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PLoS Neglected Tropical Diseases Feb 2022Monkeypox, a zoonotic disease caused by an orthopoxvirus, results in a smallpox-like disease in humans. Since monkeypox in humans was initially diagnosed in 1970 in the... (Meta-Analysis)
Meta-Analysis
Monkeypox, a zoonotic disease caused by an orthopoxvirus, results in a smallpox-like disease in humans. Since monkeypox in humans was initially diagnosed in 1970 in the Democratic Republic of the Congo (DRC), it has spread to other regions of Africa (primarily West and Central), and cases outside Africa have emerged in recent years. We conducted a systematic review of peer-reviewed and grey literature on how monkeypox epidemiology has evolved, with particular emphasis on the number of confirmed, probable, and/or possible cases, age at presentation, mortality, and geographical spread. The review is registered with PROSPERO (CRD42020208269). We identified 48 peer-reviewed articles and 18 grey literature sources for data extraction. The number of human monkeypox cases has been on the rise since the 1970s, with the most dramatic increases occurring in the DRC. The median age at presentation has increased from 4 (1970s) to 21 years (2010-2019). There was an overall case fatality rate of 8.7%, with a significant difference between clades-Central African 10.6% (95% CI: 8.4%- 13.3%) vs. West African 3.6% (95% CI: 1.7%- 6.8%). Since 2003, import- and travel-related spread outside of Africa has occasionally resulted in outbreaks. Interactions/activities with infected animals or individuals are risk behaviors associated with acquiring monkeypox. Our review shows an escalation of monkeypox cases, especially in the highly endemic DRC, a spread to other countries, and a growing median age from young children to young adults. These findings may be related to the cessation of smallpox vaccination, which provided some cross-protection against monkeypox, leading to increased human-to-human transmission. The appearance of outbreaks beyond Africa highlights the global relevance of the disease. Increased surveillance and detection of monkeypox cases are essential tools for understanding the continuously changing epidemiology of this resurging disease.
Topics: Adolescent; Adult; Child; Child, Preschool; Democratic Republic of the Congo; Female; History, 20th Century; History, 21st Century; Humans; Male; Mpox (monkeypox); Monkeypox virus; Travel-Related Illness; Young Adult
PubMed: 35148313
DOI: 10.1371/journal.pntd.0010141 -
Infection Feb 2021The clinical characteristics of various adenovirus (ADV) infection are underexplored up till now. To investigate the risk factors, manifestation, current status of ADV... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The clinical characteristics of various adenovirus (ADV) infection are underexplored up till now. To investigate the risk factors, manifestation, current status of ADV species, treatment and prognosis of this disease.
METHODS
We performed a Pubmed and Embase systematic review for case report reporting the ADV infection to analyze the clinical characteristics of disease.
RESULTS
Initial database searched identified articles of which 168 (228 cases) were included in the final analysis. Previous solid organ transplantation [odds ratio (OR) = 3.45, 95% CI 1.31-9.08, P = 0.01], hematopoietic stem cell transplant (OR = 4.24, 95% CI 1.33-13.51, P = 0.01) and hematological malignancy (OR = 4.78, 95% CI 1.70-13.46, P = 0.01) were associated with increased risk of disseminated ADV infection. Use of corticosteroids (OR = 3.86, 95% CI 1.21-12.24, P = 0.02) was a significant risk factor for acquiring urinary tract infections. A total of six species (21 types) of ADV infection have been identified in 100/228 (43.9%) cases. ADV B was the most common species. ADV B species (26/60, 52.0% or 5/41, 12.2% P = 0.001) were more isolated in patients with ADV pneumonia. ADV C (13/15, 86.7% versus 35/86, 40.7% P = 0.001) species were more identified in patients with disseminated disease. The species associated with keratoconjunctivitis is only ADV D in our analysis. Urinary tract ADV infections were observed in ADV A/B/D species. Cidofovir (CDV) (82/228, 36.0%) remained the most commonly antiviral therapy in our cases, followed by ribavirin (15/228, 6.6%), ganciclovir (18/228, 7.9%), and brincidofovir (12/228, 5.3%). Brincidofovir was administered as salvage therapy in 10 cases. Death was reported in 81/228 (35.5%) patients. Mortality rate was higher among patients with gastrointestinal (GI) ADV infection (5/10, 50.0%), ADV pneumonia (20/45, 44.4%) and disseminated ADV infection (53/122, 43.4%).
