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The Lancet. Infectious Diseases Feb 2019Global genetic diversity of HIV-1 is a major challenge to the development of HIV vaccines. We aimed to estimate the regional and global distribution of HIV-1 subtypes...
BACKGROUND
Global genetic diversity of HIV-1 is a major challenge to the development of HIV vaccines. We aimed to estimate the regional and global distribution of HIV-1 subtypes and recombinants during 1990-2015.
METHODS
We searched PubMed, EMBASE (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) for HIV-1 subtyping studies published between Jan 1, 1990, and Dec 31, 2015. We collected additional unpublished HIV-1 subtyping data through a global survey. We included prevalence studies with HIV-1 subtyping data collected during 1990-2015. We grouped countries into 14 regions and analysed data for four time periods (1990-99, 2000-04, 2005-09, and 2010-15). The distribution of HIV-1 subtypes, circulating recombinant forms (CRFs), and unique recombinant forms (URFs) in individual countries was weighted according to the UNAIDS estimates of the number of people living with HIV (PLHIV) in each country to generate regional and global estimates of HIV-1 diversity in each time period. The primary outcome was the number of samples designated as HIV-1 subtypes A, B, C, D, F, G, H, J, K, CRFs, and URFs. The systematic review is registered with PROSPERO, number CRD42017067164.
FINDINGS
This systematic review and global survey yielded 2203 datasets with 383 519 samples from 116 countries in 1990-2015. Globally, subtype C accounted for 46·6% (16 280 897/34 921 639 of PLHIV) of all HIV-1 infections in 2010-15. Subtype B was responsible for 12·1% (4 235 299/34 921 639) of infections, followed by subtype A (10·3%; 3 587 003/34 921 639), CRF02_AG (7·7%; 2 705 110/34 921 639), CRF01_AE (5·3%; 1 840 982/34 921 639), subtype G (4·6%; 1 591 276/34 921 639), and subtype D (2·7%; 926 255/34 921 639). Subtypes F, H, J, and K combined accounted for 0·9% (311 332/34 921 639) of infections. Other CRFs accounted for 3·7% (1 309 082/34 921 639), bringing the proportion of all CRFs to 16·7% (5 844 113/34 921 639). URFs constituted 6·1% (2 134 405/34 921 639), resulting in recombinants accounting for 22·8% (7 978 517/34 921 639) of all global HIV-1 infections. The distribution of HIV-1 subtypes and recombinants changed over time in countries, regions, and globally. At a global level during 2005-15, subtype B increased, subtypes A and D were stable, and subtypes C and G and CRF02_AG decreased. CRF01_AE, other CRFs, and URFs increased, leading to a consistent increase in the global proportion of recombinants over time.
INTERPRETATION
Global and regional HIV diversity is complex and evolving, and is a major challenge to HIV vaccine development. Surveillance of the global molecular epidemiology of HIV-1 remains crucial for the design, testing, and implementation of HIV vaccines.
FUNDING
None.
Topics: AIDS Vaccines; Genetic Variation; Genome, Viral; Genotype; Genotyping Techniques; Global Health; HIV Infections; HIV-1; Humans; Serogroup; Serotyping; Surveys and Questionnaires
PubMed: 30509777
DOI: 10.1016/S1473-3099(18)30647-9 -
Danish Medical Journal Oct 2020Although acute otitis media (AOM) is a very frequent illness in children, it remains unclear to what extent children with AOM benefit from antibiotics (ABX). This...
INTRODUCTION
Although acute otitis media (AOM) is a very frequent illness in children, it remains unclear to what extent children with AOM benefit from antibiotics (ABX). This systematic review aimed to clarify this subject by including randomised clinical trials (RCTs) from the pneumococcal vaccine era only.
METHODS
We performed a systematic literature search in four databases from 1 January 2000 to 1 January 2019 for RCTs comparing ABX to placebo in patients with AOM. Pain was registered as the main outcome. Adverse events (AE), development of contralateral otitis media, tympanic membrane perforation, late AOM recurrence, abnormal tympanometry and time to resolution of middle ear effusion were registered as secondary outcomes.
