Dataset: 11.1K articles from the COVID-19 Open Research Dataset (PMC Open Access subset)
All articles are made available under a Creative Commons or similar license. Specific licensing information for individual articles can be found in the PMC source and CORD-19 metadata.
More datasets: Wikipedia | CORD-19
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)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
Malnutrition is the most common cause of immune deficiency worldwide and a balanced diet is fundamental for a healthy immune system. Vitamin D deficiency has been associated with increased risk of infections, early-life wheeze and reduced asthma control. Vitamin A derivatives are involved in the regulation of the immune system and tissue inflammation as well as prevention of respiratory infections. Zinc, selenium and other trace elements are necessary for function of both innate and adaptive immune function. A high intake of fruit and vegetables ensures adequate consumption of nutrients and antioxidants and appears to be beneficial for asthma. Although recent reviews have shown that zinc, garlic, Echinacea purpurea or Ginseng supplementation for several months may reduce cold incidence, there is insufficient evidence to recommend any vitamin or mineral supplementation in the management of asthmatic children without nutrient deficiency. However, a large controlled trial showed Echinacea was ineffective in reducing infection rate or symptom severity of HRV infection in healthy young adult volunteers. Vitamin C supplementation failed to reduce the incidence of colds in the general population except in those exposed to short periods of extreme physical stress. Finally, it is worth remembering that infants who are not breastfed have significantly higher risk of respiratory, gastrointestinal, and other infections, as breast milk is a biologically active substance containing antimicrobial and immunomodulatory elements.
PCV2-SD is a recently characterized disease of pigs. The confirmation of PCV2 infections is by demonstration of viral antigens or DNA through IHC or in situ hybridisation, and PCR. These two diagnostic techniques require well established laboratory facilities and trained personnel. Since Uganda currently lacks these facilities at district level; confirmatory diagnosis, surveillance and subsequent information dissemination to pig farmers (mainly small holders) may not be possible. This may partly explain the limited level of awareness of animal health practitioners and the farmers.
Lack of appropriate information on PCV2 infections and associated diseases is likely to contribute to the propagation of these infections. Also, appropriate management aimed at minimizing the risk factors, may be overlooked by farmers. For example, 99.2% (P < .001) of the farmers mixed weaned piglets from different sows thus age groups and different sources. Also, early weaning (below five weeks) was being practiced by over 30% of the farmers. The later contributes to early withdrawal of maternal antibodies before development of the immune system. The risk of occurrence and aggravation of morbidity due to PCV2 infections is known to be compounded by the above factors,,,. Moreover, most pig farms in Uganda hardly implement proper bio-security measures. Although effective commercial vaccines against PCV2 infections have been developed,, their use to control PCVADs has never been explored in Uganda. Occurrence of PCV2 infections on some farms as revealed by this study indicates failure to control triggers for onset of PCV2-SD which presents a big risk for occurrence of epidemic outbreaks.
PCV2 infections are immunosuppressive and frequently occur with persistent secondary bacterial infections. Limited knowledge of pig farmers and field animal health workers (AHWs) on the existence of PCV2-SD presents clinical diagnostic errors which may inadvertently contribute to unwarranted use of antibiotics and other chemotherapeutic agents targeting diseases with similar manifestations. Indeed, 87% of the farmers reported persistent diarrhea in this study continued treating refractory cases when the pigs did not improve after the first treatment regimen. Such practices may result in contamination of pork and pork products with antibiotic and other drug residues.
Immunosuppression, a major feature of infected pigs, may also contribute to pig products contamination with food borne pathogens like Salmonella typhimurium, Campylobacter jejuni and Yersinia enterocolitica
. Also, persistent use of antibiotics among pigs with PCV2-SD may contribute to the emergence of multi-antibiotic resistant bacteria. The above health hazards may discourage consumers from the consumption of pig products. This may retard the growth of the pig industry, one of the most rapidly growing animal enterprises in Uganda.
Only five (25%) of the 20 chronically wasted pigs were positive for PCV2. This emphasizes the importance of confirmatory diagnosis in disease management. Prolonged fixation of tissues in formalin may affect the sensitivity of IHC and PCR. In this study, samples were processed within two weeks to minimize the effects of prolonged fixation of tissues in formalin. Despite the confirmation of PCV2 infections from one district (Wakiso), the extent of the problem may be widespread since there is a limited control in the movement of breeding stock amidst poor diagnosis, subclinical states and limited knowledge. Actually, the study sampled only pigs presenting with chronic diarrhea for laboratory detection of PCV2 in tissues hence subclinical infections which are highly prevalent in other regions of Uganda, were not investigated. Chronic wasting among pigs that were negative for PCV2 could not be fully characterized as their causes were not investigated. Such may include malnutrition and viral enteropathies such as rotavirus, parvovirus and corona virus infections among others. Future studies are recommended to investigate the extent of PCVADs and other enteropathies and their contribution to the onset of PCV2-SD.
Upper respiratory tract infections (URTIs) are one of the most common reasons for presentation to primary practice by adults and children, and are a major cause of mild morbidity 56. Symptoms range from the common cold, cough, pharyngitis and fever to occasionally more serious complications, and are associated with high societal costs due to loss in productivity, absenteeism from school and medical resources 57. Most URTIs are caused by viruses, such as adenovirus, rhinovirus, influenza, coxsackievirus, herpes simplex virus, coronavirus and respiratory simplex virus 58. However, current practices do not often consider the aetiological basis of the URTI, leading to inappropriate antibiotic prescription for URTI that are of viral origin 59. This is particularly evident in the treatment of pharyngitis or sore throat, where only 5–30% of cases are because of bacterial infections 60. Inappropriate and overuse of antibiotics further reinforce the importance of identifying alternative anti‐infective agents 61 to complement physical and barrier interventions e.g. handwashing and wearing of masks to prevent and interrupt the spread of respiratory pathogens.
