One Health timeliness metrics to track and evaluate outbreak response reporting: A scoping review.

Background: As the global population soars, human behaviours are increasing the risk of epidemics. Objective performance evaluation of outbreak responses requires that metrics of timeliness, or speed in response time, be recorded and reported. We sought to evaluate how timeliness data are being conveyed for multisectoral outbreaks and make recommendations on how One Health metrics can be used to improve response success. Methods: We conducted a scoping review of outbreaks reported January 1, 2010- March 15, 2020, in organizational reports and peer-reviewed literature on PubMed and Embase databases. We tracked 11 outbreak milestones and calculated timeliness metrics, the median time in days, between the following: 1) Predict; 2) Prevent; 3) Start; 4) Detect; 5) Notify; 6) Verify; 7) Diagnostic; 8) Respond; 9) Communication; 10) End; and 11) After-Action Review. Findings: We identified 26783 outbreak reports, 1014 of which involved more than just the human health sector. Only six of the eleven milestones were mentioned in >50% of reports. The time between most milestones was on average shorter for outbreaks reporting both Predict (alert of a potential outbreak) and Prevent (response to predictive alert) events. Interpretation: Tracking progress in timeliness during outbreaks can focus efforts to prevent outbreaks from evolving into epidemics or pandemics. Response to predictive alerts demonstrated improved expediency in time to most milestones. We recommend the adoption of universally defined One Health outbreak milestones, including After Action Review, such that timeliness metrics can be used to assess outbreak response improvements over time. Funding: This study was made possible by the United States Agency for International Development's One Health Workforce-Next Generation Project (Cooperative Agreement 7200AA19CA00018).

Panspecies molecular assays detect viral pathogens missed by real-time PCR/reverse-transcriptase PCR among pneumonia patients, Sarawak, Malaysia.

BACKGROUND: In a year-long pneumonia etiology study conducted June 2017 to May 2018 in Sarawak, Malaysia, 599 patients' nasopharyngeal swab specimens were studied with real-time polymerase chain reaction (rPCR)/ reverse-transcription (rRT-PCR) assays for respiratory pathogens known to contribute to the high burden of lower respiratory tract infections. The study team sought to compare real-time assay results with panspecies conventional molecular diagnostics to compare sensitivities and learn if novel viruses had been missed. METHODS: Specimens were studied for evidence of adenovirus (AdV), enterovirus (EV) and coronavirus (CoV) with panspecies gel-based nested PCR/RT-PCR assays. Gene sequences of specimens positive by panspecies assays were sequenced and studied with the NCBI Basic Local Alignment Search Tool software. RESULTS: There was considerable discordance between real-time and conventional molecular methods. The real-time AdV assay found a positivity of 10.4%; however, the AdV panspecies assay detected a positivity of 12.4% and the conventional AdV-Hexon assay detected a positivity of 19.6%. The CoV and EV panspecies assays similarly detected more positive specimens than the real-time assays, with a positivity of 7.8% by the CoV panspecies assay versus 4.2% by rRT-PCR, and 8.0% by the EV panspecies assay versus 1.0% by rRT-PCR. We were not able to ascertain virus viability in this setting. While most discordance was likely due to assay sensitivity for previously described human viruses, two novel, possible zoonotic AdV were detected. CONCLUSIONS: The observed differences in the two modes of amplification suggest that where a problem with sensitivity is suspected, real-time assay results might be supplemented with panspecies conventional PCR/RT-PCR assays.

First sequence of influenza D virus identified in poultry farm bioaerosols in Sarawak, Malaysia.

In 2018, our team collected aerosols samples from five poultry farms in Malaysia. Influenza D virus was detected in 14% of samples. One sample had an 86.3% identity score similar to NCBI accession number MH785020.1. This is the first molecular sequence of influenza D virus detected in Southeast Asia from a bioaerosol sample. Our findings indicate that further study of role of IDV in poultry is necessary.

Are adenoviruses zoonotic? A systematic review of the evidence.

