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Hyperemesis hiemis—a sick hazard
Journal
of
Hospital
Injection
(1995)
30 (Supplement),
Hyperemesis
498-502
hiemis-a
sick
hazard
E. 0. Caul Regional Virus Laboratory, Public Health Laboratory, Kingsdown, Bristol BS2 8EL, UK
Myrtle
Road,
Summary:
Epidemic non-bacterial gastroenteritis or winter vomiting disease is a well recognized clinical syndrome causing significant morbidity in the general population and in semi-closed communities. The Norwalk group of viruses has become established as the aetiological agents responsible for this important clinical syndrome. As a result of their historically poorlydefined taxonomic status they have been alternatively described as small round structured viruses (SRSVs) which allow their differentiation from other morphologically distinct small round viruses, e.g. astroviruses, and classical human enteric caliciviruses. The Norwalk viruses are highly infectious, give rise to high secondary attack rates through person-to-person transmission and are common causes of outbreaks in hospitals leading to either ward or hospital closures. Transmission occurs via the faecal/oral route but also, and probably more importantly, from projectile vomiters, through environmental contamination. Inhalation of aerosolized virus arising from projectile vomiters is a possibility which requires further study. Laboratory diagnosis is currently achieved by electron microscopy but the recent molecular characterization of this group of viruses will allow the development of sensitive and specific assays. The future control of hospital outbreaks will rely heavily on effective control of infection procedures.
Keywords: ‘projectile’
Epidemic vomiters;
non-bacterial epidemiology;
gastroenteritis; Norwalk virus, SRSV, diagnosis; molecular characterization.
Introduction Hyperemesis hiemis (winter vomiting disease), now universally recognized as epidemic non-bacterial gastroenteritis, was originally described by Zahorsky in 1929.l Some 40 years later an aetiological agent (Norwalk agent)’ was identified and subsequently other morphologically identical but antigenically distinct viruses have been described.3 The latter viruses were ascribed geographical names to reflect their sources and as a result of their poorly-defined taxonomic status they were collectively called small round structured viruses (SRSVS).~ The illnesses produced by all these agents have a common clinical presentation. Epidemiology
and clinical
features
SRSVs are an important cause of mild self-limiting epidemic gastroenteritis2 which circulate throughout the year in the general population and produce 019%6701/95/060498+05
$0%00/O
0 1995 The Hospital
498
Infection
Society
Epidemic
non-bacterial
gastroenteritis
and hospital
control
499
high attack rates in semi-closed communities. They are also significant causes of food- and waterborne outbreaks5 Following a dose-dependent incubation period of 15-50 h patients present with an acute influenza-like illness, explosive diarrhoea and/or vomiting’ although a defined prodrome is not recognized. Significant spread (>50% attack rate)‘j to secondary contacts usually occurs and often results in closure of hospital wards. Transmission
Human volunteer studies in the 1950s and 1960s by American workers established that SRSVs are transmitted by the faecal/oral route’ and subsequent field outbreak investigations reinforced these observations. Nevertheless this route of transmission is not the full explanation for the explosive outbreaks that have been documented and currently vomit is recognized as a more important vehicle for transmission.7 Virus particles have been detected by electron microscopy in vomit samples’-a technique which requires a minimum of lo6 particles mL-‘. Assuming that symptomatic patients vomit a bolus of 30 mL, then 30 000 000 virus particles will be liberally distributed into the immediate environment. Environmental contamination will be compounded as the number of vomiting patients increases and given an infectious dose of 1O-l 00 particles it is not surprising that large outbreaks associated with secondary spread occur in semi-closed communities. All these observations explain the rapid spread of SRSVs via hand/ mouth transmission from the contaminated environment. In addition the ‘projectile’ nature of vomiting episodes in affected patients give rise to ‘aerosolized’ virus particles and inhalation of airborne droplets is a real possibility although unproven.9-” Furthermore dispersion of aerolized virus particles may occur as a result of air currents ensuring widespread environmental contamination in confined spaces. To date there is no evidence that SRSVs replicate in the respiratory tract or are spread by the respiratory route.7 Control
of infection
The projectile vomiter is an important source of infectious virus. This poses significant problems for infection control in semi-closed communities. Three aspects are applicable to the control of SRSV infections. These are introduction of SRSV into hospitals, containment of infection at ward level, and lastly control of the spread of SRSVs to other wards. All of these aspects have been recently addressed.7 The introduction of SRSVs into hospitals is inevitable since these infections lack a defined prodrome, the onset of symptoms is usually sudden and they commonly circulate widely in the community. In spite of this situation fundamental guidelines are appropriate. All health care workers should stay away from work after an
500
E. 0. Caul
