A5069144137- Pneumonia and Respiratory Infections
- Pneumocystis jirovecii pneumonia detection and treatment
- SARS-CoV-2 and COVID-19 Research
- Respiratory viral infections research
- HIV Research and Treatment
- COVID-19 epidemiological studies
- COVID-19 Clinical Research Studies
- Vaccine Coverage and Hesitancy
- Viral Infections and Outbreaks Research
- Immune responses and vaccinations
- HIV-related health complications and treatments
- Tuberculosis Research and Epidemiology
- Immune Cell Function and Interaction
- Bacterial Infections and Vaccines
- Immunodeficiency and Autoimmune Disorders
- SARS-CoV-2 detection and testing
- Ethics in Clinical Research
- HIV/AIDS Research and Interventions
- Viral gastroenteritis research and epidemiology
- Immune cells in cancer
- COVID-19 Pandemic Impacts
- COVID-19 diagnosis using AI
- Vibrio bacteria research studies
- Salmonella and Campylobacter epidemiology
- Cardiovascular Disease and Adiposity
Liverpool School of Tropical Medicine
2015-2024
Malawi-Liverpool-Wellcome Trust Clinical Research Programme
2015-2024
University of Liverpool
2015-2024
Kamuzu University of Health Sciences
2021-2024
Queen Elizabeth Central Hospital
2008-2024
Kamuzu Central Hospital
2021-2024
University of Malawi
2011-2023
Public Health Institute of Malawi
2023
Leiden University Medical Center
2023
University of Edinburgh
2023
In this study, we detail a novel approach that combines bacterial fitness fluorescent reporter strains with scRNA-seq to simultaneously acquire the host transcriptome, surface marker expression, and phenotype for each infected cell. This facilitates dissection of functional heterogeneity M. tuberculosis–infected alveolar (AMs) interstitial macrophages (IMs) in vivo. We identify clusters pro-inflammatory AMs associated stressed bacteria, addition three different populations IMs heterogeneous...
In December 2019, a new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and associated disease, coronavirus disease 2019 (COVID-19), was identified in China. This virus spread quickly March, 2020, it declared pandemic. Scientists predicted the worst scenario to occur Africa since least developed of continents terms human development index, lagged behind others achievement United Nations sustainable goals (SDGs), has inadequate resources for provision social...
HIV-1-infected persons are at higher risk of lower respiratory tract infections than HIV-1-uninfected individuals. This suggests strongly that HIV-infected have specific impairment pulmonary immune responses, but current understanding how HIV alters immunity is incomplete. Alveolar macrophages (AMs), comprising small and large macrophages, major effectors innate in the lung. We postulated HIV-1 impairs through AM physiological functions. AMs were obtained by bronchoalveolar lavage from...
In low-income countries, like Malawi, important public health measures including social distancing or a lockdown have been challenging to implement owing socioeconomic constraints, leading predictions that the COVID-19 pandemic would progress rapidly. However, due limited capacity test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, there are no reliable estimates of true burden infection and death. We, therefore, conducted SARS-CoV-2 serosurvey amongst care...
The COVID-19 pandemic has profoundly impacted health systems globally and robust surveillance been critical for control, however not all countries can currently sustain community pathogen programs. Wastewater proven valuable in high-income settings, but less is known about the utility of water pathogens low-income countries. Here we show how wastewater SAR-CoV-2 be used to identify temporal changes help determine circulating variants quickly. In Malawi, a country with limited community-based...
Malawi experienced its deadliest Vibrio cholerae (Vc) outbreak following devastating cyclones, with >58,000 cases and >1700 deaths reported between March 2022 May 2023. Here, we use population genomics to investigate the attributes origin of 2022-2023 Vc isolates. Our results demonstrate predominance ST69 clone, also known as seventh cholera pandemic El Tor (7PET) lineage, expressing O1 Ogawa (~ 80%) serotype followed by Inaba 16%) sporadic non-O1/non-7PET serogroups 4%). Phylogenetic...
<h3>Rationale</h3> HIV-infected adults are at an increased risk of lower respiratory tract infections. HIV infection impairs systemic acquired immunity, but there is limited information in humans on HIV-related cell-mediated immune defects the lung. <h3>Objective</h3> To investigate antigen-specific CD4<sup>+</sup> T cell responses to influenza virus, <i>Streptococcus pneumoniae</i> and <i>Mycobacterium tuberculosis</i> antigens bronchoalveolar lavage (BAL) peripheral blood between...
Pneumococcal carriage is both immunising and a pre-requisite for mucosal systemic disease. Murine models of pneumococcal colonisation show that IL-17A-secreting CD4+ T-cells (Th-17 cells) are essential clearance pneumococci from the nasopharynx. Pneumococcal-responding have not been described in adult human lung it unknown whether they can be elicited by protect infection. We investigated direct effect experimental nasal (EHPC) on frequency phenotype cognate broncho-alveolar lavage blood...
