Publications by authors named "James Nuttall"

Background: Data on tuberculosis (TB) incidence and risk factors among children living with HIV (CLHIV) in the universal ART era are limited.

Methods: We analysed routinely-collected data on TB diagnoses for CLHIV age ≤5 years, born 2018-2022, in the Westen Cape, South Africa. We examined factors associated with TB diagnosis, with death and loss to follow-up as competing events.

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This study describes ceftazidime-avibactam use in 17 young children from a resource-constrained country, where intra-abdominal infection was common. All-cause mortality was 53%. Earlier initiation, dose optimization, recording infusion times, and reviewing the need for additional antibiotics were identified as easy-to-implement-antimicrobial-stewardship interventions.

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Tuberculous meningitis (TBM) occurs when tuberculosis (TB) bacilli disseminate and seed into the meninges, triggering a severe inflammatory response that often leads to brain infarction. It is the most severe and debilitating form of childhood TB with high mortality, and children who survive TBM often suffer lifelong physical and neuro-disability resulting in emotional, social, and economic burdens for families. In the early stages the symptoms may be non-specific and so the diagnosis is often made late when the patient already has significant brain injury.

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Article Synopsis
  • - The study aimed to see if weekly vitamin D supplementation affects growth, body composition, pubertal development, or lung function in South African schoolchildren aged 6-11 years, through a rigorous 3-year double-blind trial.
  • - 1682 children participated, with one group receiving 10,000 IU of vitamin D weekly and a control group receiving a placebo, while growth and health measures were closely monitored.
  • - Results showed that while vitamin D levels increased significantly in the supplemented group, there were no meaningful changes in growth, body composition, or lung function compared to the placebo group.
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Article Synopsis
  • There is a lack of randomized controlled trials (RCTs) investigating the impact of vitamin D on bone mineral content (BMC) and fracture risk in Black African children, leading to this sub-study among 450 Cape Town schoolchildren aged 6-11.
  • The study found that after a 3-year vitamin D supplementation of 10,000 IU weekly, participants had higher serum vitamin D levels and lower parathyroid hormone (PTH) levels, but no significant differences in BMC or bone turnover markers between the vitamin D and placebo groups.
  • Fractures were infrequent in both the vitamin D and placebo groups, suggesting that while vitamin D supplementation improved some biochemical markers, it did not significantly affect bone density or
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Background: Antimicrobial stewardship principles guide the clinical use of antimicrobials, including vancomycin, but paediatric vancomycin prescribing practices have not been evaluated in South Africa.

Objectives: To document the use, prescribing practices and monitoring of intravenous vancomycin and the spectrum of bacteria isolated on microbiological culture in children treated with intravenous vancomycin during a 12-month period at Red Cross War Memorial Children's Hospital (RCWMCH).

Method: A retrospective audit of intravenous vancomycin use in children admitted to RCWMCH during 2019 was performed.

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Objectives: To determine whether weekly oral supplementation with 10,000 IU vitamin D for 3 years reduces the risk of sensitization to M. tuberculosis in South African schoolchildren aged 6-11 years with negative QuantiFERON-tuberculosis (TB) Gold Plus (QFT-Plus) assay results at baseline.

Methods: We conducted a phase 3 randomized placebo-controlled trial in 1682 children attending 23 primary schools in Cape Town.

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Background: Candida bloodstream infection (BSI) causes appreciable mortality in neonates and children. There are few studies describing the epidemiology of Candida BSI in children living in sub-Saharan Africa.

Methods: A retrospective descriptive study was conducted at three public sector hospitals in Cape Town, South Africa.

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Introduction: Studies examining hospitalization among infants with HIV in resource-limited settings, in the context of early infant diagnosis and early antiretroviral therapy (ART) initiation, are limited.

Methods: We used routinely collected data on infants who initiated ART aged <3 months (Western Cape province, South Africa; 2013-2017) to describe hospitalization from birth until 12 months post-ART initiation. Record reviews were additionally performed at three tertiary-level facilities.

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We report the first case of Balamuthia mandrillaris granulomatous amoebic encephalitis definitively acquired in Africa. Our case emphasizes initial nonspecific dermatological features, delays in confirmation of the diagnosis, difficulties accessing recommended medication, and uncertainty about optimal treatment of a disease with a frequently fatal outcome.

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The increased incidence and absence of antibiotic treatment options for New Delhi metallo-β-lactamase (NDM)-producing carbapenem-resistant Enterobacterales (CRE) infection are concerning. Recent reports have highlighted NDM-producing , as a specific concern, as it is an organism which is intrinsically resistant to colistin. In this study, a descriptive analysis of NDM-producing CRE infections was performed at the Red Cross War Memorial Children's Hospital.

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Background: Microbiological confirmation of pulmonary tuberculosis (PTB) in children is a well-documented challenge. This study evaluated Xpert Mycobacterium Tuberculosis (MTB)/Rifampicin (RIF) Ultra (Ultra) and mycobacterial cultures in routine clinical care at a tertiary paediatric hospital.

Methods: Children treated for PTB and who had at least one respiratory specimen investigated by Ultra and mycobacterial culture before tuberculosis (TB) treatment was commenced were included.

