Bloodstream infections at a tertiary level paediatric hospital in South Africa

BACKGROUND: Bloodstream infection (BSI) in children causes significant morbidity and mortality. There are few studies describing the epidemiology of BSI in South African children. METHODS: A retrospective descriptive cohort study was conducted at a paediatric referral hospital in Cape Town, South Africa. The National Health Laboratory Service (NHLS) microbiology database was accessed to identify positive blood culture specimens during the period 2011-2012. Demographic and clinical details, antimicrobial management and patient outcome information were extracted from medical and laboratory records. Antibiotic susceptibility results of identified organisms were obtained from the NHLS database. RESULTS: Of the 693 unique bacterial and fungal BSI episodes identified during the study period, 248 (35.8%) were community-acquired (CA), 371 (53.5%) hospital-acquired (HA) and 74 (10.7%) healthcare-associated (HCA). The overall risk was 6.7 BSI episodes per 1000 admissions. Escherichia coli, Staphylococcus aureus and Streptococcus pneumoniae were the most frequent causes of CA-BSI and Klebsiella pneumoniae, Acinetobacter baumanii and S.aureus were most commonly isolated in HA-BSI. On multivariable analysis, severe underweight, severe anaemia at the time of BSI, admission in the ICU at the time of BSI, and requiring ICU admission after BSI was diagnosed were significantly associated with 14-day mortality. CONCLUSION: This study adds to the limited literature describing BSI in children in Africa. Further studies are required to understand the impact that BSI has on the paediatric population in sub-Saharan Africa

Guidelines for the management of HIV-infected children (National Department of Health, South Africa, 2005): A summary of antiretroviral treatment guidelines

National guidelines for the management of HIV-infected children in South Africa have been developed as a consensus document by practising HIV clinicians around the country. Guidelines for antiretroviral (ARV) management of children appear in a booklet distributed by the National Department of Health (DoH) since mid-2004 (National Antiretroviral Treatment Programme Guideline for Carers, National Department of Health, South Africa, 2004). A comprehensive booklet on management of HIV-infected children has also been produced for the DoH which includes recommendations on management with antiretroviral (ARV) therapy. The South African national paediatric guidelines are based on the recommendations provided by the World Health Organization (WHO) (Scaling up antiretroviral therapy in resource limited settings; treatment guidelines for a public health approach WHO 2003). It is important to note that WHO are updating their recommendations. Based on this some amendments, e.g. the staging system, have already been incorporated into the final version of the South African national guidelines. Other recommendations are more recent and have yet to undergo broader review. These have therefore not formed part of the printed version of the South African guidelines. It is anticipated that a process of updating the guidelines needs to be put in place urgently. The national guidelines are available on the government website (www.health.gov.za), and clinicians are advised to update themselves regularly at this website for any amendments that may be made to the guidelines

HIV-infected infants born to women who tested HIV-negative during pregnancy

The prevention of mother-to-child transmission (PMTCT) programme in the Western Cape is said to have achieved 100% coverage.1 This implies that all pregnant women who attend an antenatal health care facility in the public sector are offered voluntary counselling and testing (VCT). Uptake varies but has been reported to be as high as 90% in the Guguletu district.1 Currently, women who test HIV-positive qualify for the nevirapine-based PMTCT programme. Transmission rates below 10% have been achieved in some health districts (Médecins sans Frontières — unpublished research). Mothers of several perinatally infected infants recently diagnosed in our institution have indicated that they tested HIV-negative during their pregnancy. In some cases we have verified their statements with clinical and laboratory documentation. There is a need to determine the frequency of this phenonomen. Pregnant women are encouraged to book at their nearest antenatal clinic before 5 months’ gestation, although this frequently does not occur. We are concerned about women who do book early and test HIV-negative. Some may be in the ‘window period’ of the infection or become infected from a sexual partner during the latter stages of pregnancy. At present, there is no provision within the PMTCT programme for repeat HIV testing during pregnancy. Some women may, therefore, be denied the benefits of prevention measures including counselling on infant feeding options