episode of gastroenteritis, however mild, for 48 h after recovery. Notification of illness to line managers is essential to raise awareness as is education of all staff about SRSV transmission routes. Handwashing, both before and after attending is crucial to individual patients-failure to do so will contribute significantly to the spread of SRSVs. Specific instructions relating to the hazard of vomit, environmental contamination and handwashing should be included in control of infection policies. Following the presentation of the index case (vomiter) within a ward, immediate isolation of the case and the area is essential. Projectile vomiting is pathognomonic of SRSV infections, and in the absence of other causes is sufficient for a presumptive diagnosis. Rapid secondary spread to other patients and staff will confirm the diagnoses and signals the need for urgent control of infection measures. These include enteric precautions as well as the measures outlined above. Attention must be directed towards deep environmental cleansing of all hard surfaces with hypochlorite especially for high risk areas such as toilets. Air currents can be reduced by closing windows. Carpeted areas should be cleaned by gloved personnel and then decontaminated with hot detergent (100°C) using a heavy duty vacuum cleaner. Contaminated and potentially contaminated linen (adjacent beds) and removable fabrics should be removed and laundered; and exposed consumables such as fruit discarded. Nursing staff will be at special risk from aerosolized virus from vomit and the use of respiratory masks should be evaluated. The ward should be closed to new admissions if secondary spread occurs. The most achievable aim is to eliminate spread to other wards. Total restriction of staff movements from the affected ward, including communal rooms, should be imposed. This policy must be instigated immediately. Patient movement should also be restricted unless clinically imperative. Symptomatic staff should be cohorted within the affected ward or at their place of residence if symptoms arise elsewhere. An important aspect of containment is the immobilization of the symptomatic patient. Anti-emetics (intramuscularly) should be considered to rapidly terminate vomiting, reduce dehydration and to act as a sedative thus reducing patient mobility. Our observations indicate that this is essential to avoid the spread of SRSVs in semi-closed communites. Laboratory
diagnosis
Currently within the UK the incidence of SRSV outbreaks in hospitals is increasing although better investigation may explain this increased level of reporting. Specific identification of SRSV infections depends on expert electron microscopy although laboratory diagnosis rarely affects control of infection measures as the diagnosis is retrospective. Current techniques are directed towards antibody capture of the virus onto electron microscopy grids using solid phase electron microscopy.‘2 In our hands this is the most
Epidemic
non-bacterial
gastroenteritis
and hospital
control
501
sensitive technique for visualizing the virus, and allows recognition of four serotypes (including Norwalk virus). Serotypes 2 and 3 have been most prevalent in recent years and we continue to monitor the geographical distribution of these important gastrointestinal infections. Molecular
characterization
As a family, the SRSVs have resisted all attempts at propagation ‘in vitro’. This limitation has hampered progress in terms of taxonomy and the development of specific reagents for laboratory diagnosis. The situation has been changed recently by characterization of the complete genomes of one SRSV (Southampton virus)” and the Norwalk virus.13 Southampton virus (serotype 3) has been circulating in the community in recent years unlike Norwalk virus. The genome organization of the SRSVs indicate that they are members of the Caliciviridiae family, although recent genomic studies have shown that they are distinct from ‘classical’ human enteric caliciviruses14 and probably represent a new subgroup. Further genomic studies involving amplification of the RNA polymerase region by means of the polymerase chain reaction (PCR) has, surprisingly, revealed a considerable degree of diversity,‘5,‘6 and recently SRSVs have been divided into two distinct genotypes.” Thus a simple ‘catch-all’ PCR technique, applicable to rapid virus diagnosis, is not yet available but will undoubtedly be developed in the near future. The variability of the RNA polymerase region of SRSVs allows not only the differentiation of similar outbreaks but also identifies common source outbreaks in geographically distinct settings. Thus the SRSVs isolated from two distinct hospital outbreaks17 have been linked by their identical RNA polymerase nucleotide sequence. Molecular epidemiology will play an important part in future studies of point source outbreaks involving either food or water. Future
prospects
Following the characterization of the RNA genome of SRSVs and the development of new primers to study their diversity there is every possibility of developing recombinant vaccines. Such vaccines will nevertheless take some time to develop and clinical trials will be essential to elucidate further the unusual immunobiology of SRSVs where symptomatic reinfection to homologous virus challenge is well documented. Much needs to be learned about the immunopathogenesis of SRSVs before we can contemplate vaccine-induced immunity as our main defence against hospital SRSV infections. Until such time we should concentrate our efforts towards effective control of infection procedures7,‘* to limit the spread of SRSV which often leads to the closure of hospital wards and sometimes the whole hospital.
