Edinburgh Infectious Diseases
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Research focus: from eye infection to future pandemic preparedness

Publication highlights from the Edinburgh Infectious Diseases network in the past month.

Duox and Jak/Stat signalling influence disease tolerance in Drosophila during Pseudomonas entomophila infection

Summary: Researchers from the School of Biological Sciences and collaborators from France studied disease tolerance in infected hosts. They focused on the Jak/Stat pathway's role in innate immunity and its potential as a tolerance mechanism. Using Drosophila melanogaster infected with Pseudomonas entomophila, they found that disrupting ROS-producing dual oxidase (duox) and the negative regulator of Jak/Stat, Socs36E, reduced tolerance in male flies.

However, the negative regulator G9a did not affect tolerance of bacterial infection as it does in viral infection. These findings highlight the influence of ROS production and Jak/Stat signaling on tolerance to bacterial infections in a sex-specific manner in Drosophila.

Prakash A, Monteith KM, Bonnet M, Vale PF, Dev Comp Immunol. 2023 Jun 9;147:104756. doi: 10.1016/j.dci.2023.104756.

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New technologies to study helminth development and host-parasite interactions

Summary: Researchers from the Moredun Research Institute studied how parasites develop, survive, and interact with host immune responses. Traditional gene expression analysis techniques have provided valuable insights, but they have limitations in capturing cell heterogeneity and spatial organization. Single-cell RNA sequencing (scRNA-seq) offers a new approach by profiling gene expression at the individual cell level.

In this review, the application of scRNA-seq is discussed in establishing gene expression cell atlases for multicellular helminths and exploring host cell types involved in parasite immunity and tissue repair.

The review also briefly explores the use of organoids, stem-cell derived mini-tissues, for studying host-parasite interactions at the local level and parasite development in vitro. Organoid technology shows promise as an alternative in vitro system for helminth parasite research.

Britton C, Roz Laing 2 , McNeilly TN, Perez MG, Otto TD , Hildersley KA, Maizels RM, Devaney E, Gillan V, Int J Parasitol. 2023 Jul;53(8):393-403. doi: 10.1016/j.ijpara.2022.11.012.

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Development of an amplicon-based sequencing approach in response to the global emergence of mpox

Summary: The global study involved the Viral Genotyping Reference Laboratory and Institute of Ecology and Evolution from Edinburgh. During the 2022 multicountry monkeypox outbreak and the ongoing COVID-19 pandemic, there was a need for rapid whole-genome sequencing. Traditional methods were resource-intensive and required high viral DNA concentrations.

To overcome this, amplicon-based sequencing (PrimalSeq) was used for human monkeypox virus sequencing. It provided higher genome coverage and minimal drop-outs, even in samples with lower DNA titer. The correlation between PCR cycle threshold (Ct) value, sequencing reads, and genome coverage was observed. To optimize limited resources, samples with a PCR Ct below 31 Ct and 1 million sequencing reads per sample were recommended.

The primer scheme was successfully implemented in multiple public health laboratories across different countries and workflows. Amplicon-based sequencing offers a rapid, cost-effective approach for pathogen whole-genome sequencing and outbreak response, especially when integrated into existing SARS-CoV-2 workflows.

McHugh MP, Maloney DM, Dewar R, Kenicer J, Parker A, Mathers K, Wild J, Cotton S, Templeton KE at all., PLoS Biol. 2023 Jun 13;21(6):e3002151. doi: 10.1371/journal.pbio.3002151.

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Dogs' health and demographics in wildlife-populated and tsetse-infested villages of Mambwe district, eastern Zambia

Summary: This text highlights the importance of proper dog care and access to veterinary services in rural areas of Zambia. A study conducted by researchers from the Centre for Discovery Brain Sciences and Infection Medicine followed 162 indigenous dogs in wildlife-populated and tsetse-infested villages. The study revealed that these dogs lacked essential care, including food, veterinary attention, and tick control. Some dogs were found to have worm infestations. The dogs' exposure to tsetse bites and consumption of raw game meat increased their risk of African trypanosomiasis.

During the study, approximately 20% of the dogs were lost, primarily due to poor health, predation by wild carnivores, and owner intervention. The well-being and survival of these indigenous dogs were influenced by various factors, including their environment, infectious diseases, injuries from interactions with other dogs and wildlife, and community attitudes and practices related to dog ownership.

Lisulo M, Namangala B, Mweempwa C, Banda M, Picozzi K, Maciver SK, MacLeod ET, Prev Vet Med. 2023 Jun 27;217:105969. doi: 10.1016/j.prevetmed.2023.105969.

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Value profile for respiratory syncytial virus vaccines and monoclonal antibodies

Summary: RSV is a major cause of respiratory infections in young children, yet no licensed vaccine is available. Existing monoclonal antibody prophylaxis is not practical for low-income settings. However, there are promising candidates in the pipeline, including maternal vaccines and long-acting infant monoclonal antibodies. Licensure of these candidates is feasible in the next few years and could be cost-effective.

Effective coordination between maternal and child health programs is crucial for successful implementation. The Vaccine Value Profile (VVP) assesses the potential value of RSV vaccines, developed by experts and stakeholders, including the Usher Institute, using existing information.

