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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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Emerging infectious diseases under this category were subcategorized into 1a, 1b and 1c. Subcategory 1a covers known pathogens that occur in new ecological niches/geographical areas. A few past examples belonging to this subcategory are the introduction and spread of West Nile virus in North America; chikungunya virus of the Central/East Africa genotype in Reunion Island, the Indian subcontinent and South East Asia; and dengue virus of different serotypes in the Pacific Islands and Central and South America.18,19,20,21,22,23 Factors that contributed to the occurrence of emerging infectious diseases in this subcategory include population growth; urbanization; environmental and anthropogenic driven ecological changes; increased volume and speed of international travel and commerce with rapid, massive movement of people, animals and commodities; and deterioration of public health infrastructure. Subcategory 1b includes known and unknown infectious agents that occur in new host ‘niches'. Infectious microbes/agents placed under this subcategory are better known as ‘opportunistic' pathogens that normally do not cause disease in immunocompetent human hosts but that can lead to serious diseases in immunocompromised individuals. The increased susceptibility of human hosts to infectious agents is largely due to the HIV/acquired immune deficiency syndrome pandemic, and to a lesser extent, due to immunosuppression resulting from cancer chemotherapy, anti-rejection treatments in transplant recipients, and drugs and monoclonal antibodies that are used to treat autoimmune and immune-mediated disorders. A notable example is the increased incidence of progressive multifocal leukoencephalopathy, a demyelinating disease of the central nervous system that is caused by the polyomavirus ‘JC' following the increased use of immunomodulatory therapies for anti-rejection regimens and for the treatment of autoimmune diseases.24,25,26 Subcategory 1c includes known and unknown infectious agents causing infections associated with iatrogenic modalities. Some examples of emerging infections under this subcategory include therapeutic epidural injection of steroids that are contaminated with Exserhilum rostratum and infectious agents transmitted from donor to recipients through organ transplantation, such as rabies virus, West Nile virus, Dandenong virus or Acanthamoeba.27,28,29,30,31
A larger number of AstVs were detected in both rodent and shrew samples (Additional file 1: Table S4). Fifty-five AstVs were selected for sequencing. Most of the rodent AstVs sequenced belonged to four main genetic lineages 1 to 4 within the genus Mamastrovirus and had less sequence similarity with AstVs in other hosts (Fig. 5c). One rodent AstV, RtRn-AstV-1/GD2015, was closely related to AstVs of cattle, deer, and pigs with > 90% nt identity. Two shrew AstVs, Shrew-AstV/SAX2015 and Shrew-AstV/GX2016, were related to mouse AstV with ~ 70% nt identity in the genus Mamastrovirus. Lineage 5 contained one shrew AstV and one mouse AstV, with 79% nt identity with each other. Lineage 5 branched out of the genus Mamastrovirus and showed a closer relationship with the genus Avastrovius.
Sixty rodent samples were identified as PicoV positive, and 23 strains underwent genome sequencing (Additional file 1: Table S4). Rodent viruses from the genera Enterovirus, Hunnivirus, Mosavirus, Cardiovirus, Rosavirus, Kobuvirus, and Parechovirus were found in this study and showed 48.3–56.4%, 80.4–80.8%, 47%, 46.8–60.3%, 60.9%, 63–76.9%, and 43.7–87.3% RdRp aa identities with known members in each genus, respectively (Fig. 5b and Additional file 1: Table S11). Eight viruses formed lineages 1 and 2 close to the bat PicoV clade with 38.1–43.6%, 33.5–38.8%, and 48.2–56.7% aa identities with bat PicoVs in the P1, P2, and P3 regions, respectively. Two novel lineages 3 and 4 were identified with < 10.2–28.9% aa identities in the P1 region, 17.3–23.6% in the P2 region, and 21.8–28.4% in the P3 region compared with other PicoVs (Additional file 1: Table S10). Viruses closely related to known PicoVs of other hosts were found (e.g., rodent viruses related to human aichivirus, human rosavirus, and bovine hunnivirus).
Examples of past emerging infectious diseases under this category are antimicrobial resistant microorganisms (e.g., Mycobacterium tuberculosis, Plasmodium falciparum, Staphylococcus aureus) and pandemic influenza due to a new subtype or strain of influenza A virus (e.g., influenza virus A/California/04/2009(H1N1)).9,32,33,34,35 Factors that contribute to the emergence of these novel phenotype pathogens are the abuse of antimicrobial drugs, ecological and host-driven microbial mixing, microbial mutations, genetic drift or re-assortment and environmental selection. Accidental or potentially intentional release of laboratory manipulated strains resulting in epidemics is included in this category.
