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The Cochrane Database of Systematic... Dec 2019Poliomyelitis mainly affects unvaccinated children under five years of age, causing irreversible paralysis or even death. The oral polio vaccine (OPV) contains live... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Poliomyelitis mainly affects unvaccinated children under five years of age, causing irreversible paralysis or even death. The oral polio vaccine (OPV) contains live attenuated virus, which can, in rare cases, cause a paralysis known as vaccine-associated paralytic polio (VAPP), and also vaccine-derived polioviruses (VDPVs) due to acquired neurovirulence after prolonged duration of replication. The incidence of poliomyelitis caused by wild polio virus (WPV) has declined dramatically since the introduction of OPV and later the inactivated polio vaccine (IPV), however, the cases of paralysis linked to the OPV are currently more frequent than those related to the WPV. Therefore, in 2016, the World Health Organization (WHO) recommended at least one IPV dose preceding routine immunisation with OPV to reduce VAPPs and VDPVs until polio could be eradicated.
OBJECTIVES
To assess the effectiveness, safety, and immunogenicity of sequential IPV-OPV immunisation schemes compared to either OPV or IPV alone.
SEARCH METHODS
In May 2019 we searched CENTRAL, MEDLINE, Embase, 14 other databases, three trials registers and reports of adverse effects on four web sites. We also searched the references of identified studies, relevant reviews and contacted authors to identify additional references.
SELECTION CRITERIA
Randomised controlled trials (RCTs), quasi-RCTs, controlled before-after studies, nationwide uncontrolled before-after studies (UBAs), interrupted time series (ITS) and controlled ITS comparing sequential IPV-OPV schedules (one or more IPV doses followed by one or more OPV doses) with IPV alone, OPV alone or non-sequential IPV-OPV combinations.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 21 studies: 16 RCTs involving 6407 healthy infants (age range 96 to 975 days, mean 382 days), one ITS with 28,330 infants and four nationwide studies (two ITS, two UBA). Ten RCTs were conducted in high-income countries; five in the USA, two in the UK, and one each in Chile, Israel, and Oman. The remaining six RCTs were conducted in middle-income countries; China, Bangladesh, Guatemala, India, and Thailand. We rated all included RCTs at low or unclear risk of bias for randomisation domains, most at high or unclear risk of attrition bias, and half at high or unclear risk for conflict of interests. Almost all RCTs were at low risk for the remaining domains. ITSs and UBAs were mainly considered at low risk of bias for most domains. IPV-OPV versus OPV It is uncertain if an IPV followed by OPV schedule is better than OPV alone at reducing the number of WPV cases (very low-certainty evidence); however, it may reduce VAPP cases by 54% to 100% (three nationwide studies; low-certainty evidence). There is little or no difference in vaccination coverage between IPV-OPV and OPV-only schedules (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.96 to 1.06; 1 ITS study; low-certainty evidence). Similarly, there is little or no difference between the two schedule types for the number of serious adverse events (SAEs) (RR 0.88, 95% CI 0.46 to 1.70; 4 studies, 1948 participants; low-certainty evidence); or the number of people with protective humoral response P1 (moderate-certainty evidence), P2 (for the most studied schedule; two IPV doses followed by OPV; low-certainty evidence), and P3 (low-certainty evidence). Two IPV doses followed by bivalent OPV (IIbO) may reduce P2 neutralising antibodies compared to trivalent OPV (moderate-certainty evidence), but may make little or no difference to P1 or P2 neutralising antibodies following an IIO schedule or OPV alone (low-certainty evidence). Both IIO and IIbO schedules may increase P3 neutralising antibodies compared to OPV (moderate-certainty evidence). It may also lead to lower mucosal immunity given increased faecal excretion of P1 (low-certainty evidence), P2 and P3 (moderate-certainty evidence) after OPV challenge. IPV-OPV versus IPV It is uncertain if IPV-OPV is more effective than IPV alone at reducing the number of WPV cases (very low-certainty evidence). There were no data regarding VAPP cases. There is no clear evidence of a difference between IPV-OPV and OPV schedules for the number of people with protective humoral response (low- and moderate-certainty evidence). IPV-OPV schedules may increase mean titres of P1 neutralising antibodies compared to OPV alone (low- and moderate-certainty evidence), but the effect on P2 and P3 titres is not clear (very low- and moderate-certainty evidence). IPV-OPV probably reduces the number of people with P3 poliovirus faecal excretion after OPV challenge with IIO and IIOO sequences (moderate-certainty evidence), and may reduce the number with P2 (low-certainty evidence), but not with P1 (very low-certainty evidence). There may be little or no difference between the schedules in number of SAEs (RR 0.92, 95% CI 0.60 to 1.43; 2 studies, 1063 participants, low-certainty evidence). The number of persons with P2 protective humoral immunity and P2 neutralising antibodies are probably lower with most sequential schemes without P2 components (i.e. bOPV) than with trivalent OPV or IVP alone (moderate-certainty evidence). IPV (3)-OPV versus IPV (2)-OPV One study (137 participants) showed no clear evidence of a difference between three IPV doses followed by OPV and two IPV doses followed by OPV, on the number of people with P1 (RR 0.98, 95% CI 0.93 to 1.03), P2 (RR 1.00, 95% CI 0.97 to 1.03), or P3 (RR 1.01, 95% CI 0.97 to 1.05) protective humoral and intestinal immunity; all moderate-certainty evidence. This study did not report on any other outcomes.