RESULTS
Six publications based on five RCTs with 1,862 patients were included. The number needed to treat (NNT) to reduce pain varied from seven (pain at day 7-10) to 28 (pain at day 2-3). The NNT for preventing contralateral otitis was ten. AE were seen in every 13th patient treated with ABX.
CONCLUSIONS
ABX appears to have a limited effect on both primary and secondary outcomes compared with placebo. A substantial number of patients experienced AE. New RCTs are needed to further clarify the effect. Ideally, RCTs could be conducted in Danish general practices in collaboration with practicing ear, nose and throat specialists to obtain large unselected populations with high rates of vaccine coverage. Until more evidence is provided, ABX should be considered among children younger than two years of age with severe symptoms of AOM, i.e. fewer and affected well-being.
Topics: Acute Disease; Anti-Bacterial Agents; Child; Humans; Infant; Neoplasm Recurrence, Local; Otitis Media; Tympanic Membrane Perforation
PubMed: 33215607
DOI: No ID Found -
The Lancet. Healthy Longevity Apr 2022Given the substantial impact of herpes zoster on health and quality of life, and its considerable economic burden, prevention through vaccination is a priority. We aimed... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Given the substantial impact of herpes zoster on health and quality of life, and its considerable economic burden, prevention through vaccination is a priority. We aimed to evaluate the effectiveness of the herpes zoster vaccines (recombinant zoster vaccine [RZV] and zoster vaccine live [ZVL]) against incident herpes zoster and postherpetic neuralgia in older adults.
METHODS
We did a systematic review and meta-analysis of studies assessing the effectiveness of herpes zoster vaccines in adults aged 50 years or older, compared with no vaccination or another vaccine. We searched published literature on MEDLINE, Embase, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, ProQuest Central, and Dimensions, as well as unpublished studies, grey literature, and the reference lists of included studies. Observational studies published in any language between May 25, 2006, and Dec 31, 2020, were included. Eligible studies were appraised for methodological quality using standardised critical appraisal instruments from the Joanna Briggs Institute, and data were extracted from selected studies using a standardised tool. Random-effects meta-analysis models were used to estimate pooled vaccine effectiveness for outcomes of interest (herpes zoster, herpes zoster ophthalmicus, and postherpetic neuralgia) among clinically and methodologically comparable studies, with a fixed-effects model also used for herpes zoster ophthalmicus. Vaccine effectiveness was also assessed in people with comorbidities. As a post-hoc analysis, a forward citation search was done on Jan 31, 2021. This study is registered on PROSPERO, CRD42021232383.
FINDINGS
Our search identified 1240 studies, of which 1162 were excluded based on title and abstract screening. A further 56 articles were excluded on reading the full text. 22 studies (21 cohort studies and one case-control study, involving 9 536 086 participants and 3·35 million person-years in the USA, UK, Canada, and Sweden) were included in the quantitative analysis. Of these, 13 articles were included in the meta-analysis. The overall quality of evidence was very low for all outcomes. The pooled vaccine effectiveness for ZVL against herpes zoster in adults was 45·9% (95% CI 42·2-49·4; seven studies). The vaccine effectiveness for ZVL against postherpetic neuralgia was 59·7% (58·4-89·7; three studies) and against herpes zoster ophthalmicus (in a fixed-effects model) was 30·0% (20·5-38·4; two studies). ZVL was effective in preventing herpes zoster in people with comorbidities, including diabetes (vaccine effectiveness 49·8%, 45·1-54·1; three studies), chronic kidney disease (54·3%, 49·0-59·1; four studies), liver disease (52·9%, 41·6-62·1; two studies), heart disease (52·3%, 45·0-58·7; two studies), and lung disease (49·0%, 32·2-66·2; two studies). In a post-hoc analysis of two studies from the USA published after 2020, the pooled vaccine effectiveness for RZV against herpes zoster in adults was 79·2% (57·6-89·7). Substantial heterogeneity (I≥75%) was observed in 50% of the meta-analyses.