∘Several types: A, B, C, D, E.∘Clinical findings: abdominal pain, nausea, anorexia, fevers progressing to jaundice, transaminitis.•Hepatitis A (Picornaviridae, +RNA virus):
∘Acute only. Not chronic.∘Spreads rapidly in emergency conditions.∘Can last 1 year in a minority of cases.∘Low fatality rate.∘Incubation: 30 days average∘Transmission: Fecal-oral route.∘Prevention: sanitation, hygiene, water supply, vaccine if in epidemic area, immunoglobulin in special cases.∘Management: supportive.•Hepatitis B (Hepadnavirus, dsDNA virus);
∘Acute infection, but can progress to chronic. Can result in hepatocellular carcinoma, cirrhosis.∘Diagnosis: analysis of antigens and antibodies to different components of the virus in the serum.∘2 billion persons infected globally by WHO estimates.∘Incubation: 2-3 months.∘Transmission: bodily fluid exposure, and even up to 7 days outside of human reservoirs on objects.∘Prevention: vaccine, blood bank control.∘Treatment: supportive. In some cases, although high cost, anti-viral medications can be given.•Hepatitis C (Hepacivirus, of the Flaviviridae, enveloped RNA virus):
∘75% become chronic infections. 20% of these will develop cirrhosis over 20 years. Some will develop hepatocellular carcinoma.∘Diagnosis: analysis of antigens and antibodies to HCV.∘150 million people are chronically infected with HCV according to WHO.∘Incubation: 6-9 weeks average.∘Transmission: parenteral (at-risk populations: drug abusers sharing needles, those receiving blood products frequently, hemodialysis patients)∘Prevention: no vaccine. Blood bank control. Needle exchange.∘Management: supportive. Anti-viral medications can clear the infection in some cases.•Hepatitis D (delta antigen of Hepatitis B)
∘Requires co-infection with Hepatitis B.∘More severe form of Hepatitis B.•Hepatitis E (Hepeviridae, single-stranded RNA virus)
∘Similar to Hepatitis A, but shorter course.∘High mortality in pregnant women.∘Co-infection indicates higher infectivity of Hepatitis B in adults.
The MAstV-1 species is comprised of HAstV-1–8, and surveillance has revealed that HAstV-1 is the most commonly detected type in children, followed by HAstV-2–5, whereas HAstV-6–8 have been rarely detected. HAstV-4 and HAstV-8 have been associated with infection of older children and longer duration of diarrhea (>7 days). A HAstV-4 strain was also isolated from an infant with fatal meningoencephalitis. Based upon the phylogenetic analysis of the ORF2 region, different lineages within each HAstV type have been proposed; HAstV-1 (HAstV-1a–d) and HAstV-2 (HAstV-2a–d) have been divided into four lineages, whereas HAstV-3 (HAstV-3a–b) and HAstV-4 (HAstV-4a–c) have been classified into two and three lineages, respectively.
The first “non-classic” HAstV strain characterized was MLB1, the virus was detected in a stool sample from a 3 year old Australian child with acute diarrhea in 1999; the child had previously received a liver transplant. The majority of MLB1 strains characterized to date have been detected in India, Kenya, and Japan with limited detected in the USA, China, Bhutan, Egypt, Brazil, and Italy and prevalence has been reported in the range of 0.2% to 9%. However, a seroepidemiologic study in the USA revealed that primary exposure to MLB1 occurs in childhood and that seropositivity reached 100% by adulthood suggesting the widespread circulation of the virus in the human population. MLB2 viruses were first identified in Vellore, India with the majority of strains subsequently identified in Japan, The Gambia, and Switzerland with limited detection in Turkey, USA, Kenya, China, and Thailand and prevalence reported in the range of 0.3% to 1.5%. MLB2 has been associated with meningitis and other CNS complications and has been detected in immunocompromised children. MLB3 viruses were first detected in India in 2004, with subsequent detection in Kenya and The Gambia and the prevalence in stools ranges from 0.6% to 3.1%.
The rapid development of the pig industry in China accompanies with outbreaks of epidemic diseases in recent years. Hepatitis E virus (HEV) has been identified on pig farms in many regions of the world, including China. HEV seropositivity rates of 76.6% and 90% have been reported in pig herds of large-scale and family-scale farms in China, respectively. Increasing evidence indicates that HEV can infect both humans and animal. To date, most studies of HEV based on prevalence surveys, and research into HEV-associated mortality during natural infection was limited. Mao et al. reported that co-infection with HEV and Porcine reproductive and respiratory syndrome virus (PRRSV) could lead to high mortality in swine, and they speculated that co-infection with HEV and other pathogens could cause serious disease. It has been demonstrated that HEV and Porcine circovirus 2 (PCV2) could cause infectious hepatitis, but swine naturally co-infected with HEV and PCV2 in China has rarely been reported. PCV2 infection occurs in many countries and poses a considerable threat to the swine industry. Although the recently research showed that infection of PCV2 could be effectively reduced by utilizing PCV2 vaccine, prevention of PCV2 in the pig production should be paid more attention. In the present study, pathogen identification and the observation of pathological changes demonstrated a natural co-infection with HEV and PCV2 in the swine on two pig farms in Hebei Province, China. This discovery may provide a new perspective for clinical research.