AUTHORS' CONCLUSIONS
IPV-OPV compared to OPV may reduce VAPPs without affecting vaccination coverage, safety or humoral response, except P2 with sequential schemes without P2 components, but increase poliovirus faecal excretion after OPV challenge for some polio serotypes. Compared to IPV-only schedules, IPV-OPV may have little or no difference on SAEs, probably has little or no effect on persons with protective humoral response, may increase neutralising antibodies, and probably reduces faecal excretion after OPV challenge of certain polio serotypes. Using three IPV doses as part of a IPV-OPV schedule does not appear to be better than two IPV doses for protective humoral response. Sequential schedules during the transition from OPV to IPV-only immunisation schedules seems a reasonable option aligned with current WHO recommendations. Findings could help decision-makers to optimise polio vaccination policies, reducing inequities between countries.
Topics: Adverse Drug Reaction Reporting Systems; Child, Preschool; Female; Humans; Immunity, Mucosal; Immunization Schedule; Infant; Interrupted Time Series Analysis; Male; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Randomized Controlled Trials as Topic
PubMed: 31801180
DOI: 10.1002/14651858.CD011260.pub2 -
The Cochrane Database of Systematic... Nov 2019Herpes zoster, commonly known as shingles, is a neurocutaneous disease caused by the reactivation of the virus that causes varicella (chickenpox). After resolution of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Herpes zoster, commonly known as shingles, is a neurocutaneous disease caused by the reactivation of the virus that causes varicella (chickenpox). After resolution of the varicella episode, the virus can remain latent in the sensitive dorsal ganglia of the spine. Years later, with declining immunity, the varicella zoster virus (VZV) can reactivate and cause herpes zoster, an extremely painful condition that can last many weeks or months and significantly compromise the quality of life of the affected person. The natural process of aging is associated with a reduction in cellular immunity, and this predisposes older people to herpes zoster. Vaccination with an attenuated form of the VZV activates specific T-cell production avoiding viral reactivation. The USA Food and Drug Administration has approved a herpes zoster vaccine with an attenuated active virus, live zoster vaccine (LZV), for clinical use amongst older adults, which has been tested in large populations. A new adjuvanted recombinant VZV subunit zoster vaccine, recombinant zoster vaccine (RZV), has also been approved. It consists of recombinant VZV glycoprotein E and a liposome-based AS01B adjuvant system. This is an update of a Cochrane Review last updated in 2016.
OBJECTIVES
To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults.
SEARCH METHODS
For this 2019 update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1, January 2019), MEDLINE (1948 to January 2019), Embase (2010 to January 2019), CINAHL (1981 to January 2019), LILACS (1982 to January 2019), WHO ICTRP (on 31 January 2019) and ClinicalTrials.gov (on 31 January 2019).
SELECTION CRITERIA
We included randomised controlled trials (RCTs) or quasi-RCTs comparing zoster vaccine (any dose and potency) versus any other type of intervention (e.g. varicella vaccine, antiviral medication), placebo, or no intervention (no vaccine). Outcomes were incidence of herpes zoster, adverse events (death, serious adverse events, systemic reactions, or local reaction occurring at any time after vaccination), and dropouts.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 11 new studies involving 18,615 participants in this update. The review now includes a total of 24 studies involving 88,531 participants. Only three studies assessed the incidence of herpes zoster in groups that received vaccines versus placebo. Most studies were conducted in high-income countries in Europe and North America and included healthy Caucasians (understood to be white participants) aged 60 years or over with no immunosuppressive comorbidities. Two studies were conducted in Japan. Fifteen studies used LZV. Nine studies tested an RZV. The overall quality of the evidence was moderate. Most data for the primary outcome (incidence of herpes zoster) and secondary outcomes (adverse events and dropouts) came from studies that had a low risk of bias and included a large number of participants. The incidence of herpes zoster at up to three years follow-up was lower in participants who received the LZV (one dose subcutaneously) than in those who received placebo (risk