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Journal of Infection and Public Health Oct 2023Dengue is caused by the dengue virus (DENVs) infection and clinical manifestations include dengue fever (DF), dengue hemorrhagic fever (DHF), or dengue shock syndrome...
Dengue is caused by the dengue virus (DENVs) infection and clinical manifestations include dengue fever (DF), dengue hemorrhagic fever (DHF), or dengue shock syndrome (DSS). Due to a lack of antiviral drugs and effective vaccines, several therapeutic and control strategies have been proposed. A systemic literature review was conducted according to PRISMA guidelines to select proper references to give an overview of DENV infection. Results indicate that understanding the virus characteristics and epidemiology are essential to gain the basic and clinical knowledge as well as dengue disseminated pattern and status. Different factors and mechanisms are thought to be involved in the presentation of DHF and DSS, including antibody-dependent enhancement, immune dysregulation, viral virulence, host genetic susceptibility, and preexisting dengue antibodies. This study suggests that dissecting pathogenesis and risk factors as well as developing different types of therapeutic and control strategies against DENV infection are urgently needed.
Topics: Humans; Antiviral Agents; Dengue; Genetic Predisposition to Disease; Risk Factors; Virulence
PubMed: 37595484
DOI: 10.1016/j.jiph.2023.08.001 -
Nutrients Sep 2023Both 25-autoimmunity and(25(OH)D: calcifediol) and its active form, 1,25-dihydroxyvitamin D (1,25(OH)D: calcitriol), play critical roles in protecting humans from... (Review)
Review
Both 25-autoimmunity and(25(OH)D: calcifediol) and its active form, 1,25-dihydroxyvitamin D (1,25(OH)D: calcitriol), play critical roles in protecting humans from invasive pathogens, reducing risks of autoimmunity, and maintaining health. Conversely, low 25(OH)D status increases susceptibility to infections and developing autoimmunity. This systematic review examines vitamin D's mechanisms and effects on enhancing innate and acquired immunity against microbes and preventing autoimmunity. The study evaluated the quality of evidence regarding biology, physiology, and aspects of human health on vitamin D related to infections and autoimmunity in peer-reviewed journal articles published in English. The search and analyses followed PRISMA guidelines. Data strongly suggested that maintaining serum 25(OH)D concentrations of more than 50 ng/mL is associated with significant risk reduction from viral and bacterial infections, sepsis, and autoimmunity. Most adequately powered, well-designed, randomized controlled trials with sufficient duration supported substantial benefits of vitamin D. Virtually all studies that failed to conclude benefits or were ambiguous had major study design errors. Treatment of vitamin D deficiency costs less than 0.01% of the cost of investigation of worsening comorbidities associated with hypovitaminosis D. Despite cost-benefits, the prevalence of vitamin D deficiency remains high worldwide. This was clear among those who died from COVID-19 in 2020/21-most had severe vitamin D deficiency. Yet, the lack of direction from health agencies and insurance companies on using vitamin D as an adjunct therapy is astonishing. Data confirmed that keeping an individual's serum 25(OH)D concentrations above 50 ng/mL (125 nmol/L) (and above 40 ng/mL in the population) reduces risks from community outbreaks, sepsis, and autoimmune disorders. Maintaining such concentrations in 97.5% of people is achievable through daily safe sun exposure (except in countries far from the equator during winter) or taking between 5000 and 8000 IU vitamin D supplements daily (average dose, for non-obese adults, ~70 to 90 IU/kg body weight). Those with gastrointestinal malabsorption, obesity, or on medications that increase the catabolism of vitamin D and a few other specific disorders require much higher intake. This systematic review evaluates non-classical actions of vitamin D, with particular emphasis on infection and autoimmunity related to the immune system.
Topics: Adult; Humans; Vitamin D; Autoimmunity; COVID-19; Immune System; Autoimmune Diseases; Vitamins; Vitamin D Deficiency
PubMed: 37686873
DOI: 10.3390/nu15173842 -
Safety and Efficacy of Long-Acting Injectable Agents for HIV-1: Systematic Review and Meta-Analysis.JMIR Public Health and Surveillance Jul 2023HIV-1 infection continues to affect global health. Although antiretrovirals can reduce the viral load or prevent HIV-1 infection, current drugs require daily oral use... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
HIV-1 infection continues to affect global health. Although antiretrovirals can reduce the viral load or prevent HIV-1 infection, current drugs require daily oral use with a high adherence level. Long-acting antiretrovirals (LA-ARVs) significantly improve medication adherence and are essential for HIV-1 prophylaxis and therapy.
OBJECTIVE
This study aimed to investigate the safety and efficacy of long-acting cabotegravir (CAB-LA) and long-acting rilpivirine (RPV-LA) in the prevention and treatment of HIV-1 infection.