The first step in the development of URTIs is the adherence and colonisation of the respiratory pathogen to the oropharyngeal mucosa. Assuming oral entry of such pathogens, gargling offers a practical measure for their eradication 62. Gargling has been strongly advocated for both prevention and treatment of URTIs in Japan, a practice supported by findings from studies that looked at the role of gargling in both healthy individuals and those with frequent or persistent respiratory infections 62, 63, 64. In these studies, gargling with either water or PVP‐I (four times daily), respectively, were found to reduce the incidence of URTIs. Furthermore, in patients experiencing chronic respiratory infections, PVP‐I was found to reduce the episodes of infections with P. aeruginosa, S. aureus (including MRSA) and H. influenzae by half 62. These findings were further corroborated by a non‐randomised study in which gargling with diluted PVP‐I reduced the incidence of influenza‐like illnesses or the common cold and subsequent absenteeism from school and the work place 65. While the mechanism of gargling in the prevention of respiratory infections requires further investigation, an early study suggests that gargling may lead to the removal of oral/pharyngeal house dust mite protease which has been shown to increase infectivity of the influenza virus 64, 66. Gargling, intensified by the presence of PVP‐I, may therefore play an important role in the prevention or reduction in the incidence of infection through droplet transmission.
Indeed, the benefit of gargling with PVP‐I has been noted in Japanese clinical respiratory guidelines that recommend gargling with PVP‐I (four times a day) in both inpatients and healthcare workers for the prevention of hospital‐acquired pneumonia 67. PVP‐I has also been recommended as a preventative measure against pandemic influenza 68, 69.
The bactericidal activities of PVP‐I gargle were further explored in a study of children attending middle schools in Japan and their effects on absenteeism because of colds or influenza were assessed 34. The mean reduction rate in bacterial count immediately after gargling with PVP‐I was 99.4% vs. 59.7% and 97.0% with CHG and CPC respectively. Furthermore, the more effective reduction in bacteria count with PVP‐I correlated with lower absence rates because of cold and influenza compared with the other schools where the use of other gargles were encouraged 34.
Respiratory infections in the hospital setting such as aspiration pneumonia or VAP are major issues, especially in elderly people and immunocompromised patients and are associated with high rates of mortality 70, 71. Moreover, individuals with gastro‐oesophageal reflux disease (10–20%) can develop recurrent or chronic aspiration pneumonia because of aspiration of gastric contents into the lungs 72. Pneumonia is also common in patients on mechanical ventilation resulting from aspiration of salivary bacteria into the lower respiratory tract 73.
In a prospective, randomised study, the efficacy of a PVP‐I rinse on the prevalence of VAP in patients with severe head trauma who were expected to need ventilation, was assessed. When compared with those who received saline and control (no rinsing), significantly fewer patients in the PVP‐I group (p = 0.03 and 0.01, respectively) developed VAP 74.
In another randomised study, the efficacy of PVP‐I in mechanical and chemical prophylactic oral cleansing in reducing oral respiratory pathogens in patients requiring endotracheal intubation was assessed. Cleaning with PVP‐I resulted in significant reductions in microbial counts of S. pneumoniae (p < 0.05) and H. influenzae (p < 0.05) 75. In a separate study assessing the prophylactic use of PVP‐I gargle in reducing the risk of nosocomial pneumonia, PVP‐I was found to eradicate both general bacteria and MRSA colonies in the pharynx before intubation and at the tip of the tube after extubation 76.
These studies provide a strong rationale for the use of PVP‐I as an effective oral care measure to reduce the burden of potential pathogens and minimise the risk of infection in both community‐acquired and hospital‐acquired settings.
This study demonstrated the occurrence of PCV2 infections associated with chronic wasting and persistent diarrhea in pigs on farms in Central Uganda and low levels of knowledge on PCV2-SD among farmers and AHWs. It is therefore imperative to sensitize farmers and veterinary practitioners about the existence of PCV2 infections and PCVADs with their possible effects on the Ugandan pig industry, public health and pig welfare. Further studies on the prevalence and mapping of PCV2 infections and PCVADs are required to establish the extent of the infection to guide interventions. Vaccination against PCVADs should also be encouraged to control the disease on pig farms.
Air pollutants (nitrogen dioxide, ozone, particulate matter) and environmental tobacco smoke (ETS) have long been correlated with multiple adverse effects on the immune system and susceptibility to viral respiratory tract infections in children. Studies in Europe and the United States have shown that 40% of children live with a smoker and they have approximately twice the risk of contracting a serious respiratory tract infection in early life. Cigarette smoking leads to a longer duration of cough, greater frequency of abnormal auscultatory findings during acute respiratory tract illness and higher risk for severe exacerbations. Urinary leukotriene E4 levels identify children exposed to ETS at high risk for asthma exacerbation.
Causative agents of diarrhea were detected in 164 of 207 diarrheal calves (79.2%). The remaining diarrheal calves were placed in the following diagnostic categories: abomasal impaction (n = 6), abomasal ulcer (n = 3), and others, which included diarrhea with unknown causes and undetected causative agents owing to insufficient fecal samples.
Fourteen species of causative agents were detected in 164 of 207 diarrheal calves. Rotavirus was the most common causative agent (57/164 calves, 34.8%), followed by Eimeria spp. (52/164, 31.7%), E. coli (36/164, 22.0%), Giardia spp. (23/164, 14.0%), Clostridium difficle (C. difficile, 16/164, 9.8%), BVDV (14/164, 8.5%), coronavirus (13/164, 7.9%), Cryptosporidium spp. (12/164, 7.3%), torovirus (11/164, 6.7%), parvovirus (9/164, 5.5%), norovirus (8/164, 4.9%), kobuvirus (3/164, 1.8%), adenovirus (2/164, 1.2%), and Salmonella spp. (1/164, 0.6%).
Viruses (117/164, 71.3%) were the most common causative agent, followed by protozoans (87/164, 53.1%) and bacteria (53/164, 32.3%). Although several causative agents were detected, rotavirus, Eimeria spp., Giardia spp., E. coli, Cryptosporidium spp., C. difficile, BVDV, and coronavirus were the main causative agents in KNC.
A total of 95 from 164 calves (57.9%) were infected with a single causative agent, while 69 calves (42.1%) were infected with multiple causative agents. A total of 48 of 164 calves (29.3%) were infected with viruses alone, while 18 (10.9%) and 29 (17.7%) were infected with bacteria and protozoans alone, respectively (Table 1).
In cases of mixed infection (69 out of 164 calves, 42.1%), 53 calves (32.3%) were infected with double causative agents and 9 (5.5%), 6 (3.7%), and 1 (0.6%) were infected with triple agents, quadruple agents, and quintuple agents, respectively (Table 2). Eimeria spp. (32/164, 19.5%), rotavirus (29/164, 17.7%), and E. coli (23/164, 14.0%) were the most commonly detected agents in calves with mixed infections (Table 3). Most causative agents were related to mixed infection rather than single infection.
