Alessandro Rivetti - Academia.edu (original) (raw)
Papers by Alessandro Rivetti
The Cochrane library, Feb 1, 2018
Trusted evidence. Informed decisions. Better health.
ABSTRACT Tetanus is an acute, often fatal, disease caused by an exotoxin produced by Clostridium ... more ABSTRACT Tetanus is an acute, often fatal, disease caused by an exotoxin produced by Clostridium tetani. It occurs in newborn infants born to mothers who do not have sufficient circulating antibodies to protect the infant passively, by transplacental transfer. Prevention may be possible by the vaccination of pregnant and/or non-pregnant women with tetanus toxoid, and the provision of clean delivery services. Tetanus toxoid consists of a formaldehyde-treated toxin which stimulates the production of antitoxin. To assess the effectiveness of tetanus toxoid, administered to women of childbearing age or pregnant women, to prevent cases of, and deaths from, neonatal tetanus. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (December 2004) , The Cochrane Library (Issue 1, 2005), MEDLINE (1966 to December 2004), EMBASE (1974 to December 2004). We also used the results from handsearching and consultations with manufacturers and authors. Randomised or quasi-randomised trials evaluating the effects of tetanus toxoid in pregnant women or women of childbearing age on numbers of neonatal tetanus cases and deaths. Three review authors independently assessed trials for inclusion, data extraction and trial quality. Two trials (10,560 infants) were included. One study (1919 infants) assessed the effectiveness of tetanus toxoid in preventing neonatal tetanus deaths. After a single dose, the relative risk (RR) was 0.57 (95% confidence interval (CI) 0.26 to 1.24), and the vaccine effectiveness was 43%. With a two or three dose course, the RR was 0.02 (95% CI 0.00 to 0.30); vaccine effectiveness was 98%. No effect was detected on causes of death other than tetanus. The RR of cases of neonatal tetanus after at least one dose of tetanus toxoid was 0.20 (95% CI 0.10 to 0.40); vaccine effectiveness was 80%. Another study, involving 8641 children, assessed the effectiveness of tetanus-diptheria toxoid in preventing neonatal mortality after one or two doses. The RR was 0.68 (95% CI 0.56 to 0.82); vaccine effectiveness was 32%. In preventing deaths at 4 to 14 days, the RR was 0.38 (95% CI 0.27 to 0.55), and vaccine effectiveness 62% (95% CI 45% to 73%). Available evidence supports the implementation of immunisation practices on women of childbearing age or pregnant women in communities with similar, or higher, levels of risk of neonatal tetanus, to the two study sites. More information is needed on possible interference of vaccination by malaria chemoprophylaxis on the roles of malnutrition and vitamin A deficiency, and on the quality of tetanus toxoid production and storage.
Cochrane Database of Systematic Reviews, Oct 17, 2010
Background: Viral epidemics or pandemics of acute respiratory infections like influenza or severe... more Background: Viral epidemics or pandemics of acute respiratory infections like influenza or severe acute respiratory syndrome pose a worldwide threat. Antiviral drugs and vaccinations may be insufficient to prevent catastrophe. Objectives: To systematically review the effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses.
Cochrane Database of Systematic Reviews, Oct 19, 2005
The Cochrane library, Feb 1, 2018
Analysis 1.5. Comparison 1 Live vaccine versus placebo (RCTs), Outcome 5 Working days lost (numbe... more Analysis 1.5. Comparison 1 Live vaccine versus placebo (RCTs), Outcome 5 Working days lost (number of events, parents)........ Analysis 1.6. Comparison 1 Live vaccine versus placebo (RCTs), Outcome 6 Drug prescriptions
The Cochrane library, Sep 5, 2018
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:To evaluat... more This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:To evaluate the safety and the effects of influenza vaccines on disease activity in people with multiple sclerosis (MS).