In 2008–2017, morbidity of Class B infectious diseases showed a significant downward trend, from 185.34/100,000 in 2008 to 54.36/100,000 in 2017 (χ2trend = 11,093.22, p < 0.05), with an annual morbidity of 90.39/100,000; morbidity of Class C infectious diseases showed a fluctuating upward trend, from 1352.97/100,000 in 2008 to 2549.03/100,000 in 2017 (χ2trend = 97,595.69, p < 0.05), with an average annual morbidity rate of 2412.47/100,000 (Table 1).
The top 5 reported Class B infectious diseases were dysentery, scarlet fever, measles, Influenza A (H1N1) and syphilis. The morbidity of measles, dysentery and syphilis showed a decline (measles: χ2trend = 10,156.59, p < 0.05; dysentery: χ2trend = 6301.75, p < 0.05; syphilis: χ2trend = 3376.99, p < 0.05); and that of scarlet fever was on the rise in recent years (χ2trend = 4185.20, p < 0.05). Influenza A (H1N1) was classified as a Class B infectious disease in 2009; 5805 cases of influenza A (H1N1) were reported in 2009, ranking first among Class B infectious diseases reported in the same year. This disease showed a decline in 2010 (χ2 = 5126.04, p < 0.05), and the number of cases reported was between 3 and 259 in 2010–2013. Since 1 January 2014, it was removed from Class B to Class C under the management of existing influenza (Figure 1).
The top 5 reported Class C infectious diseases were hand-foot-and-mouth disease (HFMD), other infectious diarrheal diseases, mumps, influenza and acute hemorrhagic conjunctivitis, among which the morbidity of HFMD, other infectious diarrheal diseases, and influenza were on the rise, while the morbidity of acute hemorrhagic conjunctivitis and mumps were decreasing year by year. In 2010, 11,789 cases of acute hemorrhagic conjunctivitis were reported, and thereafter the number of cases reported decreased rapidly (Figure 2).
The financing, provision, and quality of healthcare systems; the availability of vaccines, antivirals, and antibiotics medicines, and appropriate compliance to treatment protocols are all important determinants of infectious disease transmission. Although the correlation between healthcare system financing and efficacy is not perfect, recent budget cuts to healthcare are an important consideration when anticipating infectious disease risk. In part related to the global economic crisis, it has been reported that many high-income governments have introduced policies to lower spending through cutting the prices of medical products and, for example, through budget restrictions and wage cuts in hospitals (54). There are many indirect and direct pathways through which budget cuts could affect disease transmission; to provide just one example, it has been estimated that 20–30% of healthcare-associated infections are preventable with intensive hygiene and control programmes2 – should investments in this area diminish, then healthcare-acquired infections could become an even more problematic issue. There are currently roughly 4.1 million healthcare-associated infections each year in the EU alone.3
A broader issue related to healthcare provision is population mobility for both healthcare professionals and patients who might increasingly seek work or healthcare in other countries – the provision of cross-border healthcare and the mitigation of cross-border health threats will necessitate collaboration across borders (55, 56) and solutions for the brain-drain of medical personnel from resource-poor countries (57). Also related to the healthcare provision and practice is the over-prescription or overuse of antibiotics. In combination with a lag in pharmaceutical innovation, rapid transmission, and poor infection control measures, this has driven resistance of organisms such as methicillin-resistant Staphylococcus aureus, or extended-spectrum beta-lactamases, and carbapenemase-producing gram-negatives such as Klebsiella pneumoniae carbapenemase (KPC) (58). Antimicrobial resistance is currently one of the major health risks facing society (59).
Food production systems remain a persistent source for human infectious diseases. Attempts are underway to estimate the global burden of food-borne disease (60), which is likely substantial. Many factors in food production affect human health. A vast range of familiar human pathogens can be acquired through the consumption of animal products and other disease drivers, such as global travel, further provoke this (61). In addition to farmed animals, the hunting and slaughtering of wild animals has led to the emergence of more exotic pathogens: SARS originated in wildlife markets and restaurants in southern China (62) and HIV and Ebola have both been linked to the hunting or slaughtering of primates and other wild animals (33, 63, 64). The density and health of livestock, meanwhile, have been linked to disease in humans (65, 66). Although inconclusive, there is some evidence to suggest that livestock production may lead to increased antibiotic resistance in human pathogens. There are certainly many pathways by which drug resistant pathogens could transmit from livestock to humans, including environmental contamination by excreted veterinary antibiotics (33, 67, 68).
•Zoonotic disease.•Bunyaviridae virus.•Two different syndromes.
