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Expert Review of Vaccines Sep 2019: In Asia Pacific, most countries recommend a monovalent hepatitis B virus (HBV) vaccine dose at birth followed by primary vaccination series including three or four...
Integration of hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B virus, inactivated poliomyelitis and Haemophilus influenzae type b conjugate vaccine within existing national recommendations following a birth dose of monovalent hepatitis B virus vaccine: results of a systematic...
: In Asia Pacific, most countries recommend a monovalent hepatitis B virus (HBV) vaccine dose at birth followed by primary vaccination series including three or four doses of combination vaccines against diphtheria, tetanus, and pertussis, with or without type b (Hib), HBV or poliomyelitis antigens. If hexavalent conjugate vaccines against diphtheria-tetanus-acellular pertussis-HBV-inactivated poliovirus-Hib (DTPa-HBV-IPV/Hib) replace the vaccines included in the primary vaccination series, co-administration of lower-valent vaccines would be avoided but infants would receive ≥4 doses of HBV-containing vaccines before the age of 2 years. : We searched for clinical trials conducted in the South-East Asia and Western Pacific Regions (World Health Organization geographic definition), investigating vaccination regimens with >3 doses of HBV-containing vaccines in infants, including a monovalent HBV vaccine birth dose and ≥1 dose of GSK's hexavalent DTPa-HBV-IPV/Hib vaccine. : The six clinical trials included in this review showed that infants who received the monovalent HBV vaccine at birth and three or four doses of DTPa-HBV-IPV/Hib vaccine achieved protective immunogenic titers with a clinically acceptable safety profile. Our results support the integration of hexavalent DTPa-HBV-IPV/Hib vaccine within existing national recommendations in the Asia Pacific region to reduce the number of injections during infancy.
Topics: Databases, Factual; Diphtheria; Diphtheria-Tetanus-acellular Pertussis Vaccines; Haemophilus Infections; Haemophilus influenzae type b; Hepatitis B; Hepatitis B Vaccines; Hepatitis B virus; Humans; Immunization Schedule; Poliomyelitis; Tetanus; Vaccines, Combined; Vaccines, Conjugate; Whooping Cough
PubMed: 31328999
DOI: 10.1080/14760584.2019.1646643 -
The Cochrane Database of Systematic... Aug 2018People affected with sickle cell disease (SCD) are at high risk of infection from Haemophilus influenzae type b (Hib). Before the implementation of Haemophilus...
BACKGROUND
People affected with sickle cell disease (SCD) are at high risk of infection from Haemophilus influenzae type b (Hib). Before the implementation of Haemophilus influenzae type b conjugate vaccination in high-income countries, this was responsible for a high mortality rate in children under five years of age. In African countries, where coverage of this vaccination is still extremely low, Hib remains one of the most common causes of bacteraemias in children with SCD. The increased uptake of this conjugate vaccination may substantially improve the survival of children with SCD. This is an update of a previously published Cochrane Review.
OBJECTIVES
The primary objective was to determine whether Hib conjugate vaccines reduce mortality and morbidity in children and adults with SCD.The secondary objectives were to assess the following in children and adults with SCD: the immunogenicity of Hib conjugate vaccines; the safety of these vaccines; and any variation in effect according to type of vaccine, mode of administration (separately or in combination with other vaccines), number of doses, and age at first dose.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched trial registries (04 July 2018) and contacted relevant pharmaceutical companies to identify unpublished trials.Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinoapthies Trials Register: 18 December 2017.
SELECTION CRITERIA
All randomised controlled trials (RCTs) and quasi-RCTs comparing Hib conjugate vaccines with placebo or no treatment, or comparing different types of Hib conjugate vaccines in people with SCD.
DATA COLLECTION AND ANALYSIS
No trials of Hib conjugate vaccines in people with SCD were found.
MAIN RESULTS
There is an absence of evidence from RCTs relating to the subject of this review.
AUTHORS' CONCLUSIONS
There has been a dramatic decrease in the incidence of invasive Hib infections observed in the post-vaccination era in people with SCD living in high-income countries. Therefore, despite the absence of evidence from RCTs, it is expected that Hib conjugate vaccines may be useful in children affected with SCD, especially in African countries where there is a high prevalence of the disease. The implementation of childhood immunisation schedules, including universal Hib conjugate vaccination, may substantially improve the survival of children with SCD living in low-income countries. We currently lack data to evaluate the potential effect of Hib vaccination among unvaccinated adults with SCD. Further research should assess the optimal Hib immunisation schedule in children and adults with SCD.