Weekly releases (1997–2007), Aug 17, 2006
An integrated epidemiological surveillance and response system was set up for the 2006 Olympic Wi... more An integrated epidemiological surveillance and response system was set up for the 2006 Olympic Winter Games in Torino [1] between 1 February
The Cochrane library, Nov 22, 2021
BackgroundMeasles, mumps, rubella, and varicella (chickenpox) are serious diseases that can lead ... more BackgroundMeasles, mumps, rubella, and varicella (chickenpox) are serious diseases that can lead to serious complications, disability, and death. However, public debate over the safety of the trivalent MMR vaccine and the resultant drop in vaccination coverage in several countries persists, despite its almost universal use and accepted effectiveness. This is an update of a review published in 2005 and updated in 2012.ObjectivesTo assess the effectiveness, safety, and long‐ and short‐term adverse effects associated with the trivalent vaccine, containing measles, rubella, mumps strains (MMR), or concurrent administration of MMR vaccine and varicella vaccine (MMR+V), or tetravalent vaccine containing measles, rubella, mumps, and varicella strains (MMRV), given to children aged up to 15 years.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2019, Issue 5), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to 2 May 2019), Embase (1974 to 2 May 2019), the WHO International Clinical Trials Registry Platform (2 May 2019), and ClinicalTrials.gov (2 May 2019).Selection criteriaWe included randomised controlled trials (RCTs), controlled clinical trials (CCTs), prospective and retrospective cohort studies (PCS/RCS), case‐control studies (CCS), interrupted time‐series (ITS) studies, case cross‐over (CCO) studies, case‐only ecological method (COEM) studies, self‐controlled case series (SCCS) studies, person‐time cohort (PTC) studies, and case‐coverage design/screening methods (CCD/SM) studies, assessing any combined MMR or MMRV / MMR+V vaccine given in any dose, preparation or time schedule compared with no intervention or placebo, on healthy children up to 15 years of age.Data collection and analysisTwo review authors independently extracted data and assessed the methodological quality of the included studies. We grouped studies for quantitative analysis according to study design, vaccine type (MMR, MMRV, MMR+V), virus strain, and study settings. Outcomes of interest were cases of measles, mumps, rubella, and varicella, and harms. Certainty of evidence of was rated using GRADE.Main resultsWe included 138 studies (23,480,668 participants). Fifty‐one studies (10,248,159 children) assessed vaccine effectiveness and 87 studies (13,232,509 children) assessed the association between vaccines and a variety of harms. We included 74 new studies to this 2019 version of the review.EffectivenessVaccine effectiveness in preventing measles was 95% after one dose (relative risk (RR) 0.05, 95% CI 0.02 to 0.13; 7 cohort studies; 12,039 children; moderate certainty evidence) and 96% after two doses (RR 0.04, 95% CI 0.01 to 0.28; 5 cohort studies; 21,604 children; moderate certainty evidence). The effectiveness in preventing cases among household contacts or preventing transmission to others the children were in contact with after one dose was 81% (RR 0.19, 95% CI 0.04 to 0.89; 3 cohort studies; 151 children; low certainty evidence), after two doses 85% (RR 0.15, 95% CI 0.03 to 0.75; 3 cohort studies; 378 children; low certainty evidence), and after three doses was 96% (RR 0.04, 95% CI 0.01 to 0.23; 2 cohort studies; 151 children; low certainty evidence). The effectiveness (at least one dose) in preventing measles after exposure (post‐exposure prophylaxis) was 74% (RR 0.26, 95% CI 0.14 to 0.50; 2 cohort studies; 283 children; low certainty evidence).The effectiveness of Jeryl Lynn containing MMR vaccine in preventing mumps was 72% after one dose (RR 0.24, 95% CI 0.08 to 0.76; 6 cohort studies; 9915 children; moderate certainty evidence), 86% after two doses (RR 0.12, 95% CI 0.04 to 0.35; 5 cohort studies; 7792 children; moderate certainty evidence). Effectiveness in preventing cases among household contacts was 74% (RR 0.26, 95% CI 0.13 to 0.49; 3 cohort studies; 1036 children; moderate certainty evidence). Vaccine effectiveness against rubella, using a vaccine with the BRD2 strain which is only used in China, is 89% (RR 0.11, 95% CI 0.03 to 0.42; 1 cohort study; 1621 children; moderate certainty evidence). Vaccine effectiveness against varicella (any severity) after two doses in children aged 11 to 22 months is 95% in a 10 years follow‐up (rate ratio (rr) 0.05, 95% CI 0.03 to 0.08; 1 RCT; 2279 children; high certainty evidence).SafetyThere is evidence supporting an association between aseptic meningitis and MMR vaccines containing Urabe and Leningrad‐Zagreb mumps strains, but no evidence supporting this association for MMR vaccines containing Jeryl Lynn mumps strains (rr 1.30, 95% CI 0.66 to 2.56; low certainty evidence). The analyses provide evidence supporting an association between MMR/MMR+V/MMRV vaccines (Jeryl Lynn strain) and febrile seizures. Febrile seizures normally occur in 2% to 4% of healthy children at least once before the age of 5. The attributable risk febrile seizures vaccine‐induced is estimated to be from 1 per 1700 to 1 per 1150 administered doses.The analyses provide evidence supporting an association between MMR vaccination and idiopathic thrombocytopaenic purpura (ITP). However, the risk of ITP after vaccination is smaller than after natural infection with these viruses. Natural infection of ITP occur in 5 cases per 100,000 (1 case per 20,000) per year. The attributable risk is estimated about 1 case of ITP per 40,000 administered MMR doses.There is no evidence of an association between MMR immunisation and encephalitis or encephalopathy (rate ratio 0.90, 95% CI 0.50 to 1.61; 2 observational studies; 1,071,088 children; low certainty evidence), and autistic spectrum disorders (rate ratio 0.93, 95% CI 0.85 to 1.01; 2 observational studies; 1,194,764 children; moderate certainty). There is insufficient evidence to determine the association between MMR immunisation and inflammatory bowel disease (odds ratio 1.42, 95% CI 0.93 to 2.16; 3 observational studies; 409 cases and 1416 controls; moderate certainty evidence).Additionally, there is no evidence supporting an association between MMR immunisation and cognitive delay, type 1 diabetes, asthma, dermatitis/eczema, hay fever, leukaemia, multiple sclerosis, gait disturbance, and bacterial or viral infections. Authors' conclusionsExisting evidence on the safety and effectiveness of MMR/MMRV vaccines support their use for mass immunisation. Campaigns aimed at global eradication should assess epidemiological and socioeconomic situations of the countries as well as the capacity to achieve high vaccination coverage. More evidence is needed to assess whether the protective effect of MMR/MMRV could wane with time since immunisation.