This study contributes with information concerning the dynamics of a specific subtype of VTEC O157:H7 colonisation in dairy calves. This subtype, VTEC O157:H7 (PT4;vtx2;vtx2c), is frequently isolated from Swedish cattle and has also been found to cause the majority of reported human infections in Sweden during the past 15 years. In most calves, inoculated with a representative strain of this specific subtype, the numbers of shed bacteria declined over the first two weeks. One calf could possibly be classified as a high-shedder, excreting high levels of the bacterium for a prolonged period.
The overall results agree with other experimental infection studies in cattle. Thus, this VTEC O157:H7 subtype probably does not exhibit any differences in shedding pattern, neither in number of bacteria shed, nor in duration of shedding, compared to other VTEC O157:H7 described in the literature. Further investigations are needed to establish if this particular subtype harbours certain traits that distinguish it from other VTEC O157:H7 strains.
Seven studies reported on the hazard of micro-organisms to HCWs and/or patients, see Table 5 study characteristics hazard in healthcare and the dental setting [12, 31, 34, 45, 77–79] Three studies looked into the risks for patients when exposed to Legionella pneumophila containing sources that may produce bio-aerosols [34, 38, 78]. They reported that cooling towers, air conditioning or mechanical ventilation systems could be a source of L. pneumophila. Kool et al. concluded that patients had an increased risk to acquire L. pneumophila in hospitals when they used corticosteroids (OR = 13; 95CI% 1.6–102) and when intubated (OR = 10; 95%CI 1.3–73). Another study identified smoking, drinking alcohol, having chronic lung disease and cancer as risk factors for getting an infection with L. pneumophila. For the dental clinic there is one case study reported that reported of irreversible septic shock and died after two days in a patient that was infected with L. pneumophila.
One systematic review reported on the pooled odds ratio (OR) for the transmission and exposure to Severe Acute Respiratory Syndrome (SARS) in HCWs during bio-aerosol generating procedures. Tracheal intubation (OR = 6.6; 95%CI 2.3–18.9) and noninvasive ventilation (OR = 3.1; 95%CI 1.4–6.8) were risk factors for acquiring SARS. Other bio-aerosol generating interventions such as manipulation of an oxygen mask were not significant risk factors. Another study calculated that the risk ratio for acquiring clinical respiratory infections was 2.5 (95%CI 1.3–6.5) for HCWs performing a high risk procedure. Augustowska et al. studied the effect of bacteria and fungi on asthmatic patients. They reported a decrease in maximum breathing capacity due to the increase of bacterial or fungal load in the air.
A case-study in a dental clinic described the risk of acquiring Herpes Simplex Virus (HSV)-1 for the dentist and the dental hygienists when they treated a patient with active HSV-1. One member of the treatment team became infected with HSV-1, probably by the bio-aerosol containing HSV-1, induced by ultrasonic scaling or by rubbing her eyes while working. The infected HCWs manifested recurrent HSV-1 infections.
To identify the onset age of diarrhea according to the causative agents, the causative agents and onset age of diarrhea in 164 calves were examined. The mean onset age of diarrhea was 33.7 ± 42.0 days, with a minimum age of 2 days and maximum age of 210 days.
Distribution of major causative agents according to onset age of diarrhea is presented as Table 4. The occurrence of diarrhea caused by rotavirus gradually reduced with an increase in calf age. Rotavirus was undetected at 9 weeks of age and over. The occurrence of diarrhea caused by rotavirus differed significantly with onset age (p < 0.001).
No diarrhea was caused by Eimeria spp. in KNC within 20 days of age. The diarrhea caused by Eimeria spp. (31/52 calves, 59.6%) was most prevalent in KNC between 3 weeks and 6 weeks of age. The occurrence of diarrhea caused by Eimeria spp. differed significantly with onset age (p < 0.001).
Diarrhea caused by Giardia spp. occurred in KNC between 2 and 10 weeks of age.
The occurrence of diarrhea by Giardia spp. differed significantly with onset age (p = 0.002).
Viral and bacterial causative agents were mainly detected in KNC within 3 weeks of age, but these causative agents were usually distributed up to 8 weeks of age. Protozoal causative agents were mainly detected in KNC between 3 and 10 weeks.
To improve prevention and control of melioidosis, we recommend that physicians consider melioidosis in the differential diagnosis of patients with (1) acute febrile illnesses; (2) risk factors for melioidosis (impaired neutrophil function, diabetes mellitus, pre-existing renal or lung diseases, malignancy, thalassemia and/or excessive alcohol consumption); and (3) compatible occupational or recreational exposure history (soil and water exposure: i.e., farmers, gardeners). However, healthy people can also get the disease if they are infected with a high bacterial load, such as contact with muddy soil without good hand and foot protection. Clinical manifestations are broad, and range from subclinical infection to localized abscess formation, pneumonia, and systemic sepsis. Pneumonia is the most commonly recognized presentation of melioidosis associated with high fever, significant muscle aches, and chest pain. Melioidosis could easily be confused with tuberculosis or even plague, particularly in Madagascar, where this disease is prevalent, or with pneumonia caused by other pathogens. Acute melioidosis septicemia is the most severe form of the infection. It presents as a typical sepsis syndrome with hypotension, high cardiac output, and low systemic vascular resistance. In many cases, a primary focus in the soft tissues or lungs can be found. The syndrome, usually in patients with underlying risk factors, is characteristically associated with multiple abscesses involving soft tissues, the lung, the liver, and spleen. Blood culture is an effective way to diagnose many melioidosis cases, as 50% or more of infections have bacteremia.
With the exception of a localized hospital-based study of patients with hyperthermia (≥39 °C), with or without shivering and septic shock, in Mahajanga in 2012, which led to the recognition of cases #8 and #9, no systematic case finding of B. pseudomallei infection has been conducted in the western Indian Ocean islands. Generally, there is no awareness of melioidosis in the population and among clinicians, because its diagnosis has been rare, despite the very high prevalence of diabetes in Mauritius. Some laboratory technicians and the clinical microbiologists who diagnosed the cases described above are aware that B. pseudomallei is a possibility when they isolate an oxidase-positive Gram-negative bacillus that is resistant to colistin and aminoglycosides, and which produces wrinkled colonies and/or has an earthy smell. However, this knowledge is not universal.