Topics: Anemia, Sickle Cell; Bacterial Capsules; Haemophilus Infections; Haemophilus Vaccines; Haemophilus influenzae type b; Humans; Vaccines, Conjugate
PubMed: 30125338
DOI: 10.1002/14651858.CD011199.pub3 -
Alimentary Pharmacology & Therapeutics Mar 2020Proton pump inhibitors (PPI) are widely used to treat acid-related disorders of the upper gastrointestinal tract. However, large observational studies have raised...
BACKGROUND
Proton pump inhibitors (PPI) are widely used to treat acid-related disorders of the upper gastrointestinal tract. However, large observational studies have raised concerns about PPI-associated adverse events. In recent years, data from next-generation sequencing studies suggested that PPIs affect the composition of the intestinal microbiota, while a balanced gut microbiome is essential for maintaining health.
AIM
To review the available evidence from next-generation sequencing studies on the effect of PPIs on the intestinal microbiome and to discuss possible implications of PPI-induced dysbiosis in health and disease.
METHODS
A systematic review was conducted following the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. A PubMed query yielded 197 results. 19 publications met the prespecified eligibility criteria.
RESULTS
Twelve observational study cohorts with 708 PPI users and 11 interventional cohorts with 180 PPI users were included in the review. In most studies, PPI treatment did not affect microbiological richness and diversity, but was associated with distinct taxonomic alterations: In the upper gastrointestinal tract, PPI users showed overgrowth of orally derived bacteria, mostly Streptococcaceae (findings based on six independent cohorts with 126 PPI users). In faecal samples, PPIs increased multiple taxa from the orders Bacillales (eg, Staphylococcaceae), Lactobacillales (eg, Enterococcaceae, Lactobacillaceae, Streptococcaceae) and Actinomycetales (eg, Actinomycetaceae, Micrococcaceae), the families Pasteurellaceae and Enterobacteriaceae and the genus Veillonella. Taxa decreased by PPIs include Bifidobacteriaceae, Ruminococcaceae, Lachnospiraceae and Mollicutes (findings in faecal samples based on 19 independent cohorts with 790 PPI users).
CONCLUSION
PPI use is associated with moderate alterations to upper and distal gut microbiota. The available data suggest that PPI-induced hypochlorhydria facilitates colonization of more distal parts of the digestive tract by upper gastrointestinal microbiota.
Topics: Bacteria; Cohort Studies; DNA, Bacterial; Dysbiosis; Feces; Gastrointestinal Microbiome; Gastrointestinal Tract; High-Throughput Nucleotide Sequencing; Humans; Observational Studies as Topic; Proton Pump Inhibitors; Sequence Analysis, DNA
PubMed: 31990420
DOI: 10.1111/apt.15604 -
Clinical Oral Investigations Mar 2022To investigate the global prevalence of the JP2 genotype of Aggregatibacter actinomycetemcomitans (Aa).
PURPOSE
To investigate the global prevalence of the JP2 genotype of Aggregatibacter actinomycetemcomitans (Aa).
METHODS
A comprehensive electronic search of databases, PUBMED, MEDLINE, EMBASE, BIOSIS, and SCOPUS, was conducted up to August 2021. All published articles and studies were considered, excluding animal studies, editorials, personal opinions, letters to editor, conference abstracts, posters, and those studies without full text. The primary objective of this systematic review was to determine the presence of the JP2 genotype of Aa in the world population.
RESULTS
A total of 295 articles were identified, of which 62 were preselected, and 51 were finally included in this review. Due to variable study designs and high heterogeneity, a meta-analysis was not conducted. A total of 9744 subjects were screened for the presence of the JP2 genotype of Aa worldwide, and only 621 cases were found positive.
CONCLUSIONS
A relatively high presence of JP2 genotype of Aa was found in subjects from South America, North America, and Africa. There were no studies estimating the presence of the JP2 genotype of Aa in the Oceania region. The heterogeneity and quality of the included publications suggest that caution should be exercised when interpreting the data and that there remains an important need for additional evidence.