∘Shared features: fever prodrome, thrombocytopenia, and leukocytosis.∘Hemorrhagic Fever with Renal Syndrome (HFRS): fever for 3-7 days then severe back or abdominal pain, hypotension/shock, oliguria/renal failure, diuresis, then a long protracted convalescence phase if the patient survives.∘Hantavirus Pulmonary Syndrome (HPS): pulmonary edema/respiratory distress and shock. More fatal than HFRS.•Diagnosis: IgG and IgM in serum. Virus usually not detectable.•Reservoir: rodents.•Incubation: 2-4 weeks. Faster for HPS (2 weeks).•Transmission: aerosol from rodent excrement most likely.•Prevention: rodent control, disinfect rodent infested areas, vaccine (only available for Hantaan and Seoul viruses).•Treatment: supportive care. Dialysis for HFRS. Ribvarin in some early cases. Avoid supplementing too much fluids with HPS. Respiratory ICU level of care for HPS.
Hepatitis A virus is a small, single stranded, and non-enveloped RNA virus of the Picornaviridae family 18. It can be grouped into I, II and III genotypes based on its genomic characterisation. Hepatitis A virus infections are the leading cause of viral hepatitis, with 1.4 million of new cases worldwide annually 19. The cost of foodborne hepatitis A is estimated to be more than 36,000 U. S. dollars per individual in the United States.
Hepatitis A virus can be infectious at low doses of 10-100 viral particles 20. It is transmitted through the fecal-oral route in humans, as well as intake of contaminated water and foods such as fruits, uncooked vegetable, and shellfish. Waterborne and foodborne infection of hepatitis A viruses accounts for 2-7% of the total disease burden, and foodborne infection is common, often resulting in a larger and prolonged outbreak.
Four distinct papillomavirus sequences were identified in two bat species, E. helvum (Eidolon helvum papillomavirus 8; EhPv-8) and T. perforatus (T. perforatus papillomavirus 1, 2 and 3; TpPv-1, -2, -3). Complete coding sequences were recovered for EhPv-8 (acc. no. KX434763, 6985 bp), TpPv-1 (acc. no. KX434764, 7180 bp) and TpPv-3 (acc. no. KX434767, 7083bp). EpPv-8 shared 63% aa similarity to E. helvum papillomavirus type 1 across the DNA helicase protein (E1). TpPv-1, TpPv-2, and TpPv-3 (acc. no. KX434766, partial genome) shared 44%, 47% and 44% aa similarity across the E1 protein with human papillomavirus 63, Miniopterus schrebersii papillomavirus 1, and Castor canadensis papillomavirus 1, respectively (Fig 7).
Social and demographic contexts can significantly influence the transmission of infectious disease, while also creating increased vulnerabilities for some population subgroups. The elderly are at greater risk of many infectious diseases, and the ageing trend in many high-income countries could increase the challenges related to nosocomial (hospital-acquired) and nursing-home acquired infections. An additional challenge related to population ageing is that the share of employed workers in a country decreases. The combination of more people to care for and fewer tax-related revenues may challenge publicly financed public health and disease control programmes (7).
When persons from regions with high endemicity of a given disease move to ones with lower endemicity, new challenges for public health are created. In addition migrant communities can be highly vulnerable to certain infectious diseases. In the EU, for example, approximately 37% of HIV cases reported in 2011 were among people born abroad, and the equivalent number of cases for tuberculosis was 25% (40). Similarly, migrants suffer from a higher burden of chronic hepatitis B infections (41).
It is widely established that socially and economically disadvantaged groups suffer disproportionally from disease (42). This is applicable to infectious disease burdens in both high- and low-income settings (43, 44). Income inequalities are generally widening globally, and this appears to be have been exacerbated in many countries due to the global economic crisis (45). Rising unemployment and the prospect of public health budget cuts can increase the risk of infectious disease transmission (44, 46), with a prominent example being an outbreak of HIV among people who inject drugs (PWID) in Greece (see ‘Measles among Roma in Bulgaria and HIV among PWID in Greece: the impact of socioeconomic contexts’ section) (47, 48). In a similar fashion, it has been speculated that tuberculosis rates could rise in some countries in Central and Eastern Europe (49).
Social trends and behaviours can also play a significant role in infectious disease transmission. The most notable example would be vaccine hesitancy, the phenomenon through which vaccination coverage rates remain suboptimal due to the varying and complicated reasons that individuals may have for not getting vaccinated (50, 51). In some cases, this might be related to misconceptions about the safety or efficacy of vaccines (50, 52), whereas in others this may be related to religious or cultural beliefs (53).
Hepatitis B virus is a partially double stranded, enveloped, and parenterally transmitted circular DNA virus 21. Hepatitis B virus infection is the tenth leading cause of death and a major health threat globally 22. As the major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma, the infection is spreading to more than 350 million people as its carriers disburse globally. It has infected about 30% of the world population, causing more than 780,000 death annually from complications. A total hepatitis B virus related cost is more than 600 million Euro in western countries annually.
Hepatitis B virus is transmitted by contact with infected individuals through blood or other body fluids 23. It is at high risk when the viral concentration reaches 105 copies/mL, which is associated with liver diseases including cancer. The exposure to contaminated blood or body fluids is considered to be the major transmission routes for the virus. Antibodies against the surface antigens of the virus are produced to high levels following hepatitis B virus infection.