The Cochrane library, Feb 1, 2018
Analysis 1.9. Comparison 1 Inactivated parenteral influenza vaccine versus placebo or 'do nothing... more Analysis 1.9. Comparison 1 Inactivated parenteral influenza vaccine versus placebo or 'do nothing', Outcome 9 Clinical cases
The Lancet, 2006
Background Use of antivirals is recommended for the control of seasonal and pandemic influenza. O... more Background Use of antivirals is recommended for the control of seasonal and pandemic influenza. Our aim was to review the evidence of efficacy, effectiveness, and safety of registered antivirals against naturally occurring influenza in healthy adults. Methods We searched various Databases to October, 2005, and contacted manufacturers and corresponding authors. We included randomised controlled trials comparing prophylactic (n=27) or treatment (n=27) efficacy against symptomatic or asymptomatic influenza. We did a meta-analysis and expressed prophylactic efficacy as a proportion (1-relative risk [RR]). For treatment trials, because of inconsistent and non-standardised reporting, we expressed continuous outcomes either as means or as hazard ratios. Findings We included 51 reports of 52 randomised controlled trials. Amantadine prevented 61% (95% CI 35-76) of influenza A cases and 25% (13-36) of cases of influenza-like illness, but caused nausea (OR 2•56, 1•37-4•79), insomnia and hallucinations (2•54, 1•50-4•31), and withdrawals because of adverse events (2•54, 1•60-4•06). There was no effect on asymptomatic cases (RR 0•85, 0•40-1•80). In treatment, amantadine significantly shortened duration of fever compared with placebo (by 0•99 days, Ϫ1•26 to Ϫ0•71), but had no effect on nasal shedding of influenza A viruses (0•93, 0•71-1•21). The fewer data for rimantadine showed comparable effects. In prophylaxis, compared with placebo, neuraminidase inhibitors have no effect against influenza-like illness (1•28, 0•45-3•66 for oral oseltamivir 75 mg daily, 1•51, 0•77-2•95 for inhaled zanamivir 10 mg daily). Higher doses appear to make no difference. The efficacy of oral oseltamivir 75 mg daily against symptomatic influenza is 61% (15-82), or 73% (33-89) at 150 mg daily. Inhaled zanamivir 10 mg daily is 62% efficacious (15-83). Neither neuraminidase inhibitor appeared effective against asymptomatic influenza. Oseltamivir induces nausea (OR 1•79, 1•10-2•93), especially at higher prophylactic doses (2•29, 1•34-3•92). Oseltamivir in a post-exposure prophylaxis role has a protective efficacy of 58•5% (15•6-79•6) for households and from 68% (34•9-84•2) to 89% (67-97) in contacts of index cases. In influenza cases, compared with placebo the hazard ratios for time to alleviation of symptoms were 1•33, 1•29-1•37 for zanamivir; 1•30, 1•13-1•50 for oseltamivir provided medication was started within 48 h of symptom onset. Viral nasal titres were significantly diminished by both drugs (weighted mean difference-0•62,-0•82 to-0•41). Oseltamivir at 150 mg daily was effective in preventing lower respiratory tract complications in influenza cases (OR 0•32, 0•18-0•57). We could find no credible data on the effects of oseltamivir on avian influenza. Interpretation The use of amantadine and rimantadine should be discouraged. Because of their low effectiveness, neuraminidase inhibitors should not be used in seasonal influenza control and should only be used in a serious epidemic or pandemic alongside other public-health measures.