CLINICAL RELEVANCE
Periodontitis is a highly prevalent inflammatory oral disorder with substantial aesthetic, functional, and psychological implications for patients. The JP2 genotype of Aa is implicated in the pathogenesis of periodontitis. To the best of our knowledge, there is a lack of systematic reviews estimating the presence of the JP2 genotype of Aa in the global population. We identified a relatively high presence of the JP2 genotype of Aa in specific geographic areas of the world, and we propose that cross-sectional and longitudinal studies are lacking in the Oceania region and need to be conducted to estimate the presence of the JP2 genotype of Aa in this region.
Topics: Aggregatibacter actinomycetemcomitans; Cross-Sectional Studies; Genotype; Humans; Periodontitis; Prevalence
PubMed: 35066686
DOI: 10.1007/s00784-021-04343-3 -
The Cochrane Database of Systematic... Jun 2017Chronic bronchitis and chronic obstructive pulmonary disease (COPD) are serious conditions in which patients are predisposed to viral and bacterial infections resulting... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic bronchitis and chronic obstructive pulmonary disease (COPD) are serious conditions in which patients are predisposed to viral and bacterial infections resulting in potentially fatal acute exacerbations. Chronic obstructive pulmonary disease is defined as a lung disease characterised by obstruction to lung airflow that interferes with normal breathing. Antibiotic therapy has not been particularly useful in eradicating bacteria such as non-typeable Haemophilus influenzae (NTHi) because they are naturally occurring flora of the upper respiratory tract in many people. However, they can cause opportunistic infection. An oral NTHi vaccine has been developed to protect against recurrent infective acute exacerbations in chronic bronchitis.
OBJECTIVES
To assess the effectiveness of an oral, whole-cell NTHi vaccine in protecting against recurrent episodes of acute exacerbations of chronic bronchitis and COPD in adults. To assess the effectiveness of NTHi vaccine in reducing NTHi colonising the respiratory tract during recurrent episodes of acute exacerbations of COPD.
SEARCH METHODS
We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 1), MEDLINE (1946 to January 2017), Embase (1974 to January 2017), CINAHL (1981 to January 2017), LILACS (1985 to January 2017), and Web of Science (1955 to January 2017). We also searched trials registries and contacted authors of trials requesting unpublished data.
SELECTION CRITERIA
We included randomised controlled trials comparing the effects of an oral monobacterial NTHi vaccine in adults with recurrent acute exacerbations of chronic bronchitis or COPD when there was overt matching of the vaccine and placebo groups on clinical grounds. The selection criteria considered populations aged less than 65 years and those older than 65 years.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data from original records and publications for incidence and severity of bronchitis episodes and carriage rate of NTHi measured in the upper respiratory tract, as well as data relevant to other primary and secondary outcomes.
MAIN RESULTS
We identified six placebo-controlled randomised controlled trials with a total of 557 participants. These trials investigated the efficacy of enteric-coated, killed preparations of H influenzae in populations prone to recurrent acute exacerbations of chronic bronchitis or COPD. The vaccine preparation and immunisation regimen in all trials consisted of at least three courses of formalin-killed H influenzae in enteric-coated tablets taken at intervals (e.g. days 0, 28, and 56). Each course generally consisted of two tablets taken after breakfast over three consecutive days. In all cases the placebo groups took enteric-coated tablets containing glucose. Risk of bias was moderate across the studies, namely due to the lack of information provided about methods and inadequate presentation of results.Meta-analysis of the oral NTHi vaccine showed a small, non-statistically significant reduction in the incidence of acute exacerbations of chronic bronchitis or COPD (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.57 to 1.10; P = 0.16). There was no significant difference in mortality rate between the vaccine and placebo groups (odds ratio (OR) 1.62, 95% CI 0.63 to 4.12; P = 0.31).We were unable to meta-analyse the carriage levels of NTHi in participants as each trial reported this result using different units and tools of measurement. Four trials showed no significant difference in carriage levels, while two trials showed a significant decrease in carriage levels in the vaccinated group compared with the placebo group.Four trials assessed severity of exacerbations measured by requirement for antibiotics. Three of these trials were comparable and when meta-analysed showed a statistically significant 80% increase in antibiotic courses per person in the placebo group (RR 1.81, 95% CI 1.35 to 2.44; P < 0.001). There was no significant difference between the groups with regard to hospital admission rates (OR 0.96, 95% CI 0.13 to 7.04; P = 0.97). Adverse events were reported in five trials but were not necessarily related to the vaccine; a point estimate is suggestive that they occurred more frequently in the vaccine group, however this result was not statistically significant (RR 1.43, 95% CI 0.70 to 2.92; P = 0.87). Quality of life was not meta-analysed but was reported in two trials, with results at six months showing an improvement in quality of life in the vaccinated group (scoring at least two points better than placebo).
