Quantifying hospital-community transmission of extended spectrum beta-lactamase producing Enterobacteriaceae in sub-Saharan Africa

Extended spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) pose a major threat to health, especially in settings where third-generation cephalosporins are the antibiotics of first choice. ESBL-E infections are often untreatable by available antibiotics in Low Income Countries such as those in sub-Saharan Africa (SSA), where Watch and Reserve antibiotics are infrequently available, resulting in prolonged illnesses and high mortality.

ESBL-Infections are often preceded by ESBL-E carriage, which has been shown to be highly prevalent in both community and hospital settings in SSA. Evidence of hospital-community transmission of ESBL-E is emerging. In Vietnam, was recently identified community as significant source of ESBL producing Klebsiella pneumoniae carriage among hospitalised patients in two major referral hospitals, which apart from geographical proximity, shared nothing in common. In Malawi, we previously described phylogenetic inter-clustering of hospital-associated carriage and community-associated invasive isolates of both Escherichia coli and K. pneumoniae, suggesting hospital-community transmission.

The LSTM/Malawi-Liverpool Wellcome Trust Clinical Research Programme and the Wellcome Sanger Institute have sequenced large collections of ESBL producing Enterobacteriaceae collected in community settings, including from humans, animals and other ecological niches; and a collection of both invasive and carriage samples from hospitalised patients. These data have been collected at multiple sites in Malawi and Uganda, and for some individual participants and households, longitudinally, offering the opportunity for detailed study of temporal evolutionary and epidemiological dynamics of ESBL-E. This project will focus on developing mathematical and bioinformatics tools to integrate and analyse these complex data sets to quantify the transmission of ESBL-E between community and hospital settings in Uganda and Malawi.

Where does the project lie on the Translational Pathway?

T1 – Basic Research, T2 – Human/Clinical Research, T3 – Evidence into Practice, T4 – Practice to Policy/Population

Expected Outputs

Expected outputs from this study will include publications and tools/methods that combine genomic and epidemiologic data to infer transmission and policy briefs to Ministry of Health Technical Working Groups in Uganda and Malawi.

Training Opportunities

The student will be trained in microbial genomics and bioinformatics at LSTM, and infectious disease modelling at CHICAS, Lancaster University. There will be opportunities for further training in genomics and bioinformatics and access to computational resources at the Sanger Institute, with whom we have strong collaborations.

Skills Required

We are looking for candidates with a background in mathematics, statistics, or computer science, with experience of computational biology.  Additionally, they should have an interest in, and aptitude for, infectious disease modelling and bioinformatics.

Key Publications associated with this project

Pham MH, Beale MA, Khokhar F, Hoa NT, Musicha P, Blackwell G, Long HB, Huong DT, Binh NG, Giang T, Bui C. Evidence of widespread endemic populations of highly multidrug-resistant Klebsiella pneumoniae seen concurrently through the lens of two hospital intensive care units in Vietnam. medRxiv. 2021

Lewis JM, Mphasa M, Banda R, Beale MA, Heinz E, Mallewa J, Jewell C, Faragher B, Thomson NR, Feasey NA. Dynamics of gut mucosal colonisation with extended spectrum beta-lactamase producing Enterobacterales in Malawi. medRxiv. 2021.

Musicha P, Msefula CL, Mather AE, Chaguza C, Cain AK, Peno C, Kallonen T, Khonga M, Denis B, Gray KJ, Heyderman RS, et al. Genomic analysis of Klebsiella pneumoniae isolates from Malawi reveals acquisition of multiple ESBL determinants across diverse lineages. Journal of Antimicrobial Chemotherapy. 2019.

Musicha P, Feasey NA, Cain AK, Kallonen T, Chaguza C, Peno C, Khonga M, Thompson S, Gray KJ, Mather AE, et al. Genomic landscape of extended-spectrum β-lactamase resistance in Escherichia coli from an urban African setting. Journal of Antimicrobial Chemotherapy. 2017.

LSTM Themes and Topics – Key Words