Cochrane Database of Systematic Reviews, May 31, 2013
Tetanus is an acute, often fatal, disease caused by an exotoxin produced by Clostridium tetani. I... more Tetanus is an acute, often fatal, disease caused by an exotoxin produced by Clostridium tetani. It occurs in newborn infants born to mothers who do not have sufficient circulating antibodies to protect the infant passively, by transplacental transfer. Prevention may be possible by the vaccination of pregnant and/or non-pregnant women with tetanus toxoid, and the provision of clean delivery services. Tetanus toxoid consists of a formaldehyde-treated toxin which stimulates the production of antitoxin. To assess the effectiveness of tetanus toxoid, administered to women of childbearing age or pregnant women, to prevent cases of, and deaths from, neonatal tetanus. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (December 2004) , The Cochrane Library (Issue 1, 2005), MEDLINE (1966 to December 2004), EMBASE (1974 to December 2004). We also used the results from handsearching and consultations with manufacturers and authors. Randomised or quasi-randomised trials evaluating the effects of tetanus toxoid in pregnant women or women of childbearing age on numbers of neonatal tetanus cases and deaths. Three review authors independently assessed trials for inclusion, data extraction and trial quality. Two trials (10,560 infants) were included. One study (1919 infants) assessed the effectiveness of tetanus toxoid in preventing neonatal tetanus deaths. After a single dose, the relative risk (RR) was 0.57 (95% confidence interval (CI) 0.26 to 1.24), and the vaccine effectiveness was 43%. With a two or three dose course, the RR was 0.02 (95% CI 0.00 to 0.30); vaccine effectiveness was 98%. No effect was detected on causes of death other than tetanus. The RR of cases of neonatal tetanus after at least one dose of tetanus toxoid was 0.20 (95% CI 0.10 to 0.40); vaccine effectiveness was 80%. Another study, involving 8641 children, assessed the effectiveness of tetanus-diptheria toxoid in preventing neonatal mortality after one or two doses. The RR was 0.68 (95% CI 0.56 to 0.82); vaccine effectiveness was 32%. In preventing deaths at 4 to 14 days, the RR was 0.38 (95% CI 0.27 to 0.55), and vaccine effectiveness 62% (95% CI 45% to 73%). Available evidence supports the implementation of immunisation practices on women of childbearing age or pregnant women in communities with similar, or higher, levels of risk of neonatal tetanus, to the two study sites. More information is needed on possible interference of vaccination by malaria chemoprophylaxis on the roles of malnutrition and vitamin A deficiency, and on the quality of tetanus toxoid production and storage.
Evidence-Based Child Health: A Cochrane Review Journal, 2006
BMJ, 2007
Objective To review systematically the evidence of effectiveness of physical interventions to int... more Objective To review systematically the evidence of effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses. Data sources Cochrane Library, Medline, OldMedline, Embase, and CINAHL, without restrictions on language or publication. Data selection Studies of any intervention to prevent the transmission of respiratory viruses (isolation, quarantine, social distancing, barriers, personal protection, and hygiene). A search of study designs included randomised trials, cohort, case-control, crossover, before and after, and time series studies. After scanning of the titles, abstracts and full text articles as a first filter, a standardised form was used to assess the eligibility of the remainder. Risk of bias of randomised studies was assessed for generation of the allocation sequence, allocation concealment, blinding, and follow-up. Nonrandomised studies were assessed for the presence of potential confounders and classified as being at low, medium, or high risk of bias. Data synthesis 58 papers of 59 studies were included. The quality of the studies was poor for all four randomised controlled trials and most cluster randomised controlled trials; the observational studies were of mixed quality. Meta-analysis of six case-control studies suggested that physical measures are highly effective in preventing the spread of severe acute respiratory syndrome: handwashing more than 10 times daily (odds ratio 0.45, 95% confidence interval 0.36 to 0.57; number needed to treat=4, 95% confidence interval 3.65 to 5.52), wearing masks (0.32, 0.25 to 0.40; NNT=6, 4.54 to 8.03), wearing N95 masks (0.09, 0.03 to 0.30; NNT=3, 2.37 to 4.06), wearing gloves (0.43, 0.29 to 0.65; NNT=5, 4.15 to 15.41), wearing gowns (0.23, 0.14 to 0.37; NNT=5, 3.37 to 7.12), and handwashing, masks, gloves, and gowns combined (0.09, 0.02 to 0.35; NNT=3, 2.66 to 4.97). The combination was also effective in interrupting the spread of influenza within households. The highest quality cluster randomised trials suggested that spread of respiratory viruses can be prevented by hygienic measures in younger children and within households. Evidence that the more uncomfortable and expensive N95 masks were superior to simple surgical masks was limited, but they caused skin irritation. The incremental effect of adding virucidals or antiseptics to normal handwashing to reduce respiratory disease remains uncertain. Global measures, such as screening at entry ports, were not properly evaluated. Evidence was limited for social distancing being effective, especially if related to risk of exposure-that is, the higher the risk the longer the distancing period. Conclusion Routine long term implementation of some of the measures to interrupt or reduce the spread of respiratory viruses might be difficult. However, many simple and low cost interventions reduce the transmission of epidemic respiratory viruses. More resources should be invested into studying which physical interventions are the most effective, flexible, and cost effective means of minimising the impact of acute respiratory tract infections.
Cochrane Database of Systematic Reviews
Journal of Clinical Epidemiology, Feb 1, 2009
Schweiz Rundsch Med Prax, 2007
Schweiz Rundsch Med Prax, 2007
The Cochrane library, Feb 1, 2018
Trusted evidence. Informed decisions. Better health.