AUTHORS' CONCLUSIONS
Analyses demonstrate that NTHi oral vaccination of people with recurrent exacerbations of chronic bronchitis or COPD does not yield a significant reduction in the number and severity of exacerbations. Evidence was mixed, and the individual trials that showed a significant benefit of the vaccine are too small to advocate widespread oral vaccination of people with COPD.
Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bronchitis, Chronic; Disease Progression; Haemophilus Vaccines; Haemophilus influenzae; Humans; Middle Aged; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Secondary Prevention; Tablets, Enteric-Coated
PubMed: 28626902
DOI: 10.1002/14651858.CD010010.pub3 -
Expert Review of Pharmacoeconomics &... Aug 2009With the arrival of new, more expensive vaccines, economic evaluation has become an important tool for assessing the feasibility of introducing a new vaccine into a... (Review)
Review
With the arrival of new, more expensive vaccines, economic evaluation has become an important tool for assessing the feasibility of introducing a new vaccine into a country's routine immunization schedule. Haemophilus influenzae type b (Hib) vaccine has been available since the early 1990s, but uptake of the vaccine was slow in low-income countries until the GAVI Alliance started offering financial support for it. However, at some point, GAVI Alliance-supported countries will have to identify other sources of financing for Hib vaccine, meaning cost-effectiveness evidence will be important to support resource allocation decisions. Several middle-income countries have not yet introduced the vaccine. Thus, the aim of this literature review was to identify and evaluate the published evidence on the cost-effectiveness of the Hib vaccine, with particular emphasis on low- and middle-income countries. It is concluded that there are only few studies available from resource-poor countries and some of these are of low quality.
Topics: Cost-Benefit Analysis; Developing Countries; Economics, Pharmaceutical; Haemophilus Infections; Haemophilus Vaccines; Haemophilus influenzae type b; Humans; Immunization Programs
PubMed: 19670994
DOI: 10.1586/erp.09.38 -
The Cochrane Database of Systematic... Sep 2014Chronic bronchitis and chronic obstructive pulmonary disease (COPD) are serious conditions in which patients are predisposed to viral and bacterial infections resulting... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic bronchitis and chronic obstructive pulmonary disease (COPD) are serious conditions in which patients are predisposed to viral and bacterial infections resulting in potentially fatal acute exacerbations. COPD is defined as a lung disease characterised by obstruction to lung airflow that interferes with normal breathing. Antibiotic therapy has not been particularly useful in eradicating bacteria such as non-typeable Haemophilus influenzae (NTHi) because they are naturally occurring flora of the upper respiratory tract in many people. However, they can cause opportunistic infection. An oral NTHi vaccine has been developed to protect against recurrent infective acute exacerbations in chronic bronchitis.
OBJECTIVES
To assess the effectiveness of an oral, whole-cell, non-typeable H. influenzae (NTHi) vaccine in protecting against recurrent episodes of acute exacerbations of chronic bronchitis and COPD in adults. To assess the effectiveness of NTHi vaccine in reducing NTHi colonising the respiratory tract during recurrent episodes of acute exacerbations of COPD.
SEARCH METHODS
We searched the following databases: CENTRAL (2014, Issue 6), MEDLINE (1946 to July week 3, 2014), EMBASE (1974 to July 2014), CINAHL (1981 to July 2014), LILACS (1982 to July 2014) and Web of Science (1955 to July 2014). We also searched trials registries and contacted authors of trials requesting unpublished data.
SELECTION CRITERIA
We included randomised controlled trials comparing the effects of an oral monobacterial NTHi vaccine in adults with recurrent acute exacerbations of chronic bronchitis or COPD when there was overt matching of the vaccine and placebo groups on clinical grounds. The selection criteria considered populations aged less than 65 years and those older than 65 years.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial quality and extracted data from original records and publications for incidence and severity of bronchitis episodes and carriage rate of NTHi measured in the upper respiratory tract, as well as data relevant to other primary and secondary outcomes.
