Katherine E. Gallagher & Joyce Nyiro, Charles N. Agoti, Eric Maitha, James Nyagwange, Angela Karani, Christian Bottomley, Nickson Murunga, George Githinji, Martin Mutunga, Lynette Isabella Ochola-Oyier, Ivy Kombe, Amek Nyaguara, E. Wangeci Kagucia, George Warimwe, Ambrose Agweyu, Benjamin Tsofa, Philip Bejon, J. Anthony G. Scott, David James Nokes 

We estimated the secondary attack rate of SARS-CoV-2 among household contacts of PCR-confirmed cases of COVID-19 in rural Kenya and analysed risk factors for transmission. We enrolled incident PCR-confirmed cases and their household members. At baseline, a questionnaire, a blood sample, and naso-oropharyngeal swabs were collected. Household members were followed 4, 7, 10, 14, 21 and 28 days after the date of the first PCR-positive in the household; naso-oropharyngeal swabs were collected at each visit and used to define secondary cases. Blood samples were collected every 1–2 weeks. Symptoms were collected in a daily symptom diary. We used binomial regression to estimate secondary attack rates and survival analysis to analyse risk factors for transmission. Households in our setting experienced a lower 7-day attack rate than a recent meta-analysis indicated as the global average (23%–43% depending on variant), and infection is mostly asymptomatic in our setting.

Influenza & other Respiratory Diseases. September 2023

Hill, Edward M, Prosser, Naomi S, Brown, Paul E, Ferguson, Eamonn, Green, Martin J, Kaler, Jasmeet, Keeling, Matt J and Tildesley, Michael J

Human behaviour is critical to effective responses to livestock disease outbreaks, especially with respect to vaccination uptake. Traditionally, mathematical models used to inform this behaviour have not taken heterogeneity in farmer behaviour into account. We address this by exploring how heterogeneity in farmers vaccination behaviour can be incorporated to inform mathematical models. We developed and used a graphical user interface to elicit farmers (n = 60) vaccination decisions to an unfolding fast-spreading epidemic and linked this to their psychosocial and behavioural profiles. We identified, via cluster analysis, robust patterns of heterogeneity in vaccination behaviour. By incorporating these vaccination behavioural groupings into a mathematical model for a fast-spreading livestock infection, using computational simulation we explored how the inclusion of heterogeneity in farmer disease control behaviour may impact epidemiological and economic focused outcomes.

Preventive Veterinary Medicine. September 2023

Joanna N de Klerk, Erin E Gorsich, John D Grewar, Benjamin D Atkins, Warren S D Tennant, Karien Labuschagne, Michael J Tildesley

African horse sickness is an equine orbivirus transmitted by Culicoides Latreille biting midges. The disease is endemic in South Africa; however, a unique control area has been set up in the Western Cape where increased surveillance and control measures have been put in place. A deterministic metapopulation model was developed to explore if an outbreak might occur, and how it might develop, if a latently infected horse was to be imported into the control area, by varying the geographical location and months of import. A sensitivity analysis indicated that control measures such as vaccination and vector control are potentially effective to manage the spread of an outbreak, and shortening the vaccination window to July to September may reduce the risk of vaccine-associated outbreaks.

PLoS Computational Biology. September 2023

Margo Chase-Topping, Timothy J. Dallman, Lesley Allison , Nadejda Lupolova, Louise Matthews, Sonia Mitchell, Christopher J. Banks, Jamie Prentice, Helen Brown, Sue Tongue, Madeleine Henry, Judith Evans, George Gunn, Deborah Hoyle, Tom N. McNeilly, Stephen Fitzgerald, Alison Smith-Palmer, Sharif Shaaban, Anne Holmes, Mary Hanson, Mark Woolhouse, Xavier Didelot, Claire Jenkins and David L. Gall

For the last two decades, the human infection frequency of Escherichia coli O157 (O157) in Scotland has been 2.5-fold higher than in England and Wales. Results from national cattle surveys conducted in Scotland and England and Wales in 2014/2015 were combined with data on reported human clinical cases from the same time frame to determine if strain differences in national populations of O157 in cattle could be associated with higher human infection rates in Scotland. There was evidence of limited cattle strain migration between nations and clinical isolates from one nation were more similar to cattle isolates from the same nation, with sub-lineage Ic (mainly PT21/28) exhibiting clear national association and evidence of local transmission in Scotland. While we propose the higher rate of O157 clinical cases in Scotland is a consequence of the nationally higher level of Stx2a+O157 strains in Scottish cattle, we discuss the multiple additional factors that may also contribute to the different infection rates between these nations.

Microbial Genomics. September 2023

Julie Rushmore, Brianna R. Beechler, Hannah Tavalire, Erin E. Gorsich, Bryan Charleston, Anne Devan-Song, Caroline K. Glidden, Anna E. Jolles

Here, we analyzed African buffalo social networks to quantify variation in close contacts, examined drivers of contact heterogeneity, and investigated how the observed contact patterns affect pathogen invasion likelihoods for a wild social ungulate. Although the observed herd was well connected, with most individuals contacting each other during each bimonthly interval, our analyses revealed striking heterogeneity in close-contact associations among herd members. Network analysis showed that individual connectivity was stable over time and that individual age, sex, reproductive status, and pairwise genetic relatedness were important predictors of buffalo connectivityThese findings highlight the role susceptible calves may play in the transmission of pathogens within the herd. We also demonstrate that, at time scales relevant to infectious pathogens found in nature, the observed level of connectivity affects pathogen invasion likelihoods for a wide range of infectious periods and transmissibilities. Ultimately, our study identifies key predictors of social connectivity in a social ungulate and illustrates how contact heterogeneity, even within a highly connected herd, can shape pathogen invasion likelihoods.

Ecology and Evolution. August 2023

Rie Nygaard, Chris L. B. Graham, Meagan Belcher Dufrisne, Jonathan D. Colburn, Joseph Pepe, Molly A. Hydorn, Silvia Corradi, Chelsea M. Brown, Khuram U. Ashraf, Owen N. Vickery, Nicholas S. Briggs, John J. Deering, Brian Kloss, Bruno Botta, Oliver B. Clarke, Linda Columbus, Jonathan Dworkin, Phillip J. Stansfeld, David I. Roper & Filippo Mancia

Peptidoglycan (PG) assembly requires a glycosyltransferase (GT) to generate a glycan polymer using a Lipid II substrate, which is then crosslinked to the existing PG via a transpeptidase (TP) reaction. A Shape, Elongation, Division and Sporulation (SEDS) GT enzyme and a Class B Penicillin Binding Protein (PBP) form the core of the multi-protein complex required for PG assembly. Here we used single particle cryo-electron microscopy to determine the structure of a cell elongation-specific E. coli RodA-PBP2 complex. We combine this information with biochemical, genetic, spectroscopic, and computational analyses to identify the Lipid II binding sites and propose a mechanism for Lipid II polymerization. Our data suggest a hypothesis for the movement of the glycan strand from the Lipid II polymerization site of RodA towards the TP site of PBP2, functionally linking these two central enzymatic activities required for cell wall peptidoglycan biosynthesis.

Nature Communications. August 2023