INTERPRETATION
ZVL and RZV are effective in preventing herpes zoster in routine clinical practice. ZVL also reduces the risk of postherpetic neuralgia. Selection bias and confounding by unmeasured variables are inherent challenges of observational studies based on large health-care databases. Nevertheless, these findings will reassure policy makers, health practitioners, and the public that the vaccinations currently available for herpes zoster vaccination programmes are effective at preventing herpes zoster and related complications.
FUNDING
None.
Topics: Aged; Case-Control Studies; Herpes Zoster Ophthalmicus; Herpes Zoster Vaccine; Herpesvirus 3, Human; Humans; Neuralgia, Postherpetic; Quality of Life; Vaccine Efficacy; Vaccines, Synthetic
PubMed: 36098300
DOI: 10.1016/S2666-7568(22)00039-3 -
Clinical Infectious Diseases : An... Oct 2020The primary reported risk factors for herpes zoster (HZ) include increasing age and immunodeficiency, yet estimates of HZ risk by immunocompromising condition have not...
BACKGROUND
The primary reported risk factors for herpes zoster (HZ) include increasing age and immunodeficiency, yet estimates of HZ risk by immunocompromising condition have not been well characterized. We undertook a systematic literature review to estimate the HZ risk in immunocompromised patients.
METHODS
We systematically reviewed studies that examined the risk of HZ and associated complications in adult patients with hematopoietic cell transplants (HCT), cancer, human immunodeficiency virus (HIV), and solid organ transplant (SOT). We identified studies in PubMed, Embase, Medline, Cochrane, Scopus, and clinicaltrials.gov that presented original data from the United States and were published after 1992. We assessed the risk of bias with Cochrane or Grading of Recommendations Assessment, Development, and Evaluation methods.
RESULTS
We identified and screened 3765 records and synthesized 34 studies with low or moderate risks of bias. Most studies that were included (32/34) reported at least 1 estimate of the HZ cumulative incidence (range, 0-41%). There were 12 studies that reported HZ incidences that varied widely within and between immunocompromised populations. Incidence estimates ranged from 9 to 92 HZ cases/1000 patient-years and were highest in HCT, followed by hematologic malignancies, SOT, and solid tumor malignancies, and were lowest in people living with HIV. Among 17 HCT studies, the absence of or use of antiviral prophylaxis at <1 year post-transplant was associated with a higher HZ incidence.
CONCLUSIONS
HZ was common among all immunocompromised populations studied, exceeding the expected HZ incidence among immunocompetent adults aged ≥60 years. Better evidence of the incidence of HZ complications and their severity in immunocompromised populations is needed to inform economic and HZ vaccine policies.
Topics: Adult; Herpes Zoster; Herpes Zoster Vaccine; Herpesvirus 3, Human; Humans; Immunocompromised Host; Incidence; Middle Aged; Neuralgia, Postherpetic; United States
PubMed: 31677266
DOI: 10.1093/cid/ciz1090 -
Public Health Nov 2023Dengue is the most important human vector-borne disease in terms of disease burden. A first dengue vaccine has recently been licenced, and others are in advanced stages... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Dengue is the most important human vector-borne disease in terms of disease burden. A first dengue vaccine has recently been licenced, and others are in advanced stages of development. However, to date, none of these vaccines has achieved balanced efficacy and safety for all dengue serotypes. The aim of this systematic review and meta-analysis was to assess the global acceptance and willingness to pay for unspecified dengue vaccines.
METHODS
This systematic review and meta-analysis included cross-sectional and cohort studies that reported values for vaccine acceptance (percentage) and willingness to pay for currently available or hypothetical vaccines. These values were pooled using random-effects models for the acceptance, while weighted linear regression was chosen for willingness to pay. Heterogeneity between studies was assessed using prediction intervals (PIs), and a domain-based tool was used to assess the risk of bias. Subgroup and sensitivity analyses were performed where appropriate. This study was registered with PROSPERO (CRD42021255784).