ABSTRACT Tetanus is an acute, often fatal, disease caused by an exotoxin produced by Clostridium ... more ABSTRACT Tetanus is an acute, often fatal, disease caused by an exotoxin produced by Clostridium tetani. It occurs in newborn infants born to mothers who do not have sufficient circulating antibodies to protect the infant passively, by transplacental transfer. Prevention may be possible by the vaccination of pregnant and/or non-pregnant women with tetanus toxoid, and the provision of clean delivery services. Tetanus toxoid consists of a formaldehyde-treated toxin which stimulates the production of antitoxin. To assess the effectiveness of tetanus toxoid, administered to women of childbearing age or pregnant women, to prevent cases of, and deaths from, neonatal tetanus. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (December 2004) , The Cochrane Library (Issue 1, 2005), MEDLINE (1966 to December 2004), EMBASE (1974 to December 2004). We also used the results from handsearching and consultations with manufacturers and authors. Randomised or quasi-randomised trials evaluating the effects of tetanus toxoid in pregnant women or women of childbearing age on numbers of neonatal tetanus cases and deaths. Three review authors independently assessed trials for inclusion, data extraction and trial quality. Two trials (10,560 infants) were included. One study (1919 infants) assessed the effectiveness of tetanus toxoid in preventing neonatal tetanus deaths. After a single dose, the relative risk (RR) was 0.57 (95% confidence interval (CI) 0.26 to 1.24), and the vaccine effectiveness was 43%. With a two or three dose course, the RR was 0.02 (95% CI 0.00 to 0.30); vaccine effectiveness was 98%. No effect was detected on causes of death other than tetanus. The RR of cases of neonatal tetanus after at least one dose of tetanus toxoid was 0.20 (95% CI 0.10 to 0.40); vaccine effectiveness was 80%. Another study, involving 8641 children, assessed the effectiveness of tetanus-diptheria toxoid in preventing neonatal mortality after one or two doses. The RR was 0.68 (95% CI 0.56 to 0.82); vaccine effectiveness was 32%. In preventing deaths at 4 to 14 days, the RR was 0.38 (95% CI 0.27 to 0.55), and vaccine effectiveness 62% (95% CI 45% to 73%). Available evidence supports the implementation of immunisation practices on women of childbearing age or pregnant women in communities with similar, or higher, levels of risk of neonatal tetanus, to the two study sites. More information is needed on possible interference of vaccination by malaria chemoprophylaxis on the roles of malnutrition and vitamin A deficiency, and on the quality of tetanus toxoid production and storage.
Cochrane Database of Systematic Reviews, Oct 17, 2010
Background: Viral epidemics or pandemics of acute respiratory infections like influenza or severe... more Background: Viral epidemics or pandemics of acute respiratory infections like influenza or severe acute respiratory syndrome pose a worldwide threat. Antiviral drugs and vaccinations may be insufficient to prevent catastrophe. Objectives: To systematically review the effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses.
Cochrane Database of Systematic Reviews, Oct 19, 2005
The Cochrane library, Feb 1, 2018
Analysis 1.5. Comparison 1 Live vaccine versus placebo (RCTs), Outcome 5 Working days lost (numbe... more Analysis 1.5. Comparison 1 Live vaccine versus placebo (RCTs), Outcome 5 Working days lost (number of events, parents)........ Analysis 1.6. Comparison 1 Live vaccine versus placebo (RCTs), Outcome 6 Drug prescriptions
The Cochrane library, Sep 5, 2018
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:To evaluat... more This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:To evaluate the safety and the effects of influenza vaccines on disease activity in people with multiple sclerosis (MS).
