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Show how detailed incubation period estimates can be used to identify and investigate potential healthcare-associated infections and dangerous diseases.
Methods.
We used the incubation period of 9 respiratory viruses to derive decision rules for distinguishing between community- and hospital-acquired infection. We developed a method, implemented in a simple spreadsheet, that can be used to investigate the exposure history of an individual patient and more specifically to identify the probable time and location of infection. Illustrative examples are used to explain and evaluate this technique.
Results.
If the risks of hospital and community infection are equal, 95% of patients who develop symptoms of adenovirus infection within 5 days of hospital admission will have been infected in the community, as will 95% of patients who develop symptoms within 3 days for human-coronavirus infection, 2.5 days for severe acute respiratory syndrome, 1 day for influenza A, 0.5 day for influenza B, 12 days for measles, 2 days for parainfluenza, 4 days for respiratory syncytial virus infection, and 1.5 days for rhinovirus infection. Sources of infection suggested by analysis of the symptom onset times of individual patients are consistent with those from detailed investigations.
Conclusions.
This work shows how a detailed understanding of the incubation period can be an effective tool for identifying the source of infection, ultimately ensuring patient safety.
Reprinted by the John Charnley Trust, the original text having been out of print for many years, this beautifully presented book deals very simply and scientifically with most of the difficult fractures an orthopaedic surgeon is likely to meet in his/her practice. Despite the fact that the original text was published in 1950, the basic principles espoused in the book still apply today, and it remains one of the most concise and complete books on closed fracture treatment ever written. This core textbook has been basic reference for orthopaedic surgeons for half a century. It describes the elementary mechanics of reduction and immobilisation and shows how the commonest injuries can be managed by proven methods based on these general principles. It is a must for anyone embarking on a career in orthopaedics and is a classic text that all orthopaedic trainees and consultants should have on their shelves.
The association between coronaviruses and bats is a worldwide phenomenon and bats belonging to genus Rhinolophus are the reservoir host for several coronaviruses, including a large number of viruses closely related genetically to severe acute respiratory syndrome-coronavirus (SARS-CoV). We carried out a survey in colonies of Italian bats (Rhinolophus ferrumequinum) for the presence of coronaviruses. Two of 52 R. ferrumequinum captured from different Italian areas tested positive by reverse transcription–PCR for a fragment of RNA-dependent RNA polymerase (RdRp) gene of viruses related to Coronavirus. Phylogenetic analysis revealed close correlations between one of the positive samples and SARS-related CoV belonging to the genus Betacoronavirus.
Influenza viruses circulate around the world every year. From time to time new strains emerge and cause global pandemics. Many national and international health agencies recommended the use of face masks during the 2009 influenza A (H1N1) pandemic. We reviewed the English-language literature on this subject to inform public health preparedness. There is some evidence to support the wearing of masks or respirators during illness to protect others, and public health emphasis on mask wearing during illness may help to reduce influenza virus transmission. There are fewer data to support the use of masks or respirators to prevent becoming infected. Further studies in controlled settings and studies of natural infections in healthcare and community settings are required to better define the effectiveness of face masks and respirators in preventing influenza virus transmission.
Many viruses, including bovine herpesvirus-1 (BHV-1), bovine respiratory syncytial virus (BRSV), parainfluenzavirus-3 (PI3), bovine coronavirus, bovine viral diarrhea virus and bovine reovirus, have been etiologically associated with respiratory disease in cattle. This review focuses on the pathogenesis of BHV-1 and BRSV, two very different agents that primarily cause disease in the upper and lower respiratory tract, respectively.
Thirty-three volunteers were inoculated intranasally with coronavirus 229 E, and their responses monitored by antibody rises, symptomatology and virus excretion. These were related to their pre-trial immune status as indicated by concentrations of specific antibodies and non-specific proteins in serum and nasal washings. Both circulating and local specific antibodies were associated with protection from infection and disease, but only specific IgA antibodies of either type appeared to shorten the period of virus shedding. Although total secretory IgA was significantly associated only with reduction of symptoms, total protein in nasal washings appeared to protect against infection also, indicating that other locally produced proteins, not identified, may be associated with resistance.
Two of the many factors which may affect the concentration of circulating and local protective proteins and thus influence the outcome of virus inoculation, namely, sex of the volunteer and the interval since the previous cold, were examined. Male volunteers or volunteers who had had evidence of a recent respiratory infection were less likely to be infected, but if they were infected, they had lower clinical scores and stopped shedding virus earlier than the rest. These groups possessed higher concentrations of specific antibodies and non-specific proteins in their pre-challenge sera and/or nasal washings. The significance of these findings is discussed.
