Neil McKerrow

Safety and efficacy of zinc supplementation for children with HIV-1 infection in South Africa: a randomised double-blind placebo-controlled trial

BACKGROUND Zinc deficiency is associated with impaired immune function and an increased risk of infection. Supplementation can decrease the incidence of diarrhoea and pneumonia in children in resource-poor countries. However, in children with HIV-1 infection, the safety of zinc supplementation is uncertain. We aimed to assess the role of zinc in HIV-1 replication before mass zinc supplementation is recommended in regions of high HIV-1 prevalence. METHODS We did a randomised double-blind placebo-controlled equivalence trial of zinc supplementation at Greys Hospital in Pietermaritzburg, South Africa. 96 children with HIV-1 infection were randomly assigned to receive 10 mg of elemental zinc as sulphate or placebo daily for 6 months. Baseline measurements of plasma HIV-1 viral load and the percentage of CD4+ T lymphocytes were established at two study visits before randomisation, and measurements were repeated 3, 6, and 9 months after the start of supplementation. The primary outcome measure was plasma HIV-1 viral load. Analysis was per protocol. FINDINGS The mean log(10) HIV-1 viral load was 5.4 (SD 0.61) for the placebo group and 5.4 (SD 0.66) for the zinc-supplemented group 6 months after supplementation began (difference 0.0002, 95% CI -0.27 to 0.27). 3 months after supplementation ended, the corresponding values were 5.5 (SD 0.77) and 5.4 (SD 0.61), a difference of 0.05 (-0.24 to 0.35). The mean percentage of CD4+ T lymphocytes and median haemoglobin concentrations were also similar between the two groups after zinc supplementation. Two deaths occurred in the zinc supplementation group and seven in the placebo group (p=0.1). Children given zinc supplementation were less likely to get watery diarrhoea than those given placebo. Watery diarrhoea was diagnosed at 30 (7.4%) of 407 clinic visits in the zinc-supplemented group versus 65 (14.5%) of 447 visits in the placebo group (p=0.001). INTERPRETATION Zinc supplementation of HIV-1-infected children does not result in an increase in plasma HIV-1 viral load and could reduce morbidity caused by diarrhoea. RELEVANCE TO PRACTICE Programmes to enhance zinc intake in deficient populations with a high prevalence of HIV-1 infection can be implemented without concern for adverse effects on HIV-1 replication. In view of the reductions in diarrhoea and pneumonia morbidity, zinc supplementation should be used as adjunct therapy for children with HIV-1 infection.

The influence of nutritional status on the response to HAART in HIV-infected children in South Africa.

Background: While the impact of HAART on growth in children is well established, the influence of prior nutritional status on the response to HAART is not well known. Methods: A retrospective study was conducted on 120 children in South Africa. Patients were divided into 3 groups (normal, moderately underweight, and severely underweight) based on weight-for-age z-scores (WAZ). Age, weight, height, CD4 cell percentage, and viral load were recorded at initiation of HAART and after 24 months of therapy. Data were analyzed using t-tests, χ2 tests, and one-way ANOVA. Results: At baseline, 58% of children were normal weight, 18% moderately underweight, and 23% severely underweight. After 24 months of HAART, WAZ improved significantly in moderately and severely underweight patient groups compared with the normal group. Height-for-age z-scores (HAZ) increased in all 3 groups with severely underweight children gaining more height than normal weight counterparts. Weight-for-height z-scores (WHZ) normalized in the severely underweight group. Mean CD4 cell percentages increased significantly in all 3 groups while viral loads decreased significantly in all groups with no differences among the groups at the end of 24 months of therapy. Of the entire cohort, 75% achieved undetectable HIV RNA viral loads. Conclusions: Underlying malnutrition does not adversely affect growth, immunologic or virologic response to HAART in HIV-infected children. Underweight children exhibit an equally robust response to treatment as their well-nourished peers.

Feasibility and effectiveness of early initiation of combination antiretroviral therapy in HIV-infected infants in a government clinic of Kwazulu-Natal, South Africa

A recent randomized trial showed dramatic improvement in survival of HIV-infected infants receiving early combination antiretroviral therapy (cART). However, few data are available for resource-limited settings. Therefore we conducted a chart review of HIV-infected infants initiated on cART between 2005 and 2008. Of 129 treated infants, 94 completed 6 months, 62 completed 12 months, and 39 completed 18 months of cART. Median age at initiation of cART was 8.6 months (range 2.1-11.9) and 77.2% had advanced disease. Undetectable VL was found in 78.8% of children who reached 18 months of treatment. CD4% increased from a median of 15.4% at baseline to 33.1% at 18 months. Weight for age Z-score increased from a mean ± SD of -2.7 ± 1.97 to 0.02 ± 1.10 at 18 months. Findings show favourable response to cART in HIV-infected infants outside a research environment, despite initial advanced disease. Efforts should be made to initiate cART as early as possible.

