Increased vulnerability of rural children on antiretroviral therapy attending public health facilities in South Africa: a retrospective cohort study

BACKGROUND: A large proportion of the 340,000 HIV-positive children in South Africa live in rural areas, yet there is little sub-Saharan data comparing rural paediatric antiretroviral therapy (ART) programme outcomes with urban facilities. We compared clinical, immunological and virological outcomes between children at seven rural and 37 urban facilities across four provinces in South Africa. METHODS: We conducted a retrospective cohort study of routine data of children enrolled on ART between November 2003 and March 2008 in three settings, namely: urban residence and facility attendance (urban group); rural residence and facility attendance (rural group); and rural residents attending urban facilities (rural/urban group). Outcome measures were: death, loss to follow up (LTFU), virological suppression, and changes in CD4 percentage and weight-for-age-z (WAZ) scores. Kaplan-Meier estimates, logrank tests, multivariable Cox regression and generalized estimating equation models were used to compare outcomes between groups. RESULTS: In total, 2332 ART-naive children were included, (1727, 228 and 377 children in the urban, rural and rural/urban groups, respectively). At presentation, rural group children were older (6.7 vs. 5.6 and 5.8 years), had lower CD4 cell percentages (10.0% vs. 12.8% and 12.7%), lower WAZ scores (-2.06 vs. -1.46 and -1.41) and higher proportions with severe underweight (26% vs.15% and 15%) compared with the urban and rural/urban groups, respectively. Mortality was significantly higher in the rural group and LTFU significantly increased in the rural/urban group. After 24 months of ART, mortality probabilities were 3.4% (CI: 2.4-4.8%), 7.7% (CI: 4.5-13.0%) and 3.1% (CI: 1.7-5.6%) p = 0.0137; LTFU probabilities were 11.5% (CI: 9.3-14.0%), 8.8% (CI: 4.5-16.9%) and 16.6% (CI: 12.4-22.6%), p = 0.0028 in the urban, rural and rural/urban groups, respectively. The rural group had an increased adjusted mortality probability, adjusted hazards ratio 2.41 (CI: 1.25-4.67) and the rural/urban group had an increased adjusted LTFU probability, aHR 2.85 (CI: 1.41-5.79). The rural/urban group had a decreased adjusted probability of virological suppression compared with the urban group at any timepoint on treatment, adjusted odds ratio 0.67 (CI: 0.48-0.93). CONCLUSIONS: Rural HIV-positive children are a vulnerable group, exhibiting delayed access to ART and an increased risk of poor outcomes while on ART. Expansion of rural paediatric ART programmes, with future research exploring improvements to rural health system effectiveness, is required

Investigation and management of primary immunodeficiency in South African children

The primary immunodeficiency diseases (PIDs) are inherited, non-communicable diseases that cause immunological dysfunction. PIDs are seldom reported in South Africa (SA). Based on a mid-2013 population estimate of 52.98 million and assuming that the prevalence of PIDs is similar to that in well-resourced settings, the total number of individuals with PIDs in our country should range between2 850 and 45 723. However, fewer than 500 cases of PID have been reported in SA. Between five and 15 new, fully characterised PIDs are reported annually. Our understanding of the physiology of the immune system has been substantially enhanced by these discoveries, and consequently the international classification of PIDs has been updated

Role of micronutrients in HIV infection

More than 60% of the estimated 40 million persons with HIV/AIDS worldwide live in sub-Saharan Africa, where poverty, social insecurity, food shortages and malnutrition are major problems.1 In children under the age of 5 years, who live in developing countries, malnutrition has been associated with 50% of the 10.8 million deaths mainly caused by neonatal disorders, diarrhoea, pneumonia, malaria and HIV/AIDS.2 Likewise micronutrient deficiencies are widespread and are associated with increased morbidity and mortality particularly in relation to infectious diseases.3 This review focuss on the interaction between micronutrients and HIV/AIDS and discusses recent research findings that may have important public health implications in terms of the case management of persons with HIV/AIDS Southern African Journal of HIV Medicine Vol. 6 (2) 2005: pp. 18-2

Associations between diurnal preference, sleep quality and externalizing behaviours: a behavioural genetic analysis