The occupational risk of acquiring minor respiratory infections for paediatric student nurses was estimated by performing serological examinations with influenza A, B, C, parainfluenza, mumps, respiratory syncytial virus, adenovirus and Mycoplasma pneumoniae at 6-month intervals over a period of 4 years in paediatric student nurses at two schools of nursing and students at one school of medical technology, litre increases against all tested agents occurred 1·86 times more often in the student nurses than in the medical technology students, the most frequent agents in both groups being influenza A and B. No difference in the relative distribution of the agents could be verified in the two occupational groups. Data on the protective value of pre-infectious antibody levels for influenza A, B, and coronavirus OC43 and on the importance of the spread of single agents among classmates are presented.
Results from two studies involving challenge with respiratory syncytial viruses showed that volunteers who developed colds were more sensitive to a visually distracting pattern presented prior to virus challenge than were volunteers who did not get a cold. Volunteers with sub-clinical infections reported more illusions after virus challenge than they had done before, whereas uninfected volunteers and those with colds tended to report fewer illusions on the second test. These effects did not occur when volunteers were challenged with either a coronavirus or rhinovirus. Overall, the results confirm that behavioural measures may be related to susceptibility to subsequent illness, and that viral infections may influence visual perception. They also show that the effects vary according to the nature of the infecting agent, which agrees with results from studies looking at other aspects of behaviour.
This study investigated the morbidity associated with respiratory virus infections in patients with well-documented chest disease, and the risk of transmission between close contacts. Patients informed the study team if they were exposed to a family member or colleague with a cold. Patients and symptomatic index cases recorded respiratory symptoms during the study period. Acute nasopharyngeal swabs and paired sera were obtained for viral diagnosis.
Twenty-five (43%) of 58 recorded exposures resulted in a symptomatic illness and 16 (28%) patients developed lower respiratory tract symptoms. Sixteen (64%) of the 25 symptomatic patients contacted their general practitioner, 14 (56%) received antibiotics and 4 (16%) were hospitalized. Mean duration of illness was 10·6 days in symptomatic patients and 5·7 days in their corresponding index cases (P < 0·005). Mean symptom scores were 100·6 in symptomatic patients and 62.2 in index cases (P < 0·01). Respiratory viruses were identified in 19 (33%) episodes. Rhinovirus, coronavirus and respiratory syncytial virus infections were all associated with lower respiratory tract exacerbations.
Respiratory tract symptoms following exposure to a cold were comparatively severe in these patients with chronic chest disease. This group of patients might gain particular benefit from the introduction of effective vaccines or antiviral therapy.
The chemical disinfection of virus-contaminated non-porous inanimate surfaces was investigated using coxsackievirus B3, adenovirus type 5, parainfluenzavirus type 3 and coronavirus 229E as representatives of important nosocomial viral pathogens. A 10 µl amount of the test virus, suspended in either faeces or mucin, was placed onto each stainless steel disk (about 1 cm in diameter) and the inoculum allowed to dry for 1 h under ambient conditions. Sixteen disinfectant formulations were selected for this study based on the findings of an earlier investigation with a human rotavirus.After 1 min exposure to 20 µl of the disinfectant, the virus from the disks was immediately eluted into tryptose phosphate broth and plaque assayed. Using an efficacy criterion of a 3 log10 or greater reduction in virus infectivity titre and irrespective of the virus suspending medium, only the following five disinfectants proved to be effective against all the four viruses tested: (1) 2% glutaraldehyde normally used as an instrument soak.(2) a strongly alkaline mixture of 0·5% sodium o-benzyl-p-chlorophenate and 0·6% sodium lauryl sulphate, generally used as a domestic disinfectant cleaner for hard surfaces, (3) a 0·04% solution of a quaternary ammonium compound containing 7% hydrochloric acid, which is the basis of many toilet bowl cleaners. (4) chloraminc T at a minimum free chlorine level of 3000 p.p.m. and (5) sodium hypochlorite at a minimum free chlorine concentration of 5000 p.p.m. Of those chemicals suitable for use as topical antiseptics, 70% ethanol alone or products containing at least 70% ethanol were ineffective only against coxsackievirus B3. These results emphasize the care needed in selecting chemical disinfectants for routine use in infection control.