CONCLUSION
Previous solid organ transplantation, hematopoietic stem cell transplant and hematological malignancy were risk factors for disseminated ADV infection. Use of corticosteroids was significant for urinary tract ADV infection. Different species correlated with different clinical manifestations of infection. Mortality rate was higher among patients with GI disease, pneumonia and disseminated disease. Our review clarified the current treatment of ADV infections, and more treatment required further investigation.
Topics: Adenoviridae; Adenoviridae Infections; Adult; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Organ Transplantation; Risk Factors
PubMed: 32720128
DOI: 10.1007/s15010-020-01484-7 -
Vaccine Sep 2020Human papillomavirus (HPV) vaccination is essential for cervical cancer prevention. However, the value of HPV vaccination in the context excisional treatment of... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Human papillomavirus (HPV) vaccination is essential for cervical cancer prevention. However, the value of HPV vaccination in the context excisional treatment of high-grade cervical intraepithelial neoplasia (CIN 3) remains unclear.
METHODS
In this meta-analysis, three retrospective and three prospective studies, three post-hoc analyses of RCTs and one cancer registry study analysing the effect of pre- or post-conization vaccination (bi- or quadrivalent vaccine) against HPV were included after a systematic review of literature. Random-effect models were prepared to evaluate the influence of vaccination on recurrent CIN 2+.
RESULTS
Primary end point was CIN2+ in every study. The overall study population included 21,059 patients (3,939 vaccinations vs. 17,150 controls). The results showed a significant risk reduction for the development of new high-grade intraepithelial lesions after HPV vaccination (relative risk (RR) 0.41; 95% CI [0.27; 0.64]), independent from HPV type. Due to the heterogeneous study population multiple sub analyses regarding HPV type, age of patients, time of vaccination and follow-up were performed. Age-dependent analysis showed no differences between women under 25 years (RR 0.47 (95%-CI [0.28; 0.80]) and women of higher age (RR 0.52 (95%-CI [0.41; 0.65]). Results for HPV 16/18 positive CIN2+ showed a RR of 0.37 (95% CI [0.17; 0.80]). Overall, the number of women that would have to be vaccinated before or after conization to prevent one case of recurrent CIN 2+ (NNV) is 45.5.
CONCLUSION
Meta-analysis showed a significant risk reduction of developing recurrent cervical intraepithelial neoplasia after surgical excision and HPV vaccination compared to surgical excision only.
Topics: Adult; Conization; Female; Human papillomavirus 16; Human papillomavirus 18; Humans; Papillomavirus Infections; Papillomavirus Vaccines; Prospective Studies; Retrospective Studies; Uterine Cervical Neoplasms; Vaccination
PubMed: 32762871
DOI: 10.1016/j.vaccine.2020.07.055 -
Clinical Microbiology and Infection :... Aug 2021Only clinically validated HPV assays can be accepted in cervical cancer screening. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Only clinically validated HPV assays can be accepted in cervical cancer screening.
OBJECTIVES
To update the list of high-risk HPV assays that fulfil the 2009 international validation criteria (Meijer-2009).
DATA SOURCES
PubMed/Medline, Embase, Scopus, references from selected studies; published in January 2014 to August 2020.
STUDY ELIGIBILITY CRITERIA
HPV test validation studies and primary screening studies, involving testing with an index HPV test and a comparator HPV test with reporting of disease outcome (occurrence of histologically confirmed cervical precancer; CIN2+).
PARTICIPANTS
Women participating in cervical cancer screening.
INTERVENTIONS
Testing with an index and a comparator HPV test of clinician-collected cervical specimens and assessment of disease outcome (
METHODS
Assessment of relative clinical accuracy (including non-inferiority statistics index vs comparator assay) and test reproducibility in individual studies; random effects meta-analyses of the relative clinical sensitivity and specificity of index vs comparator tests.