Weekly releases (1997–2007), Aug 17, 2006
An integrated epidemiological surveillance and response system was set up for the 2006 Olympic Wi... more An integrated epidemiological surveillance and response system was set up for the 2006 Olympic Winter Games in Torino [1] between 1 February
The Cochrane library, Nov 22, 2021
BackgroundMeasles, mumps, rubella, and varicella (chickenpox) are serious diseases that can lead ... more BackgroundMeasles, mumps, rubella, and varicella (chickenpox) are serious diseases that can lead to serious complications, disability, and death. However, public debate over the safety of the trivalent MMR vaccine and the resultant drop in vaccination coverage in several countries persists, despite its almost universal use and accepted effectiveness. This is an update of a review published in 2005 and updated in 2012.ObjectivesTo assess the effectiveness, safety, and long‐ and short‐term adverse effects associated with the trivalent vaccine, containing measles, rubella, mumps strains (MMR), or concurrent administration of MMR vaccine and varicella vaccine (MMR+V), or tetravalent vaccine containing measles, rubella, mumps, and varicella strains (MMRV), given to children aged up to 15 years.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2019, Issue 5), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to 2 May 2019), Embase (1974 to 2 May 2019), the WHO International Clinical Trials Registry Platform (2 May 2019), and ClinicalTrials.gov (2 May 2019).Selection criteriaWe included randomised controlled trials (RCTs), controlled clinical trials (CCTs), prospective and retrospective cohort studies (PCS/RCS), case‐control studies (CCS), interrupted time‐series (ITS) studies, case cross‐over (CCO) studies, case‐only ecological method (COEM) studies, self‐controlled case series (SCCS) studies, person‐time cohort (PTC) studies, and case‐coverage design/screening methods (CCD/SM) studies, assessing any combined MMR or MMRV / MMR+V vaccine given in any dose, preparation or time schedule compared with no intervention or placebo, on healthy children up to 15 years of age.Data collection and analysisTwo review authors independently extracted data and assessed the methodological quality of the included studies. We grouped studies for quantitative analysis according to study design, vaccine type (MMR, MMRV, MMR+V), virus strain, and study settings. Outcomes of interest were cases of measles, mumps, rubella, and varicella, and harms. Certainty of evidence of was rated using GRADE.Main resultsWe included 138 studies (23,480,668 participants). Fifty‐one studies (10,248,159 children) assessed vaccine effectiveness and 87 studies (13,232,509 children) assessed the association between vaccines and a variety of harms. We included 74 new studies to this 2019 version of the review.EffectivenessVaccine effectiveness in preventing measles was 95% after one dose (relative risk (RR) 0.05, 95% CI 0.02 to 0.13; 7 cohort studies; 12,039 children; moderate certainty evidence) and 96% after two doses (RR 0.04, 95% CI 0.01 to 0.28; 5 cohort studies; 21,604 children; moderate certainty evidence). The effectiveness in preventing cases among household contacts or preventing transmission to others the children were in contact with after one dose was 81% (RR 0.19, 95% CI 0.04 to 0.89; 3 cohort studies; 151 children; low certainty evidence), after two doses 85% (RR 0.15, 95% CI 0.03 to 0.75; 3 cohort studies; 378 children; low certainty evidence), and after three doses was 96% (RR 0.04, 95% CI 0.01 to 0.23; 2 cohort studies; 151 children; low certainty evidence). The effectiveness (at least one dose) in preventing measles after exposure (post‐exposure prophylaxis) was 74% (RR 0.26, 95% CI 0.14 to 0.50; 2 cohort studies; 283 children; low certainty evidence).The effectiveness of Jeryl Lynn containing MMR vaccine in preventing mumps was 72% after one dose (RR 0.24, 95% CI 0.08 to 0.76; 6 cohort studies; 9915 children; moderate certainty evidence), 86% after two doses (RR 0.12, 95% CI 0.04 to 0.35; 5 cohort studies; 7792 children; moderate certainty evidence). Effectiveness in preventing cases among household contacts was 74% (RR 0.26, 95% CI 0.13 to 0.49; 3 cohort studies; 1036 children; moderate certainty evidence). Vaccine effectiveness against rubella, using a vaccine with the BRD2 strain which is only used in China, is 89% (RR 0.11, 95% CI 0.03 to 0.42; 1 cohort study; 1621 children; moderate certainty evidence). Vaccine effectiveness against varicella (any severity) after two doses in children aged 11 to 22 months is 95% in a 10 years follow‐up (rate ratio (rr) 0.05, 95% CI 0.03 to 0.08; 1 RCT; 2279 children; high certainty evidence).SafetyThere is evidence supporting an association between aseptic meningitis and MMR vaccines containing Urabe and Leningrad‐Zagreb mumps strains, but no evidence supporting this association for MMR vaccines containing Jeryl Lynn mumps strains (rr 1.30, 95% CI 0.66 to 2.56; low certainty evidence). The analyses provide evidence supporting an association between MMR/MMR+V/MMRV vaccines (Jeryl Lynn strain) and febrile seizures. Febrile seizures normally occur in 2% to 4% of healthy children at least once before the age of 5. The attributable risk febrile seizures vaccine‐induced is estimated to be from 1 per 1700 to 1 per 1150 administered doses.The analyses provide evidence supporting an association between MMR vaccination and idiopathic thrombocytopaenic purpura (ITP). However, the risk of ITP after vaccination is smaller than after natural infection with these viruses. Natural infection of ITP occur in 5 cases per 100,000 (1 case per 20,000) per year. The attributable risk is estimated about 1 case of ITP per 40,000 administered MMR doses.There is no evidence of an association between MMR immunisation and encephalitis or encephalopathy (rate ratio 0.90, 95% CI 0.50 to 1.61; 2 observational studies; 1,071,088 children; low certainty evidence), and autistic spectrum disorders (rate ratio 0.93, 95% CI 0.85 to 1.01; 2 observational studies; 1,194,764 children; moderate certainty). There is insufficient evidence to determine the association between MMR immunisation and inflammatory bowel disease (odds ratio 1.42, 95% CI 0.93 to 2.16; 3 observational studies; 409 cases and 1416 controls; moderate certainty evidence).Additionally, there is no evidence supporting an association between MMR immunisation and cognitive delay, type 1 diabetes, asthma, dermatitis/eczema, hay fever, leukaemia, multiple sclerosis, gait disturbance, and bacterial or viral infections. Authors' conclusionsExisting evidence on the safety and effectiveness of MMR/MMRV vaccines support their use for mass immunisation. Campaigns aimed at global eradication should assess epidemiological and socioeconomic situations of the countries as well as the capacity to achieve high vaccination coverage. More evidence is needed to assess whether the protective effect of MMR/MMRV could wane with time since immunisation.