E. 0. Cad
502
References Zahorsky J. Hyperemesis 46: 391-395. Kapikian AZ. Norwalk
6.
7. 8.
or the
winter
vomiting
disease.
Arch Pediatr
1929;
viruses. In: Kapikian AZ, Ed. Viral Infections New York: Marcel Dekker 1994: 471-518. Caul EO. Small round faecal viruses. In: Patterson J, Ed. Purvoviruses and Human Disease. Boca Raton, Florida: CRC Press 1988: 139-163. Caul EO, Appleton H. The electron microscopical and physical characteristics of small round human faecal viruses: an interim scheme for classification. J Med V%oZ 1982; 9: 257-265. Caul EO. Viruses in food. In: Spencer RC, Wright EP, Newsom SWB, Eds. Rapid Methods and Automation in Microbiology and Immunology. Intercept Ltd, P.O. Box 716, Andover, Hampshire 1994; 37: 347-354. Kaplan JE, Feldman R, Campbell DS, Lookabuagh C, Gary GW. The frequency of a norwalk-like pattern of illness in outbreaks of acute gastroenteritis. Am J Public Health 1982; 72: 1329-1332. Caul EO. Small round structured viruses: airborne transmission and hospital control. Lancet 1994; 343: 1240-1241. Greenberg HB, Wyatt RG, Kapikian AZ. Norwalk virus in vomitus. Lancet 1979; i:
of the Gastrontestinal
5.
hiemis and
Norwalk-like
Tract, 2nd edn.
5s. 9. Sawyer LA, Murphy JJ, Kaplan JE et al. 25 to 30 nm virus associated with a hospital outbreak of acute gastroenteritis with evidence of airborne transmission. AmJ Epidemiol 1988; 127: 1267-1271. 10. Chadwick PR, Walker M, Rees AE. Airborne transmission of a small round structured virus. Lancet 1994; 343: 171. GA, Glass RI. Airborne transmission of a small round structured virus. Lancet 11. Gellert 1994; 343: 609. 12. Lambden PR, Caul EO, Ashley CR, Clarke IN. Sequence and general organization of a human small round structured (Norwalk-like) virus. Science 1993; 259: 516-518. 13. Jiang X, Wang K, Graham DY, Estes MK. Sequence and general organization of Norwalk virus. ViTology 1993; 195: 51-61. 14. Lambden PR, Caul EO, Ashley CR, Clarke IN. Human enteric caliciviruses are genetically distinct from small round structured viruses. Lancet 1994; 343: 666-667. SM, Dingle KE, Lambden PR, Caul EO, Ashley CR, Clarke IN. Human enteric 1s. Green caliciviridae: a new prevalent SRSV group defined by RNA-dependent RNA polymerase and capsid diversity. J Gen ViroZ 1994; 75: 1883-1888. J, Norcott JP, Lewis D, Arnold C, Brown DWG. Norwalk-like viruses: De16. Green monstration of genetic diversity of polymerase chain reaction. J CZin Microbial 1993; 31: 3007-3012. 17. Green SM, Lambden PR, Deng Yu, Clarke IN. PCR detection of small roundstructured viruses from two related hospital outbreaks of gastroenteritis using inosinecontaining primers. J Med VivoZ 1994; (in press). 18. Caul EO and the viral gastroenteritis sub-committee of the PHLS virology committee. Outbreaks of gastroenteritis associated with SRSVs PHLS Microbial Digest 1993; 10: 2-8.
