, 15 and 17 years on a birth cohort who have been followed since 1990. Black participants with complete dietary habits data (breakfast consumption during the week and at weekends, snacking while watching television, eating main meal with family, lunchbox use, number of tuck shop purchases, fast-food consumption, confectionery consumption and sweetened beverage consumption) at all three ages and body composition data at age 17 years were included in the analyses. Generalized estimating equations were used to test the associations between individual longitudinal dietary habits and obesity (denoted by BMI Z-score and fat mass) with adjustments for change in socio-economic status between birth and age 12 years. SETTING Birth to Twenty (Bt20) study, Soweto-Johannesburg, South Africa. SUBJECTS Adolescents (n 1298; 49·7 % male). RESULTS In males, the multivariable analyses showed that soft drink consumption was positively associated with both BMI Z-score and fat mass (P < 0·05). Furthermore, these relationships remained the same after adjustment for socio-economic indicators (P < 0·05). No associations were found in females. CONCLUSIONS Longitudinal soft drink consumption was associated with increased BMI Z-score and fat mass in males only. Fridge ownership at birth (a proxy for greater household disposable income in this cohort) was shown to be associated with both BMI Z-score and fat mass.

HLA-DRB1 shared epitope genotyping using the revised classification and its association with circulating autoantibodies, acute phase reactants, cytokines and clinical indices of disease activity in a cohort of South African rheumatoid arthritis patients

IntroductionThe revised shared epitope (SE) concept in rheumatoid arthritis (RA) is based on the presence (S) or absence (X) of the SE RAA amino acid motif at positions 72 to 74 of the third hypervariable region of the various human leucocyte antigen (HLA)-DRB1 alleles. The purpose of this study was to investigate SE subtypes on the basis of the American College of Rheumatology 1987 revised criteria for the classification of RA in a cohort of South African RA patients (n = 143) and their association with clinical and circulating biomarkers of disease activity (autoantibodies, acute phase reactants and cytokines).MethodsGenomic DNA was analysed using high-resolution recombinant sequence-specific oligonucleotide PCR typing of the HLA-DRB1 allele. Subtypes of the SE were classified according to the amino acids at positions 72 to 74 for the RAA sequence, and further sub-divided according to the amino acids at positions 70 and 71, which either contribute to (S2, S3P), or negate (S1, S3D) RA susceptibility. Disease activity was assessed on the basis of (1) Disease Activity Score in 28 joints using C-reactive protein (CRP), (2) rheumatoid factor (RF), (3) CRP and (4) serum amyloid A by nephelometry, anticyclic citrullinated peptide antibodies (aCCP) by an immunofluorometric procedure, and cytokines by multiplex bead array technology.ResultsOf the 143 RA patients, 81 (57%) were homozygous (SS) and 50 (35%) were heterozygous (SX) for the SE alleles with significant overexpression of S2 and S3P (respective odds ratios (ORs) 5.3 and 5.8; P < 0.0001), and 12 (8%) were classified as no SE allele (XX). Both the SS and SX groups showed a strong association with aCCP positivity (OR = 10.2 and P = 0.0010, OR = 9.2 and P = 0.0028, respectively) relative to the XX group. Clinical scores and concentrations of the other biomarkers of disease activity (RF, CRP and T helper cell type 1 (Th1), Th2, macrophage and fibroblast cytokines) were also generally higher in the SS group than in the SX and XX groups.ConclusionsRA susceptibility alleles investigated according to revised criteria for the classification of RA were significantly increased in South African RA patients and strongly associated with aCCP in particular as well as with circulating cytokines and disease severity.

The contribution of spatial analysis to understanding HIV/TB mortality in children: a structural equation modelling approach