MAIN RESULTS
We identified six placebo-controlled randomised controlled trials with a total of 557 participants. They investigated the efficacy of enteric-coated, killed preparations of H. influenzae in populations prone to recurrent acute exacerbations of chronic bronchitis or COPD. The vaccine preparation and immunisation regime in all trials consisted of at least three courses of formalin-killed H. influenzae in enteric-coated tablets taken at intervals (for example, days 0, 28 and 56). Each course generally consisted of two tablets taken after breakfast over three consecutive days. In all cases the placebo groups took enteric-coated tablets containing glucose. Risk of bias was moderate across the studies, namely due to the lack of information provided about methods and inadequate presentation of results.Meta-analysis of the oral NTHi vaccine showed a small, non-statistically significant reduction in the incidence of acute exacerbations of chronic bronchitis or COPD by 2.048% (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.84 to 1.12, P value = 0.68). There was no significant difference in mortality rate between the vaccine and placebo groups (odds ratio (OR) 1.62, 95% CI 0.63 to 4.12, P value = 0.31).We were unable to meta-analyse the carriage levels of NTHi in participants as each trial reported this result using different units and tools of measurement. Four trials showed no significant difference in carriage levels, while two trials showed a significant decrease in carriage levels in the vaccinated group compared with placebo.Four trials assessed severity of exacerbations measured by requirement for antibiotics. Three of these trials were comparable and when meta-analysed showed a statistically significant 80% increase in antibiotic courses per person in the placebo group (RR 1.81, 95% CI 1.35 to 2.44, P value < 0.0001). There was no significant difference between the groups with regards to hospital admission rates (OR 0.96, 95% CI 0.13 to 7.04, P value = 0.97). Adverse events were reported in all six trials with a point estimate suggestive that they occurred more frequently in the vaccine group, however, this result was not statistically significant (RR 1.43, 95% CI 0.70 to 2.92, P value = 0.87). Quality of life was not meta-analysed but was reported in two trials, with results at six months showing an improvement in quality of life in the vaccinated group (scoring at least two points better than placebo).
AUTHORS' CONCLUSIONS
Analyses demonstrate that NTHi oral vaccination of patients with recurrent exacerbations of chronic bronchitis or COPD does not yield a significant reduction in the number and severity of exacerbations. Evidence is mixed and the individual trials that show a significant benefit of the vaccine are too small to advocate widespread oral vaccination of people with COPD.
Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bronchitis, Chronic; Disease Progression; Haemophilus Vaccines; Haemophilus influenzae; Humans; Middle Aged; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Secondary Prevention
PubMed: 25201571
DOI: 10.1002/14651858.CD010010.pub2 -
The Cochrane Database of Systematic... 2003Haemophilus influenzae (H. influenzae) is an important cause of meningitis and pneumonia in children, causing an estimated three million cases of serious disease and... (Review)
Review
BACKGROUND
Haemophilus influenzae (H. influenzae) is an important cause of meningitis and pneumonia in children, causing an estimated three million cases of serious disease and hundreds of thousands of deaths annually worldwide. The introduction of H. influenzae type b (Hib) vaccines into routine immunisation schedules in developed countries has been followed by a rapid decline in disease occurrence, but vaccine cost is a significant barrier to use in developing countries. There is a need to determine the size of the effects of the vaccine, to enable cost-effectiveness comparisons with competing priorities in developing countries.
OBJECTIVES
1. To determine the effects of conjugate Hib vaccine in preventing Hib disease or death in children under five years.2. To determine any serious adverse outcomes.
SEARCH STRATEGY
Searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (issue 1, 2003); MEDLINE (January 1966 to April 2003), EMBASE (1990 to April 2003); and scanning of reference lists and contacting of authors of trial reports. Reports in all languages were considered.
SELECTION CRITERIA
All randomised controlled trials or quasi-randomised trials of conjugate H. influenzae type b vaccines compared with placebo or no treatment in children who were followed until at least two years of age.
DATA COLLECTION AND ANALYSIS
Two investigators independently selected eligible studies and extracted data. Differences were resolved by discussion.