METHODS
PubMed, Embase, and the Cochrane Library were searched for studies from database inception to November 12, 2022. We included studies that reported efficacy and safety data on LA-ARV intervention in people living with HIV and excluded reviews, animal studies, and articles with missing or duplicate data. Virological suppression was defined as plasma viral load <50 copies/mL 6 months after antiviral therapy initiation. We extracted outcomes for analysis and expressed dichotomous data as risk ratios (RRs) and continuous data as mean differences. Depending on the heterogeneity assessment, a fixed- or random-effects model was used for data synthesis. We performed subgroup analyses of the partial safety and efficacy outcomes of CAB-LA+RPV-LA. The protocol was registered with the Open Science Framework.
RESULTS
We included 12 trials comprising 10,957 individuals, of which 7 were prevention trials and 5 were treatment trials. CAB-LA and RPV-LA demonstrated safety profiles comparable with those of the placebo in terms of adverse event-related withdrawal. Moreover, the efficacy data showed that CAB-LA had a better effect on HIV-1 prevention than tenofovir disoproxil fumarate-emtricitabine (17/5161, 0.33% vs 75/5129, 1.46%; RR 0.21, 95% CI 0.07-0.61; I=70%). Although CAB-LA+RPV-LA had more drug-related adverse events (556/681, 81.6% vs 37/598, 6.2%; RR 12.50, 95% CI 3.98-39.23; I=85%), a mild or moderate injection site reaction was the most common reaction, and its frequency decreased over time. The efficacy of CAB-LA+RPV-LA was comparable with that of daily oral drugs at 48 and 96 weeks (1302/1424, 91.43% vs 915/993, 92.2%; RR 0.99, 95% CI 0.97-1.02; I=0%), and a high level of virological suppression of 80.9% (186/230) was maintained even after 5 years of LA-ARV use. Similar efficacy outcomes were observed in both treatment-naive and treatment-experienced patients (849/911, 93.2% vs 615/654, 94%; RR 0.99, 95% CI 0.96-1.02; I=0%). According to the questionnaires, more than 85% of people living with HIV favored LA-ARVs.
CONCLUSIONS
LA-ARVs showed favorable safety profiles for both the prevention and treatment of HIV-1 infection and were well tolerated. CAB-LA has more satisfactory efficacy than tenofovir disoproxil fumarate-emtricitabine, significantly reducing the rate of HIV-1 infection. CAB-LA+RPV-LA maintains virological suppression for a long time and may be a viable switching strategy with enhanced public health benefits by reducing transmission. However, further trials are required to confirm the efficacy of these drugs.
Topics: Humans; Anti-HIV Agents; Emtricitabine; HIV Infections; HIV-1; Tenofovir
PubMed: 37498645
DOI: 10.2196/46767 -
Supportive care and antiviral treatments in primary herpetic gingivostomatitis: a systematic review.Clinical Oral Investigations Nov 2023Herpes simplex virus 1 (HSV-1) is the main pathogen responsible for herpes infections. In 13-30% of the cases, primary HSV-1 leads to the primary herpetic... (Review)
Review
OBJECTIVES
Herpes simplex virus 1 (HSV-1) is the main pathogen responsible for herpes infections. In 13-30% of the cases, primary HSV-1 leads to the primary herpetic gingivostomatitis (PHGS), often a self-limiting infection; however, it can limit the ability to drink/eat with, sometimes, the need for hospitalization. Multiple therapeutic methods have been proposed. This systematic review aims to collect and critically appraise the available evidence about the clinical management of PHGS.
MATERIALS AND METHODS
Literature search including three databases (PubMed, Scopus, Embase), study design, and data analysis were performed following PRISMA guidelines, according to the PICO tool (PROSPERO n° CRD42023391386). Risk of bias was assessed with RoB 2 and ROBINS-I.
RESULTS
Five studies on a total of 364 patients (average age: 7.6 years) were identified. The treatment regimens were summarized in acyclovir; acyclovir + honey; fluids and analgesic; maalox + diphenhydramine; lidocaine; chlorhexidine (CHX); CHX + ialuronic acid; CHX + Mucosyte®; antimicrobial photodynamic therapy (aPDT); topical antiviral; topical antiviral + aPDT; and others.
CONCLUSIONS
Although PHGS is a disease with a high worldwide prevalence, the lack of consensus about therapeutic management indicates gaps in existing evidence. Most of the proposed treatment consists in symptomatic drugs with empiric regimens which are ineffective for the viral replication. The main limit to realize randomized clinical trial is due to the rapid onset and remission of the disease. In fact, the diagnostic delay, estimated in 72 h, decreases the effectiveness of any antiviral drugs.