ratio (RR) 0.49, 95% confidence interval (CI) 0.43 to 0.56; risk difference (RD) 2%; number needed to treat for an additional beneficial outcome (NNTB) 50; moderate-quality evidence) in the largest study, which included 38,546 participants. There were no differences between the vaccinated and placebo groups for serious adverse events (RR 1.08, 95% CI 0.95 to 1.21) or deaths (RR 1.01, 95% CI 0.92 to 1.11; moderate-quality evidence). The vaccinated group had a higher incidence of one or more adverse events (RR 1.71, 95% CI 1.38 to 2.11; RD 23%; number needed to treat for an additional harmful outcome (NNTH) 4.3) and injection site adverse events (RR 3.73, 95% CI 1.93 to 7.21; RD 28%; NNTH 3.6) of mild to moderate intensity (moderate-quality evidence). These data came from four studies with 6980 participants aged 60 years or over. Two studies (29,311 participants for safety evaluation and 22,022 participants for efficacy evaluation) compared RZV (two doses intramuscularly, two months apart) versus placebo. Participants who received the new vaccine had a lower incidence of herpes zoster at 3.2 years follow-up (RR 0.08, 95% CI 0.03 to 0.23; RD 3%; NNTB 33; moderate-quality evidence). There were no differences between the vaccinated and placebo groups in incidence of serious adverse events (RR 0.97, 95% CI 0.91 to 1.03) or deaths (RR 0.94, 95% CI 0.84 to 1.04; moderate-quality evidence). The vaccinated group had a higher incidence of adverse events, any systemic symptom (RR 2.23, 95% CI 2.12 to 2.34; RD 33%; NNTH 3.0), and any local symptom (RR 6.89, 95% CI 6.37 to 7.45; RD 67%; NNTH 1.5). Although most participants reported that there symptoms were of mild to moderate intensity, the risk of dropouts (participants not returning for the second dose, two months after the first dose) was higher in the vaccine group than in the placebo group (RR 1.25, 95% CI 1.13 to 1.39; RD 1%; NNTH 100, moderate-quality evidence). Only one study reported funding from a non-commercial source (a university research foundation). All of the other included studies received funding from pharmaceutical companies. We did not conduct subgroup and sensitivity analyses AUTHORS' CONCLUSIONS: LZV and RZV are effective in preventing herpes zoster disease for up to three years (the main studies did not follow participants for more than three years). To date, there are no data to recommend revaccination after receiving the basic schedule for each type of vaccine. Both vaccines produce systemic and injection site adverse events of mild to moderate intensity.
Topics: Aged; Aged, 80 and over; Antiviral Agents; Herpes Zoster; Herpes Zoster Vaccine; Herpesvirus 3, Human; Humans; Middle Aged; Randomized Controlled Trials as Topic; Vaccination; Vaccines, Attenuated
PubMed: 31696946
DOI: 10.1002/14651858.CD008858.pub4 -
The Cochrane Database of Systematic... Oct 2019Rotavirus results in more diarrhoea-related deaths in children under five years than any other single agent in countries with high childhood mortality. It is also a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Rotavirus results in more diarrhoea-related deaths in children under five years than any other single agent in countries with high childhood mortality. It is also a common cause of diarrhoea-related hospital admissions in countries with low childhood mortality. Rotavirus vaccines that have been prequalified by the World Health Organization (WHO) include a monovalent vaccine (RV1; Rotarix, GlaxoSmithKline), a pentavalent vaccine (RV5; RotaTeq, Merck), and, more recently, another monovalent vaccine (Rotavac, Bharat Biotech).
OBJECTIVES
To evaluate rotavirus vaccines prequalified by the WHO (RV1, RV5, and Rotavac) for their efficacy and safety in children.
SEARCH METHODS
On 4 April 2018 we searched MEDLINE (via PubMed), the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (published in the Cochrane Library), Embase, LILACS, and BIOSIS. We also searched the WHO ICTRP, ClinicalTrials.gov, clinical trial reports from manufacturers' websites, and reference lists of included studies and relevant systematic reviews.
SELECTION CRITERIA
We selected randomized controlled trials (RCTs) in children comparing rotavirus vaccines prequalified for use by the WHO versus placebo or no intervention.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial eligibility and assessed risks of bias. One review author extracted data and a second author cross-checked them. We combined dichotomous data using the risk ratio (RR) and 95% confidence interval (CI). We stratified the analysis by country mortality rate and used GRADE to evaluate evidence certainty.