MAIN RESULTS
Five studies were included in the review, and four in meta-analyses. The overall quality of the trials was good. The relative risk for invasive Hib disease was 0.20 (95% confidence interval 0.07 to 0.54; random effects model), but there was statistically significant unexplained variation (heterogeneity) in the effects of the four trials in the meta-analysis (p = 0.002). The size of the effects found in the trials did not appear to differ consistently with different vaccine types, the number of vaccine doses, age at first vaccination or use in developed vs developing countries, but the confidence intervals for the effect estimates were wide.Hib-related mortality data showed a non-significant trend towards benefit (relative risk was 0.29; 95% confidence interval 0.07 to 1.20; random effects model). The relative risk for all cause mortality in the single trial from which data were available was 1.01 (95% confidence interval 0.38 to 2.67, random effects model). No serious adverse effects were reported in any of the trials, involving a total of 257,000 infants.
REVIEWER'S CONCLUSIONS
Hib vaccine is safe and effective. The size of the effect could plausibly be anywhere between a 46% and 93% reduction in Hib invasive disease, before the effect of herd immunity is taken into account. In resource-poor settings, decisions to use the vaccine will depend on its cost, the local burden of Hib disease and competing priorities. Insufficient evidence from randomised controlled trials was identified of the effects of Hib conjugate vaccine on either Hib-specific or on all-cause mortality.
Topics: Bacterial Capsules; Developing Countries; Haemophilus Infections; Haemophilus Vaccines; Haemophilus influenzae type b; Humans; Polysaccharides, Bacterial; Randomized Controlled Trials as Topic; Vaccines, Conjugate
PubMed: 14583937
DOI: 10.1002/14651858.CD001729 -
The Cochrane Database of Systematic... Jun 2015Infections during pregnancy confers increased risk of maternal and perinatal morbidity and mortality. However, the case for advocating Haemophilus influenzae type B... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Infections during pregnancy confers increased risk of maternal and perinatal morbidity and mortality. However, the case for advocating Haemophilus influenzae type B (Hib) and viral Influenza vaccinations in pregnancy is still debatable.
OBJECTIVES
To assess the impact of Hib and viral Influenza vaccinations during pregnancy on maternal, neonatal and infant health outcomes compared to placebo/control.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (29 January 2015) and reference lists of retrieved studies.
SELECTION CRITERIA
All randomised controlled clinical trials (including cluster-randomised trials) and quasi-randomised trials evaluating Hib or viral influenza vaccination during pregnancy compared with no vaccination or placebo.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion, risk of bias and extracted data. Data were checked for accuracy.
MAIN RESULTS
Two trials were included this review. One (involving 213 women and 213 neonates) evaluated the impact of Hib vaccination during pregnancy and the other study (involving 2116 women and 2049 neonates) evaluated the impact of viral influenza vaccination during pregnancy. Overall, the HiB vaccination trial was judged to be at 'high risk of bias' due to inadequate randomisation while the other trial was judged to be at 'low risk of bias'. Hib vaccination during pregnancy versus placeboOne trial involving 213 women and 213 neonates evaluating the impact of Hib vaccination during pregnancy was included under this comparison. The study did not report on any of this review's prespecified primary outcomes (including mortality, respiratory tract infection and sepsis) or secondary outcomes (including adverse events) except preterm delivery. There was no clear difference between the Hib vaccination and placebo control groups in terms of preterm delivery (risk ratio (RR) 1.28, 95% confidence interval (CI) 0.12 to 13.86, one study, 213 participants), fetal distress (RR 1.23, 95% CI 0.67 to 2.26, one study, 213 infants), intubation (RR 1.03, 95% CI 0.55 to 1.95, one study, 213 infants) and neonatal jaundice (RR 1.01, 95% CI 0.52 to 1.97, one study, 213 infants). We could not grade the evidence for quality due to lack of outcome data. Viral influenza vaccination during pregnancy versus placeboOne trial involving 2116 women and 2049 infants evaluating the impact of trivalent inactivated influenza vaccine (IIV3) during pregnancy was included under this comparison.There was no clear difference between the viral influenza and placebo control group in terms of most of this review's