Similar to previous studies [2, 3], the cause of death in the majority of mink kits examined grossly in this study was not determined. As kit weight increased, the odds of being born dead decreased and more than 50% of fetuses that were born dead were <11 g, suggesting that low kit birth weight may contribute to increased risk of early mortality. In 2013, the incidence of producer-reported mink kit preweaning mortality (of those born alive) ranged from 3 to 15%; environmental conditions were within those expected, and likely not contributing significantly to the incidence of preweaned kit mortality. Gross findings are not expected for a range of other infectious and noninfectious causes of preweaning mortality in kits, including various virus infections (kit or pregnant female), chilling, poor maternal care, lack of milk, and failure to thrive syndrome. A shortcoming of this study was the lack of statistical power. Had more producers participated in both parts of the study, additional associations between biosecurity practices and post mortem findings may have been identified.
Mink producers assisted with the development of national mink biosecurity guidelines which have been widely available to producers for close to a year at the time the survey was conducted [7, 15]. Despite this, only 45% of respondents in this study felt that the industry had adequate biosecurity standards. This was also reflected in the overall lack of consistency of implementation of recommended biosecurity practices by the producers surveyed in the second part of this study. To that end, the results of this study will provide a benchmark for the Canadian mink industry to assess areas in which greater attention should be given to enhance biosecurity practices. The industry may also use this as an opportunity to provide additional training and educational programs for producers.
Although certain enteric viral pathogens, such as mink enteritis virus (MEV) and epizootic catarrhal gastroenteritis of mink (a coronavirus) [17, 18], are known to cause significant morbidity and mortality in mink, the role of specific bacterial agents as a primary cause of preweaned kit enteropathy is not as well-established. Samples from 45 of 69 kits with suspected enteritis were culture positive for at least 1 bacterial species. Enterococcus spp. were most common, with E. faecalis isolated from 43% of samples and E. faecium from nearly 20%. These agents are both common, commensal gastrointestinal tract bacteria of most mammals, including mink, and may not have been the primary cause of enteritis [20–22]. Enterococcus gallinarum was cultured in 3 of 69 samples and likely represents another commensal organism, as it has not previously been associated with disease in mink. Both E. avium and E. hirae are common gastrointestinal bacteria of birds, including poultry [23, 24]. Given the frequent use of poultry offal for mink feed this finding is not unexpected. Some strains of E. coli are thought to be a significant cause of morbidity and mortality in farmed mink and this bacterium has been implicated as a cause of hemorrhagic pneumonia, enteritis, mastitis, and septicemia [16, 17, 25]. However, E. coli has also been shown to have a high prevalence in apparently healthy adult female mink and their kits and further genotyping and toxin isolation is needed to determine the significance of isolated strains [22, 26, 27]. Additionally, when prevalence of E. coli serotype was investigated, there was no difference between healthy kits and those affected by sticky kit disease.
Of concern was identification of Salmonella enterica serovar Heidelberg from 11% (5 of 45) of culture positive samples, an agent of significant public health concern. This bacterium has been associated with food-borne disease outbreaks in Canada and the USA [28, 29]. Salmonellosis is usually food-borne, with poultry and pork products representing the most common sources of contamination. Salmonella spp. infection has been linked to abortion and stillbirths in mink, dogs and cats [31–34]. Furthermore, although less common, an asymptomatic carrier state can also occur in humans and animals. Less than 50% of producers (5/11) in this study reported that employees washed their hands after handling mink and only one producer had hand-washing policies in place. Thus, inadvertent zoonotic transmission from contaminated fecal matter could occur when poor hygiene practices are present, emphasizing again the importance of biosecurity practices on-farm.
Staphylococcus delphini, identified in 15% of gastrointestinal tract samples from kits with suspected enteritis and one skin sample, has previously been associated with an outbreak of ‘sticky kit’ syndrome with high mortality in the USA. This syndrome presents as neonatal diarrhea characterized by mucoid feces and wet and sticky fur of affected kits [36, 37]. Both bacterial and viral agents have been isolated from affected kits in other studies, including astrovirus, coronavirus, mink enteric calicivirus, S. delphini, and Salmonella spp. [31, 36–39] and the precise etiology of ‘sticky kit’ syndrome is unknown. Although enteritis was not a common finding in the present study, outbreaks of neonatal diarrhea can be a significant cause of morbidity and mortality on mink farms and the etiology is likely multifactorial.
Lesions were present in 29% of kits examined in this study and the most common abnormality noted was excessive fluid accumulation, including hydrothorax, hydroperitoneum, subcutaneous fluid, and anasarca. Abnormal fluid distribution is a nonspecific clinical sign, which can arise from increased hydrostatic pressure, decreased oncotic pressure, increased vascular permeability or obstruction of fluid clearance. In dogs inoculated with minute virus of canines (a parvovirus), some dams had stillbirths or whelped pups with anasarca. Further, causes of fading pups, pup abortion and pup stillbirth in dogs can include infection with canine herpes virus 1a [41–43] and canine parvovirus [40, 44]. Similarly, in cats, abortion, stillbirth and fading kittens have been linked to infection with feline panleukopenia virus (a parvovirus) or feline infectious peritonitis virus [45–51]. Infection with Aleutian mink disease virus, a parvovirus of significant concern in mink, has been shown to decrease conception rate, litter size and weight, and increase neonatal mortality, even in kits born to clinically healthy females. Mink-specific viruses are less well characterized compared with those of domestic dogs and cats and their role in kit stillbirth, abortion, and abnormal development are largely unknown. Moreover, mink have been shown to be susceptible to infection with feline panleukopenia virus and canine distemper virus [11, 54], which reinforces that companion animals should be excluded from mink sheds. Findings from this study suggest that more work is needed to characterize viral infections of mink and their impact on kit mortality.
