High incidence of tuberculosis in young children living with HIV in the Western Cape, South Africa.

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.

Transition to dolutegravir-based ART in 35 low- and middle-income countries: a global survey of HIV care clinics.

Objective: We studied the transition to dolutegravir-containing antiretroviral therapy (ART) at HIV treatment clinics within the International epidemiology Databases to Evaluate AIDS (IeDEA).

Design: Site-level survey conducted in 2020-2021 among HIV clinics in low- and middle-income countries (LMICs).

Methods: We assessed the status of dolutegravir rollout and viral load and drug resistance testing practices for persons on ART switching to dolutegravir-based regimens.

Ceftazidime-Avibactam Treatment for Carbapenemase-Producing Enterobacterales in a South African Children's Hospital.

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.

Integration and validation of host transcript signatures, including a novel 3-transcript tuberculosis signature, to enable one-step multiclass diagnosis of childhood febrile disease.

Background: Whole blood host transcript signatures show great potential for diagnosis of infectious and inflammatory illness, with most published signatures performing binary classification tasks. Barriers to clinical implementation include validation studies, and development of strategies that enable simultaneous, multiclass diagnosis of febrile illness based on gene expression.

Methods: We validated five distinct diagnostic signatures for paediatric infectious diseases in parallel using a single NanoString nCounter® experiment.

The Retrospective Implementation of Standardized In Utero HIV Exposure Definitions Using Routinely Collected Public Sector Data Across the Western Cape Province, South Africa.

Using the Data Evaluation and Preparation for HIV-Exposed Uninfected Child Cohorts project's standardized child HIV exposure definitions, 64%, 64% and 90% of children exposed to HIV in utero could be classified as HIV-uninfected with moderate or high certainty at the ages of 1 and 3 years and at the time of first infectious disease hospitalization, respectively. These definitions can be applied retrospectively to routine datasets with linked mother-child data.

Correcting mortality estimates among children and youth on antiretroviral therapy in southern Africa: A comparative analysis between a multi-country tracing study and linkage to a health information exchange.

Objectives: The objective of this study is to assess the outcomes of children, adolescents and young adults with HIV reported as lost to follow-up, correct mortality estimates for children, adolescents and young adults with HIV for unascertained outcomes in those loss to follow-up (LTFU) based on tracing and linkage data separately using data from the International epidemiology Databases to Evaluate AIDS in Southern Africa.

Methods: We included data from two different populations of children, adolescents and young adults with HIV; (1) clinical data from children, adolescents and young adults with HIV aged ≤24 years from Lesotho, Malawi, Mozambique, Zambia and Zimbabwe; (2) clinical data from children, adolescents and young adults with HIV aged ≤14 years from the Western Cape (WC) in South Africa. Outcomes of patients lost to follow-up were available from (1) a tracing study and (2) linkage to a health information exchange.

Self-transfers, Hospital Admissions and Mortality Among Children and Adolescents Lost to Follow-up From Antiretroviral Therapy Programs in the Western Cape, South Africa Between 2004 and 2019: Linkage to Provincial Records.

Background: Pediatric programs face a high rate of loss to follow-up (LTFU) among children and adolescents living with HIV (CAHIV). We assessed true outcomes and predictors of these among CAHIV who were LTFU using linkage to the Western Cape Provincial Health Data Centre at Western Cape sites of the International epidemiology Databases to Evaluate AIDS-Southern Africa collaboration.

Methods: We examined factors associated with self-transfer, hospital admission and mortality using competing risks regression in a retrospective cohort of CAHIV initiating antiretroviral therapy <15 years old between 2004 and 2019 and deemed LTFU (no recorded visit at the original facility for ≥180 days from the last visit date before database closure and not known to have officially transferred out or deceased).

A descriptive study of vancomycin use at Red Cross War Memorial Children's Hospital, Cape Town.

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.

