Use of antiretrovirals in HIV-infected children in a tuberculosis prevention trial: IMPAACT P1041.

Setting: International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1041, a tuberculosis (TB) prevention trial conducted among children enrolled from 2004 to 2008 during South Africa's roll-out of combination antiretroviral therapy (ART).

Objective: To estimate TB incidence and mortality and the effect of ART.

Design: Children were pre-screened to exclude TB disease and exposure, actively screened 3-monthly for TB exposure and symptoms, and provided post-exposure isoniazid prophylaxis therapy (IPT).

Surveillance of healthcare-associated infection in hospitalised South African children: Which method performs best?

Background: In 2012, the South African (SA) National Department of Health mandated surveillance of healthcare-associated infection (HAI), but made no recommendations of appropriate surveillance methods.

Methods: Prospective clinical HAI surveillance (the reference method) was conducted at Tygerberg Children's Hospital, Cape Town, from 1 May to 31 October 2015. Performance of three surveillance methods (point prevalence surveys (PPSs), laboratory surveillance and tracking of antimicrobial prescriptions) was compared with the reference method using surveillance evaluation guidelines.

A Prospective Cohort Study of Common Childhood Infections in South African HIV-exposed Uninfected and HIV-unexposed Infants.

Background: Much evidence of HIV-exposed uninfected (HEU) infant infectious morbidity predates availability of maternal combination antiretroviral therapy and does not control for universal risk factors (preterm birth, low birth weight, suboptimal breastfeeding and poverty).

Methods: This prospective cohort study identified HIV-infected and HIV-uninfected mothers and their newborns from South African community midwife unit. The primary outcome, infectious cause hospitalization or death before 6 months of age, was compared between HEU and HIV-unexposed (HU) infants and classified for type and severity using validated study-specific case definitions.

Antiretroviral Treatment Initiated in the First Month of Life.

Background: Earlier diagnosis of HIV-infected infants facilitates earlier access to therapy and improved clinical outcomes. The aim of this study was to describe the management of infants who started antiretroviral therapy (ART) in the first month of life.

Methods: A retrospective review was performed on HIV-infected neonates who started ART within the first month of life between January 2013 and March 2015.

Safety and Immunogenicity of the Recombinant Mycobacterium bovis BCG Vaccine VPM1002 in HIV-Unexposed Newborn Infants in South Africa.

Tuberculosis is a global threat to which infants are especially vulnerable. Effective vaccines are required to protect infants from this devastating disease. VPM1002, a novel recombinant Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine previously shown to be safe and immunogenic in adults, was evaluated for safety in its intended target population, namely, newborn infants in a region with high prevalence of tuberculosis.

Genetic interrogation of circulating multiple myeloma cells at single-cell resolution.

Multiple myeloma (MM) remains an incurable disease, with a treatment-refractory state eventually developing in all patients. Constant clonal evolution and genetic heterogeneity of MM are a likely explanation for the emergence of drug-resistant disease. Monitoring of MM genomic evolution on therapy by serial bone marrow biopsy is unfortunately impractical because it involves an invasive and painful procedure.

Burden, spectrum, and impact of healthcare-associated infection at a South African children's hospital.

Background: In most African countries the prevalence and effects of paediatric healthcare-associated infection (HCAI) and human immunodeficiency virus (HIV) infection are unknown.

Aim: To investigate the burden, spectrum, risk factors, and impact of paediatric HCAI by prospective clinical surveillance at a South African referral hospital.

Methods: Continuous prospective clinical and laboratory HCAI surveillance using Centers for Disease Control and Prevention (CDC)/National Healthcare Safety Network (NHSN) definitions was conducted at Tygerberg Children's Hospital, South Africa, from May 1 to October 31 in 2014 and 2015.

Assessment of terminal cleaning in pediatric isolation rooms: Options for low-resource settings.

Background: Few studies have evaluated terminal cleaning in low-resource settings.

Methods: Adequacy of pediatric isolation room terminal cleaning was evaluated using quantitative bacterial surface cultures, ATP bioluminescence assays, and fluorescent high-touch surface markers at Tygerberg Children's Hospital in South Africa (August 1, 2014-October 31, 2015). Cleaning adequacy was assessed by comparing pre- and postcleaning measurements.

Early Antiretroviral Therapy in HIV-Infected Children Is Associated with Diffuse White Matter Structural Abnormality and Corpus Callosum Sparing.

Background And Purpose: Fractional anisotropy in the frontal white matter, corpus callosum, and internal capsule is abnormal in human immunodeficiency virus-positive (HIV+) adults. We describe the distribution and nature of white matter abnormalities in a cohort of children who started antiretroviral therapy within the first year of life and the benefit of early treatment by using DTI measures (fractional anisotropy and mean, axial, and radial diffusion).

Materials And Methods: DTI was performed on children in a neurodevelopmental substudy from the Children with HIV Early Antiretroviral trial.

Sacrifice, the Bush Way: From Self to Others.

The Walker Bush dynasty has marked the last American century, promoting "corporate democracy" as a means to expand its wealth. As 43rd President of the United States, George Walker Bush's biography illustrates how the members of our powerful elite sacrifice the inner self of their own children for the sake of political success. In his case, the childrearing violence and emotional neglect he experienced created the psychological basis for his later re-enactments as commander-in-chief in the wake of 9/11.