A significant noninfectious factor in mink kit survival is the mothering ability of the female, particularly nest building, kit retrieval, and nursing. Mink kits are dependent on the female for warmth and nutrition, as they are altricial at birth with an undeveloped thermoregulatory system and minimal fat stores [55–58]. Kits are especially susceptible to hypothermia and lose heat quickly during the first few days of life when exposed to cold [56, 57]. Females with higher kit survival rates spend significantly more time exhibiting kit-directed behavior. Further, compared to kits from females provided with either straw as a nesting substrate, a plastic or artificial nest, or both, kits from females provided with only a nest box and wood shavings (the current standard on most Canadian mink farms) had significantly lower body weights 1 week after birth and higher mortality rates compared to the other groups. Females provided with nesting material were also quicker to retrieve kits that had been removed from the nest. This suggests that provision of supplemental nesting materials and selection of females for mothering abilities, a heritable trait in many mammals, could significantly decrease kit mortality and contribute to overall greater production yields and improved kit welfare.
In addition to human activity and companion animals as a source of pathogen introduction, wildlife pose a significant risk to mink health [8–12]. National mink biosecurity guidelines recommend the use of effective security fences, self-closing, lockable gates, and enclosed sheds to minimize wildlife access to mink [7, 15]. Just over half of respondents reported having fences around their mink sheds/farm, although information on the types of sheds used was not collected. Reasons for not having such measures were not collected, but cost is a possible explanation. The logic for implementing biosecurity standards, specifically in mink production, is evident in the near eradication of Aleutian disease virus in Denmark. Voluntary implementation of testing, quarantine, and limited movement of mink decreased the number of positive farms from 100% in 1976 to 15% in 1996; further reduced to <5% in 2001 following implementation of additional government-mandated biosecurity measures. Even if the goal is not eradication of a specific disease from a geographical area, limiting the spread of potential pathogens and preventing outbreaks of infectious disease should represent a viable goal for the Canadian mink farming industry.
Despite mortality of preweaned kits being a significant cause of loss to producers, few studies have evaluated specific causes of death. In this study, we sought to estimate associations between management practices of farmers with causes of preweaned kit mortality, as well as characterizing the current state of biosecurity practices of the Canadian mink farming industry. Enhancing on-farm biosecurity practices as per national industry recommendations will assist with reducing infectious and contagious causes of mortality in mink kits, likely resulting in increased productivity and animal well-being.
A variety of health problems for both kits and adult females were reported to be seen commonly by producers (Fig. 2). Ninety-one percent of producers (10 of 11; 95% CI 58.7 to 99.7) responded that they used antimicrobials to treat disease of suspected bacterial origin. Various formulations were reported, which most frequently fell into the penicillin class, used either alone or as a combination product (9 of 11; 82%; 95% CI 48.2 to 97.7%). Other classes of antimicrobials used alone or as a combination product, included macrolides, sulfonamides tetracyclines, and fluoroquinolones (4 of 11; 36%; 95% CI 10.9 to 69.2%) and polypeptides (3 of 11; 27%; 95% CI 6.0 to 61.0). Two producers reported using an antimicrobial combination product that included a penicillin, tetracycline, and sulfonamide. Only 2 of 11 producers (18%; 95% CI 2.3 to 52.8%) reported using antimicrobials in the feed or water regularly.
One producer reported increased mortality in preweaned kits, one producer reported increased mortality in weaned kits, and one producer reported increased mortality in both preweaned and weaned kits in 2013 compared to previous years. Estimates of overall kit mortality ranged from 4.5 to 10%, with one producer reporting simply that it was more than 50% higher than the previous year. Only one farm reported treating kits with antimicrobials.
The most common diseases reported (that is, specifically related to mortality, rather than a health problem not resulting in death) in post-weaned kits were heat stress, foot pad disease, hemorrhagic pneumonia, diarrhea, and dermatitis (‘sticky kits’). Only one producer reported increased mortality in adult females for 2013. The most common diseases reported in adult females (specifically related to mortality) were foot pad disease, hemorrhagic pneumonia (likely bacterial), and mastitis. Three farms provided an estimate of female mortality, which ranged from 0.5 to 1.5%. Two farms indicated that enrofloxacin was given to adult females; however, information on frequency of use was not provided.
In this experimental study, the shedding pattern of a specific strain of VTEC O157:H7 in cattle was investigated. The strain was chosen as a representative of the VTEC O157:H7 (PT4;vtx2;vtx2c) subtype, and was isolated from cattle on a farm previously linked to direct transmission of infection to man. This particular subtype of VTEC O157:H7 is prevalent among cattle in Sweden and predominates among the human cases reported to the SMI. There have been two larger human outbreaks of VTEC O157:H7 in Sweden, both caused by this subtype of VTEC O157:H7.
In the present study the shedding patterns following experimental infection in different calves were very similar, and for most of the calves shedding ceased within two weeks. Previous experimental and field studies have shown large variations in the magnitude and duration of VTEC O157:H7-shedding in beef and dairy cattle. However, in most studies the same pattern is observed; after an intial period of shedding in high levels there is a decline towards lower levels whitin 2-3 weeks, except for a small subset of animals where shedding may persist at high levels for longer periods. One of the experimentally infected calves shed the bacterium for 43 days. For practical reasons, a high-shedding animal has been defined as excreting enough bacteria to be detected by direct plating, i.e. between 103 and 104 cfu/g faeces. With this definition, the long-term shedder in the study would qualify as a high-shedder. It has previously been observed that calves colonised by direct contact transmission from calf to calf excrete E. coli O157:H7 at levels ranging from <30 to 106 cfu/g for up to 6 weeks. This was supported in the present study, where both of the non-inoculated calves began faecal excretion after a few days. One of these calves shed bacteria in similarly high numbers and for a similarly long period as the inoculated calves.
At a point when no positive samples had been obtained from Stall B for three weeks, Calf V was re-inoculated with an equally high dose of CCUG 53931 as used in the first inoculation. Calf VI in the same stall, which had been naturally infected and had shed intermittently at low levels, was also challenged with the same infectious dose. After challenge, Calf V shed the bacterium for a similar period as after the first inoculation; approximately 11 days. However, after the first inoculation the shedding persisted at levels of approximately 105 cfu/g for 7 days (even with a small initial upturn) whereas after re-inoculation the numbers shed declined more rapidly and within 3 days reached levels of approximately 104 cfu/g. Thus, there is some indication that the total number of bacteria shed after re-infection was reduced compared to the first challenge. This is consistent with results obtained by Naylor et al who demonstrated that re-infection of calves with a homologous strain led to a humoral response that could reduce the number of bacteria shed. On the other hand, after the high challenge dose, calf VI exhibited no shedding pattern indicative of any protective immunity. We therefore speculate that the first exposure, which led to the natural infection with intermittent low-level shedding from calf VI, only induced a transient colonisation that was insufficient to produce a protective immunity.
