Characterization of an IL-8 cleavage inhibition assay to determine the functionality of anti-SpyCEP antibodies in human sera.

Exposure to Group A Streptococcus leads to a broad spectrum of disease and sequelae, as the bacterium employs a wide range of virulence factors to facilitate colonization of the host, propagation and onward transmission, disrupting both innate and adaptive immune responses. The protease SpyCEP has a crucial role in contributing to bacterial immune evasion by impairing neutrophil recruitment and killing of bacteria through the cleavage of interleukin-8 (IL-8). Given this critical function, SpyCEP represents a key vaccine antigen and quantifying functional anti-SpyCEP antibodies represents not only an important marker of vaccine efficacy, but also a tool to dissect the natural immune response.

Molecular methods enhance the detection of pyoderma-related Streptococcus pyogenes and emm-type distribution in children.

Background: Streptococcus pyogenes-related skin infections are increasingly implicated in the development of rheumatic heart disease (RHD) in lower-resourced settings, where they are often associated with scabies. The true prevalence of S. pyogenes-related pyoderma may be underestimated by bacterial culture.

Streptococcus pyogenes carriage and infection within households in The Gambia: a longitudinal cohort study.

Background: Streptococcus pyogenes causes more than 500 000 deaths per year globally, which occur disproportionately in low-income and middle-income countries. The roles of S pyogenes skin and pharyngeal carriage in transmission are unclear. We aimed to investigate the clinical epidemiology and household transmission dynamics of both S pyogenes asymptomatic carriage and infection in a high-burden setting.

Health-seeking behaviour and beliefs around sore throat in The Gambia: A qualitative study.

Group A Streptococcus (Strep A) bacteria causes a broad spectrum of diseases. The most common manifestations of Strep A infection are sore throat and pus-producing skin infections such as impetigo. Complications of Strep A infection can lead to inflammation in the bones, muscles, joints, and internal organs causing acute rheumatic fever and rheumatic heart disease (RHD).

A flow cytometry-based assay to determine the ability of anti-Streptococcus pyogenes antibodies to mediate monocytic phagocytosis in human sera.

Streptococcus pyogenes, commonly referred to as Group A Streptococcus (Strep A), causes a spectrum of diseases, with the potential to progress into life-threatening illnesses and autoimmune complications. The escalating threat of antimicrobial resistance, stemming from the prevalent reliance on antibiotic therapies to manage Strep A infections, underscores the critical need for the development of disease control strategies centred around vaccination. Phagocytes play a critical role in controlling Strep A infections, and phagocytosis-replicating assays are essential for vaccine development.

Development and characterization of a hemolysis inhibition assay to determine functionality of anti-Streptolysin O antibodies in human sera.

The high burden of disease and the long-lasting sequelae following Streptococcus pyogenes (Strep A) infections make the development of an effective vaccine a global health priority. Streptolysin O (SLO), is a key toxin in the complex pathogenesis of Strep A infection. Antibodies are elicited against SLO after natural exposure and represent a key target for vaccine-induced immunity.

Streptococcus pyogenes Colonization in Children Aged 24-59 Months in the Gambia: Impact of Live Attenuated Influenza Vaccine and Associated Serological Responses.

Background: Immunity to Streptococcus pyogenes in high burden settings is poorly understood. We explored S. pyogenes nasopharyngeal colonization after intranasal live attenuated influenza vaccine (LAIV) among Gambian children aged 24-59 months, and resulting serological response to 7 antigens.

Development and Characterisation of a Four-Plex Assay to Measure Antigen-Specific IgG in Human Sera.

The measurement of antibodies to vaccine antigens is crucial for research towards a safe and effective vaccine for (Strep A). We describe the establishment and detailed characterisation of a four-plex assay to measure IgG to the Strep A vaccine antigens SpyCEP, Slo, SpyAD and GAC using the Luminex multiplex platform. A standard curve was established and characterized to allow the quantification of antigen-specific IgG.

Altered subgenomic RNA abundance provides unique insight into SARS-CoV-2 B.1.1.7/Alpha variant infections.

B.1.1.

Improving sepsis care in Africa: an opportunity for change?

Sepsis is common and represents a major public health burden with significant associated morbidity and mortality. However, despite substantial advances in sepsis recognition and management in well-resourced health systems, there remains a distinct lack of research into sepsis in Africa. The lack of evidence affects all levels of healthcare delivery from individual patient management to strategic planning at health-system level.

Impact of intra-partum azithromycin on carriage of group A streptococcus in the Gambia: a posthoc analysis of a double-blind randomized placebo-controlled trial.

Background: Group A Streptococcus (GAS) is a major human pathogen and an important cause of maternal and neonatal sepsis. Asymptomatic bacterial colonization is considered a necessary step towards sepsis. Intra-partum azithromycin may reduce GAS carriage.

