Interventions for the interruption or reduction of the spread of respiratory viruses
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To systematically review the evidence of effectiveness of interventions to interrupt or reduce the spread of respiratory viruses causing influenza‐like illnesses (excluding vaccines and antivirals, which have already been covered by Cochrane Reviews) (Demicheli 2004; Jefferson 1999; Jefferson 2006b; Matheson 2003; Smith 2006; Swingler 2003).
Background
There is increasing concern that a global pandemic viral infection may seriously affect humans. In 2002 to 2003 a novel Severe Acute Respiratory Syndrome (SARS) epidemic, caused by a coronavirus, swept the world. About 8000 people were affected and 780 (including a high number of healthcare workers) died. Overshadowing this calamity was an enormous social and economic crisis, especially in Asia (Shute 2003). There is now increasing concern about the threat of a new viral pandemic, arising from avian influenza, caused by the H5N1 strain (WHO 2004). Although most influenza cases recover fully, in the USA, influenza causes approximately 36,000 deaths and 226,000 hospitalisations annually (USDHHS 2005). It is estimated that annually, approximately 10% to 15% of people globally contract influenza. During major epidemics, the attack rate of influenza may be as high as 50%. It is associated with increased general practice consultation rates, hospital admissions (Fleming 2000) and excess deaths (Fleming 2000; Simonsen 1997). It must also be considered in terms of increased days lost to absence from work and school, health care planning and influenza pandemic planning (Smith 2006).
High viral load and high viral infectiousness are likely to be the drivers of an influenza pandemic (Jefferson 2006a) and other serious epidemics such as SARS. Other factors which contribute to influenza pandemics include an antigenic shift in the virus. An antigenic shift is a major change in the genetic makeup of the virus which creates a new subtype against which there is little circulating natural immunity (Smith 2006), as most people have not been exposed to this new virus and therefore are susceptible to infection. These pandemics are thought to originate in southern China, where ducks (the animal reservoir and breeding ground for new strains), pigs (which are thought to be the biological intermediate host or 'mixing vessel') and humans live in very close proximity (Bonn 1997). Pigs are considered plausible intermediate hosts, as their respiratory epithelium cells have receptors for both avian (such as duck) and human viral hemagglutinins (Bonn 1997). Minor changes in viral antigenic configurations, known as 'drift', cause local or more circumscribed epidemics (Smith 2006).
There is increasing evidence (Jefferson 2005a; Jefferson 2005b; Jefferson 2005c; Jefferson 2006a) that single measures (such as the use of vaccines or antivirals) may be insufficient to interrupt the spread of influenza while there are no virus‐specific interventions for other agents. A recent trial showed that handwashing may be effective in diminishing mortality for respiratory disease (Luby 2005), but other public health measures such as isolation, social distancing and barriers may have major social implications for any community adopting them (CDC 2005a; CDC 2005b; WHO 2006). Given the potential global importance of interrupting viral transmission, up‐to‐date, concise estimates of effectiveness are necessary to inform planning and decision‐making. We are unaware of the existence of a systematic review of the evidence of the effects of these measures, either as single or combined, simultaneous interventions.
Objectives
To systematically review the evidence of effectiveness of interventions to interrupt or reduce the spread of respiratory viruses causing influenza‐like illnesses (excluding vaccines and antivirals, which have already been covered by Cochrane Reviews) (Demicheli 2004; Jefferson 1999; Jefferson 2006b; Matheson 2003; Smith 2006; Swingler 2003).
Methods
Criteria for considering studies for this review
Types of studies
We will consider individual‐level or cluster randomised or quasi‐randomised controlled trials. To enhance public health relevance we will also consider observational studies (cohort and case‐control designs), and any other comparative design, provided some attempt has been made to control for confounding.
Types of participants
People of all ages.
Types of interventions
Any method (excluding vaccines and antivirals, which have already been covered by Cochrane Reviews) of preventing viral animal‐to‐human or human‐to‐human transmission of respiratory viruses (isolation, quarantine, social distancing, barriers, personal protection and hygiene) compared with none, or any other method.
Types of outcome measures
Deaths.
Numbers of cases of viral illness.
Severity of viral illness in the compared populations. In children and healthy adults, we will measure burden by consequences of influenza, for example, losses in productivity due to absenteeism by parents. For the elderly in the community, we will measure the burden by repeated primary healthcare contacts, hospital admissions and the risk of complications.
Any proxies for these.
Search methods for identification of studies
We will search the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library latest issue); MEDLINE (1966 to present); OLDMEDLINE (1950 to 1965); EMBASE (1990 to present); and CINAHL (1982 to present).
We will use the following search terms in MEDLINE and CENTRAL and modify them for OLDMEDLINE, EMBASE and CINAHL. There will be no language restrictions.