In this study the bacterium was administered orally. It has been suggested that the recto-anal junction mucosa (RAJ) is the site of E. coli O157:H7 colonisation in cattle and that rectal administration of a high dose E. coli O157:H7 in cattle more effectively produces an experimental colonisation than does oral administration. All calves in this experiment shed the bacterium following oral administration in numbers indicative of proliferation. It is difficult to determine if this is equivalent with colonisation. However, the shedding pattern observed in calf II indicates that this calf was successfully colonised.
Occasionally, a positive faecal sample was obtained from a previously culture-negative animal. This might have been because the calf excreted bacterial numbers below the detection limit of the IMS method, which was calculated to approx. 1 cfu/g faeces under these experimental conditions (unpublished data). It could also have been caused by intermittent excretion or to spontaneous re-infection by direct contact transmission from the other calves or the environment.
There were no findings of VTEC O157:H7 in samples from the pharynx, thus corroborating another study where E. coli O157:H7 was not isolated from the oral cavity. In view of the findings in the present study, i.e. that some animals at the same time were faecal culture-positive, the inoculation dose was high and the environment was contaminated with VTEC O157:H7, one would expect to find VTEC O157:H7 in the pharynx. However, if shedding is intermittent, presence in the oral cavity may also be intermittent. In contrast to the present study, Keen and Elder reported that E. coli O157 was detected in more than 70% of samples collected from the oral cavity of beef cattle in one feedlot, but results from feedlot cattle may not be readily applicable to Swedish dairy calves.
A method for enumerating VTEC O157:H7 was developed by direct plating of dilutions of faeces on ChromO157 plates supplemented with potassium tellurite. VTEC O157:H7 was recovered in satisfactory numbers and the background flora was suppressed so that the VTEC O157:H7 colonies became prominent and showed a distinct morphological pattern with pink colour that could readily be recognized and counted on the agar plate. A very close correlation between VTEC O157:H7 and the formation of pink-coloured colonies on ChromO157 plates has been described earlier. Direct plating on Sorbitol McConkey agar plates supplemented with cefixime and potassium tellurite (CT-SMAC) is a common method for counting E. coli O157:H7 in experimental studies. In the present study however, CT-SMAC was found to restrain the growth of the strain substantially and was rejected for that reason (unpublished data). The method described here has only been evaluated for the particular bacterial strain used in this study, and with calves from one single farm. A general method for counting VTEC O157:H7 in cattle faeces by direct plating on ChromO157 plates, would be interesting to investigate further.
PFGE was performed on selected isolates throughout the experiment, to ascertain that the excreted bacteria emanated from the inoculated strain (CCUG 53931). Twentysix out of 28 of the isolates subjected to analysis exhibited the same pulsotype as the inoculum. One possible explanation for finding slightly differing PFGE profiles in two isolates, from 2 calves on day 5 pi of the re-inoculation, is that the original bacterial strain may have changed during passage through the GI tract of one of the calves. There are reports of clonal turnover of VTEC O157:H7 colonising cattle. The finding that both calves in stall B harboured the differing pulsotypes could be due to contact transmission from one calf to the other. Interestingly, when VTEC O157:H7 (PT4;vtx2;vtx2c) is isolated from Swedish human cases a predominant pulsotype is found, but many closely related subtypes to this pulsotype have also been demonstrated. Possibly, these different subtypes arise due to clonal turnover within the GI tract of colonised cattle. Likewise, the clonal turnover may also take place in the human GI tract.
Further studies are needed in order to investigate the true burden of melioidosis in the western Indian Ocean, and especially Madagascar, since it is likely to be higher than currently reported. This could be done by enhancing diagnostic microbiology provision and surveillance systems, training and education of healthcare staff, serological studies and environmental investigations.
Given the issue of antibiotic resistance, a critical characteristic of an antiseptic is one that has no or low resistance potential 20, 51. From our extensive review of the literature, there have been no clinical reports of microbial resistance development in response to PVP‐I treatment. This is likely due to its action on multiple pathogenic targets 52. In contrast, bacterial resistance to chlorhexidine has been documented 53. Resistance may result in alteration in bacterial susceptibility, in part, by altering the outer membranes of Gram‐negative bacteria and preventing antiseptic adsorption 20. Genes conferring resistance to chlorhexidine and quaternary ammonium compounds have been identified in up to 42% of S. aureus isolates in Europe and Japan 54, 55; and while there are reports of cross‐resistance between antiseptics, PVP‐I has remained unaffected 46, 52.
In conclusion our study showed HRV16 infection is associated with strong trends towards increases in the relative abundances of Haemophilus and Neisseria and a weaker trend towards increases in the relative abundance of Staphylococcus. Even if the observed changes of upper respiratory tract microbiota are minor overall, they may be of great clinical significance and could help explain why HRV infection predisposes to bacterial otitis media, sinusitis and pneumonia.
Many marine invertebrates, particularly sessile or slow-moving organisms, are a rich source of valuable bioactive metabolites. Among marine invertebrates, sea cucumbers, or holothurians, have been utilized as food and folk medicines by Asia and Middle East communities. Asian people, especially Chinese believe that consuming holothurians may treat a variety of impediments and illnesses such as weakness, impotence, debility of the aged, constipation due to intestinal dryness, and frequent urination. As a consequence, these reported beneficial effects lead to the high demand for holothurians in Chinese markets.
Among holothurians, Stichopus vastus and Holothuria leucospilota were reported to have medicinal application. S. vastus is well-known for its wound healing activities which were proven by pre-clinical test in rats. In addition, the integument tissue is rich in collagen and can be used as a functional ingredient in nutraceuticals, cosmetics and food products. Furthermore, S. vastus contains novel bioactive peptides which inhibit angiotensin I converting enzyme (ACE) and also possesses radical scavenging activities. H. leucospilota is widespread throughout the Red Sea, Persian Gulf and the entire Indo-Pacific. Its main habitat are shallow areas, such as reef flats, shallow costal lagoons, and seagrass beds. In some areas such as the Federated States of Micronesia (FSM), Marshall Islands, Kiribati, Samoa, Tonga, Cook Islands, Papua New Guinea (PNG), Solomon Islands and Fiji, people consume holothurian´s gonad as food delicacies and as additional protein diets. H. leucospilota has shown antioxidant effects as well as anticancer activities against HeLa, human lung carcinoma (A549) and skin melanoma (B16F10) cells. Several bioactive compounds have been isolated from it such as leucospilotaside A to C, echinoside B, holothurin A, holothurin B, and holothurin B2. Organic extracts of body wall, gonad and intestine of H. leucospilota exhibited bacteriostatic rather than bactericidal activity against Gram-positive Bacillus subtilis and Staphylococcus aureus. This bacteriostatic effect from the organic extracts was confirmed against the Gram-negative bacteria like Escherichia coli, Salmonella typhi, and Pseudomonas aeruginosa and against the Gram-positive S. aureus and the filamentous fungi Aspergillus niger, A. fumigatus, A. flavus and A. brasilensis.