RESULTS
Seven hrHPV DNA tests consistently fulfilled all validation criteria in multiple studies using predefined test positivity cut-offs (Abbott RealTime High Risk HPV, Anyplex II HPV HR Detection, BD Onclarity HPV Assay, Cobas 4800 HPV Test, HPV-Risk Assay, PapilloCheck HPV-Screening Test and Xpert HPV). Another assay (Alinity m HR HPV Assay) was fully validated in one validation study. The newer Cobas 6800 HPV Test, was validated in two studies against Cobas 4800. Other tests partially fulfilled the international validation criteria (Cervista HPV HR Test, EUROArray HPV, Hybribio's 14 High-Risk HPV, LMNX Genotyping Kit GP HPV, MALDI-TOF, RIATOL qPCR and a number of other in-house developed assays) since the non-inferior accuracy was reached after a posteriori cut-off optimization, inconsistent accuracy findings in different studies, and/or insufficient reproducibility assessment. The APTIMA HPV Assay targeting E6/E7 mRNA of hrHPV was fully validated in one formal validation study and showed slightly lower pooled sensitivity but higher specificity than the standard comparator tests in seven screening studies. However, the current international validation criteria relate to DNA assays. The additional requirement for longitudinal performance data required for non-DNA based HPV assays was not assessed in this review.
CONCLUSIONS
Eleven hrHPV DNA assays fulfil all requirements for use in cervical cancer screening using clinician-collected specimens.
Topics: Alphapapillomavirus; Early Detection of Cancer; Female; Genotyping Techniques; Humans; Papillomaviridae; Papillomavirus Infections; Reproducibility of Results; Sensitivity and Specificity; Uterine Cervical Neoplasms
PubMed: 33975008
DOI: 10.1016/j.cmi.2021.04.031 -
Brazilian Journal of Otorhinolaryngology 2021The association between uterine cervix and anogenital carcinomas and human papillomavirus, HPV, is well established, however the involvement of this virus in the... (Review)
Review
INTRODUCTION
The association between uterine cervix and anogenital carcinomas and human papillomavirus, HPV, is well established, however the involvement of this virus in the development of oral squamous cell carcinomas remains controversial.
OBJECTIVES
To evaluate the relationship between HPV infection and oral squamous cell carcinomas, and to estimate the incidence of this infection in these patients.
METHODS
Four electronic databases were searched to find studies that met the following inclusion criteria: i) performed in humans; ii) were cohort, case-control or cross-sectional; iii) assessed the HPV oncogenic activity by the E6 and E7 mRNA; iv) included primary oral squamous cell carcinomas which; v) diagnosis had been confirmed by biopsy. Information about the country; study period; sample obtainment; sites of oral squamous cell carcinomas; number, gender and age range of the population; the prevalence of HPV infection and subtypes detected; use of tobacco or alcohol and oral sex practice were extracted. The methodological quality of included articles was assessed using 14 criteria.
RESULTS
The search strategy retrieved 2129 articles. Assessment of the full text was done for 626 articles, but five were included. The total of participants included was 383, most of them male with mean age between 51.0 and 63.5 years old. Seventeen patients were HPV/mRNA-positive, being the subtypes 16 and 18 detected more frequently. Nine of the HPV/mRNA-positive oral squamous cell carcinomas occurred on the tongue. The quality score average of included articles was five points.
CONCLUSIONS
Among the 383 oral squamous cell carcinoma patients included, 17 (4.4%) were HPV/mRNA-positive, nevertheless it was not possible to assess if HPV infection was associated with oral squamous cell carcinomas because none of the studies included was longitudinal and cross-sectional investigations do not have control group.