Background - Certain aspects of sleep co-occur with externalizing behaviours in youth, yet little is known about these associations in adults. The present study: (1) examines the associations between diurnal preference (morningness versus eveningness), sleep quality and externalizing behaviours; (2) explores the extent to which genetic and environmental influences are shared between or are unique to these phenotypes; (3) examines the extent to which genetic and environmental influences account for these associations. Method - Questionnaires assessing diurnal preference, sleep quality and externalizing behaviours were completed by 1556 young adult twins and siblings. Results - A preference for eveningness and poor sleep quality were associated with greater externalizing symptoms [r=0.28 (95% CI 0.23–0.33) and 0.34 (95% CI 0.28–0.39), respectively]. A total of 18% of the genetic influences on externalizing behaviours were shared with diurnal preference and sleep quality and an additional 14% were shared with sleep quality alone. Non-shared environmental influences common to the phenotypes were small (2%). The association between diurnal preference and externalizing behaviours was mostly explained by genetic influences [additive genetic influence (A)=80% (95% CI 0.56–1.01)], as was the association between sleep quality and externalizing behaviours [A=81% (95% CI 0.62–0.99)]. Non-shared environmental (E) influences accounted for the remaining variance for both associations [E=20% (95% CI −0.01 to 0.44) and 19% (95% CI 0.01–0.38), respectively]. Conclusions - A preference for eveningness and poor sleep quality are moderately associated with externalizing behaviours in young adults. There is a moderate amount of shared genetic influences between the phenotypes and genetic influences account for a large proportion of the association between sleep and externalizing behaviours. Further research could focus on identifying specific genetic polymorphisms common to both sleep and externalizing behaviours

Safety and immunogenicity of TetractHib (a vaccine combining DTP vaccine and Haemophilus influenza type b conjugate vaccine) administered to infants at 6, 10 and 14 weeks of age

The safety and immunogenicity of TETRActHIB (a vaccine combining diphtheria and tetanus toxoids-pertussis vaccine (DTP) with Haemophilus influenzae type b (Hib) conjugate vaccine (polyribosyl ribitol phosphate conjugated to tetanus protein) (PRP-T)) was assessed in 131 Cape Town infants immunised at 6, 10 and 14 weeks of age. Serological responses to all component antigens were measured before the first dose and at 18 weeks of age. In addition, anti-PRP antibodies were measured at 9 and 18 months of age to determine long-term immunogenicity. The vaccine was well tolerated by infants and no significant side-effects were reported. Responses to Hib at 18 weeks of age were good in that most infants achieved a level of anti-PRP antibodies <". 0.15 μg/ml, indicative of short-term protection, and 70% achieved a level<". 1 μg/ml, indicative of long-term protection. The proportions of children with protective levels<". 0.15 μg/ml and<". 1 μg/ml were similar at 9 and 18 months of age, i.e. approximately 75% and 45%, respectively. Responses to tetanus and diphtheria toxoids were excellent and all infants achieved protective serological levels. Responses to pertussis were moderate in that approximately 65% achieved 'protective' serum levels of pertussis agglutinins, i.e. titres <". 320. In conclusion, this study has shown that the DTP /PRP-T vaccine is safe, immunogenic and well tolerated in infants immunised at 6, 10 and 14 weeks of age. TETRActHIB is therefore suitable for inclusion in the World Health Organisation Expanded Programme on Immunisation (WHO EPI) schedule

Short-term outcomes of down-referral in provision of paediatric antiretroviral therapy at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa: A retrospective cohort study

Background. The large scale-up of paediatric HIV care necessitated down-referral of many children receiving antiretroviral therapy (ART) from Red Cross War Memorial Children’s Hospital (RCWMCH), Cape Town, South Africa. Few published data exist on the outcomes of these children.Objectives. To assess outcomes of children receiving ART in the first 12 months after down-referral to primary healthcare (PHC) clinics and identify determinants of successful down-referral.Methods. A retrospective cohort study of children <15 years of age who initiated ART at RCWMCH and were subsequently down-referred to one of two PHC clinics between January 2006 and December 2012 was completed. Baseline characteristics of patients and caregivers as well as CD4+ counts, viral loads (VLs) and weights were collected 6 and 12 months after down-referral. Outcomes included retention in care and viral suppression.Results. Of 116 children down-referred to the two study PHC clinics, 81.9% arrived at the designated PHC clinic and a further 8.6% continued care at other clinics, the remaining 9.5% being lost to follow-up. Of those successfully down-referred, 11.4% took >8 weeks to present, possibly experiencing treatment interruption. At 12 months after down-referral, only 81.0% remained in care. No factors were associated with retention in care in multivariable analysis. For children who remained in care at the designated PHC clinics, the clinical and immunological gains achieved prior to down-referral were sustained through 12 months of follow-up, and 54.7% of this cohort had documented viral suppression at 12 months. However, if only children with VL results are considered, 75.9% (41/54) were virally suppressed 12 months after down-referral.Conclusions. Down-referral of children on ART is complex, with risk of loss to follow-up and treatment interruption.