RESULTS
We included 19 studies from the Americas and Asia in the quantitative meta-analysis. The risk of bias was mainly related to the selection of participants and to the assumptions about the safety and efficacy of the vaccines. The percentage of vaccine acceptance was 88.3% (95% CI: 81.0%-93.0%), with some heterogeneity between studies (80% PI: 52.9%-98.1%). Willingness to pay was US$ 46.7 (95% CI: 25.9-67.5) per vaccine recipient. There were differences between continents, with higher acceptance in the Americas.
CONCLUSIONS
We were able to obtain global estimates of vaccine acceptance and willingness to pay and identify the associated factors that influence these values. This knowledge is relevant for the planning of future vaccination strategies.
Topics: Humans; Dengue Vaccines; Dengue; Patient Acceptance of Health Care; Vaccination Hesitancy
PubMed: 37741155
DOI: 10.1016/j.puhe.2023.08.022 -
Nature Communications May 2024The Modified Vaccinia Ankara vaccine developed by Bavarian Nordic (MVA-BN) was widely deployed to prevent mpox during the 2022 global outbreak. This vaccine was... (Meta-Analysis)
Meta-Analysis
The Modified Vaccinia Ankara vaccine developed by Bavarian Nordic (MVA-BN) was widely deployed to prevent mpox during the 2022 global outbreak. This vaccine was initially approved for mpox based on its reported immunogenicity (from phase I/II trials) and effectiveness in animal models, rather than evidence of clinical efficacy. However, no validated correlate of protection after vaccination has been identified. Here we performed a systematic search and meta-analysis of the available data to test whether vaccinia-binding ELISA endpoint titer is predictive of vaccine effectiveness against mpox. We observe a significant correlation between vaccine effectiveness and vaccinia-binding antibody titers, consistent with the existing assumption that antibody levels may be a correlate of protection. Combining this data with analysis of antibody kinetics after vaccination, we predict the durability of protection after vaccination and the impact of dose spacing. We find that delaying the second dose of MVA-BN vaccination will provide more durable protection and may be optimal in an outbreak with limited vaccine stock. Although further work is required to validate this correlate, this study provides a quantitative evidence-based approach for using antibody measurements to predict the effectiveness of mpox vaccination.
Topics: Animals; Humans; Antibodies, Viral; Enzyme-Linked Immunosorbent Assay; Smallpox Vaccine; Vaccination; Vaccine Efficacy; Vaccinia; Monkeypox virus
PubMed: 38719852
DOI: 10.1038/s41467-024-48180-w -
Italian Journal of Pediatrics Jul 2023Robust routine immunization schedules for pertussis-containing vaccines have been applied for years, but pertussis outbreaks remain a worldwide problem. This study aimed... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Robust routine immunization schedules for pertussis-containing vaccines have been applied for years, but pertussis outbreaks remain a worldwide problem. This study aimed to investigate the association between vaccine hesitancy and pertussis in infants and children.
METHODS
We searched PubMed, Cochrane, Web of Science, Embase, and China National Knowledge Internet for studies published between January 2012 and June 2022. This study included case-control and cohort studies that assessed the association between childhood/maternal vaccine hesitancy and odds ratios (ORs), risk ratios (RRs), and vaccine effectiveness (VE) related to pertussis in infants and children [Formula: see text] 9 years old. ORs/VEs with a 95% confidence interval (CI) were calculated. Random-effects meta-analysis models were used for appropriate pooled estimates, and heterogeneity was assessed using [Formula: see text]. Cumulative meta-analysis and subgroup analyses stratified by study characteristics were performed.