MAIN RESULTS
Fifty-five trials met the inclusion criteria and enrolled a total of 216,480 participants. Thirty-six trials (119,114 participants) assessed RV1, 15 trials (88,934 participants) RV5, and four trials (8432 participants) Rotavac. RV1 Children vaccinated and followed up the first year of life In low-mortality countries, RV1 prevents 84% of severe rotavirus diarrhoea cases (RR 0.16, 95% CI 0.09 to 0.26; 43,779 participants, 7 trials; high-certainty evidence), and probably prevents 41% of cases of severe all-cause diarrhoea (RR 0.59, 95% CI 0.47 to 0.74; 28,051 participants, 3 trials; moderate-certainty evidence). In high-mortality countries, RV1 prevents 63% of severe rotavirus diarrhoea cases (RR 0.37, 95% CI 0.23 to 0.60; 6114 participants, 3 trials; high-certainty evidence), and 27% of severe all-cause diarrhoea cases (RR 0.73, 95% CI 0.56 to 0.95; 5639 participants, 2 trials; high-certainty evidence). Children vaccinated and followed up for two years In low-mortality countries, RV1 prevents 82% of severe rotavirus diarrhoea cases (RR 0.18, 95% CI 0.14 to 0.23; 36,002 participants, 9 trials; high-certainty evidence), and probably prevents 37% of severe all-cause diarrhoea episodes (rate ratio 0.63, 95% CI 0.56 to 0.71; 39,091 participants, 2 trials; moderate-certainty evidence). In high-mortality countries RV1 probably prevents 35% of severe rotavirus diarrhoea cases (RR 0.65, 95% CI 0.51 to 0.83; 13,768 participants, 2 trials; high-certainty evidence), and 17% of severe all-cause diarrhoea cases (RR 0.83, 95% CI 0.72 to 0.96; 2764 participants, 1 trial; moderate-certainty evidence). No increased risk of serious adverse events (SAE) was detected (RR 0.88 95% CI 0.83 to 0.93; high-certainty evidence). There were 30 cases of intussusception reported in 53,032 children after RV1 vaccination and 28 cases in 44,214 children after placebo or no intervention (RR 0.70, 95% CI 0.46 to 1.05; low-certainty evidence). RV5 Children vaccinated and followed up the first year of life In low-mortality countries, RV5 probably prevents 92% of severe rotavirus diarrhoea cases (RR 0.08, 95% CI 0.03 to 0.22; 4132 participants, 5 trials; moderate-certainty evidence). We did not identify studies reporting on severe all-cause diarrhoea in low-mortality countries. In high-mortality countries, RV5 prevents 57% of severe rotavirus diarrhoea (RR 0.43, 95% CI 0.29 to 0.62; 5916 participants, 2 trials; high-certainty evidence), but there is probably little or no difference between vaccine and placebo for severe all-cause diarrhoea (RR 0.80, 95% CI 0.58 to 1.11; 1 trial, 4085 participants; moderate-certainty evidence). Children vaccinated and followed up for two years In low-mortality countries, RV5 prevents 82% of severe rotavirus diarrhoea cases (RR 0.18, 95% CI 0.08 to 0.39; 7318 participants, 4 trials; moderate-certainty evidence). We did not identify studies reporting on severe all-cause diarrhoea in low-mortality countries. In high-mortality countries, RV5 prevents 41% of severe rotavirus diarrhoea cases (RR 0.59, 95% CI 0.43 to 0.82; 5885 participants, 2 trials; high-certainty evidence), and 15% of severe all-cause diarrhoea cases (RR 0.85, 95% CI 0.75 to 0.98; 5977 participants, 2 trials; high-certainty evidence). No increased risk of serious adverse events (SAE) was detected (RR 0.93 95% CI 0.86 to 1.01; moderate to high-certainty evidence). There were 16 cases of intussusception in 43,629 children after RV5 vaccination and 20 cases in 41,866 children after placebo (RR 0.77, 95% CI 0.41 to 1.45; low-certainty evidence). Rotavac Children vaccinated and followed up the first year of life Rotavac has not been assessed in any RCT in countries with low child mortality. In India, a high-mortality country, Rotavac probably prevents 57% of severe rotavirus diarrhoea cases (RR 0.43, 95% CI 0.30 to 0.60; 6799 participants, moderate-certainty evidence); the trial did not report on severe all-cause diarrhoea at one-year follow-up. Children vaccinated and followed up for two years Rotavac probably prevents 54% of severe rotavirus diarrhoea cases in India (RR 0.46, 95% CI 0.35 to 0.60; 6541 participants, 1 trial; moderate-certainty evidence), and 16% of severe all-cause diarrhoea cases (RR 0.84, 95% CI 0.71 to 0.98; 6799 participants, 1 trial; moderate-certainty evidence). No increased risk of serious adverse events (SAE) was detected (RR 0.93 95% CI 0.85 to 1.02; moderate-certainty evidence). There were eight cases of intussusception in 5764 children after Rotavac vaccination and three cases in 2818 children after placebo (RR 1.33, 95% CI 0.35 to 5.02; very low-certainty evidence). There was insufficient evidence of an effect on mortality from any rotavirus vaccine (198,381 participants, 44 trials; low- to very low-certainty evidence), as the trials were not powered to detect an effect at this endpoint.
AUTHORS' CONCLUSIONS
RV1, RV5, and Rotavac prevent episodes of rotavirus diarrhoea. Whilst the relative effect estimate is smaller in high-mortality than in low-mortality countries, there is a greater number of episodes prevented in these settings as the baseline risk is much higher. We found no increased risk of serious adverse events. 21 October 2019 Up to date All studies incorporated from most recent search All published trials found in the last search (4 Apr, 2018) were included and 15 ongoing studies are currently awaiting completion (see 'Characteristics of ongoing studies').
Topics: Adult; Child; Child, Preschool; Diarrhea; Diarrhea, Infantile; Humans; Infant; Infant, Newborn; Randomized Controlled Trials as Topic; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Vaccination; Vaccines, Attenuated; Young Adult
PubMed: 31684685
DOI: 10.1002/14651858.CD008521.pub5 -
Pediatrics Sep 2019Live vaccines usually provide robust immunity but can transmit the vaccine virus.