Occupants of 482 long-stay and 33 short-stay beds in 11 Leicester City Council homes for the elderly were studied during a 30-week period from September 1988 to March 1989 to determine the incidence, aetiology, morbidity, and mortality of acute upper respiratory tract viral infections and the use of influenza vaccine.
Influenza immunization rates by home ranged from 15·4 to 90% (mean 45%). There were no differences in the distribution of medical conditions by home. The highest immunization rates were seen in people with chest disease (77%), heart disease (60%), diabetes (56%), and those with three medical conditions (75%). There was an average of 0·7 upper respiratory episodes per bed per annum with a mortality of 3·4% (6/179). Half of all episodes were seen by a general medical practitioner and 81 of 90 (90%) referrals were prescribed antibiotics costing approximately £7.50 per patient. Lower respiratory tract complications developed during 45 (25%) of 179 episodes including 3 of 12 coronavirus infections, 3 of 9 respiratory syncytial virus infections, 2 of 4 adenovirus infections, 1 of 11 rhinovirus infections, but none of 5 influenza infections. Respiratory infections were caused mostly by pathogens other than influenza virus during the influenza period documented nationally. This highlights the role of coronaviruses, respiratory syncytial virus, and unidentified agents in the elderly, and questions the assumptions made in American estimates on the impact of influenza and the value of influenza vaccines.
The ability of three avian viruses to elicit antibody response in humans was surveyed for the purpose of identifying zoonotic diseases. Antibody levels in people associated with poultry were compared to those in people having limited poultry association. Antibody levels to three avian viruses: infectious bursal disease virus, a birnavirus; Newcastle disease virus, a paramyxovirus; and avian infectious bronchitis virus, a coronavirus were determined by enzyme–linked immunosorbent assays (ELISA). Differences between the two study groups were evident: people having a known association with poultry showed significantly higher levels of antibodies to Newcastle disease and avian infectious bronchitis virus. Antibodies detected may be due to virus exposure rather than zoonoses.
Faeces samples from diarrhoeic and non-diarrhoeic lambs and goat kids aged 1–45 days were examined for enteric pathogens. Cryptosporidium parvum was detected in both diarrhoeic lambs (45%) and goat kids (42%) but not in non-diarrhoeic animals. F5+ (K99+) and/or F41+Escherichia coli strains were isolated from 26% and 22% of the diarrhoeic lambs and goat kids, respectively, although these strains, which did not produce enterotoxins ST I or LT I, were found with similar frequencies in non-diarrhoeic animals. A F5−F41−ST I+E. coli strain was isolated from a diarrhoeic lamb (0·6%). Verotoxigenic E. coli was isolated from both diarrhoeic and non-diarrhoeic lambs (4·1% and 8·2%, respectively) and there was no association between infection and diarrhoea. The prevalence of group A rotavirus infection in diarrhoeic lambs was very low (2·1%). Groups A and B rotaviruses were detected in three (8·1%) and five (13·5%) diarrhoeic goat kids from two single outbreaks. Group C rotaviruses were detected in four non-diarrhoeic goat kids. An association of diarrhoea and infection was demonstrated only for group B rotavirus. Clostridium perfringens was isolated from 10·8% of the diarrhoeic goat kids but not from non-diarrhoeic goat kids or lambs. Salmonella arizonae was isolated from a diarrhoeic goat kid (2·7%) and the clinical characteristics of the outbreaks where these two latter enteropathogens were found different from the rest. Picobirnaviruses were detected in a diarrhoeic lamb. No coronaviruses were detected using a bovine coronavirus ELISA. No evidence was found of synergistic effect between the agents studied. Enteric pathogens were not found in four (8·7%) and three (20%) outbreaks of diarrhoea in lambs and goat kids, respectively.
No animals tested were positive for feline leukaemia virus antigen and Chlamydia psittaci antibodies, but all were positive for antibodies to feline calicivirus (FCV), feline herpesvirus 1 (FHV1) and rotavirus. They had antibodies to feline parvovirus (96%), feline coronavirus (84%) and cowpox virus (2%). Antibody to feline immunodeficiency virus (FIV) was found in 53% of animals, which were less likely to be infected with Haemobartonella felis, and had higher FHV antibody titres than cats without FIV. FCV was isolated from 51% cats and FHV1 and feline reovirus each from 4%. H. felis was present in 42% of animals, and antibody to Toxoplasma gondii in 62%. Clinical abnormality had a significant association with FIV and feline calicivirus infections, but sex, age, social status and feeding group had no significant association with prevalence of any parasites. Toxocara cati and Toxascaris leonina eggs were found, respectively, in 91% and 82% of animals tested.
