Common variable immunodeficiency disorders: What generalists should know.

Primary immune deficiency disorders (PIDDs) are common and underdiagnosed. Predominant antibody deficiencies (PADs) are the most common type of immune deficiency and comprise 55% of the immune deficiencies diagnosed.[1] Although immunoglobulin A (IgA) deficiency remains the most common type of PID, common variable immunodeficiency disorders remain the most common symptomatic PID for which medical therapy is sought.

Investigating lipid headgroup composition within epithelial membranes: a systematic review.

Membrane lipid composition is often quoted within the literature, but with very little insight into how or why these compositions vary when compared to other biological membranes. One prominent area that lacks understanding in terms of rationale for lipid variability is the human gastro-intestinal tract (GIT). We have carried out a comprehensive systematic literature search to ascertain the key lipid components of epithelial membranes, with a particular focus on addressing the human GIT and to use compositional data to understand structural aspects of biological membranes. Both bacterial outer membranes and the human erythrocyte membrane were used as a comparison for the mammalian [epithelial] membranes and to understand variations in lipid presence. We show that phosphatidylcholine (PC) lipid types tend to dominate (33%) with phosphatidylethanolamines (PE) and cholesterol having very similar abundances (25 and 23% respectively). This systematic review presents a detailed insight into lipid headgroup composition and roles in various membrane types, with a summary of the distinction between the major lipid bilayer forming lipids and how peripheral lipids regulate charge and fluidity. The variety of lipids present in biological membranes is discussed and rationalised in terms function as well as cellular position.

Parental access to hospitalised children during infectious disease pandemics such as COVID-19.

The COVID-19 pandemic has resulted in many hospitals severely limiting or denying parents access to their hospitalised children. This article provides guidance for hospital managers, healthcare staff, district-level managers and provincial managers on parental access to hospitalised children during a pandemic such as COVID-19. It: (i) summarises legal and ethical issues around parental visitation rights; (ii) highlights four guiding principles; (iii) provides 10 practical recommendations to facilitate safe parental access to hospitalised children; (iv) highlights additional considerations if the mother is COVID-19-positive; and (v) provides considerations for fathers. In summary, it is a child's right to have access to his or her parents during hospitalisation, and parents should have access to their hospitalised children; during an infectious disease pandemic such as COVID-19, there is a responsibility to ensure that parental visitation is implemented in a reasonable and safe manner. Separation should only occur in exceptional circumstances, e.g. if adequate in-hospital facilities do not exist to jointly accommodate the parent/caregiver and the newborn/infant/child. Both parents should be allowed access to hospitalised children, under strict infection prevention and control (IPC) measures and with implementation of non-pharmaceutical interventions (NPIs), including handwashing/sanitisation, face masks and physical distancing. Newborns/infants and their parents/caregivers have a reasonably high likelihood of having similar COVID-19 status, and should be managed as a dyad rather than as individuals. Every hospital should provide lodger/boarder facilities for mothers who are COVID-19-positive, COVID-19-negative or persons under investigation (PUI), separately, with stringent IPC measures and NPIs. If facilities are limited, breastfeeding mothers should be prioritised, in the following order: (i) COVID-19-negative; (ii) COVID-19 PUI; and (iii) COVID-19-positive. Breastfeeding, or breastmilk feeding, should be promoted, supported and protected, and skin-to-skin care of newborns with the mother/caregiver (with IPC measures) should be discussed and practised as far as possible. Surgical masks should be provided to all parents/caregivers and replaced daily throughout the hospital stay. Parents should be referred to social services and local community resources to ensure that multidisciplinary support is provided. Hospitals should develop individual-level policies and share these with staff and parents. Additionally, hospitals should ideally track the effect of parental visitation rights on hospital-based COVID-19 outbreaks, the mental health of hospitalised children, and their rate of recovery.

Transition from a uni- to a bimodal interfacial charge distribution in [Formula: see text]/[Formula: see text] upon cooling.

We present a combined resonant soft X-ray reflectivity and electric transport study of [Formula: see text]/[Formula: see text] field effect devices. The depth profiles with atomic layer resolution that are obtained from the resonant reflectivity reveal a pronounced temperature dependence of the two-dimensional electron liquid at the [Formula: see text]/[Formula: see text] interface. At room temperature the corresponding electrons are located close to the interface, extending down to 4 unit cells into the [Formula: see text] substrate. Upon cooling, however, these interface electrons assume a bimodal depth distribution: They spread out deeper into the [Formula: see text] and split into two distinct parts, namely one close to the interface with a thickness of about 4 unit cells and another centered around 9 unit cells from the interface. The results are consistent with theoretical predictions based on oxygen vacancies at the surface of the [Formula: see text] film and support the notion of a complex interplay between structural and electronic degrees of freedom.