During the period of 2008–2017, a total of 32 types and 1,994,740 cases of notifiable diseases in children aged 0–14 years, including 266 deaths, were reported in Zhejiang Province, with an annual average morbidity rate of 2502.87/100,000 and an annual average mortality rate of 0.33/100,000. There were no cases and deaths involving plague, cholera, infectious atypical pneumonia, human infection with avian influenza, polio, anthrax, diphtheria and filariasis. No Class A infectious diseases were reported. Twenty-two types and 72,041 cases of Class B infectious diseases were reported, including 138 deaths; 10 types and 1,922,699 cases of Class C infectious diseases were reported, including 128 deaths.
Hepatitis B is found in virtually every region of the globe. Of the more than 2 billion people who are or have been infected, 350 to 400 million are carriers of the chronic disease; the remainder undergo spontaneous recovery and production of protective antibodies. Nearly 100% of infected infants (that is, those born to HBV-infected mothers) become chronically infected. The risk of developing a chronic infection decreases with age.
At least 30% of those with chronic HBV infection experience significant morbidity or mortality, including cirrhosis and hepatocellular carcinoma. Most people do not know they are infected until they present with symptoms of advanced liver disease, which means that infected individuals can spread the infection unknowingly, sometimes for many years. Although oral antiviral therapies are effective at stopping HBV replication, they do not cure the disease. Therefore, therapy is usually lifelong. Treatment is also complicated by the development of drug resistance and side effects. A vaccine against HBV is safe and effective in 90 to 95% of people; however, the individuals who are most at risk of becoming infected are often those with limited access to the vaccine, such as marginalized populations or people living in resource-limited countries.
There is substantial evidence that an individual's likelihood of recovering from an acute HBV infection or developing severe sequelae from infection is influenced, in part, by genes [39–45]. Candidate gene and genome-wide association studies have identified variants associated with HBV-related disease progression or hepatocellular carcinoma in various populations [46–52]. Treatment response to interferon (IFN)-α has been associated in some, but not all, studies with IFNλ3 polymorphisms. Finally, specific gene variants (HLA and non-HLA alleles) have been associated with vaccine response and non-response [54–57].
Nearly 60% of emerging infectious diseases in humans are zoonotic, with up to 70% of them being found to originate from wildlife. Bats have been identified as natural reservoirs of many viruses. Some of these viruses cause outbreaks of severe disease in humans, including the Ebola virus, the lyssavirus, the severe acute respiratory syndrome coronavirus, and henipaviruses. Interestingly, these viruses rarely cause apparent clinical signs in bats. Bats possess unique characteristics that may contribute to their ability to act as a major natural reservoir for viruses, including a high level of species diversity, a long lifespan, a high population density, and high levels of spatial mobility.
Previous studies mainly focused on bat-borne viruses that are transmitted via respiratory droplets. However, in recent years, several hepatitis virus-related sequences, including those associated with hepadnaviruses, hepeviruses, hepatoviruses, and hepaciviruses, have been found in bats across the globe, indicating the importance of bats as the natural reservoirs of these viruses [5–9].
Hepatitis viruses include hepatitis viruses A, B, C, D, and E, which cause human hepatitis diseases. Hepatitis A virus (HAV) is classified as belonging to the genus Hepatovirus in the family Picornaviridae. Hepatitis B virus (HBV) is classified as belonging to the genus Orthohepadnavirus in the family Hepadnaviridae. Hepatitis C virus (HCV) is classified as belonging to the genus Hepacivirus in the family Flaviriridae. Hepatitis D virus (HDV) is considered to be a subviral satellite because it can only propagate in the presence of HBV. Hepatitis E virus (HEV) is classified as belonging to the genus Orthohepevirus in the family Hepeviridae. Hepatovirus-related sequences have been identified in 13 species of bat collected in North America, Europe, and Africa. Hepadnavirus-related sequences have been discovered in five species of bat collected in Panama, Gabon, Myanmar, and China [6, 8–10]. Highly diverse hepacivirus-related sequences have been detected in 20 species of bat across the world. Hepevirus-related sequences have been discovered in bats in Ghana, Panama, and Germany. These results indicate that bats may be important reservoirs of these hepatitis viruses (Table 1).
There are around 120 species of bat in China; however, only limited information has been reported regarding the hepatitis viruses, a novel Orthohepadnavirus in pomona roundleaf bats from Yunnan province was identified in 2015. In this study, we report the discovery of four novel hepadnaviruses and a hepevirus in our archived bat liver samples that had been collected from several bat species and various geographical regions in China.