Nevirapine- Versus Lopinavir/Ritonavir-Based Antiretroviral Therapy in HIV-Infected Infants and Young Children: Long-term Follow-up of the IMPAACT P1060 Randomized Trial.

Background: The International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) P1060 study demonstrated short-term superiority of lopinavir/ritonavir (LPV/r) over nevirapine (NVP) in antiretroviral therapy (ART), regardless of prior NVP exposure. However, NVP-based ART had a marginal benefit in CD4 percentage (CD4%) and growth. We compared 5-year outcomes from this clinical trial.

Source case identification in HIV-exposed infants and tuberculosis diagnosis in an isoniazid prevention study.

Background: Identifying source cases of children exposed to tuberculosis (TB) is challenging. We examined the time-point of obtaining contact information of TB source cases in human immunodeficiency virus (HIV) infected and HIV-exposed uninfected (HEU) children in a randomised, placebo-controlled trial of pre-exposure to isoniazid prophylaxis.

Methods: A total of 543 HIV-infected and 808 HEU infants without TB exposure aged 3-4 months were enrolled between 2004 and 2008.

Pattern of Infectious Morbidity in HIV-Exposed Uninfected Infants and Children.

Background: Almost 30% of children in Southern Africa are HIV exposed but uninfected (HEU) and experience exposures that could increase vulnerability to infectious diseases compared to HIV unexposed (HU) children. The mechanisms of HEU infant vulnerability remain ill-defined. This review seeks to appraise the existing clinical evidence of the pattern of HEU infant infectious morbidity to aid understanding of the potential mechanism of susceptibility.

Acceptability and feasibility of mHealth and community-based directly observed antiretroviral therapy to prevent mother-to-child HIV transmission in South African pregnant women under Option B+: an exploratory study.

Objective: To examine the acceptability and feasibility of mobile health (mHealth)/short message service (SMS) and community-based directly observed antiretroviral therapy (cDOT) as interventions to improve antiretroviral therapy (ART) adherence for preventing mother-to-child human immunodeficiency virus (HIV) transmission (PMTCT).

Design And Methods: A mixed-method approach was used. Two qualitative focus group discussions with HIV-infected pregnant women (n=20) examined the acceptability and feasibility of two ART adherence interventions for PMTCT: 1) SMS text messaging and 2) patient-nominated cDOT supporters.

Feeding practices and nutritional status of HIV-exposed and HIV-unexposed infants in the Western Cape.

Background: Optimal infant- and young child-feeding practices are crucial for nutritional status, growth, development, health and, ultimately, survival. Human breast milk is optimal nutrition for all infants. Complementary food introduced at the correct age is part of optimal feeding practices.

Delayed BCG immunization does not alter antibody responses to EPI vaccines in HIV-exposed and -unexposed South African infants.

Background: Bacille Calmette-Guérin (BCG) is routinely given at birth in tuberculosis-endemic settings due to its protective effect against disseminated tuberculosis in infants. BCG is however contraindicated in HIV-infected infants. We investigated whether delaying BCG vaccination to 14 weeks of age affected vaccine-induced antibody responses to Haemophilus influenzae type b (Hib)-conjugate, pertussis, tetanus and Hepatitis B (HBV) vaccines, in HIV-exposed uninfected (HEU) and -unexposed uninfected (HUU) infants.

HIV-associated CD4+/CD8+ depletion in infancy is associated with neurometabolic reductions in the basal ganglia at age 5 years despite early antiretroviral therapy.

Objective: Investigating consequences of early or late antiretroviral therapy (ART) initiation in infancy on young brain development using magnetic resonance spectroscopy.

Design: Most pediatric HIV/ART-related neurological studies are from neuropsychological/clinical perspectives. Magnetic resonance spectroscopy can elucidate the mechanisms underpinning neurocognitive outcomes by quantifying the brain's chemical condition through localized metabolism to provide insights into health and development.

The Effect of Deworming on Tests of Tuberculosis Infection in Children With Recent Tuberculosis Exposure: A Randomized Controlled Trial.

Background: Helminth infestations are associated with T-helper cell type 2 (Th2) immune responses, leading to suppression of Th1 responses required to control Mycobacterium tuberculosis infection. We hypothesized that deworming after documented M. tuberculosis exposure might improve Th1 immune responses.

Low Vitamin-D Levels Combined with PKP3-SIGIRR-TMEM16J Host Variants Is Associated with Tuberculosis and Death in HIV-Infected and -Exposed Infants.

Background: This study examined the associations of 25-hydroxyvitamin D and specific host genetic variants that affect vitamin D levels or its effects on immune function, with the risk of TB or mortality in children.

Methods: A case-cohort sample of 466 South African infants enrolled in P1041 trial (NCT00080119) underwent 25-hydroxyvitamin D testing by chemiluminescent immunoassay. Single nucleotide polymorphisms (SNPs) that alter the effect of vitamin D [e.

An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma.

Translocation events are frequent in cancer and may create chimeric fusions or 'regulatory rearrangements' that drive oncogene overexpression. Here we identify super-enhancer translocations that drive overexpression of the oncogenic transcription factor MYB as a recurrent theme in adenoid cystic carcinoma (ACC). Whole-genome sequencing data and chromatin maps highlight distinct chromosomal rearrangements that juxtapose super-enhancers to the MYB locus.