High prevalence of lipoatrophy in pre-pubertal South African children on antiretroviral therapy : a cross-sectional study

Publication of this article was funded by the Stellenbosch University Open Access Fund.The original publication is available at http://www.biomedcentral.com/bmcpediatrBackground: Despite changes in WHO guidelines, stavudine is still used extensively for treatment of pediatric HIV in the developing world. Lipoatrophy in sub-Saharan African children can be stigmatizing and have far-reaching consequences. The severity and extent of lipoatrophy in pre-pubertal children living in sub-Saharan Africa is unknown. Methods: In this cross-sectional study, children who were 3-12 years old, on antiretroviral therapy and pre-pubertal were recruited from a Family HIV Clinic in South Africa. Lipoatrophy was identified and graded by consensus between two HIV pediatricians using a standardized grading scale. A professional dietician performed formal dietary assessment and anthropometric measurements of trunk and limb fat. Previous antiretroviral exposures were recorded. In a Dual-Energy X-ray Absorbtiometry (DXA) substudy body composition was determined in 42 participants. Results: Among 100 recruits, the prevalence of visually obvious lipoatrophy was 36% (95% CI: 27%–45%). Anthropometry and DXA measurements corroborated the clinical diagnosis of lipoatrophy: Both confirmed significant, substantial extremity fat loss in children with visually obvious lipoatrophy, when adjusted for age and sex. Adjusted odds ratio for developing lipoatrophy was 1.9 (95% CI: 1.3 - 2.9) for each additional year of accumulated exposure to standard dose stavudine. Cumulative time on standard dose stavudine was significantly associated with reductions in biceps and triceps skin-fold thickness (p=0.008). Conclusions: The prevalence of visually obvious lipoatrophy in pre-pubertal South African children on antiretroviral therapy is high. The amount of stavudine that children are exposed to needs review. Resources are needed to enable low-and-middle-income countries to provide suitable pediatric-formulated alternatives to stavudine-based pediatric regimens. The standard stavudine dose for children may need to be reduced. Diagnosis of lipoatrophy at an early stage is important to allow timeous antiretroviral switching to arrest progression and avoid stigmatization. Diagnosis using visual grading requires training and experience, and DXA and comprehensive anthropometry are not commonly available. A simple objective screening tool is needed to identify early lipoatrophy in resourcelimited settings where specialized skills and equipment are not available.Stellenbosch University Open Access FundPublishers' versio

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

The effect of an enriched nutritional supplement on growth and inflammatory markers in underweight HIV-positive children aged 24-72 months