Change in HIV-related characteristics of children hospitalised with infectious diseases in Western Cape, South Africa, 2008-2021: a time trend analysis.

Introduction: With the scaling up of vertical HIV transmission prevention programmes, the HIV-related population profile of children in South Africa has shifted. We described temporal changes in HIV-related characteristics of children, aged ≤3 years (up to the third birthday), with infectious disease hospitalisations across the Western Cape province.

Methods: We used routinely collected electronic data to identify children born in the Western Cape with infectious disease hospital records for lower respiratory tract infections, diarrhoea, meningitis and tuberculous meningitis, from 2008 to 2021.

A rare mutation causing autosomal dominant STAT1 deficiency in a South African multiplex kindred with disseminated BCG infection.

Background: Autosomal dominant signal transducer and activator of transcription 1 (STAT1) deficiency, part of the Mendelian susceptibility to mycobacterial disease (MSMD) group, frequently causes disseminated Bacillus Calmette-Guérin (BCG) infections, but has not been reported from Sub-Saharan Africa (SSA) where routine birth BCG vaccination is practiced.

Case Presentation: Two half-siblings presented five years apart, with multifocal osteomyelitis as the dominant feature of disseminated BCG, which was successfully treated with antimycobacterial therapy. Whole exome sequencing demonstrated a novel heterozygous substitution in the splice site between intron 13 and exon 14 of the STAT1 gene, NM_007315: c.

An analysis of patterns of distribution of buprenorphine in the United States using ARCOS, Medicaid, and Medicare databases.

Opioid overdose remains a problem in the United States despite pharmacotherapies, such as buprenorphine, in the treatment of opioid use disorder. This study characterized changes in buprenorphine use. Using the Drug Enforcement Administration's ARCOS, Medicaid, and Medicare claims databases, patterns in buprenorphine usage in the United States from 2018 to 2020 were analyzed by examining percentage changes in total grams distributed and changes in grams per 100 K people in year-to-year usage based on ZIP code and state levels.

Genetically confirmed chronic granulomatous disease in a Kenyan child: case report.

Introduction: We report the first case of genetically confirmed chronic granulomatous disease (CGD) in a Kenyan child.

Clinical Findings: A 7-month-old male infant, the only child of non-consanguineous parents, presented with cough, fever, fast breathing, oral thrush, and axillary lymphadenopathy ipsilateral to the Calmette-Guérin bacillus scar. He had been hospitalized 5 weeks prior for severe pneumonia.

Abacavir safety and effectiveness in young infants with HIV in South African observational cohorts.

Background: WHO guidelines recommend abacavir in first-line antiretroviral treatment for children and neonates. However, there is no approved dose <3 months of age, and data in neonates are limited.

Methods: We included infants who initiated ART aged <3 months, between 2006 and 2019, in nine South African cohorts.

Comparison of paediatric infectious disease deaths in public sector health facilities using different data sources in the Western Cape, South Africa (2007-2021).

Background: Routinely collected population-wide health data are often used to understand mortality trends including child mortality, as these data are often available more readily or quickly and for lower geographic levels than population-wide mortality data. However, understanding the completeness and accuracy of routine health data sources is essential for their appropriate interpretation and use. This study aims to assess the accuracy of diagnostic coding for public sector in-facility childhood (age < 5 years) infectious disease deaths (lower respiratory tract infections [LRTI], diarrhoea, meningitis, and tuberculous meningitis [TBM]) in routine hospital information systems (RHIS) through comparison with causes of death identified in a child death audit system (Child Healthcare Problem Identification Programme [Child PIP]) and the vital registration system (Death Notification [DN] Surveillance) in the Western Cape, South Africa and to calculate admission mortality rates (number of deaths in admitted patients per 1000 live births) using the best available data from all sources.

Candida bloodstream infection among children hospitalised in three public-sector hospitals in the Metro West region of Cape Town, South Africa.

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.