CONTEXT
Live vaccines usually provide robust immunity but can transmit the vaccine virus.
OBJECTIVE
To assess the characteristics of secondary transmission of the vaccine-strain varicella-zoster virus (Oka strain; vOka) on the basis of the published experience with use of live varicella and zoster vaccines.
DATA SOURCES
Systematic review of Medline, Embase, the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, and Scopus databases for articles published through 2018.
STUDY SELECTION
Articles that reported original data on vOka transmission from persons who received vaccines containing the live attenuated varicella-zoster virus.
DATA EXTRACTION
We abstracted data to describe vOka transmission by index patient's immune status, type (varicella or herpes zoster) and severity of illness, and whether transmission was laboratory confirmed.
RESULTS
Twenty articles were included. We identified 13 patients with vOka varicella after transmission from 11 immunocompetent varicella vaccine recipients. In all instances, the vaccine recipient had a rash: 6 varicella-like and 5 herpes zoster. Transmission occurred mostly to household contacts. One additional case was not considered direct transmission from a vaccine recipient, but the mechanism was uncertain. Transmission from vaccinated immunocompromised children also occurred only if the vaccine recipient developed a rash postvaccination. Secondary cases of varicella caused by vOka were mild.
LIMITATIONS
It is likely that other vOka transmission cases remain unpublished.
CONCLUSIONS
Healthy, vaccinated persons have minimal risk for transmitting vOka to contacts and only if a rash is present. Our findings support the existing recommendations for routine varicella vaccination and the guidance that persons with vaccine-related rash avoid contact with susceptible persons at high risk for severe varicella complications.
Topics: Chickenpox Vaccine; Exanthema; Herpes Zoster Vaccine; Humans; Immunocompetence; Immunocompromised Host; Risk Factors; Seroconversion; Severity of Illness Index; Vaccines, Attenuated; Varicella Zoster Virus Infection
PubMed: 31471448
DOI: 10.1542/peds.2019-1305 -
Expert Review of Vaccines May 2019Preterm infants (PIs) are at increased risk of vaccine-preventable diseases (VPDs). However, delayed vaccination start and low vaccine coverage are still reported. Areas...
Update on vaccination of preterm infants: a systematic review about safety and efficacy/effectiveness. Proposal for a position statement by Italian Society of Pediatric Allergology and Immunology jointly with the Italian Society of Neonatology.
Preterm infants (PIs) are at increased risk of vaccine-preventable diseases (VPDs). However, delayed vaccination start and low vaccine coverage are still reported. Areas covered: This systematic review includes 37 articles on preterm vaccination published in 2008-2018 in PubMed. Both live attenuated and inactivated vaccines are safe and well tolerated in PIs. Local reactions, apnea, and reactivity changes are the most frequently reported adverse events. Lower gestational age and birth weight, preimmunization apnea, longer use of continuous positive airway pressure (CPAP) are risk factors for apnea. The proportion of PIs who develop protective humoral and cellular immunity is generally similar to full terms although later gestational age is associated with increased antibody IgG concentrations (i.e. against certain pneumococcal serotypes, influenza, hepatitis B virus and poliovirus 1) and increased mononuclear cells proliferation (i.e. after inactivated poliovirus). Expert opinion: PIs can be safely and adequately protected by available vaccines with the same schedule used for full terms. Data at this regard have been retrieved by studies using a 3-dose primary series for pneumococcal and hexavalent vaccines. Further studies are needed regarding the 2 + 1 schedule. Apnea represents a nonspecific stress response in PIs, thus those hospitalized at 2 months should have cardio-respiratory monitoring after their first vaccination.
Topics: Drug-Related Side Effects and Adverse Reactions; Humans; Immunity, Cellular; Immunity, Humoral; Immunization Schedule; Infant, Premature; Italy; Vaccines; Vaccines, Attenuated; Vaccines, Inactivated
PubMed: 30952198
DOI: 10.1080/14760584.2019.1604230 -
The Cochrane Database of Systematic... Mar 2019Rotavirus results in more diarrhoea-related deaths in children under five years than any other single agent in countries with high childhood mortality. It is also a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Rotavirus results in more diarrhoea-related deaths in children under five years than any other single agent in countries with high childhood mortality. It is also a common cause of diarrhoea-related hospital admissions in countries with low childhood mortality. Rotavirus vaccines that have been prequalified by the World Health Organization (WHO) include a monovalent vaccine (RV1; Rotarix, GlaxoSmithKline), a pentavalent vaccine (RV5; RotaTeq, Merck), and, more recently, another monovalent vaccine (Rotavac, Bharat Biotech).
OBJECTIVES
To evaluate rotavirus vaccines prequalified by the WHO (RV1, RV5, and Rotavac) for their efficacy and safety in children.
SEARCH METHODS
On 4 April 2018 we searched MEDLINE (via PubMed), the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (published in the Cochrane Library), Embase, LILACS, and BIOSIS. We also searched the WHO ICTRP, ClinicalTrials.gov, clinical trial reports from manufacturers' websites, and reference lists of included studies and relevant systematic reviews.
