1. What is the underlying genetic epidemiology and evolution of key pathogens of importance to human health in Africa?
a. What is the genetic relatedness of pathogen isolates circulating in Malawi compared to isolates from other (African) countries?
b. How are vaccine and/or antibiotic use driving the evolution of key pathogens in Malawi?
2. How does genotype (human and pathogen) influence disease severity and susceptibility?
a. Can we identify virulence factors in the genomes of key pathogens circulating in Malawi?
b. Can we identify loci in the genomes of the host that associate with susceptibility to infection with key pathogens?
3. How are hospital acquired (nosocomial) infections impacting human health in Malawi?
a. Particular focus is applied to map ESKAPE pathogens in order to develop hospital interventions.
The aim of the Pathogen Biology group is to define how a pathogen interacts with its environment. A pathogens environment can refer to its niche neighbours, its host or its discrete population, whether in country, across a region, continent or even globally. Defining pathogen behavior in all of these contexts is key to identifying potential intervention and new diagnostic measures. 1. To maintain a robust surveillance platform/cohort for respiratory pathogens as a basis to inform the group’s key questions.
2. Undertake longitudinal genomic analyses across a range of major respiratory (SPN, GAS, Staph, Flu, RSV) and ESKAPE (Enterobacter cloacae, Staph aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aurogenosa and Enterococcus spp) pathogens to identify niche specific markers, host response markers and possible targets for intervention.
3. To develop a vibrant multinational bioinformatics group that can independently generate high quality pathogen analyses from patient to annotated genome in Malawi (H3BioNet)
a. Expand and increase on bioinformatics links and discuss developing analytic algorithms including machine-learning approaches with computer scientists for big data sets.
b. Investigate possibility of collaborating with modelers around respiratory pathogen data
4. Expand basic biological work in conjunction with Edinburgh particularly around CHIM study (Human challenge)
1. Pathogen Biology group is one of only three groups within Africa to have secured a $6 million CDC co-operative agreement to study the epidemiology of respiratory pathogens. Pathogen Biology group acts as the only low-income Africa country involved in this study
2. Reporting the population structure, antibiotic resistance, capsule switching and evolution of invasive pneumococci before conjugate vaccination in Malawi, which identified serotypes with potential to cause serotype replacement post-vaccination such as 12F (Chaguza et al. 2018)
3. Reporting the global distribution and diversity of protein vaccine candidate antigens in the highly virulent Steptococcus pneumoniae serotype 1, which highlighted the importance of importance of taking geographic differences into account when designing global vaccine interventions (Cornick et al. 2017)
4. Our Pneumococcal African Genomics (PAGe) paper published in the inaugural edition of Microbial Genomics, reported the genetic epidemiology of the highly invasive S. penumoniae serotype 1 globally and provided novel evidence that serotype 1 in Africa commonly recombines and acquires antibiotic resistance genes (Cornick et al., 2015).
5. Reporting the trends in bacterial meningitis in Malawi during the era of ART role out and in introduction of the HiB vaccine (Wall et al., 2014).