primary outcomes: maternal death (RR 4.96, 95% CI 0.24 to 103.24, moderate quality evidence), infant death up to 175 days after birth (RR 0.71, 95% CI 0.37 to 1.37, moderate quality evidence), perinatal death (stillbirth and death in the first week of life) (RR 1.32, 95% CI 0.73 to 2.38, moderate quality evidence), influenza-like illness in women (RR 0.96, 95% CI 0.79 to 1.16) or their babies (RR 1.02, 95% CI 0.94 to 1.09), any respiratory illness in women (RR 0.97, 95% CI 0.91 to 1.04, high quality evidence) or their babies (RR 1.01, 95% CI 0.95 to 1.07, high quality evidence). There were also no clear differences between vaccination and placebo control groups in terms of maternal hospitalisation for any infection (RR 2.27, 95% CI 0.94 to 5.49; 2116 women, moderate quality evidence), and neonatal hospitalisation for sepsis (RR 1.60, 95% CI 0.73 to 3.50; 2049 infants, moderate quality evidence). However, viral influenza vaccination during pregnancy was associated with a reduction in reverse-transcriptase-polymerase-chain-reaction (RT-PCR) confirmed influenza among infants (RR 0.51, 95% CI 0.30 to 0.88, one study, 2049 infants) and women (RR 0.50, 95% CI 0.29 to 0.86, one study, 2116 women).In terms of this review's secondary outcomes, there were no clear differences in terms of the impact on pregnancy outcomes (miscarriage, preterm labour and stillbirth), hospitalisation for respiratory infection among women and infants. Similarly, there was no difference between the viral influenza vaccine and placebo control groups in terms of any adverse systemic reactions.
AUTHORS' CONCLUSIONS
There is limited evidence (from one small trial at a high risk of bias) on the effectiveness on Hib during pregnancy for improving maternal, neonatal and infant health outcomes.Evidence from one large high quality trial on the effectiveness of viral influenza vaccine during pregnancy suggests reduced RT-PCR confirmed influenza among women and their babies, suggesting the potential of this strategy for scale up but further evidence from varying contexts is required.Further trials for both Hib and viral influenza vaccines with appropriate study designs and suitable comparison groups are required. There are currently two 'ongoing' studies - these will be incorporated into the review in future updates.
Topics: Adolescent; Adult; Female; Haemophilus influenzae type b; Humans; Infant, Newborn; Influenza Vaccines; Influenza, Human; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Randomized Controlled Trials as Topic; Vaccination; Vaccines, Inactivated
PubMed: 26059051
DOI: 10.1002/14651858.CD009982.pub2 -
The Cochrane Database of Systematic... Aug 2018This is an update of a Cochrane Review first published in 2015. The conclusions have not changed.Hypodermic needles of different sizes (gauges and lengths) can be used... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This is an update of a Cochrane Review first published in 2015. The conclusions have not changed.Hypodermic needles of different sizes (gauges and lengths) can be used for vaccination procedures. The gauge (G) refers to the outside diameter of the needle tubing. The higher the gauge number, the smaller the diameter of the needle (e.g. a 23 G needle is 0.6 mm in diameter, whereas a 25 G needle is 0.5 mm in diameter). Many vaccines are recommended for injection into muscle (intramuscularly), although some are delivered subcutaneously (under the skin) and intradermally (into skin). Choosing an appropriate length and gauge of a needle may be important to ensure that a vaccine is delivered to the appropriate site and produces the maximum immune response while causing the least possible harm. Guidelines conflict regarding the sizes of needles that should be used for vaccinating children and adolescents.
OBJECTIVES
To assess the effects of using needles of different sizes for administering vaccines to children and adolescents on vaccine immunogenicity (the ability of the vaccine to elicit an immune response), procedural pain, and other reactogenicity events (adverse events following vaccine administration).
SEARCH METHODS
We updated our searches of CENTRAL, MEDLINE, Embase, and CINAHL to October 2017. We also searched proceedings of vaccine conferences and two trials registers.
SELECTION CRITERIA
Randomised controlled trials evaluating the effects of using hypodermic needles of any gauge or length to administer any type of vaccine to people aged from birth to 24 years.
DATA COLLECTION AND ANALYSIS
Three review authors independently extracted trial data and assessed the risk of bias. We contacted trial authors for additional information. We rated the quality of evidence using the GRADE system.