RESULTS
Twenty-two studies were included, with a mean quality score of 7.0 (range 6.0-9.0). Infants and children with pertussis were associated with higher vaccine hesitancy to all doses (OR = 4.12 [95% CI: 3.09-5.50]). The highest OR was between children who were unvaccinated over four doses and children who were fully vaccinated (OR = 14.26 [95%CI: 7.62-26.70]); childhood vaccine delay was not statistically significantly associated with pertussis risk (OR = 1.18 [95% CI: 0.74-1.89]). Maternal vaccine hesitancy was associated with significantly higher pertussis risk in infants aged 2 and 3 months old, with higher pertussis ORs in infants [Formula: see text] 2 months old (OR = 6.02 [95%CI: 4.31-8.50], OR = 5.14 [95%CI: 1.95-13.52] for infants [Formula: see text] 2 and [Formula: see text] 3 months old, respectively). Maternal and childhood VEs were high in reducing pertussis infection in infants and children. The administration time of maternal vaccination had little effect on VE.
CONCLUSION
Vaccine hesitancy increased pertussis risks in infants and children. Ensuring that children receive up-to-date pertussis vaccines is essential; short delays in receiving childhood vaccinations may be unimportant. Maternal vaccinations for pertussis should be encouraged.
Topics: Child; Infant; Humans; Whooping Cough; Vaccination Hesitancy; Vaccination; Immunization Schedule; Vaccines
PubMed: 37443026
DOI: 10.1186/s13052-023-01495-8 -
Parasitology Dec 2021Ascariasis is the most prevalent helminth infection in the world and leads to significant, life-long morbidity, particularly in young children. Current efforts to...
Ascariasis is the most prevalent helminth infection in the world and leads to significant, life-long morbidity, particularly in young children. Current efforts to control and eradicate ascariasis in endemic regions have been met with significant challenges including high-rates of re-infection and potential development of anthelminthic drug resistance. Vaccines against ascariasis are a key tool that could break the transmission cycle and lead to disease eradication globally. Evolution of the vaccine pipeline has progressed, however no vaccine product has been brought to human clinical trials to date. Advancement in recombinant protein technology may provide the first step in generating an vaccine as well as a pan-helminthic vaccine ready for human trials. However, several roadblocks remain and investment in new technologies will be important to develop a successful human vaccine that is critically needed to prevent significant morbidity in -endemic regions around the world.
Topics: Animals; Ascariasis; Ascaris; Humans; Vaccine Development; Vaccines
PubMed: 35586777
DOI: 10.1017/s0031182021001347 -
The Cochrane Database of Systematic... Dec 2022The common cold is a spontaneously remitting infection of the upper respiratory tract, characterised by a runny nose, nasal congestion, sneezing, cough, malaise, sore... (Review)
Review
BACKGROUND
The common cold is a spontaneously remitting infection of the upper respiratory tract, characterised by a runny nose, nasal congestion, sneezing, cough, malaise, sore throat, and fever (usually < 37.8 ºC). Whilst the common cold is generally not harmful, it is a cause of economic burden due to school and work absenteeism. In the United States, economic loss due to the common cold is estimated at more than USD 40 billion per year, including an estimate of 70 million workdays missed by employees, 189 million school days missed by children, and 126 million workdays missed by parents caring for children with a cold. Additionally, data from Europe show that the total cost per episode may be up to EUR 1102. There is also a large expenditure due to inappropriate antimicrobial prescription. Vaccine development for the common cold has been difficult due to antigenic variability of the common cold viruses; even bacteria can act as infective agents. Uncertainty remains regarding the efficacy and safety of interventions for preventing the common cold in healthy people, thus we performed an update of this Cochrane Review, which was first published in 2011 and updated in 2013 and 2017.
OBJECTIVES
To assess the clinical effectiveness and safety of vaccines for preventing the common cold in healthy people.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (April 2022), MEDLINE (1948 to April 2022), Embase (1974 to April 2022), CINAHL (1981 to April 2022), and LILACS (1982 to April 2022). We also searched three trials registers for ongoing studies, and four websites for additional trials (April 2022). We did not impose any language or date restrictions.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of any virus vaccine compared with placebo to prevent the common cold in healthy people.