From November to December 2013, an outbreak of an unknown disease occurred at two small-scale pig farms (103 pigs in farm A and 101 pigs in farm B), operating for a short time in Hebei Province, China. All of the piglets fed in both pig farm A and B were aged 2–3 months. Pig farm A reported the deaths of 93 piglets (mortality rate was 90.3%), and pig farm B the deaths of 90 pigs (mortality rate was 89.1%). The affected animals on both farms presented with symptoms of fever, dyspnea, diarrhea, and anorexia. In pig farm A, the veterinary administrated timicosin and doxycycline to treat the pigs. And in pig farm B, florfenicol was administrated. However, the swine did not respond to antibiotic treatment.
This study is a preliminary assessment of viral sequences in the fecal matter of healthy commercial mink on 40 Ontario farms, and the diversity of bacteriophage and eukaryotic virus sequences was fairly consistent with previous research on the fecal virome of carnivorous species (Fehér et al., 2014; Ng et al., 2014; Phan et al., 2015; Smits et al., 2013; Zhang et al., 2014). The 12 most prevalent phages detected in this study represent 70% (76,558/109,612) of all detected phage sequences. Comparison between the phage sequences and their respective bacterial hosts in the same cohort of mink fecal samples show that Enterococcus, Lactobacillus, Lactococcus, Clostridium, Escherichia, Streptococcus, and Pseudomonas species were also prevalent in the mink microbiome (unpublished data). Bacillus, Salmonella, Shigella, Staphylococcus, and Proteus bacterial populations were not found to be highly prevalent in the mink fecal microbiome study (unpublished data). In a fecal microbiome study conducted on samples from mink in Northeast China, Zhao et al. (2017) showed that the two most prevalent bacterial genera were Clostridium and Escherichia, phages, both of which were found in our study. Interestingly, significantly higher numbers of Pseudomonas‐associated phage sequences were detected in adult female fecal samples compared to kit samples (q = 0.02), but since the detected sequences may not represent colonization by Pseudomonas species, the implications of these results remain unclear. Although previous studies have shown that lytic phage therapies may be useful in controlling Pseudomonas bacterial populations (Cao et al., 2015; Gu et al., 2016), further investigation is required to understand the natural role that the associated bacteriophage species play in bacterial populations. Producers were asked to voluntarily report the use of antimicrobials on farms, but due to only partial completion of the survey, the information collected on antimicrobial use from the 2014 sample cohort may not be fully representative. Therefore, any relationship between antimicrobial use and the relative abundance of targeted bacterial species could not be analyzed.
This study found the highest number of vertebrate viral sequences from the families Herpesviridae, Parvoviridae, Circoviridae, Anelloviridae, and Picornaviridae. Previous fecal virome studies in ferrets and felids have also found high numbers of viral sequences belonging to the families Parvoviridae, Anelloviridae, and Picornaviridae, but have also detected sequences from the families Astroviridae, Reoviridae, Hepeviridae, Papillomaviridae, Picobirnaviridae, and Coronaviridae (Fehér et al., 2014; Ng et al., 2014; Smits et al., 2013; Zhang et al., 2014). High numbers of sequences with 84%–96% identity to posavirus 3 strain 958‐4 were identified, which has been previously detected in fecal samples collected from commercial swine in high animal density farms (Hause, Hesse, & Anderson, 2015). Hause et al. (2015) suggest that this strain of posavirus is derived from nematodes parasitizing commercial swine. The detected posavirus sequences may be the result of contamination from the soil at the time of fecal sample collection, but also could be attributed to the mink diet, which often consists of pork and poultry products, or nematode infections in the mink gut (Krog, Breum, Jenson, & Larsen, 2013). Similarly, the identified avian‐associated viral sequences (chicken anemia virus, parvovirus, smacovirus, and avian adeno‐associated virus) were most likely the result of mink diet. Previous evidence from viral metagenomic studies and case reports in ferrets, felids, mink, and other wild carnivores have also hypothesized that the presence of avian viruses and swine viruses in fecal samples is due to the diet of the animals (Bodewes et al., 2014; Fehér et al., 2014; Krog et al., 2013; Smits et al., 2013). Further research is required to determine the correlation between diet and the fecal virome of mink. This is also the first report of mink bocavirus sequences in commercial mink fecal samples in Canada, with 98%–100% identity to the strain identified in 2016 in China (Yang et al., 2016). This strain was most closely related to feline bocavirus (JQ692585). Yang et al. (2016) found no correlation between mink bocavirus and diarrhea, but stated that these results may not be fully representative due to the small sample size.