The Cochrane library, Feb 1, 2018
Analysis 1.9. Comparison 1 Inactivated parenteral influenza vaccine versus placebo or 'do nothing... more Analysis 1.9. Comparison 1 Inactivated parenteral influenza vaccine versus placebo or 'do nothing', Outcome 9 Clinical cases
The Lancet, 2006
Background Use of antivirals is recommended for the control of seasonal and pandemic influenza. O... more Background Use of antivirals is recommended for the control of seasonal and pandemic influenza. Our aim was to review the evidence of efficacy, effectiveness, and safety of registered antivirals against naturally occurring influenza in healthy adults. Methods We searched various Databases to October, 2005, and contacted manufacturers and corresponding authors. We included randomised controlled trials comparing prophylactic (n=27) or treatment (n=27) efficacy against symptomatic or asymptomatic influenza. We did a meta-analysis and expressed prophylactic efficacy as a proportion (1-relative risk [RR]). For treatment trials, because of inconsistent and non-standardised reporting, we expressed continuous outcomes either as means or as hazard ratios. Findings We included 51 reports of 52 randomised controlled trials. Amantadine prevented 61% (95% CI 35-76) of influenza A cases and 25% (13-36) of cases of influenza-like illness, but caused nausea (OR 2•56, 1•37-4•79), insomnia and hallucinations (2•54, 1•50-4•31), and withdrawals because of adverse events (2•54, 1•60-4•06). There was no effect on asymptomatic cases (RR 0•85, 0•40-1•80). In treatment, amantadine significantly shortened duration of fever compared with placebo (by 0•99 days, Ϫ1•26 to Ϫ0•71), but had no effect on nasal shedding of influenza A viruses (0•93, 0•71-1•21). The fewer data for rimantadine showed comparable effects. In prophylaxis, compared with placebo, neuraminidase inhibitors have no effect against influenza-like illness (1•28, 0•45-3•66 for oral oseltamivir 75 mg daily, 1•51, 0•77-2•95 for inhaled zanamivir 10 mg daily). Higher doses appear to make no difference. The efficacy of oral oseltamivir 75 mg daily against symptomatic influenza is 61% (15-82), or 73% (33-89) at 150 mg daily. Inhaled zanamivir 10 mg daily is 62% efficacious (15-83). Neither neuraminidase inhibitor appeared effective against asymptomatic influenza. Oseltamivir induces nausea (OR 1•79, 1•10-2•93), especially at higher prophylactic doses (2•29, 1•34-3•92). Oseltamivir in a post-exposure prophylaxis role has a protective efficacy of 58•5% (15•6-79•6) for households and from 68% (34•9-84•2) to 89% (67-97) in contacts of index cases. In influenza cases, compared with placebo the hazard ratios for time to alleviation of symptoms were 1•33, 1•29-1•37 for zanamivir; 1•30, 1•13-1•50 for oseltamivir provided medication was started within 48 h of symptom onset. Viral nasal titres were significantly diminished by both drugs (weighted mean difference-0•62,-0•82 to-0•41). Oseltamivir at 150 mg daily was effective in preventing lower respiratory tract complications in influenza cases (OR 0•32, 0•18-0•57). We could find no credible data on the effects of oseltamivir on avian influenza. Interpretation The use of amantadine and rimantadine should be discouraged. Because of their low effectiveness, neuraminidase inhibitors should not be used in seasonal influenza control and should only be used in a serious epidemic or pandemic alongside other public-health measures.