Topics: Carcinoma, Squamous Cell; Cross-Sectional Studies; DNA, Viral; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Mouth Neoplasms; Papillomaviridae; Papillomavirus Infections; Squamous Cell Carcinoma of Head and Neck
PubMed: 33339760
DOI: 10.1016/j.bjorl.2020.10.017 -
The Lancet. Oncology Apr 2023Human papillomavirus (HPV) DNA and p16 positivity have crucial roles in the pathogenesis of vulvar cancer and vulvar intraepithelial neoplasia. We aimed to examine the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Human papillomavirus (HPV) DNA and p16 positivity have crucial roles in the pathogenesis of vulvar cancer and vulvar intraepithelial neoplasia. We aimed to examine the pooled prevalence of HPV DNA and p16 positivity in vulvar cancer and vulvar intraepithelial neoplasia worldwide.
METHODS
In this systematic review and meta-analysis, we searched PubMed, Embase, and the Cochrane Library databases for studies published between Jan 1, 1986, and May 6, 2022, that reported the prevalence of HPV DNA, or p16 positivity, or both, in histologically verified vulvar cancer or vulvar intraepithelial neoplasia. Studies on a minimum of five cases were included. Study-level data were extracted from the published studies. Random effect models were used to examine the pooled prevalence of HPV DNA and p16 positivity in both vulvar cancer and vulvar intraepithelial neoplasia, which were further investigated using stratified analyses by histological subtype, geographical region, HPV DNA or p16 detection method, tissue sample type, HPV genotype, publication year, and age at diagnosis. Additionally, meta-regression was applied to explore sources of heterogeneity.
FINDINGS
We retrieved 6393 search results, of which 6233 were excluded for being duplicates or after application of our inclusion and exclusion criteria. We also identified two studies from manual searches of references lists. 162 studies were eligible for inclusion in the systematic review and meta-analysis. The prevalence of HPV in vulvar cancer (91 studies; n=8200) was 39·1% (95% CI 35·3-42·9) and in vulvar intraepithelial neoplasia (60 studies; n=3140) was 76·1% (70·7-81·1). The most predominant HPV genotype in vulvar cancer was HPV16 (78·1% [95% CI 73·5-82·3]), followed by HPV33 (7·5% [4·9-10·7]). Similarly, HPV16 (80·8% [95% CI 75·9-85·2]) and HPV33 (6·3% [3·9-9·2]) were also the most two predominant HPV genotypes in vulvar intraepithelial neoplasia. The distribution of type-specific HPV genotypes in vulvar cancer among geographical regions was different, with HPV16 varying between regions, showing a high prevalence in Oceania (89·0% [95% CI 67·6-99·5]) and a low prevalence in South America (54·3% [30·2-77·4]). The prevalence of p16 positivity in patients with vulvar cancer was 34·1% (95% CI 30·9-37·4; 52 studies; n=6352), and it was 65·7% (52·5-77·7; 23 studies; n=896) in patients with vulvar intraepithelial neoplasia. Furthermore, among patients with HPV-positive vulvar cancer, p16 positivity prevalence was 73·3% (95% CI 64·7-81·2), compared with 13·8% (10·0-18·1) in HPV-negative vulvar cancer. The prevalence of double positivity for HPV and p16 was 19·6% (95% CI 16·3-23·0) in vulvar cancer and 44·2% (26·3-62·8) in vulvar intraepithelial neoplasia. Most analyses had large heterogeneity (I>75%).
INTERPRETATION
The high prevalence of HPV16 and HPV33 in vulvar cancer and vulvar intraepithelial neoplasia emphasised the importance of nine-valent HPV vaccination in preventing vulvar neoplasm. Additionally, this study highlighted the potential clinical significance of double positivity for HPV DNA and p16 in vulvar neoplasm.
FUNDING
Taishan Scholar Youth Project of Shandong Province, China.
Topics: Female; Humans; Adolescent; Vulvar Neoplasms; Cyclin-Dependent Kinase Inhibitor p16; Human Papillomavirus Viruses; DNA, Viral; Prevalence; Papillomavirus Infections; Carcinoma in Situ; Carcinoma, Squamous Cell; Papillomaviridae; Human papillomavirus 16
PubMed: 36933562
DOI: 10.1016/S1470-2045(23)00066-9 -
The Journal of Antibiotics Sep 2020Ivermectin proposes many potentials effects to treat a range of diseases, with its antimicrobial, antiviral, and anti-cancer properties as a wonder drug. It is highly...