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Vitamin D deficiency (25-hydroxyvitamin D[25(OH)D] <50 nmol/L) is common among adults in Cape Town, South Africa, but studies investigating vitamin D status of children in this setting are lacking. We conducted a cross-sectional study to determine the prevalence and determinants of vitamin D deficiency in 1825 Cape Town schoolchildren aged 6−11 years. Prevalence of vitamin D deficiency was 7.

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Standard treatment guidelines (STGs) are an important tool for ensuring high quality clinical care and prudent antimicrobial use (AMU) and stewardship (AMS). In 2018, African Union (AU) member state representatives recognized the lack of STGs as a barrier to AMS at national and facility levels. Previous research reported that only 17 of 55 (31%) member states had STGs that provided disease- or pathogen-specific antimicrobial treatment recommendations, excluding those that covered only treatment of HIV, malaria, and tuberculosis).

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Antiretroviral treatment has undergone major changes in the last 20 years, from monotherapy, to dual therapy and finally to triple therapy. Lately, more focus has been placed on better, more well-tolerated combinations and formulations. As in most other disciplines in medicine, the development of paediatric HIV dosages and formulations always tends to lag behind adult research.

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Introduction: There are few studies describing colonisation with extended spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) and carbapenem-resistant Enterobacterales (CRE) among children in sub-Saharan Africa. Colonisation often precedes infection and multi-drug-resistant Enterobacterales are important causes of invasive infection.

Methods: In this prospective cross-sectional study, conducted between April and June 2017, 200 children in a tertiary academic hospital were screened by rectal swab for EBSL-PE and CRE.

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Background And Aim: Ostomy is a radical treatment that is sometimes required due to severe inflammatory bowel disease (IBD), colorectal cancer (CRC), and so on. Around 8000 people in New Zealand live with stoma bags. We studied factors associated with poor quality of life (QoL) in ostomy patients to improve patient care.

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Background: This study describes the disease burden, clinical characteristics, antibiotic management, impact of multidrug resistance and outcome of Pseudomonas aeruginosa bloodstream infection (PABSI) among children admitted to a tertiary referral hospital for children in Cape Town, South Africa.

Methods: A retrospective descriptive study was conducted at a paediatric referral hospital in Cape Town, South Africa. Demographic and clinical details, antibiotic management and patient outcome information were extracted from medical and laboratory records.

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A subset of peroxisomes is retained at the mother cell cortex by the Pex3-Inp1 complex. We identify Inp1 as the first known plasma membrane-peroxisome (PM-PER) tether by demonstrating that Inp1 meets the predefined criteria that a contact site tether protein must adhere to. We show that Inp1 is present in the correct subcellular location to interact with both the plasma membrane and peroxisomal membrane and has the structural and functional capacity to be a PM-PER tether.

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Introduction: There is very limited published experience with intravenous (IV) antituberculosis (anti-TB) and antiretroviral therapy (ART) especially in children. We have described a human immunodeficiency virus (HIV)-infected child with complicated abdominal tuberculosis who was initially treated with IV anti-TB and a partially IV ART regimen before transitioning to oral therapy.

Patient Presentation: A 3-year-old boy presented with hypovolaemic shock with a 3-day history of inability to pass stools, abdominal distension and bile-stained vomiting.

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Therapeutic antibodies are the fastest growing class of drugs in the treatment of cancer, and autoimmune and inflammatory diseases that require the concomitant development of assays to monitor therapeutic antibody levels. Here, we demonstrate that the use of Affimer nonantibody binding proteins provides an advantage over current antibody-based detection systems. For four therapeutic antibodies, we used phage display to isolate highly specific anti-idiotypic Affimer reagents, which selectively bind to the therapeutic antibody idiotype.

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Introduction: There are few studies describing Escherichia coli (E. coli) bloodstream infection (BSI) among children in Africa, yet E.coli is increasing in importance as a cause of antibiotic resistant infection in paediatric settings.

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Every year, about 1 million people living with HIV worldwide develop tuberculosis. Although the drug regimens used to treat tuberculosis in these patients are the same as those used in HIV-negative patients, cotreatment of tuberculosis with antiretroviral therapy involves challenges including the optimal timing of antiretroviral initiation, drug-drug interactions, drug tolerability, and the prevention and treatment of tuberculosis-associated immune reconstitution syndrome. Furthermore, mortality is high in people with HIV who are diagnosed with tuberculosis during a hospital admission, and in those with tuberculous meningitis.

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Background: Managing virologic failure (VF) in HIV-infected children is especially difficult in resource-limited settings, given limited availability of alternative drugs, concerns around adherence, and the development of HIV resistance mutations. We aimed to evaluate 4 management strategies for children following their first episode of VF by comparing their immunologic and virologic outcomes.

Methods: We included children (< 16 years of age) with VF from 8 International Epidemiologic Database to Evaluate AIDS Southern Africa cohorts, initiating combination antiretroviral therapy (cART) between 2004 and 2010, who followed one of the 4 management strategies: continuing on their failing regimen; switching to a second-line regimen; switching to a holding regimen (either lamivudine monotherapy or other non-cART regimen); discontinuing all ART.

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