The panzootic spread of highly pathogenic avian influenza H5N1 sublineage 2.3.4.4b: a critical appraisal of One Health preparedness and prevention.

Changes in the epidemiology and ecology of H5N1 highly pathogenic avian influenza are devastating wild bird and poultry populations, farms and communities, and wild mammals worldwide. Having originated in farmed poultry, H5N1 viruses are now spread globally by wild birds, with transmission to many mammal and avian species, resulting in 2024 in transmission among dairy cattle with associated human cases. These ecological changes pose challenges to mitigating the impacts of H5N1 highly pathogenic avian influenza on wildlife, ecosystems, domestic animals, food security, and humans. H5N1 highly pathogenic avian influenza highlights the need for One Health approaches to pandemic prevention and preparedness, emphasising multisectoral collaborations among animal, environmental, and public health sectors. Action is needed to reduce future pandemic risks by preventing transmission of highly pathogenic avian influenza among domestic and wild animals and people, focusing on upstream drivers of outbreaks, and ensuring rapid responses and risk assessments for zoonotic outbreaks. Political commitment and sustainable funding are crucial to implementing and maintaining prevention programmes, surveillance, and outbreak responses.

Population structure and pathogen interaction of Escherichia coli in freshwater: Implications of land-use for water quality and public health in Aotearoa New Zealand.

Freshwater samples (n = 199) were obtained from 41 sites with contrasting land-uses (avian, low impact, dairy, urban, sheep and beef, and mixed sheep, beef and dairy) and the E. coli phylotype of 3980 isolates (20 per water sample enrichment) was determined. Eight phylotypes were identified with B1 (48.04%), B2 (14.87%) and A (14.79%) the most abundant. Escherichia marmotae (n = 22), and Escherichia ruysiae (n = 1), were rare (0.68%) suggesting that these environmental strains are unlikely to confound water quality assessments. Phylotypes A and B1 were overrepresented in dairy and urban sites (p < 0.0001), whilst B2 were overrepresented in low impact sites (p < 0.0001). Pathogens ((Salmonella, Campylobacter, Cryptosporidium or Giardia) and the presence of diarrhoeagenic E. coli-associated genes (stx and eae) were detected in 89.9% (179/199) samples, including 80.5% (33/41) of samples with putative non-recent faecal inputs. Quantitative PCR to detect microbial source tracking targets from human, ruminant and avian contamination were concordant with land-use type and E. coli phylotype abundance. This study demonstrated that a potential recreational health risk remains where pathogens occurred in water samples with low E. coli concentration, potential non-recent faecal sources, low impact sites and where human, ruminant and avian faecal sources were absent.

Quantifying Replication Slippage Error in Cryptosporidium Metabarcoding Studies.

Genetic variation in Cryptosporidium, a common protozoan gut parasite in humans, is often based on marker genes containing trinucleotide repeats, which differentiate subtypes and track outbreaks. However, repeat regions have high replication slippage rates, making it difficult to discern biological diversity from error. Here, we synthesized Cryptosporidium DNA in clonal plasmid vectors, amplified them in different mock community ratios, and sequenced them using next-generation sequencing to determine the rate of replication slippage with dada2. Our results indicate that slippage rates increase with the length of the repeat region and can contribute to error rates of up to 20%.

Modelling Lassa virus dynamics in West African Mastomys natalensis and the impact of human activities.

Lassa fever is a West African rodent-borne viral haemorrhagic fever that kills thousands of people a year, with 100 000 to 300 000 people a year probably infected by Lassa virus (LASV). The main reservoir of LASV is the Natal multimammate mouse, Mastomys natalensis. There is reported asynchrony between peak infection in the rodent population and peak Lassa fever risk among people, probably owing to differing seasonal contact rates. Here, we developed a susceptible-infected-recovered ([Formula: see text])-based model of LASV dynamics in its rodent host, M. natalensis, with a persistently infected class and seasonal birthing to test the impact of changes to seasonal birthing in the future owing to climate and land use change. Our simulations suggest shifting rodent birthing timing and synchrony will alter the peak of viral prevalence, changing risk to people, with viral dynamics mainly stable in adults and varying in the young, but with more infected individuals. We calculate the time-average basic reproductive number, [Formula: see text], for this infectious disease system with periodic changes to population sizes owing to birthing using a time-average method and with a sensitivity analysis show four key parameters: carrying capacity, adult mortality, the transmission parameter among adults and additional disease-induced mortality impact the maintenance of LASV in M. natalensis most, with carrying capacity and adult mortality potentially changeable owing to human activities and interventions.