The patterns of disease caused by five common viruses which infect the respiratory tract are described. The viruses were strains of rhinovirus types 2, 9, and 14, a strain of coronavirus type 229E and of respiratory syncytial virus. Volunteers were given nasal drops containing a low infections dose of one of the viruses, quarantined from 2 days before to 5 days after inoculation, and examined daily by a clinician using a standard checklist of respiratory signs and symptoms. Only subjects who developed clinical illness accompanied by viral shedding and/or specific antibody production were analysed [n = 116]. The results confirm indication from earlier studies that the main difference between colds induced by different viruses is in duration of the incubation period. Patterens of symptom development were not substantially different with different viruses. Analyses of signs and symptoms in different categories, e.g. nasal symptoms v. coughing, justify treatment with different drugs either successively or simultaneously.
Ten porcine enteroviruses, 2 porcine adenoviruses and 1 coronavirus were isolated directly from 32 samples ofslurry collected from a pig fattening house. Concentration of the same samples by adsorption with the polyelectrolyte PE-60 yielded 24 porcine enteroviruses and 3 porcine adenoviruses. A porcine enterovirus was isolated, following PE-60 concentration, from 1 of 6 slurry samples from a sow farrowing house. No virus was isolated from 12 samples of slurry from dairy cows nor from 6 slurry samples from a calf-rearing unit. A porcine enterovirus was isolated from soil samples, after concentration with PE-60, collected 1, 2 and 8 days after pig slurry was spread on hay stubble. Two porcine enteroviruses were isolated by membrane filtration from 26 samples of surface run-off from land on which pig slurry was routinely spread, and 2 bovine enteroviruses were isolated from cattle feedlot run-off after adsorption to layers of talc and celite followed by hydroextraction. A porcine enterovirus was also isolated from 1 of 33 samples of surface water collected on farms on which pig slurry was routinely spread on the land, but no virus was isolated from 36 samples of ground water from the same farms. The surface water and ground water samples were concentrated by talc-celite adsorption and hydroextraction.
Six coronaviruses isolated in the U.S.A. have been inoculated into volunteers and all produced colds. Between 10 and 20 % of infected volunteers developed heterologous antibody responses after these and other experimental infections with coronaviruses. The haemagglutination-inhibition test with the OC43 virus strain was found to detect antibody rises after infection with a variety of strains.
Studies on normal adult sera taken between 1965 and 1970 revealed a high frequency of neutralizing antibody to one strain (229E) and a frequency of HI antibody to strain OC43 which fluctuated from year to year. Complement-fixing antibodies to these two viruses were also found, revealing an apparent increase in the activity of coronaviruses in the general population of the U.K., during the winter of 1968–9.
After preliminary trials, the detailed changes in the concentration of specific circulating and local antibodies were followed in 15 volunteers inoculated with coronavirus 229E. Ten of them, who had significantly lower concentrations of pre-existing antibody than the rest, became infected and eight of these developed colds. A limited investigation of circulating lymphocyte populations showed some lymphocytopenia in infected volunteers. In this group, antibody concentrations started to increase 1 week after inoculation and reached a maximum about 1 week later. Thereafter antibody titres slowly declined. Although concentrations were still slightly raised 1 year later, this did not always prevent reinfection when volunteers were then challenged with the homologous virus. However, the period of virus shedding was shorter than before and none developed a cold. All of the uninfected group were infected on re-challenge although they also appeared to show some resistance to disease and in the extent of infection. These results are discussed with reference to natural infections with coronavirus and with other infections, such as rhinovirus infections.
Thirteen men wintering on an Antarctic base were isolated from other human contact for 10 months. During this period Coxsackievirus A21 and later influenza A2 virus were administered to some of the men. Serum samples were collected from each of the men at monthly intervals.
Coxsackievirus A21 produced symptoms and apparently spread to uninoculated men. It also appears that repeated re-infections occurred and that the virus persisted in this small community for most of the period of isolation. HI antibody responses in the absence of neutralizing antibody responses seem to be transient.
The vaccine strain of influenza virus induced antibody responses but did not cause symptoms. There was no evidence of spread to uninoculated men.
Antibody titres against influenza C, parainfluenzaviruses 1 and 2 and coronavirus OC43 did not fall significantly during isolation.
An outbreak of respiratory illness occurred at the end of isolation and its origin was traced. No causative agent was detected.