Infectious Diseases - Research Publications

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    The APPRISE Virtual Biobank for Infectious Diseases
    Smith, MZ ; Turner, M ; Haurat, J ; Thevarajan, I ; Denholm, J ; Tong, SYC ; Matthews, G ; Bull, RA ; Martinello, M ; Mcmahon, J ; Imrie, A ; Pillai, PE (AUSTRALIAN GOVERNMENT, DEPT HEALTH & AGEING, 2023-11-16)
    The Australian Partnership for Preparedness Research on InfectiouS disease Emergencies (APPRISE) has developed a virtual biobank to support infectious disease research in Australia. The virtual biobank (https://apprise.biogrid.org.au) integrates access to existing distributed infectious disease biospecimen collections comprising multiple specimen types, including plasma, serum, and peripheral blood mononuclear cells. Through the development of a common data model, multiple collections can be searched simultaneously via a secure web portal. The portal enhances the visibility and searchability of existing collections within their current governance and custodianship arrangements. The portal is easily scalable for integration of additional collections.
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    Trabid patient mutations impede the axonal trafficking of adenomatous polyposis coli to disrupt neurite growth
    Frank, D ; Bergamasco, M ; Mlodzianoski, MJ ; Kueh, A ; Tsui, E ; Hall, C ; Kastrappis, G ; Voss, AK ; McLean, C ; Faux, M ; Rogers, KL ; Tran, B ; Vincan, E ; Komander, D ; Dewson, G ; Tran, H (eLIFE SCIENCES PUBL LTD, 2023-12-15)
    ZRANB1 (human Trabid) missense mutations have been identified in children diagnosed with a range of congenital disorders including reduced brain size, but how Trabid regulates neurodevelopment is not understood. We have characterized these patient mutations in cells and mice to identify a key role for Trabid in the regulation of neurite growth. One of the patient mutations flanked the catalytic cysteine of Trabid and its deubiquitylating (DUB) activity was abrogated. The second variant retained DUB activity, but failed to bind STRIPAK, a large multiprotein assembly implicated in cytoskeleton organization and neural development. Zranb1 knock-in mice harboring either of these patient mutations exhibited reduced neuronal and glial cell densities in the brain and a motor deficit consistent with fewer dopaminergic neurons and projections. Mechanistically, both DUB-impaired and STRIPAK-binding-deficient Trabid variants impeded the trafficking of adenomatous polyposis coli (APC) to microtubule plus-ends. Consequently, the formation of neuronal growth cones and the trajectory of neurite outgrowth from mutant midbrain progenitors were severely compromised. We propose that STRIPAK recruits Trabid to deubiquitylate APC, and that in cells with mutant Trabid, APC becomes hyperubiquitylated and mislocalized causing impaired organization of the cytoskeleton that underlie the neuronal and developmental phenotypes.
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    Trabid patient mutations impede the axonal trafficking of adenomatous polyposis coli to disrupt neurite growth
    Frank, D ; Bergamasco, M ; Mlodzianoski, MJ ; Kueh, A ; Tsui, E ; Hall, C ; Kastrappis, G ; Voss, AK ; McLean, C ; Faux, M ; Rogers, KL ; Tran, B ; Vincan, E ; Komander, D ; Dewson, G ; Tran, H (eLife Sciences Publications, Ltd, )
    ZRANB1 (human Trabid) missense mutations have been identified in children diagnosed with a range of congenital disorders including reduced brain size, but how Trabid regulates neurodevelopment is not understood. We have characterized these patient mutations in cells and mice to identify a key role for Trabid in the regulation of neurite growth. One of the patient mutations flanked the catalytic cysteine of Trabid and its deubiquitylating (DUB) activity was abrogated. The second variant retained DUB activity, but failed to bind STRIPAK, a large multiprotein assembly implicated in cytoskeleton organization and neural development. Zranb1 knock-in mice harboring either of these patient mutations exhibited reduced neuronal and glial cell densities in the brain and a motor deficit consistent with fewer dopaminergic neurons and projections. Mechanistically, both DUB-impaired and STRIPAK-binding-deficient Trabid variants impeded the trafficking of adenomatous polyposis coli (APC) to microtubule plus-ends. Consequently, the formation of neuronal growth cones and the trajectory of neurite outgrowth from mutant midbrain progenitors were severely compromised. We propose that STRIPAK recruits Trabid to deubiquitylate APC, and that in cells with mutant Trabid, APC becomes hyperubiquitylated and mislocalized causing impaired organization of the cytoskeleton that underlie the neuronal and developmental phenotypes.