Background : South Africa accounts for more than a sixth of the global population of people infected with HIV and TB, ranking her highest in HIV/TB co-infection worldwide. Remote areas often bear the greatest burden of morbidity and mortality, yet there are spatial differences within rural settings. Objectives : The primary aim was to investigate HIV/TB mortality determinants and their spatial distribution in the rural Agincourt sub-district for children aged 1–5 years in 2004. Our secondary aim was to model how the associated factors were interrelated as either underlying or proximate factors of child mortality using pathway analysis based on a Mosley-Chen conceptual framework. Methods : We conducted a secondary data analysis based on cross-sectional data collected in 2004 from the Agincourt sub-district in rural northeast South Africa. Child HIV/TB death was the outcome measure derived from physician assessed verbal autopsy. Modelling used multiple logit regression models with and without spatial household random effects. Structural equation models were used in modelling the complex relationships between multiple exposures and the outcome (child HIV/TB mortality) as relayed on a conceptual framework. Results : Fifty-four of 6,692 children aged 1–5 years died of HIV/TB, from a total of 5,084 households. Maternal death had the greatest effect on child HIV/TB mortality (adjusted odds ratio=4.00; 95% confidence interval=1.01–15.80). A protective effect was found in households with better socio-economic status and when the child was older. Spatial models disclosed that the areas which experienced the greatest child HIV/TB mortality were those without any health facility. Conclusion : Low socio-economic status and maternal deaths impacted indirectly and directly on child mortality, respectively. These factors are major concerns locally and should be used in formulating interventions to reduce child mortality. Spatial prediction maps can guide policy makers to target interventions where they are most needed. Appendices available online under Reading Tools.BACKGROUND South Africa accounts for more than a sixth of the global population of people infected with HIV and TB, ranking her highest in HIV/TB co-infection worldwide. Remote areas often bear the greatest burden of morbidity and mortality, yet there are spatial differences within rural settings. OBJECTIVES The primary aim was to investigate HIV/TB mortality determinants and their spatial distribution in the rural Agincourt sub-district for children aged 1-5 years in 2004. Our secondary aim was to model how the associated factors were interrelated as either underlying or proximate factors of child mortality using pathway analysis based on a Mosley-Chen conceptual framework. METHODS We conducted a secondary data analysis based on cross-sectional data collected in 2004 from the Agincourt sub-district in rural northeast South Africa. Child HIV/TB death was the outcome measure derived from physician assessed verbal autopsy. Modelling used multiple logit regression models with and without spatial household random effects. Structural equation models were used in modelling the complex relationships between multiple exposures and the outcome (child HIV/TB mortality) as relayed on a conceptual framework. RESULTS Fifty-four of 6,692 children aged 1-5 years died of HIV/TB, from a total of 5,084 households. Maternal death had the greatest effect on child HIV/TB mortality (adjusted odds ratio=4.00; 95% confidence interval=1.01-15.80). A protective effect was found in households with better socio-economic status and when the child was older. Spatial models disclosed that the areas which experienced the greatest child HIV/TB mortality were those without any health facility. CONCLUSION Low socio-economic status and maternal deaths impacted indirectly and directly on child mortality, respectively. These factors are major concerns locally and should be used in formulating interventions to reduce child mortality. Spatial prediction maps can guide policy makers to target interventions where they are most needed. Appendices available online under Reading Tools.

Functional disability and health-related quality of life in South Africans with early rheumatoid arthritis

Background: The severity and predictors of functional disability and health-related quality of life (HRQoL) in a cohort of South Africans with early rheumatoid arthritis (RA) were investigated. Methods: Changes in the Health Assessment Questionnaire Disability Index (HAQ) and the 36-Item Short Form Health Survey (SF-36) following 12 months of traditional disease-modifying anti-rheumatic drugs (DMARDs) were studied in previously DMARD-naïve adults with disease duration ≤ 2 years. Results: The majority of the 171 patients were female (82%), Black Africans (89%) with a mean (SD) symptom duration of 11.6 (7.0) months. In the 134 patients seen at 12 months, there were significant improvements in the HAQ and all domains of the SF-36 but 92 (69%) still had substantial functional disability (HAQ > 0.5) and 89 (66%) had suboptimal mental health [SF-36 mental composite score (MCS) < 66.6]. Multivariate analysis showed that female sex (p = 0.05) and high baseline HAQ score (p < 0.01) predicted substantial functional disability at 12 months. Unemployment (p = 0.03), high baseline pain (p = 0.02), and HAQ score (p = 0.04) predicted suboptimal mental health, with a trend towards a low level of schooling being significant (p = 0.08). Conclusions: Early RA has a broad impact on HRQoL in indigent South Africans, with a large proportion of patients still showing substantial functional disability and suboptimal mental health despite 12 months of DMARD therapy. Further research is needed to establish the role of interventions including psychosocial support, rehabilitation programmes, and biological therapy to improve physical function and HRQoL in this population.