Neurological and neurocognitive function of HIV-infected children commenced on antiretroviral therapy

Aim: To describe neurological and neurocognitive deficits in HIV-infected children and the short-term effect of highly active antiretroviral therapy (HAART) on the observed deficits. Methods: In this prospective study, 39 children (15 females) were evaluated before the start of HAART and 30 reassessed 6 months later. The subjects were evaluated with a range of cognitive tests used in everyday clinical practice. Results: At enrolment, the mean (±SD) age was 60±46 months, 17 (44%) and 22 (56%) had Centers for Disease Control (CDC) clinical category B and C disease respectively, and 36 (92%) had severe immunosuppression. At the start of HAART no child had cranial nerve or cerebellar dysfunction, but 13/29 (33.3%) had evidence of motor dysfunction. By 6 months 1 child had developed cerebellar dysfunction, but there was no statistically significant change in the frequency of motor dysfunction. Mean baseline performances on cognitive testing were generally subnormal. Between 33% and 81% of the children recorded subnormal intelligence quotients on various cognitive tests. Mean performances did not change significantly after 6 months of HAART. Conclusion: Neurological and neurocognitive deficits are frequent in HIV-infected children. The prevalence and extent of deficits did not change significantly in response to short-term HAART, indicating neither spontaneous improvement nor deterioration during early treatment

BCG Vaccination in HIV-Infected Children

Despite the use of Bacillus Calmette-Guérin (BCG) vaccination for many years, infants and young children exposed to adults with infectious forms of tuberculosis (TB) are at high risk of developing complicated TB disease. This risk is much higher among HIV-infected children, and data on BCG protective efficacy in HIV-infected children is lacking. Recent research on BCG safety in HIV-infected infants has resulted in policy shifts, but implementation is challenging. New approaches to preventing TB among infants and children, particularly HIV-infected infants, are needed. This paper briefly reviews BCG safety and efficacy considerations in HIV-infected infants and discusses other approaches to preventing TB, including new TB vaccines and vaccination strategies

X-linked Hyper IgM (HIGM1) in an African kindred: the first report from South Africa

BACKGROUND:The objective of this study was to describe the clinical and molecular features of the first South African family with X-linked hyper-IgM syndrome (HIGM1). METHODS: Diagnoses were based on immunoglobulin results and the absence of CD40 ligand (CD40L) expression on activated T-cells. Complete molecular characterisation involved CD40L cDNA sequencing, and genomic DNA analysis by polymerase chain reaction amplification, restriction enzyme digestion and sequencing. A PCR-based diagnostic assay was established for carrier detection and prenatal diagnosis in this family. RESULTS: There were originally six children, three males and three females. The eldest boy died after being diagnosed with hypogammaglobulinaemia, before HIGM1 was considered. This disorder was diagnosed in the second eldest boy at the age of 5 years, after failing to detect CD40L expression on his activated T-cells. A deficiency of CD40L was also confirmed in the youngest male at the age of 5 years. Both younger brothers have since died of infections relating to HIGM1. Molecular investigation showed that exon 3 was deleted from the CD40L mRNA of the affected males. Genomic DNA analysis identified a 1.5 kilobase deletion, spanning exon 3 and including extended flanking intronic sequence. Carrier status in the mother was confirmed by RT-PCR of her CD40L mRNA. Genetic analysis of the three female children was deferred because they were below the legal consenting age of 18 years. A PCR-based assay for genomic DNA was established for easy identification of female carriers and affected males in the future. CONCLUSIONS: This study confirmed the diagnosis of HIGM1 in the first South African family to be investigated and identified a novel mutation in the CD40L gene

Epidemiology of Staphylococcus aureus bacteraemia at a tertiary children's hospital in Cape Town, South Africa