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    Evolution and transmission of antibiotic resistance is driven by Beijing lineage Mycobacterium tuberculosisin Vietnam
    Silcocks, M ; Chang, X ; Thuong, NTT ; Qin, Y ; Ha, DTM ; Thai, PVK ; Vijay, S ; Thu, DDA ; Ha, VTN ; Nhung, HN ; Lan, NH ; Nhu, NTQ ; Edwards, D ; Nath, A ; Pham, K ; Bang, ND ; Chau, TTH ; Thwaites, G ; Heemskerk, AD ; Chuen Khor, C ; Teo, YY ; Inouye, M ; Ong, RT-H ; Caws, M ; Holt, KE ; Dunstan, SJ ; Neyrolles, O (AMER SOC MICROBIOLOGY, 2023-12-12)
    Drug-resistant tuberculosis (TB) infection is a growing and potent concern, and combating it will be necessary to achieve the WHO's goal of a 95% reduction in TB deaths by 2035. While prior studies have explored the evolution and spread of drug resistance, we still lack a clear understanding of the fitness costs (if any) imposed by resistance-conferring mutations and the role that Mtb genetic lineage plays in determining the likelihood of resistance evolution. This study offers insight into these questions by assessing the dynamics of resistance evolution in a high-burden Southeast Asian setting with a diverse lineage composition. It demonstrates that there are clear lineage-specific differences in the dynamics of resistance acquisition and transmission and shows that different lineages evolve resistance via characteristic mutational pathways.
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    A multi-criteria framework for disease surveillance site selection: case study for Plasmodium knowlesi malaria in Indonesia
    Harrison, LE ; Flegg, JA ; Tobin, R ; Lubis, IND ; Noviyanti, R ; Grigg, MJ ; Shearer, FM ; Price, DJ (ROYAL SOC, 2024-01-10)
    Disease surveillance aims to collect data at different times or locations, to assist public health authorities to respond appropriately. Surveillance of the simian malaria parasite, Plasmodium knowlesi, is sparse in some endemic areas and the spatial extent of transmission is uncertain. Zoonotic transmission of Plasmodium knowlesi has been demonstrated throughout Southeast Asia and represents a major hurdle to regional malaria elimination efforts. Given an arbitrary spatial prediction of relative disease risk, we develop a flexible framework for surveillance site selection, drawing on principles from multi-criteria decision-making. To demonstrate the utility of our framework, we apply it to the case study of Plasmodium knowlesi malaria surveillance site selection in western Indonesia. We demonstrate how statistical predictions of relative disease risk can be quantitatively incorporated into public health decision-making, with specific application to active human surveillance of zoonotic malaria. This approach can be used in other contexts to extend the utility of modelling outputs.