Ivermectin proposes many potentials effects to treat a range of diseases, with its antimicrobial, antiviral, and anti-cancer properties as a wonder drug. It is highly effective against many microorganisms including some viruses. In this comprehensive systematic review, antiviral effects of ivermectin are summarized including in vitro and in vivo studies over the past 50 years. Several studies reported antiviral effects of ivermectin on RNA viruses such as Zika, dengue, yellow fever, West Nile, Hendra, Newcastle, Venezuelan equine encephalitis, chikungunya, Semliki Forest, Sindbis, Avian influenza A, Porcine Reproductive and Respiratory Syndrome, Human immunodeficiency virus type 1, and severe acute respiratory syndrome coronavirus 2. Furthermore, there are some studies showing antiviral effects of ivermectin against DNA viruses such as Equine herpes type 1, BK polyomavirus, pseudorabies, porcine circovirus 2, and bovine herpesvirus 1. Ivermectin plays a role in several biological mechanisms, therefore it could serve as a potential candidate in the treatment of a wide range of viruses including COVID-19 as well as other types of positive-sense single-stranded RNA viruses. In vivo studies of animal models revealed a broad range of antiviral effects of ivermectin, however, clinical trials are necessary to appraise the potential efficacy of ivermectin in clinical setting.
Topics: Animals; Antiviral Agents; Betacoronavirus; Cell Line; DNA Viruses; Disease Models, Animal; Global Health; Humans; Ivermectin; Molecular Structure; RNA Viruses; SARS-CoV-2
PubMed: 32533071
DOI: 10.1038/s41429-020-0336-z -
Bulletin of the World Health... May 2020To generate global and regional estimates for the prevalence and incidence of herpes simplex virus (HSV) type 1 and type 2 infection for 2016. (Comparative Study)
Comparative Study
OBJECTIVE
To generate global and regional estimates for the prevalence and incidence of herpes simplex virus (HSV) type 1 and type 2 infection for 2016.
METHODS
To obtain data, we undertook a systematic review to identify studies up to August 2018. Adjustments were made to account for HSV test sensitivity and specificity. For each World Health Organization (WHO) region, we applied a constant incidence model to pooled prevalence by age and sex to estimate the prevalence and incidence of HSV types 1 and 2 infections. For HSV type 1, we apportioned infection by anatomical site using pooled estimates of the proportions that were oral and genital.
FINDINGS
In 2016, an estimated 491.5 million people (95% uncertainty interval, UI: 430.4 million-610.6 million) were living with HSV type 2 infection, equivalent to 13.2% of the world's population aged 15-49 years. An estimated 3752.0 million people (95% UI: 3555.5 million-3854.6 million) had HSV type 1 infection at any site, equivalent to a global prevalence of 66.6% in 0-49-year-olds. Differing patterns were observed by age, sex and geographical region, with HSV type 2 prevalence being highest among women and in the WHO African Region.
CONCLUSION
An estimated half a billion people had genital infection with HSV type 2 or type 1, and several billion had oral HSV type 1 infection. Millions of people may also be at higher risk of acquiring human immunodeficiency virus (HIV), particularly women in the WHO African Region who have the highest HSV type 2 prevalence and exposure to HIV.
Topics: Adolescent; Adult; Age Distribution; Child; Child, Preschool; Female; Global Health; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Incidence; Infant; Male; Middle Aged; Prevalence; Young Adult
PubMed: 32514197
DOI: 10.2471/BLT.19.237149 -
BMJ Global Health May 2021The WHO recommends human papillomavirus (HPV) cervical self-sampling as an additional screening method and HPV DNA testing as an effective approach for the early...
INTRODUCTION
The WHO recommends human papillomavirus (HPV) cervical self-sampling as an additional screening method and HPV DNA testing as an effective approach for the early detection of cervical cancer for women aged ≥30 years. This systematic review assesses end user's values and preferences related to HPV self-sampling.
METHODS
We searched four electronic databases (PubMed, Cumulative Index to Nursing and Allied Health Literature, Latin American and Caribbean Health Sciences Literature and Embase) using search terms for HPV and self-sampling to identify articles meeting inclusion criteria. A standardised data extraction form was used to capture study setting, population, sample size and results related to values and preferences.