BACKGROUND: Staphylococcus aureus is an important pathogen in paediatric patients with bloodstream infections. The epidemiology of S. aureus bacteraemia, however, has not been well documented in children in South Africa. METHODS: A retrospective study was conducted at a children's hospital in Cape Town, South Africa, to investigate the epidemiology of S. aureus bacteraemia from 2007-2011. The incidence, clinical presentation, risk factors, management and outcomes of methicillin sensitive S. aureus (MSSA) and methicillin resistant S. aureus (MRSA) bacteraemia were compared. RESULTS: Over the five year study period, 365 episodes of S. aureus bacteraemia were identified. The annual incidence was 3.28 cases per 1000 hospital admissions. MRSA was responsible for 26% of S. aureus bacteraemia and 72% of nosocomial infections. Only six possible cases of community-acquired MRSA infections were described. MSSA bacteraemia was more likely to present as pulmonary and bone or joint infections, while bacteraemia without a source was the most common presentation with MRSA.  Infants, children with malnutrition, and residents of long-term care facilities were at highest risk for MRSA bacteraemia. The overall case fatality rate for S. aureus bacteraemia was 8.8% over five years, with MRSA being the only significant risk factor for mortality. CONCLUSION: The incidence of S. aureus bacteraemia and MRSA bacteraemia in children has remained stable over the past five years. MRSA is a predominantly nosocomial pathogen in children with S. aureus bacteraemia in Cape Town, South Africa

The impact of HIV infection on the nervous system of children

At the end of 2007, 33.2 million people including 2.5 million children were living with HIV; > 85% of HIV-infected children were in Africa. At the end of 2006, 115 000 children were on HAART, a global coverage rate of 15% with sub-Saharan Africa having the lowest regional coverage. HIV affects the immature brain causing static or progressive encephalopathy (PE). PE is characterized by acquired microcephaly, failure to attain or loss of neurodevelopmental milestones, or loss of intellectual ability, and acquired symmetric motor defects. Isolated neurodevelopmental delays and peripheral nervous system disease occur as a direct consequence of HIV infection. Susceptibility to opportunistic infection (OI), due to systemic immunodeficiency, predisposes HIV-infected children to CNS infections including acute bacterial and tuberculous meningitis, CMV co-infection, EBV-associated primary lymphoma and in older children cryptococcal meningitis. HAART may induce an immune reconstitution inflammatory response to several microorganisms including mycobacterium tuberculosis and JC virus, causing CNS deterioration. Neurological manifestations occur in 20– 80% of HIV-infected children. Complex clinical presentations may be difficult to classify with the layering effect of multiple pathologies. There are limited descriptive studies from resource-constrained countries. In one hospitalbased, cross-sectional survey (n = 80, median age = 5.2 years), 60% had a variety of neurological and neurodevelopmental deficits. The neuropathogenesis of HIV encephalopathy is incompletely understood. Several pathogenic events are involved including (1) CNS invasion following receptor/ co-receptor-mediated HIV infection of monocytes/macrophages and CD4+ T-lymphocytes, (2) promotion of HIVinfected PBMC trafficking across the BBB by astrocytes and microglia (Trojan-horse effect), (3) neurotoxin elaboration induced by viral factors and inflammatory mediators, (4) CD4-independent astrocyte invasion by HIV, (4) neuronal death mediated through viral-induced chemokine receptor expression, and microglial/macrophagedependent and microglial-independent apoptotic death, and (5) inhibition of neural stem cell proliferation by viral gp120. Both direct and indirect mechanisms are involved in neuronal injury and death. Early initiation of HAART during infancy prevents the development of HIV encephalopathy, lowering the prevalence of progressive encephalopathy to < 2%. HAART reverses existing neurological abnormalities, although not completely, resulting in residual motor and cognitive sequelae (arrested PE) and consequent scholastic impairments. HAART also reduces the frequency of OIs and malignancy. In conclusion, HIV-associated nervous system disease remains highly prevalent in settings where treatment is sub-optimal. Implementation of HAART during infancy and additional prophylaxis against OIs such as