Chronic rhinitis in South Africa - more than just allergy!

Chronic rhinitis is a troublesome condition for sufferers. It is tempting to label all patients with chronic nasal symptoms as having allergic rhinitis (AR), but many such patients have other causes of chronic rhinitis that need a specific diagnosis and management strategy. Even when the patient fully fits the definition of AR, their condition will be best served by combining medication with ongoing patient education.

Allergic sensitisation in South Africa: Exploring regional variation in sensitisation.

BACKGROUND: Allergy is a common health problem in South Africa (SA), and a rational approach to allergy testing is essential to ensure cost-effective as well as optimal patient diagnosis and management. OBJECTIVES: To review allergy testing data with respect to current national testing recommendations, and to explore the regional variations in sensitisation. METHODS: Retrospective data review on allergy testing from a private pathology provider in SA over a 2-year period. Data on skin-prick testing (SPT) and allergen-specific IgE testing originating from all the provinces of SA were collected and analysed with regards to allergen positivity rate and regional sensitisation patterns. RESULTS: Among the patients (N=45 0320) tested for a suspected inhalant allergy, 46% tested positive. Only 45% of these received additional testing for the nine recommended inhalant allergens included in the current national testing protocol. Among the patients (N=6 775) who received SPT for a suspected inhalant allergy, 59% yielded one or more positive results. The most frequent sensitising allergens were house dust mite (Dermatophagoides pteronyssinus) and grass pollen. The house dust mite, Blomia tropicalis, was a significant sensitiser in coastal regions. SPT identified two other important regional allergens which are not included in the current recommendations for inhalant allergen-specific IgE testing. CONCLUSIONS: The current diagnostic recommendations include allergens that demonstrate significant sensitisation in all regions of SA. Two additional allergens that show significant regional sensitisation in the South African population were identified. These findings may aid the recommendations for the most appropriate and cost-effective approach to allergy testing of symptomatic patients in SA.

COVID-19 in children: Should we be worried?

Reports indicate that children infected with SARS-CoV-2 have thus far presented with less severe disease than adults. Anxiety regarding a greater ability to transmit the virus is largely unfounded and has played a significant role in the decision to allow children to return to school. In some patients, however, especially in infants and in those with underlying comorbidities, severe disease must be anticipated and planned for accordingly. The most relevant severe clinical presentation in addition to the established respiratory complications, is that of a multisystem inflammatory disorder, with features resembling Kawasaki disease. The impact of the pandemic on the economic and social wellbeing of children, including food insecurity and care when parents are ill, cannot be ignored. During this pandemic, it is imperative to ensure access to routine and emergency medical services to sick children. In so doing, potentially devastating medical and socioeconomic consequences can be mitigated.

A case series and literature review on patients with rhinological complications secondary to the use of cocaine and levamisole.

BACKGROUND: Levamisole is an increasingly common cutting agent used with cocaine. Both cocaine and levamisole can have local and systemic effects on patients. METHODS: A retrospective case series was conducted of patients with a cocaine-induced midline destructive lesion or levamisole-induced vasculitis, who presented to a Dundee hospital or the practice of a single surgeon in Paisley, from April 2016 to April 2019. A literature review on the topic was also carried out. RESULTS: Nine patients from the two centres were identified. One patient appeared to have levamisole-induced vasculitis, with raised proteinase 3, perinuclear antineutrophil cytoplasmic antibodies positivity and arthralgia which improved on systemic steroids. The other eight patients had features of a cocaine-induced midline destructive lesion. CONCLUSION: As the use of cocaine increases, ENT surgeons will see more of the complications associated with it. This paper highlights some of the diagnostic issues and proposes a management strategy as a guide to this complex patient group. Often, multidisciplinary management is needed.

Diagnosis and management of community-acquired pneumonia in children: South African Thoracic Society guidelines.