of
Hospital
Injection
(1995)
30 (Supplement),
Hyperemesis
498-502
hiemis-a
sick
hazard
E. 0. Caul Regional Virus Laboratory, Public Health Laboratory, Kingsdown, Bristol BS2 8EL, UK
Myrtle
Road,
Summary:
Epidemic non-bacterial gastroenteritis or winter vomiting disease is a well recognized clinical syndrome causing significant morbidity in the general population and in semi-closed communities. The Norwalk group of viruses has become established as the aetiological agents responsible for this important clinical syndrome. As a result of their historically poorlydefined taxonomic status they have been alternatively described as small round structured viruses (SRSVs) which allow their differentiation from other morphologically distinct small round viruses, e.g. astroviruses, and classical human enteric caliciviruses. The Norwalk viruses are highly infectious, give rise to high secondary attack rates through person-to-person transmission and are common causes of outbreaks in hospitals leading to either ward or hospital closures. Transmission occurs via the faecal/oral route but also, and probably more importantly, from projectile vomiters, through environmental contamination. Inhalation of aerosolized virus arising from projectile vomiters is a possibility which requires further study. Laboratory diagnosis is currently achieved by electron microscopy but the recent molecular characterization of this group of viruses will allow the development of sensitive and specific assays. The future control of hospital outbreaks will rely heavily on effective control of infection procedures.
Keywords: ‘projectile’
Epidemic vomiters;
non-bacterial epidemiology;
gastroenteritis; Norwalk virus, SRSV, diagnosis; molecular characterization.
Introduction Hyperemesis hiemis (winter vomiting disease), now universally recognized as epidemic non-bacterial gastroenteritis, was originally described by Zahorsky in 1929.l Some 40 years later an aetiological agent (Norwalk agent)’ was identified and subsequently other morphologically identical but antigenically distinct viruses have been described.3 The latter viruses were ascribed geographical names to reflect their sources and as a result of their poorly-defined taxonomic status they were collectively called small round structured viruses (SRSVS).~ The illnesses produced by all these agents have a common clinical presentation. Epidemiology
and clinical
features
SRSVs are an important cause of mild self-limiting epidemic gastroenteritis2 which circulate throughout the year in the general population and produce 019%6701/95/060498+05
$0%00/O
0 1995 The Hospital
498
Infection
Society
Epidemic
non-bacterial
gastroenteritis
and hospital
control
499
high attack rates in semi-closed communities. They are also significant causes of food- and waterborne outbreaks5 Following a dose-dependent incubation period of 15-50 h patients present with an acute influenza-like illness, explosive diarrhoea and/or vomiting’ although a defined prodrome is not recognized. Significant spread (>50% attack rate)‘j to secondary contacts usually occurs and often results in closure of hospital wards. Transmission
Human volunteer studies in the 1950s and 1960s by American workers established that SRSVs are transmitted by the faecal/oral route’ and subsequent field outbreak investigations reinforced these observations. Nevertheless this route of transmission is not the full explanation for the explosive outbreaks that have been documented and currently vomit is recognized as a more important vehicle for transmission.7 Virus particles have been detected by electron microscopy in vomit samples’-a technique which requires a minimum of lo6 particles mL-‘. Assuming that symptomatic patients vomit a bolus of 30 mL, then 30 000 000 virus particles will be liberally distributed into the immediate environment. Environmental contamination will be compounded as the number of vomiting patients increases and given an infectious dose of 1O-l 00 particles it is not surprising that large outbreaks associated with secondary spread occur in semi-closed communities. All these observations explain the rapid spread of SRSVs via hand/ mouth transmission from the contaminated environment. In addition the ‘projectile’ nature of vomiting episodes in affected patients give rise to ‘aerosolized’ virus particles and inhalation of airborne droplets is a real possibility although unproven.9-” Furthermore dispersion of aerolized virus particles may occur as a result of air currents ensuring widespread environmental contamination in confined spaces. To date there is no evidence that SRSVs replicate in the respiratory tract or are spread by the respiratory route.7 Control
of infection
The projectile vomiter is an important source of infectious virus. This poses significant problems for infection control in semi-closed communities. Three aspects are applicable to the control of SRSV infections. These are introduction of SRSV into hospitals, containment of infection at ward level, and lastly control of the spread of SRSVs to other wards. All of these aspects have been recently addressed.7 The introduction of SRSVs into hospitals is inevitable since these infections lack a defined prodrome, the onset of symptoms is usually sudden and they commonly circulate widely in the community. In spite of this situation fundamental guidelines are appropriate. All health care workers should stay away from work after an
500
E. 0. Caul