Profile of babies born before arrival at hospital in a peri-urban setting

Background . Babies born before arrival (BBAs) at hospital constitute a special group at risk of high morbidity and mortality. Objective. We conducted a 12-month retrospective review to describe maternal and neonatal characteristics of BBAs, and their outcomes compared with babies born in the state health sector. Methods. Using case-control sampling, all babies born outside a health facility and who presented to hospital within 24 hours of life were included and compared to the next in-hospital delivery occurring immediately after each BBA presented. Results. During the period reviewed, 135 BBAs (prevalence 1.8%) presented; 71% after hours with most deliveries occurring at home (73.8%). There was no birth attendant present at 70.5% of deliveries. Average birth weights were similar (2.86 kg in the BBA group, 95% confidence interval (CI) 2.73 - 2.95; 2.94 kg in the control group, 95% CI 2.78 - 3.02), but significantly more preterm babies were found in the BBA group (23% v. 9%, respectively; p <0.0001). Admitted BBAs had significantly lower average weights than those who were not admitted (2.19 kg v. 2.96 kg, respectively; p <0.0001). No significant differences were found when maternal age, parity, co-morbidities and distance from the hospital were compared. There were significantly more unbooked mothers in the BBA group (23.0% v. 6.7%, respectively; p <0.0001). Only 54.40% of the admitted BBAs’ mothers had booked antenatally, compared with 78.89% of mothers whose babies were discharged. Admission and complication rates were similar between the groups, but average length of stay was longer in admitted BBAs compared with controls. Conclusion. The prevalence of BBAs in this study is comparable to that in other developing countries, and is associated with poor antenatal attendance, prematurity, delay in presentation to hospital and lengthier hospital stays. These factors have implications for prehospital care of newborns and access to maternal and child healthcare in general

Current practices around HIV disclosure to children on highly active antiretroviral therapy

Background. The introduction of antiretroviral therapy (ART) for children has resulted in survival into adolescence. This is associated with the challenge of disclosing HIV status to infected children. Objectives. To establish whether HIV disclosure had occurred, the process of disclosure or reasons for non-disclosure, and the effect of disclosure on the child’s understanding of their disease and adherence. Methods. Interviews were conducted with the caregivers of 100 HIV-positive children, aged 8 - 14 years, who were on ART for >1 year to determine if disclosure had occurred. Where disclosure had occurred, these children were interviewed. Results. Disclosure had occurred in only 27 patients. The age and gender of the caregiver and their relationship to the child did not influence the likelihood of disclosure. The educational level of the caregiver and the number of admissions of the child were both associated with disclosure. Disclosure did not improve adherence, as reflected by an increased CD4 count or reduced viral load. Conclusion. HIV disclosure to children on ART remains less than optimal despite the presence of both national and international guidelines. Caregivers cited fear on the part of the child and fear of being blamed for their illness as the main reasons that they do not disclose. Of the children who knew their status, 76.9% had already suspected that they had HIV.

Baseline chest radiographic features of HIV-infected children eligible for antiretroviral therapy

BACKGROUND South Africas HIV mortality is primarily due to pulmonary disease. No evidence exists regarding the correlation between HIV-infected children and specific chest radiographic patterns and CD4 levels of immunity in HIV-infected adults. Objectives. We aimed to determine the prevalence of specific radiographic features in HIV-infected children initiating anti-retroviral therapy (ART) to develop a guideline of expected baseline radiographic appearances, and the radiographic features that predominate at specific levels of immune suppression (defined by CD4 percentage ranges), which would narrow the radiological differential diagnosis. METHOD Retrospective review of the baseline chest radiographs of 92 consecutive paediatric outpatients initiating ART. RESULTS Normal radiographs were reported in 54% of patients. Those with radiographic abnormalities had parenchymal disease (34%), mediastinal disease (22%) and pleural disease (1%). Parenchymal disease was predominantly air space (28%), and mediastinal disease was predominantly cardiomegaly (21%); lymphadenopathy was rare (1%). Radiological appearances of TB were seen in 9% of patients. A statistically significant association was shown between immune suppression and air space disease (p=0.046) with a relative risk of 0.46 (95% CI 0.24 - 0.88) for air space disease in immune-suppressed children. This association was independent of age. CONCLUSION Baseline chest radiographs in paediatric outpatients presenting for initiation of ART are predominantly normal, but also demonstrate a significant number of pathological radiological features - primarily air space disease and cardiomegaly. The only statistically significant association between radiographic features and immune suppression was air space disease, which correlated with a higher level of immunity.