Numerous natural products from marine invertebrates show striking structural similarities to those of microbial origins, suggesting that microorganisms are at least involved in the biosynthesis of the targeted bioactive compound or they even represent the sole producer of the respective metabolites. Those findings supported efforts to isolate invertebrate associated bacteria as the real producer of the bioactive compounds to overcome the supply problem as harvest from the wild is not sustainable for most bioactive marine invertebrates.
Bioprospecting for bioactive marine bacteria recognizes the noticeable capacity of marine bacteria as a source of new natural products which can be utilized to overcome the antimicrobial resistance crisis. (Multi-)drug-resistant bacteria are becoming the global challenge leading to the strong demand for new antibiotics, either in chemical structures or mode of actions. In addition, spreading of slow progressing but deadly virus, such as Hepatitis C (HCV) menace human population particularly in developing countries. Therefore, the detection and development of new anti-infective drugs is urgently needed.
There has been an increasing number of publications focusing on the isolation of invertebrate associated bacteria for the discovery on new bioactive compounds, with sponges being the invertebrate phylum that has received most attention for isolation of the associated microbiome. However, holothurians likely present another very interesting target for the isolation of bioactive bacteria. Since they are being (a) used in traditional Chinese medicine and (b) exposed to, ingesting and reworking marine sediments, which have been shown to be a promising source for the isolation of bioactive bacteria. Even more so, if Actinobacteria, which are prolific producers of bioactive compounds, are the target bacteria phylum, since Actinobacteria have been isolated repeatedly from terrestrial soil and marine sediments. Thus, sediment bioturbating holothurians with their associated microbiome should be a promising target to isolate novel Actinobacteria. A recent publication by Gao, et al. (2014) showed that Actinobactria were enriched in the gut of four deep-water holothurian, accentuating that also shallow water holothurians could be a promising target for the isolation of bioactive Actinobacteria.
In this study, we reported the potential of bioprospecting underexplored marine associated bacteria derived from the sea cucumbers H. leucospilota and S. vastus.
A secondary objective of the study was to investigate the effect of iota-carrageenan nasal spray on virus elimination in nasal fluid samples. The incidence of viruses observed was typical for common cold (Figure 2). Topical application of the iota-carrageenan spray reduced viral loads in nasal secretions to a significantly higher degree than placebo after 3 to 5 days of treatment (p = 0.026; Figure 5), and the documented reduction in the number of viruses between visits 1 and 2 was significantly greater in the verum group. The antiviral efficacy of iota-carrageenan is further supported by the fact that 27% of patients in the verum group and less than 13% in the placebo group tested virus-negative at the second visit (Additional file 3: Figure S1B). The observed decrease in virus-positive patients between visits 1 and 2 was statistically significant only in the verum group (p < 0.001 versus p = 0.804). At the second visit, the mean number of viruses detected in the iota-carrageenan group was reduced from 1.3 to 0.8 (p < 0.001), while in the placebo group the observed reduction from 1.3 to 1.1 was not significant. Moreover, 52.2% of verum patients and 32.4% placebo patients had cleared their viruses by the second visit (p = 0.030). At visit 2, the incidence of newly acquired infections with viruses that had not been detected at visit 1 was significantly lower in the verum group (13% versus 27%; p = 0.046).
Among the 5 most abundantly identified genera, three (Streptococcus, Prevotella and Rothia) showed very limited variation during HRV16 infection (less than 10 % of the baseline abundance), whereas Veillonella decreased by approximately 25 % and Haemophilus increased by 75 %.
Paired comparisons using a linear mixed model were used to assess changes over time within individuals, days -1 and 60 being grouped as baseline non-infection measures, and days 2 and 5 being grouped as infection measures. No significant changes were observed between day -1 and day 60 specimens at genus or species level. However, at the genus level, a significant increase (p < 0.05) in relative abundance of Haemophilus and Neisseria was observed during infection. Analysis of these genera to species level show significantly increased Haemophilus parainfluenzae (p-value = 0.0098) and Neisseria subflava (p-value = 0.012). However, false discovery rate (FDR) correction for multiple comparisons showed an above threshold risk of type-I error for all these taxa (FDR = 0.12). Additionally, the largest fold-change observed was a 1200 % (13-fold) increase in the abundance of the genus Staphylococcus (p = 0.0749 FDR 0.518), which only represents 0.2 % of the total sequences identified (Fig. 5). Analysis to species level shows a weak trend towards increases in Staphylococcus aureus abundance (p-value = 0.0856 FDR = 0.245).
The increases in H. parainfluenzae during infection were observed in all volunteers, while the Neisseria species increased in 5 of 6 volunteers. Staphylococcus aureus was only present in four volunteers and increased in three, hence the observed correlation between HRV16 and Staphylococcus aureus was the weakest (p-value = 0.0856 FDR = 0.245). Observed changes in the microbiota composition did not correlate with viral loads or symptom scores (data not shown).
Climate mainly affects the range of infectious diseases, whereas weather affects the timing and intensity of outbreaks. Climate change scenarios include a change in the distribution of infectious diseases with warming and changes in outbreaks associated with weather extremes.44 Statistical models are used to estimate the global burden of some infectious diseases as a result of climate change. According to the models, by 2030, 10% more diarrheal diseases are expected, affecting primarily the young children.