Impact of infectious diseases on wild bovidae populations in Thailand: insights from population modelling and disease dynamics.

The wildlife and livestock interface is vital for wildlife conservation and habitat management. Infectious diseases maintained by domestic species may impact threatened species such as Asian bovids, as they share natural resources and habitats. To predict the population impact of infectious diseases with different traits, we used stochastic mathematical models to simulate the population dynamics over 100 years for 100 times in a model gaur (Bos gaurus) population with and without disease. We simulated repeated introductions from a reservoir, such as domestic cattle. We selected six bovine infectious diseases; anthrax, bovine tuberculosis, haemorrhagic septicaemia, lumpy skin disease, foot and mouth disease and brucellosis, all of which have caused outbreaks in wildlife populations. From a starting population of 300, the disease-free population increased by an average of 228% over 100 years. Brucellosis with frequency-dependent transmission showed the highest average population declines (-97%), with population extinction occurring 16% of the time. Foot and mouth disease with frequency-dependent transmission showed the lowest impact, with an average population increase of 200%. Overall, acute infections with very high or low fatality had the lowest impact, whereas chronic infections produced the greatest population decline. These results may help disease management and surveillance strategies support wildlife conservation.

Steps towards operationalizing One Health approaches.

One Health recognizes the health of humans, agriculture, wildlife, and the environment are interrelated. The concept has been embraced by international health and environmental authorities such as WHO, WOAH, FAO, and UNEP, but One Health approaches have been more practiced by researchers than national or international authorities. To identify priorities for operationalizing One Health beyond research contexts, we conducted 41 semi-structured interviews with professionals across One Health sectors (public health, environment, agriculture, wildlife) and institutional contexts, who focus on national-scale and international applications. We identify important challenges, solutions, and priorities for delivering the One Health agenda through government action. Participants said One Health has made progress with motivating stakeholders to attempt One Health approaches, but achieving implementation needs more guidance (action plans for how to leverage or change current government infrastructure to accommodate cross-sector policy and strategic mission planning) and facilitation (behavioral change, dedicated personnel, new training model).

High connectivity and human movement limits the impact of travel time on infectious disease transmission.

The speed of spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus disease 2019 (COVID-19) pandemic highlights the importance of understanding how infections are transmitted in a highly connected world. Prior to vaccination, changes in human mobility patterns were used as non-pharmaceutical interventions to eliminate or suppress viral transmission. The rapid spread of respiratory viruses, various intervention approaches, and the global dissemination of SARS-CoV-2 underscore the necessity for epidemiological models that incorporate mobility to comprehend the spread of the virus. Here, we introduce a metapopulation susceptible-exposed-infectious-recovered model parametrized with human movement data from 340 cities in China. Our model replicates the early-case trajectory in the COVID-19 pandemic. We then use machine learning algorithms to determine which network properties best predict spread between cities and find travel time to be most important, followed by the human movement-weighted personalized PageRank. However, we show that travel time is most influential locally, after which the high connectivity between cities reduces the impact of travel time between individual cities on transmission speed. Additionally, we demonstrate that only significantly reduced movement substantially impacts infection spread times throughout the network.

Evaluating active leprosy case identification methods in six districts of Nepal.