SELECTION CRITERIA
We selected randomized controlled trials (RCTs) in children comparing rotavirus vaccines prequalified for use by the WHO versus placebo or no intervention.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial eligibility and assessed risks of bias. One review author extracted data and a second author cross-checked them. We combined dichotomous data using the risk ratio (RR) and 95% confidence interval (CI). We stratified the analysis by country mortality rate and used GRADE to evaluate evidence certainty.
MAIN RESULTS
Fifty-five trials met the inclusion criteria and enrolled a total of 216,480 participants. Thirty-six trials (119,114 participants) assessed RV1, 15 trials (88,934 participants) RV5, and four trials (8432 participants) Rotavac.RV1 Children vaccinated and followed up the first year of life In low-mortality countries, RV1 prevents 84% of severe rotavirus diarrhoea cases (RR 0.16, 95% CI 0.09 to 0.26; 43,779 participants, 7 trials; high-certainty evidence), and probably prevents 41% of cases of severe all-cause diarrhoea (RR 0.59, 95% CI 0.47 to 0.74; 28,051 participants, 3 trials; moderate-certainty evidence). In high-mortality countries, RV1 prevents 63% of severe rotavirus diarrhoea cases (RR 0.37, 95% CI 0.23 to 0.60; 6114 participants, 3 trials; high-certainty evidence), and 27% of severe all-cause diarrhoea cases (RR 0.73, 95% CI 0.56 to 0.95; 5639 participants, 2 trials; high-certainty evidence).Children vaccinated and followed up for two yearsIn low-mortality countries, RV1 prevents 82% of severe rotavirus diarrhoea cases (RR 0.18, 95% CI 0.14 to 0.23; 36,002 participants, 9 trials; high-certainty evidence), and probably prevents 37% of severe all-cause diarrhoea episodes (rate ratio 0.63, 95% CI 0.56 to 0.71; 39,091 participants, 2 trials; moderate-certainty evidence). In high-mortality countries RV1 probably prevents 35% of severe rotavirus diarrhoea cases (RR 0.65, 95% CI 0.51 to 0.83; 13,768 participants, 2 trials; high-certainty evidence), and 17% of severe all-cause diarrhoea cases (RR 0.83, 95% CI 0.72 to 0.96; 2764 participants, 1 trial; moderate-certainty evidence).No increased risk of serious adverse events (SAE) was detected (RR 0.88 95% CI 0.83 to 0.93; high-certainty evidence). There were 30 cases of intussusception reported in 53,032 children after RV1 vaccination and 28 cases in 44,214 children after placebo or no intervention (RR 0.70, 95% CI 0.46 to 1.05; low-certainty evidence).RV5 Children vaccinated and followed up the first year of life In low-mortality countries, RV5 probably prevents 92% of severe rotavirus diarrhoea cases (RR 0.08, 95% CI 0.03 to 0.22; 4132 participants, 5 trials; moderate-certainty evidence). We did not identify studies reporting on severe all-cause diarrhoea in low-mortality countries. In high-mortality countries, RV5 prevents 57% of severe rotavirus diarrhoea (RR 0.43, 95% CI 0.29 to 0.62; 5916 participants, 2 trials; high-certainty evidence), but there is probably little or no difference between vaccine and placebo for severe all-cause diarrhoea (RR 0.80, 95% CI 0.58 to 1.11; 1 trial, 4085 participants; moderate-certainty evidence).Children vaccinated and followed up for two yearsIn low-mortality countries, RV5 prevents 82% of severe rotavirus diarrhoea cases (RR 0.18, 95% CI 0.08 to 0.39; 7318 participants, 4 trials; moderate-certainty evidence). We did not identify studies reporting on severe all-cause diarrhoea in low-mortality countries. In high-mortality countries, RV5 prevents 41% of severe rotavirus diarrhoea cases (RR 0.59, 95% CI 0.43 to 0.82; 5885 participants, 2 trials; high-certainty evidence), and 15% of severe all-cause diarrhoea cases (RR 0.85, 95% CI 0.75 to 0.98; 5977 participants, 2 trials; high-certainty evidence).No increased risk of serious adverse events (SAE) was detected (RR 0.93 95% CI 0.86 to 1.01; moderate to high-certainty evidence). There were 16 cases of intussusception in 43,629 children after RV5 vaccination and 20 cases in 41,866 children after placebo (RR 0.77, 95% CI 0.41 to 1.45; low-certainty evidence).Rotavac Children vaccinated and followed up the first year of life Rotavac has not been assessed in any RCT in countries with low child mortality. In India, a high-mortality country, Rotavac probably prevents 57% of severe rotavirus diarrhoea cases (RR 0.43, 95% CI 0.30 to 0.60; 6799 participants, moderate-certainty evidence); the trial did not report on severe all-cause diarrhoea at one-year follow-up.Children vaccinated and followed up for two yearsRotavac probably prevents 54% of severe rotavirus diarrhoea cases in India (RR 0.46, 95% CI 0.35 to 0.60; 6541 participants, 1 trial; moderate-certainty evidence), and 16% of severe all-cause diarrhoea cases (RR 0.84, 95% CI 0.71 to 0.98; 6799 participants, 1 trial; moderate-certainty evidence).No increased risk of serious adverse events (SAE) was detected (RR 0.93 95% CI 0.85 to 1.02; moderate-certainty evidence). There were eight cases of intussusception in 5764 children after Rotavac vaccination and three cases in 2818 children after placebo (RR 1.33, 95% CI 0.35 to 5.02; very low-certainty evidence).There was insufficient evidence of an effect on mortality from any rotavirus vaccine (198,381 participants, 44 trials; low- to very low-certainty evidence), as the trials were not powered to detect an effect at this endpoint.