Outcomes of the South African National Antiretroviral Treatment Programme for children: The IeDEA Southern Africa collaboration

Objectives. To assess paediatric antiretroviral treatment (ART)outcomes and their associations from a collaborative cohortrepresenting 20% of the South African national treatment programme.Design and setting. Multi-cohort study of 7 public sectorpaediatric ART programmes in Gauteng, Western Cape andKwaZulu-Natal provinces. Subjects. ART-naive children (.16 years) who commenced treatment with .3 antiretroviral drugs before March 2008.Outcome measures. Time to death or loss to follow-up were assessed using the Kaplan-Meier method. Associations between baseline characteristics and mortality were assessed with Cox proportional hazards models stratified by site. Immune status, virological suppression and growth were described in relation to duration of ART.Results. The median (interquartile range) age of 6 078 childrenwith 9 368 child-years of follow-up was 43 (15 - 83) months, with 29% bein

Development of the arterial roots and ventricular outflow tracts

\ua9 2023 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.The separation of the outflow tract of the developing heart into the systemic and pulmonary arterial channels remains controversial and poorly understood. The definitive outflow tracts have three components. The developing outflow tract, in contrast, has usually been described in two parts. When the tract has exclusively myocardial walls, such bipartite description is justified, with an obvious dogleg bend separating proximal and distal components. With the addition of non-myocardial walls distally, it becomes possible to recognise three parts. The middle part, which initially still has myocardial walls, contains within its lumen a pair of intercalated valvar swellings. The swellings interdigitate with the distal ends of major outflow cushions, formed by the remodelling of cardiac jelly, to form the primordiums of the arterial roots. The proximal parts of the major cushions, occupying the proximal part of the outflow tract, which also has myocardial walls, themselves fuse and muscularise. The myocardial shelf thus formed remodels to become the free-standing subpulmonary infundibulum. Details of all these processes are currently lacking. In this account, we describe the anatomical changes seen during the overall remodelling. Our interpretations are based on the interrogation of serially sectioned histological and high-resolution episcopic microscopy datasets prepared from developing human and mouse embryos, with some of the datasets processed and reconstructed to reveal the specific nature of the tissues contributing to the separation of the outflow channels. Our findings confirm that the tripartite postnatal arrangement can be correlated with the changes occurring during development

A retrospective description of primary immuno­deficiency diseases at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa, 1975 - 2017

Background. The primary immunodeficiency diseases (PIDs) constitute a diverse and ever-expanding group of inborn errors affecting a wide range of immune functions. They are not well documented in sub-Saharan Africa.Objectives. To describe the spectrum of PIDs at a tertiary paediatric hospital.Methods. A retrospective descriptive study of PIDs diagnosed at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa (SA), between 1975 and 2017 was undertaken.Results. We identified 252 children with PIDs, spanning eight of the nine categories listed in the 2017 classification of the International Union of Immunological Societies. Predominantly antibody deficiencies, combined immunodeficiencies with associated syndromic features, and immunodeficiencies affecting cellular and humoral immunity accounted for most children with PIDs (n=199, 79.0%). The mean age (standard deviation) at diagnosis was 46 (50) months, and the male/female ratio was 1.5:1. There was a history of parental consanguinity in 3 cases (1.2%). Recurrent infection was the most prevalent presenting phenotype, manifesting in 177 patients (70.2%). Genetic or chromosomal confirmation was obtained in 42/252 cases (16.7%). Common interventions used to prevent infection were antimicrobial prophylaxis and immunoglobulin replacement therapy, administered to 95 (37.7%) and 93 (36.9%) of the patients, respectively. Six of 7 children who underwent haematopoietic stem cell transplantation (HSCT) had successful outcomes. The 7th patient died 2 months after HSCT from overwhelming infection. Although we could not account for the children lost to follow-up during the study period, 53 deaths were confirmed (21.0%).Conclusions. Several challenges exist in the recognition and treatment of children with PIDs in our setting. These include limited access to genetic diagnostics and HSCT. Suboptimal treatment options contribute to the overall mortality of PIDs in SA.

Unexplained HIV-1 infection in children — documenting cases and assessing for possible risk factors

Background. In the year 2000 we reported possible horizontal transmission of HIV-1 infection between two siblings. An investigation of three families, each with an HIV-infected child but seronegative parents, permitted this finding. Sexual abuse and surrogate breast-feeding were thought unlikely. The children had overlapping hospitalisation in a regional hospital. Since then several cases of unexplained HIV infection in children have been reported. A registry was established at Tygerberg Children’s Hospital for collection of data on the extent of horizontal or unexplained transmission of HIV in children. Study design. Retrospective chart review. Results. Fourteen children were identified, 12 from the Western Cape and 1 each from the Eastern Cape and KwaZulu-Natal. Thirteen (92%) had been hospitalised previously. In the Western Cape, children had been hospitalised in 8 hospitals. Ten of 13 (77%) were admitted as neonates and 9 of 13 (69%) had 2 or more admissions. Intravascular cannulation and intravenous drug administration occurred in all but 2 children before HIV diagnosis. Conclusion. We have confirmed HIV infection in a number of cases where the source of infection has been inadequately explained. Circumstantial evidence supports but does not prove nosocomial transmission. Further studies and identification of medical procedures conducive to the spread of HIV are urgently needed