Cochrane Database of Systematic Reviews, May 31, 2013
Tetanus is an acute, often fatal, disease caused by an exotoxin produced by Clostridium tetani. I... more Tetanus is an acute, often fatal, disease caused by an exotoxin produced by Clostridium tetani. It occurs in newborn infants born to mothers who do not have sufficient circulating antibodies to protect the infant passively, by transplacental transfer. Prevention may be possible by the vaccination of pregnant and/or non-pregnant women with tetanus toxoid, and the provision of clean delivery services. Tetanus toxoid consists of a formaldehyde-treated toxin which stimulates the production of antitoxin. To assess the effectiveness of tetanus toxoid, administered to women of childbearing age or pregnant women, to prevent cases of, and deaths from, neonatal tetanus. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (December 2004) , The Cochrane Library (Issue 1, 2005), MEDLINE (1966 to December 2004), EMBASE (1974 to December 2004). We also used the results from handsearching and consultations with manufacturers and authors. Randomised or quasi-randomised trials evaluating the effects of tetanus toxoid in pregnant women or women of childbearing age on numbers of neonatal tetanus cases and deaths. Three review authors independently assessed trials for inclusion, data extraction and trial quality. Two trials (10,560 infants) were included. One study (1919 infants) assessed the effectiveness of tetanus toxoid in preventing neonatal tetanus deaths. After a single dose, the relative risk (RR) was 0.57 (95% confidence interval (CI) 0.26 to 1.24), and the vaccine effectiveness was 43%. With a two or three dose course, the RR was 0.02 (95% CI 0.00 to 0.30); vaccine effectiveness was 98%. No effect was detected on causes of death other than tetanus. The RR of cases of neonatal tetanus after at least one dose of tetanus toxoid was 0.20 (95% CI 0.10 to 0.40); vaccine effectiveness was 80%. Another study, involving 8641 children, assessed the effectiveness of tetanus-diptheria toxoid in preventing neonatal mortality after one or two doses. The RR was 0.68 (95% CI 0.56 to 0.82); vaccine effectiveness was 32%. In preventing deaths at 4 to 14 days, the RR was 0.38 (95% CI 0.27 to 0.55), and vaccine effectiveness 62% (95% CI 45% to 73%). Available evidence supports the implementation of immunisation practices on women of childbearing age or pregnant women in communities with similar, or higher, levels of risk of neonatal tetanus, to the two study sites. More information is needed on possible interference of vaccination by malaria chemoprophylaxis on the roles of malnutrition and vitamin A deficiency, and on the quality of tetanus toxoid production and storage.
Evidence-Based Child Health: A Cochrane Review Journal, 2006
BMJ, 2007
Objective To review systematically the evidence of effectiveness of physical interventions to int... more Objective To review systematically the evidence of effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses. Data sources Cochrane Library, Medline, OldMedline, Embase, and CINAHL, without restrictions on language or publication. Data selection Studies of any intervention to prevent the transmission of respiratory viruses (isolation, quarantine, social distancing, barriers, personal protection, and hygiene). A search of study designs included randomised trials, cohort, case-control, crossover, before and after, and time series studies. After scanning of the titles, abstracts and full text articles as a first filter, a standardised form was used to assess the eligibility of the remainder. Risk of bias of randomised studies was assessed for generation of the allocation sequence, allocation concealment, blinding, and follow-up. Nonrandomised studies were assessed for the presence of potential confounders and classified as being at low, medium, or high risk of bias. Data synthesis 58 papers of 59 studies were included. The quality of the studies was poor for all four randomised controlled trials and most cluster randomised controlled trials; the observational studies were of mixed quality. Meta-analysis of six case-control studies suggested that physical measures are highly effective in preventing the spread of severe acute respiratory syndrome: handwashing more than 10 times daily (odds ratio 0.45, 95% confidence interval 0.36 to 0.57; number needed to treat=4, 95% confidence interval 3.65 to 5.52), wearing masks (0.32, 0.25 to 0.40; NNT=6, 4.54 to 8.03), wearing N95 masks (0.09, 0.03 to 0.30; NNT=3, 2.37 to 4.06), wearing gloves (0.43, 0.29 to 0.65; NNT=5, 4.15 to 15.41), wearing gowns (0.23, 0.14 to 0.37; NNT=5, 3.37 to 7.12), and handwashing, masks, gloves, and gowns combined (0.09, 0.02 to 0.35; NNT=3, 2.66 to 4.97). The combination was also effective in interrupting the spread of influenza within households. The highest quality cluster randomised trials suggested that spread of respiratory viruses can be prevented by hygienic measures in younger children and within households. Evidence that the more uncomfortable and expensive N95 masks were superior to simple surgical masks was limited, but they caused skin irritation. The incremental effect of adding virucidals or antiseptics to normal handwashing to reduce respiratory disease remains uncertain. Global measures, such as screening at entry ports, were not properly evaluated. Evidence was limited for social distancing being effective, especially if related to risk of exposure-that is, the higher the risk the longer the distancing period. Conclusion Routine long term implementation of some of the measures to interrupt or reduce the spread of respiratory viruses might be difficult. However, many simple and low cost interventions reduce the transmission of epidemic respiratory viruses. More resources should be invested into studying which physical interventions are the most effective, flexible, and cost effective means of minimising the impact of acute respiratory tract infections.
Cochrane Database of Systematic Reviews
Journal of Clinical Epidemiology, Feb 1, 2009
Schweiz Rundsch Med Prax, 2007
Schweiz Rundsch Med Prax, 2007