AUTHORS' CONCLUSIONS
RV1, RV5, and Rotavac prevent episodes of rotavirus diarrhoea. Whilst the relative effect estimate is smaller in high-mortality than in low-mortality countries, there is a greater number of episodes prevented in these settings as the baseline risk is much higher. We found no increased risk of serious adverse events.
Topics: Adult; Child; Child, Preschool; Diarrhea; Diarrhea, Infantile; Humans; Infant; Infant, Newborn; Randomized Controlled Trials as Topic; Rotavirus Infections; Rotavirus Vaccines; Vaccines, Attenuated; Young Adult
PubMed: 30912133
DOI: 10.1002/14651858.CD008521.pub4 -
Clinical Microbiology and Infection :... Jun 2019Vaccination for dengue with the live attenuated tetravalent CYD-TDV vaccine (Dengvaxia®) is only recommended in individuals who have had prior dengue virus (DENV)...
OBJECTIVES
Vaccination for dengue with the live attenuated tetravalent CYD-TDV vaccine (Dengvaxia®) is only recommended in individuals who have had prior dengue virus (DENV) infection. Rapid diagnostic tests (RDT) for past DENV infection would offer a convenient method for pre-vaccination screening at point-of-care. A systematic review was conducted to evaluate the performance of current dengue RDTs for determining dengue serostatus, using IgG antibodies against DENV as a marker of past infection.
METHODS
PubMed and EMBASE databases were searched from 2000 to 2018 to identify studies evaluating dengue RDTs in individuals with known or possible previous DENV infection. Study quality was evaluated using GRADE and QUADAS-2 criteria. Semi-structured interviews were also performed with available dengue RDT manufacturers.
RESULTS
The performance of four dengue IgG RDTs was determined in 3137 individuals across ten studies conducted in 13 countries, with serum used in most of the studies. No studies reported data for determining dengue serostatus, and limited data were available regarding cross-reactivity with other viruses. The majority of studies demonstrated sensitivities and specificities between 80% and 100% for dengue IgG detection in samples from secondary infection or convalescent time-points after recent infection.
CONCLUSIONS
Although current dengue IgG RDTs have shown reasonable performance compared with laboratory-based tests in secondary infection, additional research is needed to determine how RDTs would perform in relevant populations targeted for vaccination. New RDTs or modifications to current RDTs are feasible and may optimize the performance of these tests for use in a pre-vaccination screening approach.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Viral; Child; Child, Preschool; Dengue; Dengue Virus; Female; Humans; Immunoassay; Immunoglobulin G; Infant; Infant, Newborn; Interviews as Topic; Male; Middle Aged; Point-of-Care Systems; Sensitivity and Specificity; Serologic Tests; Time Factors; Young Adult
PubMed: 30664935
DOI: 10.1016/j.cmi.2019.01.002 -
Open Forum Infectious Diseases Nov 2018Gastroenteritis caused by rotavirus accounts for considerable morbidity in young children. We aimed to assess the vaccine effectiveness (VE) of the oral rotavirus... (Review)
Review
BACKGROUND
Gastroenteritis caused by rotavirus accounts for considerable morbidity in young children. We aimed to assess the vaccine effectiveness (VE) of the oral rotavirus vaccine , as measured by laboratory-confirmed rotavirus infection after referral to hospital and/or emergency departments in children aged <5 years with gastroenteritis.
METHODS
We performed a systematic search for peer-reviewed studies conducted in real-life settings published between 2006 and 2016 and a meta-analysis to calculate the overall VE, which was further discriminated through stratified analyses.
RESULTS
The overall VE estimate was 69% (95% confidence interval [CI], 62% to 75%); stratified analyses revealed a non-negligible impact of factors such as study design and socioeconomic status. Depending on the control group, VE ranged from 63% (95% CI, 52% to 72%) to 81% (95% CI, 69% to 88%) for unmatched and matched rotavirus test-negative controls. VE varied with socioeconomic status: 81% (95% CI, 74% to 86%) in high-income countries, 54% (95% CI, 39% to 65%) in upper-middle-income countries, and 63% (95% CI, 50% to 72%) in lower-middle-income countries. Age, rotavirus strain, and disease severity were also shown to impact VE, but to a lesser extent.