Thesis (MNutr)--Stellenbosch University, 2016.ENGLISH SUMMARY : BACKGROUND: Infection with the human immuno-deficiency virus (HIV) causes immune impairment which leads to malnutrition. Malnutrition worsens the effects of HIV, resulting in faster progression to acquired immune-deficiency syndrome (AIDS). The combination of malnutrition and HIV in children negatively impacts their growth and immune status. Addressing malnutrition in HIV-positive individuals can potentially result in a strengthened immune system which is better able to cope with opportunistic infections. This thesis explored whether a cohort of HIV-positive children in a child outpatient healthcare setting and receiving nutritional supplementation showed associated changes in defined anthropometric indices (height, weight), and in defined immune and inflammatory markers. DESIGN: The thesis describes a sub-study within a successfully completed large randomized controlled clinical trial. The latter compared catch-up weight in HIV positive children receiving a complete nutritional supplement and were randomized to two groups. One group consumed supplement A (complete supplement) and the other consumed supplement B (complete supplement with added functional nutrients). The sub-study analysed data on the whole cohort and also conducted a sub-group analysis to determine bio-equivalence of the two supplements. METHODOLOGY: Study participants were recruited if they were HIV-positive, between the ages of 24-72 months and met the trial’s pre-determined inclusion criteria. Participants were recruited from Anti-retroviral treatment (ART) clinics within the Cape Town Metropole area. Anthropometric data (weight; height) was collected at baseline and at each of the six follow-up visits. Venous blood was drawn to analyse biomedical parameters [C-reactive protein (CRP); calprotectin; Immunoglobulin A (IgA)]. Anthropometric data was analysed using the World Health Organisation (WHO) Anthro Plus program and SAS General linear models (GLM Procedure) was used to calculate change overtime. Biomedical raw data was exported to STATA and statistical significance was calculated using the Related-Samples Wilcoxon Signed Rank test. RESULTS: The total number of children included in the study was 138 (64 boys; 74 girls). The cohort comprised of 69 (50%) children aged 2-3 years and 69 (50%) aged 4-6 years. The addition of the complete nutritional supplement, in its two variants, in the cohort increased mean energy intake by 1000kJ for both age-categories. For the 2, 4 and 5 year old children, weight and height gain from baseline to visit 6 was significant (p<0.000; p<0.001; p<0.000; p<0.000; p<0.004; p<0.000). Weight-for-age z-scores (WAZ) improved significantly for the 2-year old children (p<0.0082) only. CRP and calprotectin levels of the cohort showed a significant reduction to within normal ranges (p5th percentile for WFA, showed a significant improvement in CRP levels compared to children receiving supplement B. CONCLUSION: The findings of this study showed a positive effect on energy intake by consuming a balanced nutritional supplement, irrespective of composition, and on the growth and immune markers of HIV-positive, underweight children within in an outpatient setting. The addition of specific functional nutrients was found to be safe but efficacy needs to be further investigated.AFRIKAANSE OPSOMMING : AGTERGROND: Infeksie met die menslike immuniteitsgebreksvirus (MIV) veroorsaak immuun-inkorting wat lei tot wanvoeding. Wanvoeding vererger die effek van MIV wat lei tot vinniger vordering na vervorwe immuniteitsgebrek-sindroom (VIGS). Die kombinasie van wanvoeding en MIV het 'n negatiewe impak op die groei- en immuun-status van kinders. Die aanspreek van wanvoeding in HIV-positiewe individue kan moontlik lei tot 'n versterking van die immuunstelsel wat opportunistiese infeksies beter kan hanteer. Hierdie tesis het ten doel gehad om te ondersoek of 'n groep MIV-positiewe kinders, in 'n kinder-buitepasiënt gesondheidsorg-instelling, wat voedingsaanvullings ontvang het, ooreenstemmende veranderinge in die voorkoms van gedefinieerde antropometriese indekse (lengte, gewig) en in gedefinieerde immuun- en inflammasie merkers getoon het. ONTWERP: Die tesis beskryf 'n sub-studie binne 'n suksesvol voltooide groot ewekansige beheerde kliniese proefneming. Laasgenoemde het die inhaal-gewig in MIV-positiewe kinders wat 'n volledige voedingaanvulling ontvang het vergelyk en was lukraak toegewys in twee groepe. Een groep het aanvulling A (volledige aanvulling) ingeneem en die ander aanvulling B (volledige aanvulling met meer funksionele voedingstowwe). Die sub-studie het data ontleed van die hele kohort en het ook 'n sub-groep analise ingesluit om bio-ekwivalensie van die twee aanvullings te bepaal. METODE: Deelnemers was ingesluit indien hul MIV-positief was, tussen die ouderdomme van 24-72 maande en voldoen het aan voorafbepaalde kriteria vir insluiting in die studie. Deelnemers was gewerf uit anti-retrovirale terapie (ART) klinieke binne die Kaapse Metropool area. Antropometriese data (gewig; lengte) is tydens die basislyn versamel asook tydens elk van die ses opvolgbesoeke. Veneuse bloed was getrek om biomediese parameters te ontleed (C-reaktiewe proteïen [CRP]; calprotectin; Immunoglobulien A [IgA]). Antropometriese data was ontleed met behulp van die WGO Anthro Plus program en SAS algemene lineêre modelle (GLM Prosedure) is gebruik om verandering met verloop van tyd te bereken. Biomediese rou data is uitgevoer na STATA en statistiese betekenisvolheid was bereken deur die Verwante-Monsters Wilcoxon rangordetoets. RESULTATE: Die totale aantal kinders, ingesluit in die studie, was 138 (64 seuns, 74 dogters). Die groep het bestaan uit 69 (50%) kinders van 2-3 jaar en 69 (50%) van 4-6 jaar oud. Die byvoeging van die voedingaanvulling in die groep het die gemiddelde energie-inname met 1000kJ verhoog vir beide ouderdomskategorieë. Die gewig en lengte toename vir die 2, 4 en 5 jaar oue kinders vanaf die basislyn tot die 6de besoek was betekenisvol (p <0,000; p <0,001; p <0,000; p <0,000; p <0,004; p <0,000). Gewig vir ouderdom z-tellings het aansienlik verbeter slegs vir die 2-jarige kinders (p <0,0082). CRP en calprotectin het beduidend verlaag tot binne normale waardes (p 5de persentiel vir GVO was, het 'n beduidende verbetering in CRP vlakke getoon in vergelyking met kinders wat supplement B ontvang het. GEVOLGTREKKING: Die bevindinge van hierdie studie dui die positiewe gevolge van gebalanseerde voedingsaanvullings, ongeag die samestelling daarvan, op die groei - en immuun-merkers van MIV-positiewe, ondergewig kinders in 'n buitepasiënt omgewing aan. Die byvoeging van 'n spesifieke funksionele voedingstowwe was veilig bevind, maar doeltreffendheid moet verder ondersoek word