Viruses with low average identity were used in de novo assembly and the resulting consensus sequences were compared to closely related viruses. Most consensus sequences found to be closely related to the initial best BLASTn hit of the individual sequences, with the exception of HCBI8.215‐like virus 2014‐ON_consensus and chapparvovirus 2014‐ON_consensus. HCBI8.215‐like virus 2014‐ON_consensus was found to be more closely related to torque teno virus strain TTV‐HD14a. Chapparvovirus 2014‐ON_consensus did not cluster with the initial best BLASTn hit, Desmodus rotundus parvovirus strain DRA25, or three other parvoviruses with similar not closely related to Eidolon helvum parvovirus 2 isolate Parvo_th_node176_9_9_893755, rat parvovirus 2 strain 9 or turkey parvovirus TP1‐2012/HUN, indicating that it could be a novel mink parvovirus. Aside from mink bocavirus, the other prevalent vertebrate viruses identified in this study have been previously isolated in other species. HCBI8.215 virus was first isolated from the serum of healthy cattle, and gyrovirus Tu243 and GyV3 were isolated from human fecal samples (Lamberto, Gunst, Muller, Hausen, & de Villiers, 2014; Phan et al., 2012, 2014). Six of the 15 prevalent vertebrate viruses described in this study are of avian origin. Although virus shedding does not represent active infections, some of the viruses identified in this study may have the potential to be transmitted to the humans, commercial and wild animals in close proximity to mink farms due to poor biosecurity (Compo et al., 2017).
In conclusion, this viral metagenomic study provides a preliminary overview of the commercial mink fecal virome, showing a diverse range of bacteriophage and eukaryotic virus sequences, including a potentially novel chapparvovirus. It is not known whether the detected bacteriophage and eukaryotic virus sequences represent commensal species, or if these viruses are capable of influencing bacterial populations and causing disease in mink. Further research is required to clarify the phylogeny of low‐identity sequences identified in this study and to determine the role of these prevalent viruses in mink health.
From 2008 to 2017, China achieved impressive reductions in the burden from infectious diseases in children and adolescents aged 6 to 22 years. This complements the reduction in mortality from infectious diseases in under 5s—a longstanding focus of the Millennium Development Goals, and will contribute to reductions in the overall burden from infectious diseases in China.16
60 However, China’s rapid success poses challenges for policy makers as priorities for infectious disease control continue to evolve. Beyond maintaining the gains, the priorities for the coming decade include reducing regional inequalities; scaling-up vaccination for mumps, seasonal influenza, and hepatitis B; preventing further escalation of HIV/AIDS and other sexually transmitted diseases; and redoubling efforts around persisting diseases, including tuberculosis, rabies, and scarlet fever. Different responses will be needed by region and by age across childhood and adolescence, while the newer emerging disease epidemics will require rapid and targeted responses. Seasonal variation in respiratory infections and in gastrointestinal and enterovirus diseases reflect the high vulnerability of children and adolescents. A comprehensive national surveillance system remains an integral part of infectious disease control in these age groups to maintain the gains of recent decades and respond effectively to new epidemics.
In China, if a notifiable infectious disease is clinically diagnosed and/or laboratory confirmed according to the unified national diagnostic criteria issued by the NHFPC, cases must be reported to the national China CDC, which collects and analyses the acquired data. The health care provider enters the case information using a standard form into the Notifiable Infectious Diseases Reporting Information System (NIDRIS), a web-based system that enables all healthcare institutions to report cases of notifiable infectious diseases. Approximately 5 million infectious disease cases are reported annually (≈ 385 cases per 100,000 citizens per year). Each China CDC level can analyse its own data in NIDRIS and data from subordinate levels within its own administrative boundaries.
In the Netherlands, if a notifiable infectious disease is suspected and/or laboratory tests confirms it, the case must be reported both by the attending physician and the laboratory to the regional PHS. The case information is collected and entered by the PHS into Osiris, a web-based database that transmits the data to RIVM for further analyses. In 2014, 13,863 notifiable disease cases were reported via Osiris to RIVM (≈ 815 cases per 100,000 citizen per year).
Z-LS, BA, BH, and SOO conceptualized and designed the study. Z-LS, BA, BH, SO, and VO coordinated the study and the field work. BA, SO, VO, and SOO participated in the field work. Z-LS and BA supervised the study. BA, SOO, BH, and X-LY designed and coordinated the experiments. SOO and GO managed the storage and retrieval of specimen. BL and BH coordinated the laboratory skills training. BA and VO were responsible for application and acquisition of ethics permit. SOO performed the experiments, and analyzed and interpreted the data. KK, YF, and X-SZ assisted with data analysis. SOO and BH drafted the manuscript.
Although lower respiratory infections, including pneumonia, are one of the main causes of death worldwide, real-time surveillance systems and situational awareness are generally lacking.