CONCLUSIONS
This meta-analysis of real-world studies showed that is effective in helping to prevent hospitalizations and/or emergency department visits due to rotavirus infection.
PubMed: 30539038
DOI: 10.1093/ofid/ofy292 -
The Cochrane Database of Systematic... Dec 2018Salmonella infections are a common bacterial cause of invasive disease in people with sickle cell disease especially children, and are associated with high morbidity and...
BACKGROUND
Salmonella infections are a common bacterial cause of invasive disease in people with sickle cell disease especially children, and are associated with high morbidity and mortality rates. Although available in some centres, people with sickle cell anaemia are not routinely immunized with salmonella vaccines. This is an update of a previously published Cochrane Review.
OBJECTIVES
To determine whether routine administration of salmonella vaccines to people with sickle cell disease reduces the morbidity and mortality associated with infection.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.We also conducted a search of the LILACS database and the World Health Organization International Clinical Trials Registry Platform (www.who.int/trialsearch) and ClinicalTrials.gov (www.clinicaltrials.gov).Date of most recent searches: 17 October 2018.
SELECTION CRITERIA
We planned to select all randomized controlled trials that compared the use of either the inactivated vaccine or an oral attenuated vaccine with a placebo among people with sickle cell disease. Equally, studies that compared the efficacy of one vaccine type over another were to be selected for the review.
DATA COLLECTION AND ANALYSIS
No trials of salmonella vaccines in people with sickle cell disease were found.
MAIN RESULTS
There is an absence of randomized controlled trial evidence relating to the scope of this review.
AUTHORS' CONCLUSIONS
It is expected that salmonella vaccines may be useful in people with sickle cell disease, especially in resource-poor settings where the majority of those who suffer from the condition are found. Unfortunately, there are no randomized controlled trials on the efficacy and safety of the different types of salmonella vaccines in people with sickle cell disease. We conclude that there is a need for a well-designed, adequately-powered, randomized controlled trial to assess the benefits and risks of the different types of salmonella vaccines as a means of improving survival and decreasing mortality from salmonella infections in people with sickle cell disease. However, we believe that there are unlikely to be any trials published in this area, therefore, this review will no longer be regularly updated.
Topics: Anemia, Sickle Cell; Humans; Salmonella Infections; Salmonella Vaccines
PubMed: 30521695
DOI: 10.1002/14651858.CD006975.pub4 -
BMJ (Clinical Research Ed.) Oct 2018To compare the efficacy, effectiveness, and safety of the herpes zoster live attenuated vaccine with the herpes zoster adjuvant recombinant subunit vaccine or placebo... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare the efficacy, effectiveness, and safety of the herpes zoster live attenuated vaccine with the herpes zoster adjuvant recombinant subunit vaccine or placebo for adults aged 50 and older.
DESIGN
Systematic review with bayesian meta-analysis and network meta-analysis.
DATA SOURCES
Medline, Embase, and Cochrane Library (inception to January 2017), grey literature, and reference lists of included studies.
ELIGIBILITY CRITERIA FOR STUDY SELECTION
Experimental, quasi-experimental, and observational studies that compared the live attenuated vaccine with the adjuvant recombinant subunit vaccine, placebo, or no vaccine in adults aged 50 and older. Relevant outcomes were incidence of herpes zoster (primary outcome), herpes zoster ophthalmicus, post-herpetic neuralgia, quality of life, adverse events, and death.
RESULTS
27 studies (22 randomised controlled trials) including 2 044 504 patients, along with 18 companion reports, were included after screening 2037 titles and abstracts, followed by 175 full text articles. Network meta-analysis of five randomised controlled trials found no statistically significant differences between the live attenuated vaccine and placebo for incidence of laboratory confirmed herpes zoster. The adjuvant recombinant subunit vaccine, however, was statistically superior to both the live attenuated vaccine (vaccine efficacy 85%, 95% credible interval 31% to 98%) and placebo (94%, 79% to 98%). Network meta-analysis of 11 randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more adverse events at injection sites than the live attenuated vaccine (relative risk 1.79, 95% credible interval 1.05 to 2.34; risk difference 30%, 95% credible interval 2% to 51%) and placebo (5.63, 3.57 to 7.29 and 53%, 30% to 73%, respectively). Network meta-analysis of nine randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more systemic adverse events than placebo (2.28, 1.45 to 3.65 and 20%, 6% to 40%, respectively).
CONCLUSIONS
Using the adjuvant recombinant subunit vaccine might prevent more cases of herpes zoster than using the live attenuated vaccine, but the adjuvant recombinant subunit vaccine also carries a greater risk of adverse events at injection sites.
PROTOCOL REGISTRATION
Prospero CRD42017056389.
Topics: Adjuvants, Immunologic; Aged; Female; Health Services for the Aged; Herpes Zoster; Herpes Zoster Vaccine; Humans; Male; Middle Aged; Vaccines, Attenuated
PubMed: 30361202
DOI: 10.1136/bmj.k4029