BACKGROUND: Nepal has achieved and sustained the elimination of leprosy as a public health problem since 2009, but 17 districts and 3 provinces with 41% (10,907,128) of Nepal's population have yet to eliminate the disease. Pediatric cases and grade-2 disabilities (G2D) indicate recent transmission and late diagnosis, respectively, which necessitate active and early case detection. This operational research was performed to identify approaches best suited for early case detection, determine community-based leprosy epidemiology, and identify hidden leprosy cases early and respond with prompt treatment. METHODS: Active case detection was undertaken in two Nepali provinces with the greatest burden of leprosy, Madhesh Province (40% national cases) and Lumbini Province (18%) and at-risk prison populations in Madhesh, Lumbini and Bagmati provinces. Case detection was performed by (1) house-to-house visits among vulnerable populations (n = 26,469); (2) contact examination and tracing (n = 7608); in Madhesh and Lumbini Provinces and, (3) screening prison populations (n = 4428) in Madhesh, Lumbini and Bagmati Provinces of Nepal. Per case direct medical and non-medical costs for each approach were calculated. RESULTS: New case detection rates were highest for contact tracing (250), followed by house-to-house visits (102) and prison screening (45) per 100,000 population screened. However, the cost per case identified was cheapest for house-to-house visits [Nepalese rupee (NPR) 76,500/case], followed by contact tracing (NPR 90,286/case) and prison screening (NPR 298,300/case). House-to-house and contact tracing case paucibacillary/multibacillary (PB:MB) ratios were 59:41 and 68:32; female/male ratios 63:37 and 57:43; pediatric cases 11% in both approaches; and grade-2 disabilities (G2D) 11% and 5%, respectively. Developing leprosy was not significantly different among household and neighbor contacts [odds ratios (OR) = 1.4, 95% confidence interval (CI): 0.24-5.85] and for contacts of MB versus PB cases (OR = 0.7, 95% CI 0.26-2.0). Attack rates were not significantly different among household contacts of MB cases (0.32%, 95% CI 0.07-0.94%) and PB cases (0.13%, 95% CI 0.03-0.73) (χ2 = 0.07, df = 1, P = 0.9) and neighbor contacts of MB cases (0.23%, 0.1-0.46) and PB cases (0.48%, 0.19-0.98) (χ2 = 0.8, df = 1, P = 0.7). BCG vaccination with scar presence had a significant protective effect against leprosy (OR = 0.42, 0.22-0.81). CONCLUSIONS: The most effective case identification approach here is contact tracing, followed by house-to-house visits in vulnerable populations and screening in prisons, although house-to-house visits are cheaper. The findings suggest that hidden cases, recent transmission, and late diagnosis in the community exist and highlight the importance of early case detection.

Developing One Health surveillance systems.

The health of humans, domestic and wild animals, plants, and the environment are inter-dependent. Global anthropogenic change is a key driver of disease emergence and spread and leads to biodiversity loss and ecosystem function degradation, which are themselves drivers of disease emergence. Pathogen spill-over events and subsequent disease outbreaks, including pandemics, in humans, animals and plants may arise when factors driving disease emergence and spread converge. One Health is an integrated approach that aims to sustainably balance and optimize human, animal and ecosystem health. Conventional disease surveillance has been siloed by sectors, with separate systems addressing the health of humans, domestic animals, cultivated plants, wildlife and the environment. One Health surveillance should include integrated surveillance for known and unknown pathogens, but combined with this more traditional disease-based surveillance, it also must include surveillance of drivers of disease emergence to improve prevention and mitigation of spill-over events. Here, we outline such an approach, including the characteristics and components required to overcome barriers and to optimize an integrated One Health surveillance system.

Using drivers and transmission pathways to identify SARS-like coronavirus spillover risk hotspots.

The emergence of SARS-like coronaviruses is a multi-stage process from wildlife reservoirs to people. Here we characterize multiple drivers-landscape change, host distribution, and human exposure-associated with the risk of spillover of zoonotic SARS-like coronaviruses to help inform surveillance and mitigation activities. We consider direct and indirect transmission pathways by modeling four scenarios with livestock and mammalian wildlife as potential and known reservoirs before examining how access to healthcare varies within clusters and scenarios. We found 19 clusters with differing risk factor contributions within a single country (N = 9) or transboundary (N = 10). High-risk areas were mainly closer (11-20%) rather than far ( < 1%) from healthcare. Areas far from healthcare reveal healthcare access inequalities, especially Scenario 3, which includes wild mammals and not livestock as secondary hosts. China (N = 2) and Indonesia (N = 1) had clusters with the highest risk. Our findings can help stakeholders in land use planning, integrating healthcare implementation and One Health actions.

The differential diagnoses for severe enteropathy or severely damaged small intestinal mucosa.