Fatal Hepatitis B Infection Despite Immunization in an HIV-infected Infant: A Possible Case of Vaccine Failure and Immune Reconstitution Inflammatory Syndrome

We report a case of hepatitis B immune reconstitution inflammatory syndrome in an 8-month-old girl with Mycobacterium tuberculosis complex and human immunodeficiency virus (HIV) co-infection. In resource-constrained countries, HIV-hepatitis B co-infections are often difficult to diagnose and to treat. We highlight on the importance of hepatitis B and HIV screening in pregnant women, to implement efficient preventive measures.

A review of infant and young child feeding practice in hospital and the home in KwaZulu-Natal Midlands

Background: Malnutrition remains a major health burden globally. To date the focus in South Africa has been on exclusive breastfeeding from birth to 6 months, with less attention on feeding of the infants beyond 6 months. Objectives: To describe infant and young child feeding practices at home and in hospital in KwaZulu-Natal Midlands, South Africa, and determine if feeding practices conform to national feeding policies. No statistical correlation was done. Methodology: A descriptive study, using structured questionnaires for mothers of infants and young children up to the age of five years, and healthcare professionals in state hospitals, was conducted in 2011 in 12 hospitals in the KwaZulu-Natal Midlands, South Africa. Results: Seventy-six percent (76%) of infants were ever exclusively breastfed with just 36% being exclusively breastfed beyond three months. Complementary feeds were commenced in 84% of infants younger than 6 months of age. Age-specific meals were provided for children below 2 years (93%) and for participants above 2 years (78%). Approximately 61% of infants and children between 6 and 24 months received more than three cups of milk per day in hospital with only 26% of children between 2 to 5 years receiving any milk. Majority of children (48%) aged 2 to 5 years received only one snack per day, which is suboptimal. Conclusion: Feeding messages focus on breastfeeding. Breastfeeding rates have improved in this region since 2003, but exclusive breastfeeding is of limited duration. Early complementary feeding is a problem in the Midlands. This study has identified that age-specific feeding of infants and young children is not recognised in state hospitals, due to the inadequate frequency of feeding. There is a discrepancy between intention and practice among healthcare professionals in feeding infants and young children. Feeding messages have to expand beyond breastfeeding and complementary feeding, with ongoing training of healthcare professionals in this field.

Improving paediatric tuberculosis and HIV clinical record keeping: the use of audit and a structured pro forma in a South African regional level hospital

We report on the impact of revisions made to an existing pro forma facilitating routine assessment and the management of paediatric HIV and tuberculosis (TB) in KwaZulu-Natal, South Africa. An initial documentation audit in 2010 assessed 25 sets of case notes for the documentation of 16 select indicators based on national HIV and TB guidelines. Using the findings of this initial audit, the existing case note pro forma was revised. The introduction of the revised pro forma was accompanied by training and a similar repeat audit was undertaken in 2012. This demonstrated an overall improvement in documentation. The three indicators that improved most were documentation of maternal HIV status, child’s HIV status and child’s TB risk assessment (all P < 0.001). This study suggests that tailor-made documentation pro formas may have an important role to play in improving record keeping in low-resource settings.

Neonatal blood gas sampling methods

Blood gas sampling is part of everyday practice in the care of babies admitted to the neonatal intensive care unit, particularly for those receiving respiratory support. There is little published guidance that systematically evaluates the different methods of neonatal blood gas sampling, where each method has its individual benefits and risks. This review critically surveys the available evidence to generate a comparison between arterial and capillary blood gas sampling, focusing on their relative accuracy and complications, as well as briefly mentioning the management of such complications. This evidence-based summary and guidance should help inform best practice in the neonatal intensive care unit, and minimise the exposure of babies to unnecessary and potentially serious risk. The most accurate and non-invasive method of measuring oxygenation is oxygen saturation monitoring. Indwelling arterial catheters are a practical, reliable and accurate method of measuring acid-base parameters, provided they are inserted and maintained with the proper care. Capillary blood gas sampling is accurate, and a good substitute for radial ‘stab’ arterial puncture avoiding many of the complications of repeated arterial puncture.