episode of gastroenteritis, however mild, for 48 h after recovery. Notification of illness to line managers is essential to raise awareness as is education of all staff about SRSV transmission routes. Handwashing, both before and after attending is crucial to individual patients-failure to do so will contribute significantly to the spread of SRSVs. Specific instructions relating to the hazard of vomit, environmental contamination and handwashing should be included in control of infection policies. Following the presentation of the index case (vomiter) within a ward, immediate isolation of the case and the area is essential. Projectile vomiting is pathognomonic of SRSV infections, and in the absence of other causes is sufficient for a presumptive diagnosis. Rapid secondary spread to other patients and staff will confirm the diagnoses and signals the need for urgent control of infection measures. These include enteric precautions as well as the measures outlined above. Attention must be directed towards deep environmental cleansing of all hard surfaces with hypochlorite especially for high risk areas such as toilets. Air currents can be reduced by closing windows. Carpeted areas should be cleaned by gloved personnel and then decontaminated with hot detergent (100°C) using a heavy duty vacuum cleaner. Contaminated and potentially contaminated linen (adjacent beds) and removable fabrics should be removed and laundered; and exposed consumables such as fruit discarded. Nursing staff will be at special risk from aerosolized virus from vomit and the use of respiratory masks should be evaluated. The ward should be closed to new admissions if secondary spread occurs. The most achievable aim is to eliminate spread to other wards. Total restriction of staff movements from the affected ward, including communal rooms, should be imposed. This policy must be instigated immediately. Patient movement should also be restricted unless clinically imperative. Symptomatic staff should be cohorted within the affected ward or at their place of residence if symptoms arise elsewhere. An important aspect of containment is the immobilization of the symptomatic patient. Anti-emetics (intramuscularly) should be considered to rapidly terminate vomiting, reduce dehydration and to act as a sedative thus reducing patient mobility. Our observations indicate that this is essential to avoid the spread of SRSVs in semi-closed communites. Laboratory
diagnosis
Currently within the UK the incidence of SRSV outbreaks in hospitals is increasing although better investigation may explain this increased level of reporting. Specific identification of SRSV infections depends on expert electron microscopy although laboratory diagnosis rarely affects control of infection measures as the diagnosis is retrospective. Current techniques are directed towards antibody capture of the virus onto electron microscopy grids using solid phase electron microscopy.‘2 In our hands this is the most
Epidemic
non-bacterial
gastroenteritis
and hospital
control
501
sensitive technique for visualizing the virus, and allows recognition of four serotypes (including Norwalk virus). Serotypes 2 and 3 have been most prevalent in recent years and we continue to monitor the geographical distribution of these important gastrointestinal infections. Molecular
characterization
As a family, the SRSVs have resisted all attempts at propagation ‘in vitro’. This limitation has hampered progress in terms of taxonomy and the development of specific reagents for laboratory diagnosis. The situation has been changed recently by characterization of the complete genomes of one SRSV (Southampton virus)” and the Norwalk virus.13 Southampton virus (serotype 3) has been circulating in the community in recent years unlike Norwalk virus. The genome organization of the SRSVs indicate that they are members of the Caliciviridiae family, although recent genomic studies have shown that they are distinct from ‘classical’ human enteric caliciviruses14 and probably represent a new subgroup. Further genomic studies involving amplification of the RNA polymerase region by means of the polymerase chain reaction (PCR) has, surprisingly, revealed a considerable degree of diversity,‘5,‘6 and recently SRSVs have been divided into two distinct genotypes.” Thus a simple ‘catch-all’ PCR technique, applicable to rapid virus diagnosis, is not yet available but will undoubtedly be developed in the near future. The variability of the RNA polymerase region of SRSVs allows not only the differentiation of similar outbreaks but also identifies common source outbreaks in geographically distinct settings. Thus the SRSVs isolated from two distinct hospital outbreaks17 have been linked by their identical RNA polymerase nucleotide sequence. Molecular epidemiology will play an important part in future studies of point source outbreaks involving either food or water. Future
prospects
Following the characterization of the RNA genome of SRSVs and the development of new primers to study their diversity there is every possibility of developing recombinant vaccines. Such vaccines will nevertheless take some time to develop and clinical trials will be essential to elucidate further the unusual immunobiology of SRSVs where symptomatic reinfection to homologous virus challenge is well documented. Much needs to be learned about the immunopathogenesis of SRSVs before we can contemplate vaccine-induced immunity as our main defence against hospital SRSV infections. Until such time we should concentrate our efforts towards effective control of infection procedures7,‘* to limit the spread of SRSV which often leads to the closure of hospital wards and sometimes the whole hospital.