Aim: The aim of this study was to explore the aetiology of severe duodenal mucosal abnormality in consecutive patients who underwent gastroscopy and duodenal biopsy over the past 10 years. Background: A range of differential diagnoses have been reported for severe duodenal architectural distortion. Methods: Clinical and laboratory data of all the patients with severe duodenal architectural distortion diagnosed at MidCentral District Health Board (DHB), New Zealand were collected and statistically analysed. Ninety-five percent confidence intervals (CI) are shown. Results: Between September 2009 and April 2019, 229 patients were diagnosed with severe enteropathy. The median patient age was 41 years (range 6-83 years). Two hundred and twenty-four of these patients (97.8%, 95.0-99.3%) were diagnosed with coeliac disease (CeD), with one of these patients having gluten induced T-cell lymphoma. From the remaining five patients, one had a diagnosis of tropical sprue and four did not have a clear aetiology. There were 180 patients from 191 (94.2%, 89.9-97.1%) with at least one positive coeliac marker, all with a diagnosis of CeD. Eleven patients (5.8% of 191, 2.9-10.1%) had negative markers for both tissue transglutaminase IgA (tTG-IgA) and IgA-endomysial antibodies (EMA-IgA) with six having a diagnosis of seronegative CeD. Conclusion: Although the spectrum of histological changes in CeD may range from normal to a flat mucosa, severe duodenal architectural distortion seems to occur mainly in CeD. Idiopathic enteropathy was recorded as the second but by far less frequent presentation of severe enteropathy. This study highlights that infection and other aetiologies are rarely implicated in severe enteropathy, with one case (0.4%) of refractory CeD/T-cell lymphoma.

Low risk of variant Creutzfeldt-Jakob disease transmission from blood transfusions in Aotearoa New Zealand suggests donor exclusion policies can be relaxed.

Aotearoa New Zealand currently excludes potential blood donors who lived in the United Kingdom (UK) for 6 months or more between 1980 and 1996. This action is due to the potential for variant Creutzfeldt-Jakob disease (vCJD) following blood transfusions from preclinical vCJD cases, who themselves mostly developed disease from the consumption of cattle with bovine spongiform encephalopathy (BSE) during this period, or from those incubating the misfolded prion proteins that cause disease. This donor exclusion policy led to 10% of New Zealand's active blood donors in 2000 being excluded, and it remains today despite periodic shortages of some blood products. Globally there have been 232 vCJD cases recorded-178 in the UK-with no new cases since 2019 and the peak numbers 23 years ago in 2000. Only three confirmed cases have been linked to blood transfusion. Here, we aimed to estimate the annual risk of vCJD from blood transfusion in New Zealand after restriction removal. We used UK case numbers, population estimates, and donor and recipient transfusion numbers to calculate the risk to the New Zealand public. We calculated the risk, based on approximately 131,000 transfusions a year and accounting for multiple transfusions, might lead to 0.005 cases annually, or approximately one in one billion nationally, and comparable to recent one in 1.45 billion estimates for Australia. Our analyses suggests that relaxing current blood donation restrictions, like Ireland and Australia's recent policy changes, would lead to an extremely low risk of vCJD transfusion-transmission in New Zealand. This policy change would help increase the supply of blood products for multiple medical needs.

A novel, stain-free, natural auto-fluorescent signal, Sig M, identified from cytometric and transcriptomic analysis of infectivity of Cryptosporidium hominis and Cryptosporidium parvum.