RESULTS
Of 1858 records retrieved, 72 studies among 52 114 participants published between 2002 and 2018 were included in this review. Almost all studies were cross-sectional surveys. Study populations included end users who were mainly adolescent girls and adult women. Ages ranged from 14 to 80 years. Most studies (57%) were conducted in high-income countries. Women generally found HPV self-sampling highly acceptable regardless of age, income or country of residence. Lack of self-confidence with collecting a reliable sample was the most commonly cited reason for preferring clinician-collected samples. Most women preferred home-based self-sampling to self-sampling at a clinic. The cervical swab was the most common and most accepted HPV DNA sampling device.
CONCLUSIONS
HPV self-sampling is generally a highly accepted method of cervical cancer screening for end users globally. End user preferences for self-sampling device, method and setting can inform the development of new and expanded interventions to increase HPV screening.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alphapapillomavirus; Cross-Sectional Studies; Early Detection of Cancer; Female; Humans; Middle Aged; Papillomaviridae; Papillomavirus Infections; Self Care; Uterine Cervical Neoplasms; Young Adult
PubMed: 34011537
DOI: 10.1136/bmjgh-2020-003743 -
Frontiers in Immunology 2022Recombinant Adeno-associated virus (rAAV) is one of the main delivery vectors for gene therapy. To assess immunogenicity, toxicity, and features of AAV gene therapy in... (Meta-Analysis)
Meta-Analysis
Recombinant Adeno-associated virus (rAAV) is one of the main delivery vectors for gene therapy. To assess immunogenicity, toxicity, and features of AAV gene therapy in clinical settings, a meta-analysis of 255 clinical trials was performed. A total of 7,289 patients are planned to be dosed. AAV2 was the most dominantly used serotype (29.8%, n=72), and 8.3% (n=20) of trials used engineered capsids. 38.7% (n=91) of trials employed neutralizing antibody assays for patient enrollment, while 15.3% (n=36) used ELISA-based total antibody assays. However, there was high variability in the eligibility criteria with cut-off tiers ranging from 1:1 to 1:1,600. To address potential immunogenicity, 46.3% (n=118) of trials applied immunosuppressants (prophylactic or reactive), while 32.7% (n=18) of CNS and 37.5% (n=24) of ocular-directed trials employed immunosuppressants, possibly due to the immune-privileged status of CNS and retina. There were a total of 11 patient deaths across 8 trials, and 18 out of 30 clinical holds were due to toxicity findings in clinical studies. 30.6% (n=78) of trials had treatment-emergent serious adverse events (TESAEs), with hepatotoxicity and thrombotic microangiopathy (systemic delivery) and neurotoxicity (CNS delivery) being the most prominent. Additionally, the durability of gene therapy may be impacted by two distinct decline mechanisms: 1) rapid decline presumably due to immune responses; or 2) gradual decline due to vector dilution. The durability varied significantly depending on disease indication, dose, serotypes, and patient individuals. Most CNS (90.0%) and muscle trials (73.3%) achieved durable transgene expression, while only 43.6% of ocular trials had sustained clinical outcomes. The rAAV production system can affect rAAV quality and thus immunogenicity and toxicity. Out of 186 trials that have disclosed production system information, 63.0% (n=126) of trials used the transient transfection of the HEK293/HEK293T system, while 18.0% (n=36) applied the baculovirus/Sf9 (rBac/Sf9) system. There were no significant differences in TESAEs and durability between AAV generated by rBac/Sf9 and HEK293/HEK293T systems. In summary, rAAV immunogenicity and toxicity poses significant challenges for clinical development of rAAV gene therapies, and it warrants collaborative efforts to standardize monitoring/measurement methods, design novel strategies to overcome immune responses, and openly share relevant information.
Topics: Humans; Dependovirus; HEK293 Cells; Genetic Vectors; Genetic Therapy; Immunosuppressive Agents
PubMed: 36389770
DOI: 10.3389/fimmu.2022.1001263