Hospitalization among infants who initiate antiretroviral therapy before 3 months of age.

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.

Viral load testing among pregnant women living with HIV in Mutare district of Manicaland province, Zimbabwe.

Background: Viral load (VL) monitoring of pregnant women living with HIV (PWLHIV) and antiretroviral therapy (ART) may contribute to lowering the risk of vertical transmission of HIV. The aims of this study were to assess the uptake of HIV VL testing among PWLHIV at entry to the prevention-of-mother-to-child transmission (PMTCT) services and identify facilitatory factors and barriers to HIV VL access.

Methods: A retrospective, cross-sectional study was conducted at 15 health facilities in Mutare district, Manicaland Province, Zimbabwe from January to December 2018.

Balamuthia mandrillaris Granulomatous Amoebic Encephalitis: The First African Experience.

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.

Targeted Gene Sanger Sequencing Should Remain the First-Tier Genetic Test for Children Suspected to Have the Five Common X-Linked Inborn Errors of Immunity.

To address inborn errors of immunity (IEI) which were underdiagnosed in resource-limited regions, our centre developed and offered free genetic testing for the most common IEI by Sanger sequencing (SS) since 2001. With the establishment of The Asian Primary Immunodeficiency (APID) Network in 2009, the awareness and definitive diagnosis of IEI were further improved with collaboration among centres caring for IEI patients from East and Southeast Asia. We also started to use whole exome sequencing (WES) for undiagnosed cases and further extended our collaboration with centres from South Asia and Africa.

Xpert MTB/RIF Ultra and mycobacterial culture in routine clinical care at a paediatric hospital.

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.

Allergic manifestations of inborn errors of immunity and their impact on the diagnosis: A worldwide study.

Background: Allergies have long been observed in Inborn Errors of Immunity (IEI) and might even be the first presentation resulting in delayed diagnosis or misdiagnosis in some cases. However, data on the prevalence of allergic diseases among IEI patients are limited and contradictory.

Objective: To provide a worldwide view of allergic diseases, across a broad spectrum of IEI, and their impact on the timely diagnosis of IEI.

Treatment Response in Pediatric Pulmonary Tuberculosis-A Prospective Longitudinal Study.

Background: Data are limited on the resolution of symptoms and signs in children treated for pulmonary tuberculosis (PTB) and whether this resolution differs from children with other lower respiratory tract infections (LRTIs).

Methods: A prospective study of children ≤ 15 years presenting with features suggestive of PTB was performed. Clinical, microbiological, and radiological investigations were done at enrollment.

Post-Infectious Autoimmunity in the Central (CNS) and Peripheral (PNS) Nervous Systems: An African Perspective.

The direct impact and sequelae of infections in children and adults result in significant morbidity and mortality especially when they involve the central (CNS) or peripheral nervous system (PNS). The historical understanding of the pathophysiology has been mostly focused on the direct impact of the various pathogens through neural tissue invasion. However, with the better understanding of neuroimmunology, there is a rapidly growing realization of the contribution of the innate and adaptive host immune responses in the pathogenesis of many CNS and PNS diseases.

Using ceftazidime-avibactam for persistent carbapenem-resistant Serratia marcescens infection highlights antimicrobial stewardship challenges with new beta-lactam-inhibitor combination antibiotics.

The newer beta-lactam-inhibitor combination (BLIC) antibiotics are available in South Africa (SA) for the treatment of carbapenem-resistant Enterobacterales infections. We describe the successful use of ceftazidime-avibactam (CA) for the treatment of a child with persistent carbapenem-resistant Serratia marcescens bacteraemia, and the challenges faced using this lifesaving antibiotic, including access to susceptibility testing, procurement process, cost and complexity of deciding when, how and for how long to use it. Furthermore, the burden of carbapenem resistance is increasing in SA, and inappropriate use of CA and other newer BLIC antibiotics, such as ceftolozane-tazobactam, will inevitably endanger their longevity.