E. 0. Cad
502
References Zahorsky J. Hyperemesis 46: 391-395. Kapikian AZ. Norwalk
6.
7. 8.
or the
winter
vomiting
disease.
Arch Pediatr
1929;
viruses. In: Kapikian AZ, Ed. Viral Infections New York: Marcel Dekker 1994: 471-518. Caul EO. Small round faecal viruses. In: Patterson J, Ed. Purvoviruses and Human Disease. Boca Raton, Florida: CRC Press 1988: 139-163. Caul EO, Appleton H. The electron microscopical and physical characteristics of small round human faecal viruses: an interim scheme for classification. J Med V%oZ 1982; 9: 257-265. Caul EO. Viruses in food. In: Spencer RC, Wright EP, Newsom SWB, Eds. Rapid Methods and Automation in Microbiology and Immunology. Intercept Ltd, P.O. Box 716, Andover, Hampshire 1994; 37: 347-354. Kaplan JE, Feldman R, Campbell DS, Lookabuagh C, Gary GW. The frequency of a norwalk-like pattern of illness in outbreaks of acute gastroenteritis. Am J Public Health 1982; 72: 1329-1332. Caul EO. Small round structured viruses: airborne transmission and hospital control. Lancet 1994; 343: 1240-1241. Greenberg HB, Wyatt RG, Kapikian AZ. Norwalk virus in vomitus. Lancet 1979; i:
of the Gastrontestinal
5.
hiemis and
Norwalk-like
Tract, 2nd edn.
5s. 9. Sawyer LA, Murphy JJ, Kaplan JE et al. 25 to 30 nm virus associated with a hospital outbreak of acute gastroenteritis with evidence of airborne transmission. AmJ Epidemiol 1988; 127: 1267-1271. 10. Chadwick PR, Walker M, Rees AE. Airborne transmission of a small round structured virus. Lancet 1994; 343: 171. GA, Glass RI. Airborne transmission of a small round structured virus. Lancet 11. Gellert 1994; 343: 609. 12. Lambden PR, Caul EO, Ashley CR, Clarke IN. Sequence and general organization of a human small round structured (Norwalk-like) virus. Science 1993; 259: 516-518. 13. Jiang X, Wang K, Graham DY, Estes MK. Sequence and general organization of Norwalk virus. ViTology 1993; 195: 51-61. 14. Lambden PR, Caul EO, Ashley CR, Clarke IN. Human enteric caliciviruses are genetically distinct from small round structured viruses. Lancet 1994; 343: 666-667. SM, Dingle KE, Lambden PR, Caul EO, Ashley CR, Clarke IN. Human enteric 1s. Green caliciviridae: a new prevalent SRSV group defined by RNA-dependent RNA polymerase and capsid diversity. J Gen ViroZ 1994; 75: 1883-1888. J, Norcott JP, Lewis D, Arnold C, Brown DWG. Norwalk-like viruses: De16. Green monstration of genetic diversity of polymerase chain reaction. J CZin Microbial 1993; 31: 3007-3012. 17. Green SM, Lambden PR, Deng Yu, Clarke IN. PCR detection of small roundstructured viruses from two related hospital outbreaks of gastroenteritis using inosinecontaining primers. J Med VivoZ 1994; (in press). 18. Caul EO and the viral gastroenteritis sub-committee of the PHLS virology committee. Outbreaks of gastroenteritis associated with SRSVs PHLS Microbial Digest 1993; 10: 2-8.