Adenoviruses (AdVs) are major contributors to clinical illnesses. Novel human and animal AdVs continue to be identified and characterized. Comparative analyses using bioinformatic methods and Omics-based technologies allow insights into how these human pathogens have emerged and their potential for host cross-species transmission. Systematic review of literature published across ProQuest, Pubmed, and Web of Science databases for evidence of adenoviral zoonotic potential identified 589 citations. After removing duplicates, 327 citations were screened for relevance; of which, 74 articles received full-text reviews. Among these, 24 were included here, of which 16 demonstrated evidence of zoonotic transmission of AdVs. These documented instances of AdV crossing host species barriers between humans and non-human primate, bat, feline, swine, canine, ovine, and caprine. Eight studies sought to but did not find evidence of zoonosis. The findings demonstrate substantial evidence suggesting AdVs have previously and will continue crossing host species barriers. These have human health consequences both in terms of novel pathogen emergence and epidemic outbreaks, and of appropriate and safe use of non-human adenoviruses for therapeutics. As routine human clinical diagnostics may miss a novel cross-species adenovirus infection in humans, next generation sequencing or panspecies molecular diagnostics may be necessary to detect such incursions.

High Prevalence of Viral Infections Among Hospitalized Pneumonia Patients in Equatorial Sarawak, Malaysia.

BACKGROUND: Although pneumonia is a known cause of morbidity and mortality in Sarawak, Malaysia, the etiology and epidemiology of pneumonia are not well described in this equatorial region. Routine clinical diagnostics for pneumonia etiology at government hospitals in Sarawak had historically involved only bacterial diagnostics. Viral diagnostics were only obtained through outside consultations. METHODS: From June 15, 2017 to May 14, 2018, we collected nasopharyngeal swabs from 600 patients of all ages older than 1 month hospitalized with pneumonia at Sibu and Kapit Hospitals. Specimens were examined at our collaborating institutions with a panel of molecular assays for viral pathogens including influenza A (IAV), IBV, ICV, and IDV, human adenovirus (AdV), human enterovirus (EV), human coronavirus (CoV), respiratory syncytial virus subtype A (RSV-A) or RSV-B, and parainfluenza virus (PIV) types 1-4. RESULTS: Of 599 samples examined, 288 (48%) had molecular evidence of 1 or more respiratory viruses. Overall, the most prevalent virus detected was RSV-A (14.2%) followed by AdV (10.4%) and IAV (10.4%), then RSV-B (6.2%), EV (4.2%), IBV (2.2%), PIV-3 (1.7%), CoV (1.0%), PIV-1 (1.0%), PIV-4 (0.7%), and PIV-2 (0.2%). No specimens were confirmed positive for ICV or IDV. CONCLUSIONS: The high prevalence of viruses detected in this study suggest that respiratory viruses may be responsible for considerable morbidity in equatorial regions such as Sarawak. Access to viral diagnostics are very necessary for medical staff to determine appropriate pneumonia treatments.

A Mini Review of the Zoonotic Threat Potential of Influenza Viruses, Coronaviruses, Adenoviruses, and Enteroviruses.

During the last two decades, scientists have grown increasingly aware that viruses are emerging from the human-animal interface. In particular, respiratory infections are problematic; in early 2003, World Health Organization issued a worldwide alert for a previously unrecognized illness that was subsequently found to be caused by a novel coronavirus [severe acute respiratory syndrome (SARS) virus]. In addition to SARS, other respiratory pathogens have also emerged recently, contributing to the high burden of respiratory tract infection-related morbidity and mortality. Among the recently emerged respiratory pathogens are influenza viruses, coronaviruses, enteroviruses, and adenoviruses. As the genesis of these emerging viruses is not well understood and their detection normally occurs after they have crossed over and adapted to man, ideally, strategies for such novel virus detection should include intensive surveillance at the human-animal interface, particularly if one believes the paradigm that many novel emerging zoonotic viruses first circulate in animal populations and occasionally infect man before they fully adapt to man; early detection at the human-animal interface will provide earlier warning. Here, we review recent emerging virus treats for these four groups of viruses.

The continual threat of influenza virus infections at the human-animal interface: What is new from a one health perspective?

This year, in 2018, we mark 100 years since the 1918 influenza pandemic. In the last 100 years, we have expanded our knowledge of public health and increased our ability to detect and prevent influenza; however, we still face challenges resulting from these continually evolving viruses. Today, it is clear that influenza viruses have multiple animal reservoirs (domestic and wild), making infection prevention in humans especially difficult to achieve. With this report, we summarize new knowledge regarding influenza A, B, C and D viruses and their control. We also introduce how a multi-disciplinary One Health approach is necessary to mitigate these threats.

A systematic review of evidence that enteroviruses may be zoonotic.