Medical leadership:competencies in action

SummaryThe engagement of the medical profession in management and leadership activities has become a priority for the UK's National Health Service (NHS). It makes sense to develop these leadership competencies as early as possible, inculcating leadership skills in junior doctors. The recent core and specialist curriculum competencies address this and, together with the Medical Leadership Competency Framework developed by the Academy of Medical Royal Colleges and the NHS, sets out a blueprint for personal development plans for junior doctors. A culture shift is called for, such that doctors in training prioritise their leadership development alongside their medical training. This article is of particular relevance to educational supervisors, as it describes how they can support junior doctors in achieving the leadership and management competencies outlined in the 2009 core and specialty psychiatry curriculum.</jats:p

Carriage of chloroquine-resistant parasites and delay of effective treatment increase the risk of severe malaria in Gambian children.

Two hundred thirty-four Gambian children with severe falciparum malaria who were admitted to the pediatric ward of a rural district hospital each were matched for age with a same-sex control subject presenting as an outpatient with uncomplicated falciparum malaria. Severe malarial anemia (SMA) was the most common presentation (152 cases), followed by cerebral malaria (38 cases) and hyperparasitemia (26 cases). Children presenting with SMA were significantly younger and more likely to carry gametocytes than were children with other severe presentations. Alleles of the genes pfcrt and pfmdr1 associated with chloroquine-resistant parasites occurred together among cases presenting with SMA alone more often than among their matched controls (odds ratio, 2.08 [95% confidence interval, 1.04-4.38]; P=.039). Costs of travel to the hospital of more than US $0.20, use of mosquito repellents, and carriage of resistant parasites were identified as independent risk factors for severe malaria in the case-control analysis. We conclude that, in this setting, poor access to the hospital and a high prevalence of chloroquine-resistant parasites lead to a delay of adequate treatment for young children with malaria, who may then develop SMA

Rapid point-of-care CD4 testing at mobile units and linkage to HIV care : an evaluation of community-based mobile HIV testing services in South Africa

CITATION: Sloot, R., et al. 2020. Rapid point-of-care CD4 testing at mobile units and linkage to HIV care : an evaluation of community-based mobile HIV testing services in South Africa. BMC Public Health, 20:528, doi:10.1186/s12889-020-08643-3.The original publication is available at https://bmcpublichealth.biomedcentral.comPublication of this article was funded by the Stellenbosch University Open Access Fund.Background: Mobile HIV testing services (HTS) are effective at reaching undiagnosed people living with HIV. However, linkage to HIV care from mobile HTS is often poor, ranging from 10 to 60%. Point-of-care (POC) CD4 testing has shown to increase retention in health facilities, but little evidence exists about their use in mobile HTS. This study assessed the feasibility of POC CD4 test implementation and investigated linkage to HIV care among clients accepting a POC test at community-based mobile HTS. Methods: This retrospective study used routinely collected data from clients who utilized community-based mobile HTS in the City of Cape Town Metropolitan district, South Africa between December 2014 and September 2016. A POC CD4 test was offered to all clients with an HIV positive diagnosis during this period, and a CD4 cell count was provided to clients accepting a POC CD4 test. Random effects logistic regression was used to assess factors associated with POC CD4 test uptake and self-reported linkage to care among clients accepting a POC test. Models were adjusted for sex, age, previous HIV test done, tuberculosis status and year of HIV diagnosis. Results: One thousand three hundred twenty-five of Thirty-nine thousand seven hundred ninety clients utilizing mobile HTS tested HIV positive (3%). 51% (679/1325) accepted a POC test. The age group with the highest proportion accepting a POC test was 50+ years (60%). Females were less likely to accept a POC test than males (odds ratio = 0.7, 95%CI = 0.6–0.8). Median CD4 count was 429 cells/μl (interquartile range = 290–584). Among 679 clients who accepted a POC CD4 test, 491 (72%) linked to HIV care. CD4 cell count was not associated with linkage to care. Conclusion: Our findings suggest that mobile HTS can identify early HIV infection, and show that a high proportion of clients with a POC test result linked to care. Future research should assess factors associated with POC test acceptance and assess the impact of POC CD4 testing in comparison to alternative strategies to engage HIV positive people in care.https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-020-08643-3Publisher's versio