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    Neisseria gonorrhoeae vaccines: a contemporary overview
    Williams, E ; Seib, KL ; Fairley, CK ; Pollock, GL ; Hocking, JS ; McCarthy, JS ; Williamson, DA ; Forrest, GN (AMER SOC MICROBIOLOGY, 2024-03-14)
    SUMMARYNeisseria gonorrhoeae infection is an important public health issue, with an annual global incidence of 87 million. N. gonorrhoeae infection causes significant morbidity and can have serious long-term impacts on reproductive and neonatal health and may rarely cause life-threatening disease. Global rates of N. gonorrhoeae infection have increased over the past 20 years. Importantly, rates of antimicrobial resistance to key antimicrobials also continue to increase, with the United States Centers for Disease Control and Prevention identifying drug-resistant N. gonorrhoeae as an urgent threat to public health. This review summarizes the current evidence for N. gonorrhoeae vaccines, including historical clinical trials, key N. gonorrhoeae vaccine preclinical studies, and studies of the impact of Neisseria meningitidis vaccines on N. gonorrhoeae infection. A comprehensive survey of potential vaccine antigens, including those identified through traditional vaccine immunogenicity approaches, as well as those identified using more contemporary reverse vaccinology approaches, are also described. Finally, the potential epidemiological impacts of a N. gonorrhoeae vaccine and research priorities for further vaccine development are described.
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    Point-of-care HCV RNA testing improves hepatitis C testing rates and allows rapid treatment initiation among people who inject drugs attending a medically supervised injecting facility.
    MacIsaac, MB ; Whitton, B ; Anderson, J ; Cogger, S ; Vella-Horne, D ; Penn, M ; Weeks, T ; Elmore, K ; Pemberton, D ; Winter, RJ ; Papaluca, T ; Howell, J ; Hellard, M ; Stoové, M ; Wilson, D ; Pedrana, A ; Doyle, JS ; Clark, N ; Holmes, JA ; Thompson, AJ (Elsevier BV, 2024-01-27)
    BACKGROUND: To achieve hepatitis C virus (HCV) elimination targets, simplified care engaging people who inject drugs is required. We evaluated whether fingerstick HCV RNA point-of-care testing (PoCT) increased the proportion of clients attending a supervised injecting facility who were tested for hepatitis C. METHODS: Prospective single-arm study with recruitment between 9 November 2020 and 28 January 2021 and follow-up to 31 July 2021. Clients attending the supervised injecting facility were offered HCV RNA testing using the Xpert® HCV Viral Load Fingerstick (Cepheid, Sunnyvale, CA) PoCT. Participants with a positive HCV RNA test were prescribed direct acting antiviral (DAA) therapy. The primary endpoint was the proportion of clients who engaged in HCV RNA PoCT, compared to a historical comparator group when venepuncture-based hepatitis C testing was standard of care. RESULTS: Among 1618 clients who attended the supervised injecting facility during the study period, 228 (14%) engaged in PoCT. This was significantly higher than that observed in the historical comparator group (61/1,775, 3%; p < 0.001). Sixty-five (28%) participants were HCV RNA positive, with 40/65 (62%) receiving their result on the same day as testing. Sixty-one (94%) HCV RNA positive participants were commenced on DAA therapy; 14/61 (23%) started treatment on the same day as diagnosis. There was no difference in the proportion of HCV RNA positive participants commenced on treatment with DAA therapy when compared to the historical comparator group (61/65, 94% vs 22/26, 85%; p = 0.153). However, the median time to treatment initiation was significantly shorter in the PoCT cohort (2 days (IQR 1-20) vs 41 days (IQR 22-76), p < 0.001). Among participants who commenced treatment and had complete follow-up data available, 27/36 (75%) achieved hepatitis C cure. CONCLUSIONS: HCV RNA PoCT led to a significantly higher proportion of clients attending a supervised injecting facility engaging in hepatitis C testing, whilst also reducing the time to treatment initiation.