If global temperature increases by 2–3 °C, as it is expected to, the population at risk for malaria could increase by 3%–5%.45
The need for therapeutic strategies against URTI in children is highlighted by results of randomized studies on the use of OTC preparations for treatment of common cold in children below 12 years of age, which revealed no significant differences between verum and placebo. Due to insufficient data on the application of nasal decongestants for common cold in children, their use is not recommended in patients below 12 years of age. Upper respiratory tract infections in early childhood can contribute to significant morbidity resulting from respiratory complications even in immunocompetent individuals. To date, no causal therapy is available in most instances, because URTIs are caused predominantly by viral pathogens for which no effective therapeutic agents have been available.
The results of the present study showed no significant difference between the iota-carrageenan and the placebo group on the predefined primary endpoint, the mean of TSS between study days 2–7. This may be due to the low TSS level below 10 at inclusion, which was necessary to avoid a bias by a higher use of co-medications. Furthermore, the concentration of iota-carrageenan which was the same as used in the previous pilot study in adults, may also have an influence on symptom scores. About 90% of children in both study groups received one or more co-medications. In the verum group, predominantly antiinflammatory agents (58%) or antitussives (62%), and less frequently antibiotics (27%) or ß2-sympathomimetics (26%) were prescribed. It is conceivable that the systemic and the local symptom scores were respectively affected by the antipyretic and the antitussive medication; hence negative effects of the unusually high prevalence of patients with multiple co-medications may have masked the effect of the study medication.
The age of the patients in our study ranged between one and 18 years, with a mean of five years. In young children, it is often very difficult to evaluate symptoms like headache, muscle ache or chilliness. These difficulties in evaluating symptoms in children were recently discussed by Taylor et al., and require careful consideration in future studies in pediatric patient cohorts.
However, the mean difference in time to complete symptom alleviation between the verum and the placebo group was 1.8 days, while the reported effect of neuraminidase inhibitors on the treatment of influenza in adults showed an overall benefit over placebo treatment of approximately one day.
Another secondary objective of the study was determination of the viral pathogens and intranasal viral loads. Recent data demonstrated that specific viral infections and co-infections as well as viral load contribute to disease severity in children with respiratory infections. The viruses detected in our study were similar to earlier reports, and did not reveal constellations associated with a particularly high risk of complications. Significantly more children in the verum group tested virus-negative at visit 2, and fewer children displayed multiple viruses or revealed a new viral infection at this time. These findings may have important implications. Recurrent viral episodes prolonging reactive bronchial inflammation are frequently encountered complications of URTI. In this regard, the topical effect of iota-carrageenan could be instrumental by reducing the incidence of subsequent lower respiratory tract involvement.
The major limitations of this study include the restricted performance of no more than two nasal aspirations, because newly acquired viral infections after day 3–5 could have occurred in the placebo group during the follow up period, potentially changing the proportion of patients with no symptoms. A second limitation may be given by the TSS questionnaire, which may not be the most appropriate for a study population with a mean age of 5 years.
Despite the fact that viral load in nasal secretions were reduced by iota-carrageenan, no significant alleviation of symptoms in children with common cold could be observed in this prospective, randomized, placebo-controlled pediatric study.
Bio-aerosols are generated via multiple sources such as different interventions, instruments and human activity. Bio-aerosols have different microbiological profiles depending on the setting and the used methodology. Bio-aerosols can be hazardous to both patients and healthcare workers. Legionella species were found to be a bio-aerosol dependent hazard to elderly and patients with respiratory complaints.
El Niño Southern Oscillation is a climate event that originates in the Pacific Ocean but has wide-ranging consequences for weather around the world. Globally, it is linked to an increased impact of natural disasters and is especially associated with droughts and floods and with transmission of infectious disease, water-borne and vector-borne diseases,37 particularly malaria.38,39 Although cholera outbreaks occur in Burundi, Rwanda, Democratic Republic of Congo, Tanzania, Uganda, and Kenya almost every year since 1977, in African Great Lakes Region (AGLR) the incidence of cholera greatly increases during years of El Niño warm events and decreases or remains stable between these periods.40
El Niño events can produce significant abnormalities in atmospheric general circulations and weather conditions. El Niño events cause changes in sea surface temperature (SST) in the Pacific Ocean, impact the Walker Circulation, and displace the convective area. These changes in atmospheric circulation cause abnormalities in the monsoon system and moisture fields in eastern Asia.
As El Niño has an influence on rainfall and wind speed, it can affect the persistence or moving polluting dust. The 2015 El Niño has had significant effects on air pollution in eastern China, especially in the region including the capital city of Beijing where aerosol pollution was significantly enhanced.41 The relationship between air pollution and asthma has been well-established. Air pollution is made up of gases and particulate matters that can be transported into the alveoli depending on their size. Particulate matters can produce damage to the whole respiratory apparatus. Exposure to these agents can cause acute pulmonary diseases such as chronic obstructive pulmonary disease (COPD), asthma, and if continues for a long time, it can activate cellular mediators leading to pulmonary fibrosis.42
Finally, in rural setting, a neglected effect of warm temperature is the increased exposure to snakebites. Snakes are ectothermic organisms whose distribution, movement, and behaviors change as a function of weather fluctuations. In Costa Rica, high numbers of snakebites occur during the cold and hot phases of El Niño. Like other tropical diseases, snakebites occur more frequently in poor settings, thus reflecting the general vulnerability of impoverished human populations to the adverse effects of climate change.43
All data generated or analyzed during this study are included in this manuscript.
The mean duration of clinical and laboratory confirmed URTI was non-significantly lower in the vitamin D3 group compared to the placebo group (6.0 versus 6.2 days and 5.8 versus 6.2 days, respectively). Time to symptom resolution was not significantly different between the groups (clinical URTI HR: 1.3, CI95: 0.59, 2.90, p = 0.49; laboratory confirmed URTI HR: 1.3, CI95: 0.49,3.48, p = 0.59) (Table 2).
Gargling did not reduce the mean duration of symptoms or improve time to symptom resolution. Results were similar for clinical URTIs (HR: 0.85, CI95: 0.38,1.89, p = 0.69) and laboratory confirmed URTIs (HR:1.5, CI95:0.56,4.0, p = 0.43) (Table 3).
Mean symptom severity appeared to be greater in the vitamin D3 group for clinical and laboratory confirmed URTI (218.6 versus 199.8 and 229.7 versus 181.5, respectively) (Table 2). However, the difference was not statistically significant. Symptom severity also appeared to be greater in the gargling group for clinical and laboratory confirmed URTI, however this was not statistically significant (225.3 versus 191.8 and 210.5 versus 191.8, respectively) (Table 3).