Cryptosporidiosis is a worldwide diarrheal disease caused by the protozoan Cryptosporidium. The primary symptom is diarrhea, but patients may exhibit different symptoms based on the species of the Cryptosporidium parasite they are infected with. Furthermore, some genotypes within species are more transmissible and apparently virulent than others. The mechanisms underpinning these differences are not understood, and an effective in vitro system for Cryptosporidium culture would help advance our understanding of these differences. Using COLO-680N cells, we employed flow cytometry and microscopy along with the C. parvum-specific antibody Sporo-Glo™ to characterize infected cells 48 h following an infection with C. parvum or C. hominis. The Cryptosporidium parvum-infected cells showed higher levels of signal using Sporo-Glo™ than C. hominis-infected cells, which was likely because Sporo-Glo™ was generated against C. parvum. We found a subset of cells from infected cultures that expressed a novel, dose-dependent auto-fluorescent signal that was detectable across a range of wavelengths. The population of cells that expressed this signal increased proportionately to the multiplicity of infection. The spectral cytometry results confirmed that the signature of this subset of host cells closely matched that of oocysts present in the infectious ecosystem, pointing to a parasitic origin. Present in both C. parvum and C. hominis cultures, we named this Sig M, and due to its distinct profile in cells from both infections, it could be a better marker for assessing Cryptosporidium infection in COLO-680N cells than Sporo-Glo™. We also noted Sig M's impact on Sporo-Glo™ detection as Sporo-Glo™ uses fluoroscein-isothiocynate, which is detected where Sig M also fluoresces. Lastly, we used NanoString nCounter® analysis to investigate the transcriptomic landscape for the two Cryptosporidium species, assessing the gene expression of 144 host and parasite genes. Despite the host gene expression being at high levels, the levels of putative intracellular Cryptosporidium gene expression were low, with no significant difference from controls, which could be, in part, explained by the abundance of uninfected cells present as determined by both Sporo-Glo™ and Sig M analyses. This study shows for the first time that a natural auto-fluorescent signal, Sig M, linked to Cryptosporidium infection can be detected in infected host cells without any fluorescent labeling strategies and that the COLO-680N cell line and spectral cytometry could be useful tools to advance the understanding of Cryptosporidium infectivity.

Addressing the challenges of implementing evidence-based prioritisation in global health.

Global health requires evidence-based approaches to improve health and decrease inequalities. In a roundtable discussion between health practitioners, funders, academics and policy-makers, we recognised key areas for improvement to deliver better-informed, sustainable and equitable global health practices. These focus on considering information-sharing mechanisms and developing evidence-based frameworks that take an adaptive function-based approach, grounded in the ability to perform and respond to prioritised needs. Increasing social engagement as well as sector and participant diversity in whole-of-society decision-making, and collaborating with and optimising on hyperlocal and global regional entities, will improve prioritisation of global health capabilities. Since the skills required to navigate drivers of pandemics, and the challenges in prioritising, capacity building and response do not sit squarely in the health sector, it is essential to integrate expertise from a broad range of fields to maximise on available knowledge during decision-making and system development. Here, we review the current assessment tools and provide seven discussion points for how improvements to implementation of evidence-based prioritisation can improve global health.

Diagnosis of protozoa diarrhoea in Campylobacter patients increases markedly with molecular techniques.

Cryptosporidium and Giardia are major causes of diarrhoea globally, and two of the most notified infectious diseases in New Zealand. Diagnosis requires laboratory confirmation carried out mostly via antigen or microscopy-based techniques. However, these methods are increasingly being superseded by molecular techniques. Here we investigate the level of protozoa detection by molecular methods in campylobacteriosis cases missed through antigen-based assays and investigate different molecular testing protocols. We report findings from two observational studies; the first among 111 people during a Campylobacter outbreak and the second during normal surveillance activities among 158 people presenting with diarrhoea and a positive Campylobacter test, but negative Cryptosporidium and Giardia antigen-based test results. The molecular methods used for comparison were in-house end-point PCR tests targeting the gp60 gene for Cryptosporidium and gdh gene for Giardia. DNA extraction was performed with and without bead-beating and comparisons with commercial real-time quantitative (qPCR) were made using clinical Cryptosporidium positive sample dilutions down to 10-5. The Cryptosporidium prevalence was 9% (95% CI: 3-15; 10/111) and Giardia prevalence 21% (95% CI: 12-29; 23/111) in the 111 Campylobacter outbreak patients. The Cryptosporidium prevalence was 40% (95% CI: 32-48; 62/158) and Giardia prevalence 1.3% (95% CI: 0.2-4.5; 2/158) in the 158 routine surveillance samples. Sequencing identified Cryptosporidium hominis, C. parvum, and Giardia intestinalis assemblages A and B. We found no statistical difference in positive test results between samples using end-point PCR with or without bead-beating prior to DNA extraction, or between the in-house end-point PCR and qPCR. The qPCR Ct value was 36 (95% CI: 35-37) for 1 oocyst, suggesting a high limit of detection. In conclusion in surveillance and outbreak situations we found diagnostic serology testing underdiagnoses Cryptosporidium and Giardia coinfections in Campylobacter patients, suggesting the impact of protozoa infections may be underestimated through underdiagnosis using antigen-based assays.