Bayesian analysis of zero inflated spatiotemporal HIV/TB child mortality data through the INLA and SPDE approaches: Applied to data observed between 1992 and 2010 in rural North East South Africa.

Highlights ► South Africas HIV/TB burden in children and modelling which results in mortality risk maps. ► Analyses of hierarchical spatiotemporal data with zero inflated outcomes. ► Resolving the “Big N” on Gaussian fields (GF) by converting to Gaussian Markov Random Fields (GMRF). ► Use of fast and accurate approximate Bayesian algorithms, i.e. INLA and SPDE in lieu of MCMC. ► Medical or natural assumptions driven modelling that informs further research and policy.

Renal failure in HIV-positive patients—a South African experience

Background Kidney disease is a major complication of HIV infection, with both acute kidney injury (AKI) and chronic kidney disease (CKD) contributing to morbidity and mortality. Incidence of AKI was reported as 5.9 per 100 patient years in ambulatory patients and ∼18% in hospitalized HIV-infected patients, an almost 3-fold higher risk compared with HIV uninfected patients in developed countries. CKD was reported in 6–48.5% of HIV-infected patients in Africa. There is a paucity of data regarding the prevalence and outcomes of AKI in HIV-infected patients in sub-Saharan Africa, the region most affected by HIV. Methods A retrospective review of 101 HIV-positive anti-retroviral therapy (ART)-naïve patients presenting with renal failure from 1 October 2005 to 30 September 2006 was undertaken. Results A total of 684 patients presented with renal failure, 101 (14.8%) of whom were HIV positive. Ninety-nine (98%) of HIV-positive patients were black and 56 (55%) were male, with mean age 38 ± 9.9 years (range 21–61 years). HIV-positive patients demonstrated severe immunosuppression, with mean CD4 count of 135 cells/µL (range 1–579 cells/µL). Fifty-seven (56%) HIV-positive patients presented with AKI, 21 (21%) with acute-on-chronic kidney disease and 23 (23%) with CKD; seven patients with AKI were excluded due to lack of records. The causes of AKI in the HIV-positive group included sepsis (60%), volume depletion and haemodynamic instability (19%), toxins (9%), urological obstruction (7%) and miscellaneous (14%). Forty-four per cent of HIV-positive and 47% of HIV-negative patients with AKI demised; P = 0.45. Hyponatraemia (P = 0.018), acidosis (P = 0.018), anaemia (P = 0.019) and hyperphosphataemia (P = 0.003) were predictors of mortality in HIV-positive patients with AKI. In comparison, predictors of mortality in the HIV-negative group were age (P = 0.023) and black ethnicity (P = 0.04). Conclusion HIV-positive patients, compared with the HIV-negative group, presented with AKI at a younger age and at an advanced stage of immunosuppression. Appropriate support, including dialysis, resulted in similar outcomes in both groups.

Effects of an education and home-based pedometer walking program on ischemic heart disease risk factors in people infected with HIV: a randomized trial.

Objective:People infected with the human immunodeficiency virus are at an increased risk of developing ischemic heart disease (IHD); however, the effects of an education and home-based pedometer walking program on risk factors of IHD are not known. Methods:We conducted a 12-month randomized study of an education and home-based pedometer walking program in 84 human immunodeficiency virus–infected individuals with risk factors of IHD. Results:Pedometer step count of the control and intervention groups improved significantly (P = 0.03 for both groups) at 6 months but was not significant at 12 months (P = 0.33 and 0.21, respectively). Significant between-group effects were observed in 6-minute walk test distance (P = 0.01), waist to hip ratio (P = 0.00), glucose (P = 0.00), and high-density lipoprotein (P = 0.01) over the 12-month period. The program did not result in change in high-sensitivity C-reactive protein as it was associated with perceived stress (r = 0.23; P = 0.03), weight (r = 0.28; P = 0.01), body mass index (r = 0.35; P < 0.00), waist (r = 0.28; P = 0.01) and hip circumference (r = 0.28; P = 0.01). Multivariate generalized estimation equation analysis demonstrated an inverse association between interaction and perceived stress (logB = −0.01; 95% confidence interval: −0.02 to −0.01; P <0.00) and body mass index (logB = −0.02; 95% confidence interval: −0.03 to −0.002; P = 0.02) at group level. Conclusion:An education and home-based pedometer walking program improves physical activity levels, and beneficial changes in other IHD risk factors were noted.