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    Updating estimates of Plasmodium knowlesi malaria risk in response to changing land use patterns across Southeast Asia
    Tobin, RJ ; Harrison, LE ; Tully, MK ; Lubis, IND ; Noviyanti, R ; Anstey, NM ; Rajahram, GS ; Grigg, MJ ; Flegg, JA ; Price, DJ ; Shearer, FM ; Reithinger, R (Public Library of Science (PLoS), 2024-01)
    BACKGROUND: Plasmodium knowlesi is a zoonotic parasite that causes malaria in humans. The pathogen has a natural host reservoir in certain macaque species and is transmitted to humans via mosquitoes of the Anopheles Leucosphyrus Group. The risk of human P. knowlesi infection varies across Southeast Asia and is dependent upon environmental factors. Understanding this geographic variation in risk is important both for enabling appropriate diagnosis and treatment of the disease and for improving the planning and evaluation of malaria elimination. However, the data available on P. knowlesi occurrence are biased towards regions with greater surveillance and sampling effort. Predicting the spatial variation in risk of P. knowlesi malaria requires methods that can both incorporate environmental risk factors and account for spatial bias in detection. METHODS & RESULTS: We extend and apply an environmental niche modelling framework as implemented by a previous mapping study of P. knowlesi transmission risk which included data up to 2015. We reviewed the literature from October 2015 through to March 2020 and identified 264 new records of P. knowlesi, with a total of 524 occurrences included in the current study following consolidation with the 2015 study. The modelling framework used in the 2015 study was extended, with changes including the addition of new covariates to capture the effect of deforestation and urbanisation on P. knowlesi transmission. DISCUSSION: Our map of P. knowlesi relative transmission suitability estimates that the risk posed by the pathogen is highest in Malaysia and Indonesia, with localised areas of high risk also predicted in the Greater Mekong Subregion, The Philippines and Northeast India. These results highlight areas of priority for P. knowlesi surveillance and prospective sampling to address the challenge the disease poses to malaria elimination planning.
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    Potential Cost-Effectiveness of Maternal Influenza Immunisation in Low-Income Countries: An Explorative Modelling Study and Value of Information Analysis to Guide Future Clinical Research
    Wang, Y ; Giles, ML ; Carvalho, N (MDPI AG, 2024)
    Maternal influenza immunisation (MII) is recommended for protecting pregnant women and infants under six months of age from severe disease related to influenza. However, few low-income countries have introduced this vaccine. Existing cost-effectiveness studies do not consider potential vaccine non-specific effects (NSE) observed in some settings, such as reductions in preterm birth. A decision tree model was built to examine the potential cost-effectiveness of MII in a hypothetical low-income country compared to no vaccination, considering possible values for NSE on preterm birth in addition to vaccine-specific effects on influenza. We synthesized epidemiological and cost data from low-income countries. All costs were adjusted to 2021 United States dollars (USD). We considered cost-effectiveness thresholds that reflect opportunity costs (USD 188 per disability-adjusted life year averted; range: USD 28–538). Results suggest that even a small (5%) NSE on preterm birth may make MII a cost-effective strategy in these settings. A value of information analysis indicated that acquiring more information on the presence and possible size of NSE of MII could greatly reduce the uncertainty in decision-making on MII. Further clinical research investigating NSE in low-income countries may be of high value to optimise immunisation policy.
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    South Asian dairy smallholders: A scoping review of practices and zoonoses
    Schembri, E ; Campbell, AJD ; Villanueva-Cabezas, JP (Wolters Kluwer Medknow Publications, 2023)
    Objective: To identify and discuss on-farm management practices linked to bacterial zoonosis risk in smallholder dairy farmers in South Asia. Methods: This scoping review was conducted as per the PRISMA-ScR guidelines. Five hundred and two publications were retrieved from five online databases using a comprehensive search strategy. Studies were selected if they discussed a farm management practice which impacted human health within a South Asian country. Results: Twenty-two studies were included. Seven management practices relevant to farmers, livestock and their shared environment were identified including raw milk consumption, farm hygiene management, personal protective equipment uses, animal vaccination, cleaning udders, hand washing and disposal of afterbirth materials. Preventive practices were found to be utilized at lower frequencies compared to risk increasing practices. Awareness of bacterial zoonoses is particularly low within the region. Conclusions: Based on the results of this review, it was determined that improving farmer awareness of bacterial zoonotic diseases may favor several of the presented leverage points within the South Asian smallholder dairy system. Relying on formal school education to improve this awareness may not solve this problem, instead, more focus on accessible and affordable zoonoses education and farming programs is required.