Enteroviruses infect millions of humans annually worldwide, primarily infants and children. With a high mutation rate and frequent recombination, enteroviruses are noted to evolve and change over time. Given the evidence that human enteroviruses are commonly found in other mammalian species and that some human and animal enteroviruses are genetically similar, it is possible that enzootic enteroviruses may also be infecting human populations. We conducted a systematic review of the English and Chinese literature published between 2007 and 2017 to examine evidence that enteroviruses may be zoonotic. Of the 2704 articles screened for inclusion, 16 articles were included in the final review. The review of these articles yielded considerable molecular evidence of zooanthroponosis transmission, particularly among non-human primates. While there were more limited instances of anthropozoonosis transmission, the available data support the biological plausibility of cross-species transmission and the need to conduct periodic surveillance at the human-animal interface.

Surveillance for respiratory syncytial virus and parainfluenza virus among patients hospitalized with pneumonia in Sarawak, Malaysia.

BACKGROUND: Respiratory syncytial virus (RSV) and parainfluenza virus (PIV) are frequent causes of pneumonia and death among children at Sibu and Kapit Hospitals in Sarawak, Malaysia. OBJECTIVES: To determine the prevalence and risk factors for RSV subtypes A and B and PIV types 1-4 among patients hospitalized with pneumonia. METHODS: In a cross-sectional, pilot study nasopharyngeal swabs were studied with real-time reverse transcription polymerase chain reaction assays. Concurrently, we helped Sibu and Kapit Hospitals adapt their first molecular diagnostics for RSV and PIV. RESULTS: Of 129 specimens collected (June to July 2017), 39 tested positive for RSV-A (30.2%), two were positive for RSV B (1.6%), one was positive for PIV-3 (0.8%) and one was positive for PIV-4 (0.8%). No samples were positive for PIV-1 or PIV-2. Of the 39 RSV-A positive specimens, 46.2% were collected from children under one year of age and only 5.1% were from patients over the age of 18. A multivariable analysis found the odds of children <1 year of age testing positive for RSV-A were 32.7 (95% CI: 3.9, 276.2) times larger than >18 years of age, and the odds of patients hospitalized at Kapit Hospital testing positive for RSV-A were 3.2 (95% CI: 1.3, 7.8) times larger than patients hospitalized at Sibu Hospital. CONCLUSION: This study found an unusually high prevalence of RSV-A among pneumonia patients admitted to the two hospitals. Subsequently, Sibu Hospital adapted the molecular assays with the goal of providing more directed care for such pneumonia patients.

Surveillance for respiratory and diarrheal pathogens at the human-pig interface in Sarawak, Malaysia.

BACKGROUND: The large livestock operations and dense human population of Southeast Asia are considered a hot-spot for emerging viruses. OBJECTIVES: To determine if the pathogens adenovirus (ADV), coronavirus (CoV), encephalomyocarditis virus (EMCV), enterovirus (EV), influenza A-D (IAV, IBV, ICV, and IDV), porcine circovirus 2 (PCV2), and porcine rotaviruses A and C (RVA and RVC), are aerosolized at the animal-interface, and if humans working in these environments are carrying these viruses in their nasal airways. STUDY: This cross-sectional study took place in Sarawak, Malaysia among 11 pig farms, 2 abattoirs, and 3 animal markets in June and July of 2017. Pig feces, pig oral secretions, bioaerosols, and worker nasal wash samples were collected and analyzed via rPCR and rRT-PCR for respiratory and diarrheal viruses. RESULTS: In all, 55 pig fecal, 49 pig oral or water, 45 bioaerosol, and 78 worker nasal wash samples were collected across 16 sites. PCV2 was detected in 21 pig fecal, 43 pig oral or water, 3 bioaerosol, and 4 worker nasal wash samples. In addition, one or more bioaerosol or pig samples were positive for EV, IAV, and RVC, and one or more worker samples were positive for ADV, CoV, IBV, and IDV. CONCLUSIONS: This study demonstrates that nucleic acids from a number of targeted viruses were present in pig oral secretions and pig fecal samples, and that several viruses were detected in bioaerosol samples or in the nasal passages of humans with occupational exposure to pigs. These results demonstrate the need for future research in strengthening viral surveillance at the human-animal interface, specifically through expanded bioaerosol sampling efforts and a seroepidemiological study of individuals with exposure to pigs in this region for PCV2 infection.