BACKGROUND: Pneumonia remains a major cause of morbidity and mortality amongst South African children. More comprehensive immunisation regimens, strengthening of HIV programmes, improvement in socioeconomic conditions and new preventive strategies have impacted on the epidemiology of pneumonia. Furthermore, sensitive diagnostic tests and better sampling methods in young children improve aetiological diagnosis. OBJECTIVES: To produce revised guidelines for pneumonia in South African children under 5 years of age. METHODS: The Paediatric Assembly of the South African Thoracic Society and the National Institute for Communicable Diseases established seven expert subgroups to revise existing South African guidelines focusing on: (i) epidemiology; (ii) aetiology; (iii) diagnosis; (iv) antibiotic management and supportive therapy; (v) management in intensive care; (vi) prevention; and (vii) considerations in HIV-infected or HIVexposed, uninfected (HEU) children. Each subgroup reviewed the published evidence in their area; in the absence of evidence, expert opinion was accepted. Evidence was graded using the British Thoracic Society (BTS) grading system. Sections were synthesized into an overall guideline which underwent peer review and revision. RECOMMENDATIONS: Recommendations include a diagnostic approach, investigations, management and preventive strategies. Specific recommendations for HIV infected and HEU children are provided. VALIDATION: The guideline is based on available published evidence supplemented by the consensus opinion of SA paediatric experts. Recommendations are consistent with those in published international guidelines.

Primary immunodeficiency in Africa - a review.

BACKGROUND: Efforts have been made worldwide to improve awareness and treatment of primary immunodeficiency (PID). This has also gained momentum on the African continent albeit at a slower pace. Objective. This review reports on the current status of PID on the African continent regarding its prevalence, distribution, genetic mutations and challenges in diagnosis and treatment of affected patients. Method. We evaluated all studies published from the African continent in the field of PID dealing with prevalence, epidemiology, case reports and genetic findings. Results. The prevalence of PID on the African continent has been estimated to be as high as 902 631 individuals. PID still is mostly underdiagnosed in Africa and although progress has been made in parts of the continent many challenges still remain regarding awareness, diagnosis, registration and care of these patients. Conclusion. Given the unique genetic mutations reported in PID patients on the African continent and the feasibility of hematopoietic stem cell transplantation and gene therapy, increased awareness should be encouraged and new therapeutic options considered.

The impact of health programmes to prevent vertical transmission of HIV. Advances, emerging health challenges and research priorities for children exposed to or living with HIV: Perspectives from South Africa.

Over the past three decades, tremendous global progress in preventing and treating paediatric HIV infection has been achieved. This paper highlights the emerging health challenges of HIV-exposed uninfected (HEU) children and the ageing population of children living with HIV (CLHIV), summarises programmatic opportunities for care, and highlights currently conducted research and remaining research priorities in high HIV-prevalence settings such as South Africa. Emerging health challenges amongst HEU children and CLHIV include preterm delivery, suboptimal growth, neurodevelopmental delay, mental health challenges, infectious disease morbidity and mortality, and acute and chronic respiratory illnesses including tuberculosis, pneumonia, bronchiectasis and lymphocytic interstitial pneumonitis. CLHIV and HEU children require three different categories of care: (i) optimal routine child health services applicable to all children; (ii) routine care currently provided to all HEU children and CLHIV, such as HIV testing or viral load monitoring, respectively, and (iii) additional care for CLHIV and HEU children who may have growth, neurodevelopmental, behavioural, cognitive or other deficits such as chronic lung disease, and require varying degrees of specialised care. However, the translation thereof into practice has been hampered by various systemic challenges, including shortages of trained healthcare staff, suboptimal use of the patient-held child's Road to Health book for screening and referral purposes, inadequate numbers and distribution of therapeutic staff, and shortages of assistive/diagnostic devices, where required. Additionally, in low-middle-income high HIV-prevalence settings, there is a lack of evidence-based solutions/models of care to optimise health amongst HEU and CLHIV. Current research priorities include understanding the mechanisms of preterm birth in women living with HIV to optimise preventive interventions; establishing pregnancy pharmacovigilance systems to understand the short-, medium- and long-term impact of in utero ART and HIV exposure; understanding the role of preconception maternal ART on HEU child infectious morbidity and long-term growth and neurodevelopmental trajectories in HEU children and CLHIV, understanding mental health outcomes and support required in HEU children and CLHIV through childhood and adolescence; monitoring HEU child morbidity and mortality compared with HIV-unexposed children; monitoring outcomes of CLHIV who initiated ART very early in life, sometimes with suboptimal ART regimens owing to medication formulation and registration issues; and testing sustainable models of care for HEU children and CLHIV including later reproductive care and support.