MAIN RESULTS
We included five trials involving 1350 participants in the original review. The updated review identified no new trials. The evidence from two small trials (one trial including infants and one including adolescents) was insufficient to allow any definitive statements to be made about the effects of the needles evaluated in the trials on vaccine immunogenicity and reactogenicity.The remaining three trials (1135 participants) contributed data to comparisons between 25 G 25 mm, 23 G 25 mm, and 25 G 16 mm needles. These trials included infants predominantly aged from two to six months undergoing intramuscular vaccination in the anterolateral thigh using the World Health Organization (WHO) injection technique (skin stretched flat, needle inserted at a 90° angle and up to the needle hub in healthy infants). The vaccines administered were combination vaccines containing diphtheria, tetanus, and whole-cell pertussis antigens (DTwP). In some trials, the vaccines also contained Haemophilus influenzae type b (DTwP-Hib) and hepatitis B (DTwP-Hib-Hep B) antigen components.Primary outcomesIncidence of vaccine-preventable diseases: No trials reported this outcome.Procedural pain and crying: Using a wider gauge 23 G 25 mm needle may slightly reduce procedural pain (low-quality evidence) and probably leads to a slight reduction in the duration of crying time immediately after vaccination (moderate-quality evidence) compared with a narrower gauge 25 G 25 mm needle (one trial, 320 participants). The effects are probably not large enough to be clinically relevant.Secondary outcomesImmune response: There is probably little or no difference in immune response, defined in terms of the proportion of seroprotected infants, between use of 25 G 25 mm, 23 G 25 mm, or 25 G 16 mm needles to administer a series of three doses of a DTwP-Hib vaccine at ages two, three, and four months (moderate-quality evidence, one trial, numbers of participants in analyses range from 309 to 402. The immune response to the pertussis antigen was not measured).Severe and non-severe local reactions: 25 mm needles (either 25 G or 23 G) probably lead to fewer severe and non-severe local reactions after DTwP-Hib vaccination compared with 25 G 16 mm needles (moderate-quality evidence, one trial, 447 to 458 participants in analyses). We estimate that one fewer infant will experience a severe local reaction (extensive redness and swelling) after the first vaccine dose for every 25 infants vaccinated with the longer rather than the shorter needle (number needed to treat for an additional beneficial outcome (NNTB) with a 25 G 25 mm needle: 25 (95% confidence interval (CI) 15 to 100); NNTB with a 23 G 25 mm needle: 25 (95% CI 17 to 100)). We estimate that one fewer infant will experience a non-severe local reaction (any redness, swelling, tenderness, or hardness (composite outcome)) at 24 hours after the first vaccine dose for every 5 or 6 infants vaccinated with a 25 mm rather than a 16 mm needle (NNTB with a 25 G 25 mm needle: 5 (95% CI 4 to 10); NNTB with a 23 G 25 mm needle: 6 (95% CI 4 to 13)). The results are similar after the second and third vaccine doses.Using a narrow gauge 25 G 25 mm needle may produce a small reduction in the incidence of local reactions after each dose of a DTwP vaccine compared with a wider gauge 23 G 25 mm needle, but the effect estimates are imprecise (low-quality evidence, two trials, 100 to 459 participants in analyses).Systemic reactions: The comparative effects of 23 G 25 mm, 25 G 25 mm, and 25 G 16 mm needles on the incidence of postvaccination fever and other systemic events such as drowsiness, loss of appetite, and vomiting are uncertain due to the very low quality of the evidence.
AUTHORS' CONCLUSIONS
Using 25 mm needles (either 23 G or 25 G) for intramuscular vaccination procedures in the anterolateral thigh of infants using the WHO injection technique probably reduces the occurrence of local reactions while achieving a comparable immune response to 25 G 16 mm needles. These findings are applicable to healthy infants aged two to six months receiving combination DTwP vaccines with a reactogenic whole-cell pertussis antigen component. These vaccines are predominantly used in low- and middle-income countries. The applicability of the findings to vaccines with acellular pertussis components and other vaccines with different reactogenicity profiles is uncertain.
Topics: Adolescent; Child; Child, Preschool; Crying; Diphtheria; Equipment Design; Haemophilus Infections; Haemophilus influenzae type b; Humans; Immunization; Infant; Injections, Intramuscular; Needles; Pain, Procedural; Randomized Controlled Trials as Topic; Tetanus; Vaccines; Young Adult
PubMed: 30091147
DOI: 10.1002/14651858.CD010720.pub3