(exp Influenza, Human/ OR influenza OR flu OR exp Common Cold/ or common cold OR exp Rhinovirus OR rhinovirus$ OR exp Adenoviridae/ OR adenovirus$ OR exp Coronavirus/ OR exp Coronavirus Infections/ OR coronavirus$ OR exp Respiratory Syncytial Viruses/ OR exp Respiratory Syncytial Virus Infections/ OR respiratory syncytial virus$ OR respiratory syncythial virus$ OR exp Parainfluenza Virus/ OR parainfluenza OR para influenza OR para‐influenza OR exp Severe Acute Respiratory Syndrome/ OR severe acute respiratory syndrome OR SARS OR acute respiratory infection$ OR acute respiratory tract infection$)
AND
(exp Handwashing/ OR handwashing OR hand washing OR hand‐washing OR hand hygiene OR sanitizer$ OR sanitiser$ OR cleanser$ OR disinfectant$ OR exp Gloves, Protective/ OR exp Gloves, Surgical/ OR glov$ OR exp Masks/ OR mask$ OR exp Patient Isolators/ OR exp Patient Isolation/ OR barrier$ OR curtain$ OR partition$ OR negative pressure room$ OR reverse barrier nursing OR Cross Infection/pc [Prevention & Control] OR school closure$ OR mass gathering$ OR public gathering$ OR distancing OR outbreak control$ OR exp Quarantine/ OR quarantine$)
We will scan the references of all included trials to identify other potentially relevant studies. We will also access the archives of the former MRC Common Cold Unit (Jefferson 2005d) as a possible source for interruption of transmission evidence.
Data collection and analysis
Quality assessment
We will analyse randomised and non‐randomised studies separately. We will assess studies for quality using checklists to measure individual markers of quality. We will not use summary scores, but instead make assessment according to the estimates of bias from the individual differences in quality. We will exclude those trials whose methods we believe are so likely to be biased that their results are unreliable.
Study eligibility
Initially we will scan the titles and abstracts from the searches. We will obtain full text articles when a study appears to meet the eligibility criteria or when there is insufficient information in the abstract to assess eligibility. We will then use a standardised form to assess the eligibility of each study, based on the full article. When studies are excluded, we will document the reasons for exclusion.
Data extraction
Two authors (TOJ, CDM) will independently apply inclusion criteria to all identified and retrieved articles. Four authors (TOJ, EF, BH, AP) will extract data from included studies on standard Cochrane Vaccines Field forms. The procedure will be supervised and arbitrated by CDM. Assessment of methodological quality for randomised controlled trials will be carried out using criteria from the Cochrane Reviewers' Handbook (Alderson 2004). We will assess studies according to randomisation, generation of the allocation sequence, allocation concealment, blinding and follow up. We will assess the quality of cohorts and case‐control studies in relation to the presence of potential confounders using the appropriate Newcastle‐Ottawa Scales (NOS) (Wells 2005). We will use quality at the analysis stage as a means of interpreting the results. We will assign risk of bias categories on the basis of the number of NOS items judged inadequate in each study:
‐ low risk of bias ‐ up to one inadequate item;
‐ medium risk of bias ‐ up to three inadequate items;
‐ high risk of bias ‐ more than three inadequate items;
‐ very high risk of bias ‐ when there was no description of methods.
We will enter extracted data into Cochrane Review Manager (RevMan) software. Aggregation of data will be dependent on the sensitivity and homogeneity of definitions of exposure, populations and outcomes used. Where studies are found to be homogenous, we will perform a meta‐analysis within each design category.
We will group reports first according to the setting of the study (community or long‐term care facilities) and then by level of viral circulation (if known). Whenever a study reports data for more than one "viral season" or "epidemic wave" we will consider these separately, creating separate data sets. We will calculate the statistic I2 for each pooled estimate, in order to assess the impact on statistical heterogeneity . I2 may be interpreted as the proportion of total variation among effect estimates that is due to heterogeneity rather than sampling error, and it is intrinsically independent of the number of studies. When I2 is less than 30%, there is little concern about statistical heterogeneity (Higgins 2002; Higgins 2003). We will use random‐effects models throughout to take account of the between‐study variance in our findings (DerSimonian 1986).
When possible, we will perform a quantitative analysis. We will summarise effectiveness (against ILI) estimates as relative risk (RR) or odds ratio (OR) within 95% confidence intervals (in brackets after the summary estimate). We will express absolute intervention efficacy (VE) as a percentage using the formula VE = 1‐RR or VE* = 1‐ OR whenever significant. When statistical significance is not achieved, we will report the relevant RR or OR.
Sub‐group analysis
An a priori sub‐group analysis is planned for:
(a) pandemic influenza outbreaks;
(b) seasonal influenza;
(c) other epidemics (for example, SARS).