Neonatal, infant and child health in South Africa: Reflecting on the past towards a better future.

Although the neonatal mortality rate in South Africa (SA) has remained stagnant at 12 deaths per 1 000 live births, the infant and under-5 mortality rates have significantly declined since peaking in 2003. Policy changes that have influenced this decline include policies to prevent vertical HIV transmission, earlier treatment of children living with HIV, expanded immunisation policies, strengthening breastfeeding practices, and health policies to contain tobacco and sugar use. The Sustainable Development Goals (2016 - 2030) have shifted the focus from keeping children alive, as expressed in the Millennium Development Goals (1990 - 2015), to achieving optimal health through the 'Survive, thrive and transform' global agenda. This paper focuses on important remaining causes of childhood mortality and morbidity in SA, specifically respiratory illness, environmental pollution, tuberculosis, malnutrition and vaccine-preventable conditions. The monitoring of maternal and child health (MCH) outcomes is crucial, and has improved in SA through both the District Health Information and Civil Registration and Vital Statistics systems, although gaps remain. Intermittent surveys and research augment the routinely collected data. However, availability and use of local data to inform quality and effectiveness of care is critical, and this requires ownership at the collection point to facilitate local redress. Potential game changers to improve MCH outcomes include mobile health and community-based interventions. In SA, improved MCH remains a crucial factor for human capital development. There is a pressing need to focus beyond childhood mortality and to ensure that each child thrives.

Management of paediatric asthma

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Primary immunodeficiency in Africa ­ a review

Background. Efforts have been made worldwide to improve awareness and treatment of primary immunodeficiency (PID). This has also gained momentum on the African continent albeit at a slower pace. Objective. This review reports on the current status of PID on the African continent regarding its prevalence, distribution, genetic mutations and challenges in diagnosis and treatment of affected patients. Method. We evaluated all studies published from the African continent in the field of PID dealing with prevalence, epidemiology, case reports and genetic findings. Results. The prevalence of PID on the African continent has been estimated to be as high as 902 631 individuals. PID still is mostly underdiagnosed in Africa and although progress has been made in parts of the continent manychallenges still remain regarding awareness, diagnosis, registration and care of these patients. Conclusion. Given the unique genetic mutations reported in PID patients on the African continent and the feasibility of hematopoietic stem cell transplantation and gene therapy, increased awareness should be encouraged and new therapeutic options considered

Ethical considerations in the application of cell and gene therapies in children.

Rapidly evolving fields such as cell and gene therapies that involve state-of-the-art technology hold out possibilities that may be ahead of what ethics, guidelines and the law have considered. This results in a regulatory lag. Furthermore, ethical and legal considerations are often debated in real time as issues pertaining to these technologies that were previously not considered begin to come to the fore. Finding the appropriate balance between facilitating potential therapeutic gains and ensuring the safety interests of recipients of the new treatments requires close attention, especially for minors. This vulnerable population frequently has off-label treatment prescribed on the basis of extrapolation of clinical trial data derived from adults, which is ethically and scientifically questionable. In this article we discuss how best to maintain ethical integrity while introducing innovative cell and gene therapies to minors. We advocate that clinical trials of promising innovative therapies should be designed so that testing in adults is followed as soon as possible by testing in minors, given the impressive gains that have recently been reported.

Cell and gene therapies at the forefront of innovative medical care: Implications for South Africa.

The fields of cell and gene therapy are moving rapidly towards providing innovative cures for incurable diseases. A current and highly topical example is immunotherapies involving T-cells that express chimeric antigen receptors (CAR T-cells), which have shown promise in the treatment of leukaemia and lymphoma. These new medicines are indicative of the changes we can anticipate in the practice of medicine in the near future. Despite their promise, they pose challenges for introduction into the healthcare sector in South Africa (SA), including: (i) that they are technologically demanding and their manufacture is resource intensive; (ii) that the regulatory system is underdeveloped and likely to be challenged by ethical, legal and social requirements that accompany these new therapies; and (iii) that costs are likely to be prohibitive, at least initially, and before economies of scale take effect. Investment should be made into finding novel and innovative ways to introduce these therapies into SA sooner rather than later to ensure that SA patients are not excluded from these exciting new opportunities.