In the year after the SARS outbreak in 2003, NHFPC developed a surveillance system for unexplained pneumonia to facilitate timely detection of airborne pathogens that form a severe threat to public health. Therefore, all Chinese health care facilities are required to report any patient who has a clinical diagnosis of pneumonia with an unknown causative pathogen and whose illness meets the following five criteria (2007 modified definition): (1) fever ≥38 °C; (2) radiologic characteristics consistent with pneumonia; (3) normal or reduced leukocyte count or low lymphocyte count in early clinical stage; (4) no improvement or worsening of the patient’s condition after first-line antibiotic treatment for 3–5 days; and (5) the pneumonia etiology cannot be attributed to an alternative laboratory or clinical diagnosis (clinicians are granted flexibility to determine how to interpret this criterion and specific tests are not specified) [22, 23]. Once the case is registered in NIDRIS, the data are further analysed in CIDARS as a type 1 disease, for which a fixed-threshold method (of 1 case) is applied. A real-time SMS is followed by a field investigation, whereby case samples are tested to rule out avian influenza, SARS and Middle East respiratory syndrome coronavirus (MERS-CoV). Although physicians are required to report unexplained pneumonia cases, considerable under-reporting occurs. The aim of this surveillance system is not to detect each unexplained pneumonia case but to focus on clusters that could indicate an (unknown) emerging infectious disease outbreak.
Unexplained pneumonia is not a notifiable condition in the Netherlands as it is in China. However, according to the Public Health Act (2008), each physician should notify a case or an unusual number of cases with an (unknown) infectious disease that forms a severe threat to public health. An example is the Q fever outbreak (2007); the unusual number of atypical pneumonia cases early in the outbreak were not detected by routine surveillance systems but by astute general practitioners (GPs). Both Dutch legislation and the Chinese pneumonia surveillance system aim for early notification of (unknown) emerging infectious disease outbreaks. However, in both countries, criteria for notification are not well defined and a considerable degree of under-ascertainment and under-reporting is likely. In the Netherlands, structural syndromic pneumonia surveillance is carried out using data extracted from electronic patient files maintained by sentinel GP practices, representing 7% of the Dutch population. Moreover, sentinel registration of pneumonia cases in nursing homes takes place. A separate virologic laboratory surveillance system provides information on circulating respiratory viruses. Since 2015, a pilot study has been carried out for hospitalized severe acute respiratory infections (SARI) patients. As it includes only two of 133 hospitals in the country at present, the obtained data is not yet reliable to provide early warning of infectious pneumonia outbreaks. Currently, no set threshold exists for unusual occurrence of pneumonia. Expert opinion determines which signals are discussed by the NEWC.
More than half of the documented human pathogens are zoonotic, and emerging infectious diseases (EIDs) are more likely to be caused by pathogens of zoonotic origin (Woolhouse and Gowtage-Sequeria, 2005; Jones et al., 2008). In most instances, high impact outbreaks of the past decades and present pandemics have resulted from pathogens of wildlife origin, which usually cause little or no clinical signs of infection in their natural hosts (Wu et al., 2018), but with devastating global health and economic effects when they spill over into humans and livestock (Allen et al., 2017). The present global upsurge in outbreaks of emerging and re-emerging infectious diseases has necessitated the search for reservoirs of zoonoses of public health importance in order to develop resilient response strategies.
RNA viruses account for a large part of the known zoonotic pathogens owing to their often high rates of mutation and capacity to infect and adapt in a wide range of hosts (Woolhouse and Gowtage-Sequeria, 2005; Jones et al., 2008; Meheretu et al., 2012). Surveillance and discovery programs of EIDs in wildlife have identified rodents and shrews as natural reservoirs of diverse RNA viruses such as hantaviruses, arenaviruses, astroviruses, picornaviruses, paramyxoviruses, etc. (Klempa et al., 2006; Meheretu et al., 2012; Firth et al., 2014; Hu et al., 2014; Sasaki et al., 2014; Gryseels et al., 2015; Gouy de Bellocq et al., 2016; Těšíková et al., 2017; Wang et al., 2017). It is believed that these viruses establish themselves in their hosts through co-evolution and are maintained in nature by both vertical and horizontal transmissions (Streicker, 2013). Spillover events into humans and livestock result from encounters with these small mammals whose presence around human dwellings is on the rise either as pests or as food (Bonwitt et al., 2016). Evidently this poses a potential threat to public health and it is imperative that pathogen surveillance and discovery programs are implemented on high risk wildlife groups including rodents and shrews.
Kenya is a country rich in wildlife diversity, with a nationwide distribution of about 106 rodent and 36 shrew species (Musila et al., 2019). Expansion in agricultural activities among other anthropogenic factors encourages encroachment into wildlife habitats and amplifies the frequency of human contacts with these animals and pathogens carried by them (Young et al., 2017). However, there is currently no documentation of viruses harbored by rodents and shrews in Kenya yet they have been sighted and trapped around human dwellings. Also, there could be a possibility of misdiagnosis and underreporting of human infections with rodent-borne viruses in the country. These gaps justify the need to investigate and characterize the diversity of viruses in rodents and shrews and quantify the possible impact of these viruses on public health in Kenya. It was against this backdrop that we carried out this study, in which both wild and peridomestic species of these animals around and within agro-ecological zones near human habitations were sampled and screened for a variety of RNA viral families. This work thus constitutes the first virus surveillance study in Kenyan rodents and shrews, and provides baseline data for understanding the distribution, genetic diversity, as well as potential spillover risk of RNA viruses circulating in small mammals in Kenya.