Controlled human infection model (CHIM) studies have pivotal importance in vaccine development, being useful for proof of concept, pathogenesis, down-selection and immunogenicity studies. To date, however, they seldom been carried out low middle income countries (LMIC), which is where the greatest burden preventable illness found. This workshop discussed benefits barriers to CHIM Malawi. Benefits include improved effectiveness host country capacity development clinical, laboratory governance...
Long noncoding RNAs (lncRNAs) impart significant regulatory functions in a diverse array of biological pathways and manipulation these provides an important avenue to modulate such pathways, particularly disease. Our knowledge about lncRNAs' role determination cellular fate during HIV-1 infection remains sparse. Here, we have identified the impact lncRNA SAF regulating apoptotic effector caspases macrophages, long-lived reservoir HIV-1, that are largely immune virus-induced cell death....
<ns4:p><ns4:bold>Background</ns4:bold>: In low-income countries, like Malawi, important public health measures including social distancing or a lockdown have been challenging to implement owing socioeconomic constraints, leading predictions that the COVID-19 pandemic would progress rapidly. However, due limited capacity test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, there are no reliable estimates of true burden infection and death. We, therefore, conducted...
Abstract Background By August 2021, the COVID-19 pandemic has been less severe in sub-Saharan Africa than elsewhere. In Malawi, there have three subsequent epidemic waves. We therefore aimed to describe dynamics of SARS-CoV-2 exposure Malawi. Methods measured seroprevalence anti-SARS-CoV-2 antibodies amongst randomly selected blood transfusion donor sera Malawi from January 2020 July 2021 using a cross-sectional study design. subset, we also assessed vitro neutralisation against original...
Abstract Background Compared to the abundance of clinical and genomic information available on patients hospitalised with COVID-19 disease from high-income countries, there is a paucity data low-income countries. Our aim was explore relationship between viral lineage patient outcome. Methods We enrolled prospective observational cohort adult PCR-confirmed July 2020 March 2022 Blantyre, Malawi, covering four waves SARS-CoV-2 infections. Clinical diagnostic were collected using an adapted...
Infectious challenge of the human nasal mucosa elicits immune responses that determine fate host-bacterial interaction; leading either to clearance, colonisation and/or disease. Persistent antigenic exposure from pneumococcal can induce both humoral and cellular defences are protective against carriage We challenged healthy adults intra-nasally with live 23F or 6B Streptococcus pneumoniae in two sequential cohorts collected wash, bronchoalveolar lavage (BAL) blood before 6 weeks after...
In some instances, unsuppressed HIV has been associated with severe COVID-19 disease, but the mechanisms underpinning this susceptibility are still unclear. Here, we assessed impact of infection on quality and epitope specificity SARS-CoV-2 T cell responses in first wave second epidemic South Africa. Flow cytometry was used to measure following peripheral blood mononuclear stimulation peptide pools. Culture expansion determine immunodominance hierarchies assess potential escape from...
Abstract Background Binding and neutralising anti-Spike antibodies play a key role in immune defence against SARS-CoV-2 infection. Since it is known that wane with time new immune-evasive variants are emerging, we aimed to assess the dynamics of an African adult population prior infection determine effect subsequent COVID-19 vaccination. Methods Using prospective cohort design, recruited adults laboratory-confirmed mild/moderate Blantyre, Malawi, followed them up for 270 days ( n = 52). A...
<title>Abstract</title> <italic>Streptococcus pneumoniae</italic> can rapidly evolve within hosts through genetic mutations, recombination, and mobile elements, enabling adaptation to antibiotics immune pressures. Here, we detail a longitudinal phenotypic genomic analysis of pneumococcal serotype 3 prolonged carriage episode (> 335 days) in healthy HIV-uninfected adult Malawi. Whole Genome Sequencing (WGS) single-colony culture isolates confirmed persistent novel multidrug-resistant...
HIV-infected persons on antiretroviral therapy (ART) remain at higher risk of pulmonary tuberculosis (TB) than HIV-uninfected individuals. This increased susceptibility may be caused by impairment alveolar macrophage (AM) function and/or mycobacteria-specific CD4(+) T-cell responses observed in ART-naive adults.To determine whether ART was associated with improvement both AM function, assessed phagosomal proteolysis, and to Mycobacterium individuals.Peripheral blood drawn bronchoalveolar...
Rationale: Pneumococcal pneumonia remains a global health problem. Colonization of the nasopharynx with Streptococcus pneumoniae (Spn), although prerequisite infection, is main source exposure and immunological boosting in children adults. However, our knowledge how nasal colonization impacts on lung cells, especially predominant alveolar macrophage (AM) population, limited.Objectives: Using controlled human infection model to achieve 6B serotype, we investigated effect Spn cells.Methods: We...
<ns3:p><ns3:bold>Background</ns3:bold>: In low-income countries, like Malawi, important public health measures including social distancing or a lockdown have been challenging to implement owing socioeconomic constraints, leading predictions that the COVID-19 pandemic would progress rapidly. However, due limited capacity test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, there are no reliable estimates of true burden infection and death. We, therefore, conducted...