Fleming JA, Baral R, Higgins D, Khan S, Kochar S, Li Y, Ortiz JR, Cherian T, Feikin D, Jit M, Karron RA, Limaye RJ, Marshall C, Munywoki PK, Nair H, Newhouse LC, Nyawanda BO, Pecenka C, Regan K, Srikantiah P, Wittenauer R, Zar HJ, Sparrow E, Vaccine. 2023 Jul 6;S0264-410X(22)01212-9. doi: 10.1016/j.vaccine.2022.09.081.

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FluoroPi Device With SmartProbes: A Frugal Point-of-Care System for Fluorescent Detection of Bacteria From a Pre-Clinical Model of Microbial Keratitis

Summary: Researchers from the Centre for Inflammation Research have developed a rapid and accessible imaging device called FluoroPi, which uses fluorescent optical reporters called SmartProbes, to diagnose microbial keratitis (MK). The device, built using a Raspberry Pi computer, LED lights, and filters, was evaluated with bacterial samples obtained from ex vivo porcine corneal MK models.

FluoroPi provided high-resolution imaging, allowing for the distinction of bacteria from tissue debris. It could detect as few as 103 to 104 CFU/mL and successfully differentiate between Gram-negative and Gram-positive bacteria. The system is cost-effective, easy to use, and shows promise for the rapid diagnosis of MK. This study represents an important step toward translating this diagnostic approach to clinical settings.

Mohanan SMPC, Russell K, Duncan S, Kiang A, Lochenie C, Duffy E, Kennedy S, Prajna NV, Williams RL, Dhaliwal K, Williams GOS, Mills B, Transl Vis Sci Technol. 2023 Jul 3;12(7):1. doi: 10.1167/tvst.12.7.1.

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Age-specific impacts of vegetation functional traits on gastrointestinal nematode parasite burdens in a large herbivore

Summary: Gastrointestinal nematode (GIN) parasites have a significant impact on animal populations, but the factors driving their spatial variation are unclear. Researchers from the Institute of Ecology & Evolution studied Soay sheep and investigated how vegetation and spatial factors affect parasite burden in different age groups.

They found that parasite egg counts in immature lambs showed spatial patterns, with higher counts in the north and south. Plant traits were associated with these counts, indicating the influence of host density and habitat preference. However, no such relationship was observed in yearlings or adult sheep. Adult parasites were most prevalent in the northeast, while yearlings showed no spatial patterns. These findings underscore the importance of fine-scale environmental variation in understanding wildlife epidemiology, with varying effects across demographic groups.

Wiersma E, Pakeman RJ, Bal X, Pilkington JG, Pemberton JM, Nussey DH, Sweeny AR, J Anim Ecol. 2023 Jul 5. doi: 10.1111/1365-2656.13978.

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The Immune Response in the Uteri and Placentae of Chlamydia abortus-Infected Ewes and Its Association with Pregnancy Outcomes

Summary: Enzootic abortion of ewes, caused by Chlamydia abortus (C. abortus), is a major cause of sheep abortion. In a study by the Moredum Research Institute and the Royal (Dick) School of Veterinary Studies, researchers investigated the relationship between immune cell infiltration patterns and pregnancy outcomes in twin-bearing sheep infected with C. abortus.

Uteri and placentae samples were collected after birth and analyzed for immune cell features. Significant group effects were observed in the placentae, indicating the potential role of T helper/Treg cells in influencing pregnancy outcomes. This research sheds light on immune responses during pre-term abortion or lambing in C. abortus-infected sheep.

Caspe SG, Ewing DA, Livingstone M, Underwood C, Milne E, Sargison ND, Wattegedera SR, Longbottom D, Pathogens. 2023 Jun 19;12(6):846. doi: 10.3390/pathogens12060846.

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Patient emergency health-care use before hospital admission for COVID-19 and long-term outcomes in Scotland: a national cohort study

Summary: A Scotland-based study investigated the influence of pre-admission health-care utilization on long-term outcomes in COVID-19 patients. Researchers from the School of Informatics, Bayes Centre, Usher Institute, and Roslin Institute analyzed data from various databases, identifying patient clusters based on previous emergency hospital admissions.

The study revealed elevated mortality and emergency readmission rates within one year for COVID-19 patients. Patterns of hospital use before admission strongly correlated with mortality and readmission risk, irrespective of age, comorbidities, and vaccination status. These findings facilitate the identification of high-risk individuals and enable tailored support.

Docherty AB, Farrell J, Thorpe M, Egan C, Dunn S, Norman L, Shaw CA, Law A, Leeming G, Norris L, Brooks A, Prodan B, MacLeod R, Baxter R, Morris C, Rennie D, Oosthuyzen W, Semple MG, Baillie JK, Pius R, Seth S, Harrison EM, Lone NI, Lancet Digit Health. 2023 Jul;5(7):e446-e457. doi: 10.1016/S2589-7500(23)00051-1.

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Lessons from COVID-19 must be learned before the next outbreak

Summary: Despite COVID-19 no longer being a government priority, it continues to inflict harm on populations and disrupt healthcare systems, revealing global mismanagement and inadequate funding.

This paper from the Usher Institute highlights essential lessons learned from the past three years since the pandemic's outbreak and offers guidance on proactive preparation for future pandemics. It emphasizes the crucial need to support those affected by COVID-19 and swiftly address upcoming outbreaks amidst global shocks.

Hassan I, Fernandes G, Mukaigawara M, Sridhar D, Nat Med. 2023 Jun 28. doi: 10.1038/s41591-023-02377-6.

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