Generation of a Novel SARS-CoV-2 Sub-genomic RNA Due to the R203K/G204R Variant in Nucleocapsid: Homologous Recombination has Potential to Change SARS-CoV-2 at Both Protein and RNA Level.

Background: Genetic variations across the SARS-CoV-2 genome may influence transmissibility of the virus and the host's anti-viral immune response, in turn affecting the frequency of variants over time. In this study, we examined the adjacent amino acid polymorphisms in the nucleocapsid (R203K/G204R) of SARS-CoV-2 that arose on the background of the spike D614G change and describe how strains harboring these changes became dominant circulating strains globally.

Methods: Deep-sequencing data of SARS-CoV-2 from public databases and from clinical samples were analyzed to identify and map genetic variants and sub-genomic RNA transcripts across the genome.

Generation of a novel SARS-CoV-2 sub-genomic RNA due to the R203K/G204R variant in nucleocapsid: homologous recombination has potential to change SARS-CoV-2 at both protein and RNA level.

Background: Genetic variations across the SARS-CoV-2 genome may influence transmissibility of the virus and the host’s anti-viral immune response, in turn affecting the frequency of variants over-time. In this study, we examined the adjacent amino acid polymorphisms in the nucleocapsid (R203K/G204R) of SARS-CoV-2 that arose on the background of the spike D614G change and describe how strains harboring these changes became dominant circulating strains globally.

Methods: Deep sequencing data of SARS-CoV-2 from public databases and from clinical samples were analyzed to identify and map genetic variants and sub-genomic RNA transcripts across the genome.

Subgenomic RNA identification in SARS-CoV-2 genomic sequencing data.

We have developed periscope, a tool for the detection and quantification of subgenomic RNA (sgRNA) in SARS-CoV-2 genomic sequence data. The translation of the SARS-CoV-2 RNA genome for most open reading frames (ORFs) occurs via RNA intermediates termed "subgenomic RNAs." sgRNAs are produced through discontinuous transcription, which relies on homology between transcription regulatory sequences (TRS-B) upstream of the ORF start codons and that of the TRS-L, which is located in the 5' UTR.

Diagnostic point-of-care ultrasound in medical inpatients at Queen Elizabeth Central Hospital, Malawi: an observational study of practice and evaluation of implementation.

Background: In less well-resourced settings, where access to radiology services is limited, point-of-care ultrasound (POCUS) can be used to assess patients and guide clinical management. The aim of this study was to describe ultrasound practice in the assessment of medical inpatients at Queen Elizabeth Central Hospital, Blantyre, Malawi, and evaluate uptake and impact of POCUS following the introduction of a training programme at the college of Medicine, Blantyre, Malawi.

Methods: : A weekly prospective record review of sequential adult medical inpatients who had received an ultrasound examination was conducted.

Anakinra in the treatment of protracted paradoxical inflammatory reactions in HIV-associated tuberculosis in the United Kingdom: a report of two cases.

Paradoxical reactions, including immune reconstitution inflammatory syndrome (IRIS), are common in patients co-infected with human immunodeficiency virus (HIV) and tuberculosis (TB). Paradoxical reactions may confer substantial morbidity and mortality, especially in cases of central nervous system (CNS) TB, or through protracted usage of corticosteroids. No high-quality evidence is available to guide management in this scenario.

Roll-out of SARS-CoV-2 testing for healthcare workers at a large NHS Foundation Trust in the United Kingdom, March 2020.

Healthcare workers (HCW) are potentially at increased risk of infection with coronavirus disease (COVID-19) and may transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to vulnerable patients. We present results from staff testing at Sheffield Teaching Hospitals NHS Foundation Trust, United Kingdom. Between 16 and 29 March 2020, 1,533 symptomatic HCW were tested, of whom 282 (18%) were positive for SARS-CoV-2.

Successful conservative management of a permanent pacemaker pocket infection: a less invasive approach.

We present a successful conservative management strategy for a frail elderly patient with a cardiac resynchronisation pacemaker who presented with evidence of an pacemaker pocket infection. A device washout and debridement procedure was performed, with reburial of the device in a new prepectoral pocket and creation of a closed-loop continuous antibiotic infusion into the infected pacemaker pocket. This was followed by a 6-week course of ambulatory intravenous antibiotic therapy.

: A healthcare-associated infection of unknown significance in adults in sub-Saharan Africa.

Background: infection (CDI) causes a high burden of disease in high-resource healthcare systems, with significant morbidity, mortality, and financial implications. CDI is a healthcare-associated infection for which the primary risk factor is antibiotic usage, and it is the leading cause of bacterial diarrhoea in HIV-infected patients in the United States. Little is known about the disease burden of CDI in sub-Saharan Africa, where HIV and healthcare-associated infections are more prevalent and antibiotic usage is less restricted.