DATA COLLECTION AND ANALYSIS
We used Cochrane's Screen4Me workflow to assess the initial search results. Four review authors independently performed title and abstract screening to identify potentially relevant studies. We retrieved the full-text articles for those studies deemed potentially relevant, and the review authors independently screened the full-text reports for inclusion in the review, recording reasons for exclusion of the excluded studies. Any disagreements were resolved by discussion or by consulting a third review author when needed. Two review authors independently collected data on a data extraction form, resolving any disagreements by consensus or by involving a third review author. We double-checked data transferred into Review Manager 5 software. Three review authors independently assessed risk of bias using RoB 1 tool as outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We carried out statistical analysis using Review Manager 5. We did not conduct a meta-analysis, and we did not assess publication bias. We used GRADEpro GDT software to assess the certainty of the evidence and to create a summary of findings table. MAIN RESULTS: We did not identify any new RCTs for inclusion in this update. This review includes one RCT conducted in 1965 with an overall high risk of bias. The RCT included 2307 healthy young men in a military facility, all of whom were included in the analyses, and compared the effect of three adenovirus vaccines (live, inactivated type 4, and inactivated type 4 and 7) against a placebo (injection of physiological saline or gelatin capsule). There were 13 (1.14%) events in 1139 participants in the vaccine group, and 14 (1.19%) events in 1168 participants in the placebo group. Overall, we do not know if there is a difference between the adenovirus vaccine and placebo in reducing the incidence of the common cold (risk ratio 0.95, 95% confidence interval 0.45 to 2.02; very low-certainty evidence). Furthermore, no difference in adverse events when comparing live vaccine preparation with placebo was reported. We downgraded the certainty of the evidence to very low due to unclear risk of bias, indirectness because the population of this study was only young men, and imprecision because confidence intervals were wide and the number of events was low. The included study did not assess vaccine-related or all-cause mortality. AUTHORS' CONCLUSIONS: This Cochrane Review was based on one study with very low-certainty evidence, which showed that there may be no difference between the adenovirus vaccine and placebo in reducing the incidence of the common cold. We identified a need for well-designed, adequately powered RCTs to investigate vaccines for the common cold in healthy people. Future trials on interventions for preventing the common cold should assess a variety of virus vaccines for this condition, and should measure such outcomes as common cold incidence, vaccine safety, and mortality (all-cause and related to the vaccine).
Topics: Child; Humans; Male; Adenovirus Vaccines; Common Cold; Incidence; Systematic Reviews as Topic; Vaccines, Attenuated; Randomized Controlled Trials as Topic
PubMed: 36515550
DOI: 10.1002/14651858.CD002190.pub6 -
Acta Tropica Mar 2023It has been tested and proven that vaccination is still the best strategy to combat infectious diseases. However, to date, there are still no vaccines against human... (Review)
Review
It has been tested and proven that vaccination is still the best strategy to combat infectious diseases. However, to date, there are still no vaccines against human soil-transmitted helminthic diseases, despite their high prevalence globally, particularly in developing countries and rural areas with tropical climates and poor sanitation. The development of vaccines against helminths is riddled with obstacles. Helminths have a complex life cycle, multiple stages within the same host with stage-specific antigen expression, and the ability to regulate host immune reactions to evade the immune response. These elements contribute to the main challenge of helminthic vaccines: the identification of effective vaccine candidates. Therefore, this article reviews the current progress and potential future direction of soil-transmitted helminthic vaccines, particularly against Trichuris trichiura, Ascaris lumbricoides, Strongyloides stercoralis, Necator americanus and Ancylostoma duodenale. The study design employed was a systematic review, using qualitative meta-summary synthesis. Preclinical studies and clinical trials on the development of protein subunit vaccines against the five soil-transmitted helminths were searched on PubMed and Scopus. Effectiveness was indicated by a reduction in worm burden or larval output, an increase in specific IgG levels, or an increase in cytokine production. Our findings show that only the hookworm vaccine against N. americanus is in the clinical trial phase, while the rest is still in exploratory research and pre-clinical development phase.
Topics: Animals; Humans; Soil; Hookworm Infections; Ascaris lumbricoides; Ancylostomatoidea; Necator americanus; Vaccines; Helminthiasis; Feces
PubMed: 36586174
DOI: 10.1016/j.actatropica.2022.106796