CLINICAL RELEVANCE
Out of the five studies included in this systematic review, only one was able to provide some weak evidence that ACV is an effective treatment, improving healing of oral lesions and reducing duration of symptoms.
Topics: Humans; Child; Stomatitis, Herpetic; Delayed Diagnosis; Antiviral Agents; Acyclovir; Lidocaine; Randomized Controlled Trials as Topic
PubMed: 37733027
DOI: 10.1007/s00784-023-05250-5 -
Journal of Infection and Chemotherapy :... Mar 2024Baloxavir marboxil (BXM), a newly developed cap-dependent endonuclease inhibitor, is widely used to treat influenza virus infections in inpatients and outpatients. A... (Meta-Analysis)
Meta-Analysis
Comparison of clinical efficacy and safety of baloxavir marboxil versus oseltamivir as the treatment for influenza virus infections: A systematic review and meta-analysis.
INTRODUCTION
Baloxavir marboxil (BXM), a newly developed cap-dependent endonuclease inhibitor, is widely used to treat influenza virus infections in inpatients and outpatients. A previous meta-analysis included only outpatients and patients suspected of having an influenza virus infection based on clinical symptoms. However, whether BXM or oseltamivir is safer and more effective for inpatients remains controversial. Therefore, we conducted a systematic review and meta-analysis validating the effectiveness and safety of BXM versus oseltamivir in inpatients with influenza virus.
METHODS
The Scopus, EMBASE, PubMed, Ichushi, and CINAHL databases were systematically searched for articles published until January 2023. The outcomes were mortality, hospitalization period, incidence of BXM- or oseltamivir-related adverse events, illness duration, and changes of virus titers and viral RNA load in patients with influenza virus infections.
RESULTS
Two randomized controlled trials with 1624 outpatients and two retrospective studies with 874 inpatients were enrolled. No deaths occurred in outpatients treated with BXM or oseltamivir. Among inpatients, BXM reduced mortality (p = 0.06) and significantly shortened hospitalization period (p = 0.01) compared to oseltamivir. In outpatients, BXM had a significantly lower incidence of adverse events (p = 0.03), reductions in influenza virus titers (p < 0.001) and viral RNA loads (p < 0.001), and a tendency to be a shorter illness duration compared with that of oseltamivir (p = 0.27).
CONCLUSIONS
Our meta-analysis showed that BXM was safer and more effective in patients than oseltamivir; thus, supporting the use of BXM for the initial treatment of patients with proven influenza virus infection.
Topics: Humans; Oseltamivir; Influenza, Human; Retrospective Studies; Antiviral Agents; Oxazines; Pyridines; Thiepins; Orthomyxoviridae Infections; Treatment Outcome; RNA, Viral; Dibenzothiepins; Morpholines; Pyridones; Triazines
PubMed: 37866622
DOI: 10.1016/j.jiac.2023.10.017 -
Lancet (London, England) Aug 2023The risk of sexual transmission of HIV from individuals with low-level HIV viraemia receiving antiretroviral therapy (ART) has important public health implications,...
BACKGROUND
The risk of sexual transmission of HIV from individuals with low-level HIV viraemia receiving antiretroviral therapy (ART) has important public health implications, especially in resource-limited settings that use alternatives to plasma-based viral load testing. This Article summarises the evidence related to sexual transmission of HIV at varying HIV viral load levels to inform messaging for people living with HIV, their partners, their health-care providers, and the wider public.
METHODS
We conducted a systematic review and searched PubMed, MEDLINE, Cochrane Central Register of Controlled Trials, Embase, Conference Proceedings Citation Index-Science, and WHO Global Index Medicus, for work published from Jan 1, 2010 to Nov 17, 2022. Studies were included if they pertained to sexual transmission between serodiscordant couples at various levels of viraemia, the science behind undetectable=untransmittable, or the public health impact of low-level viraemia. Studies were excluded if they did not specify viral load thresholds or a definition for low-level viraemia or did not provide quantitative viral load information for transmission outcomes. Reviews, non-research letters, commentaries, and editorials were excluded. Risk of bias was evaluated using the ROBINS-I framework. Data were extracted and summarised with a focus on HIV sexual transmission at varying HIV viral loads.
FINDINGS
244 studies were identified and eight were included in the analysis, comprising 7762 serodiscordant couples across 25 countries. The certainty of evidence was moderate; the risk of bias was low. Three studies showed no HIV transmission when the partner living with HIV had a viral load less than 200 copies per mL. Across the remaining four prospective studies, there were 323 transmission events; none were in patients considered stably suppressed on ART. Among all studies there were two cases of transmission when the index patient's (ie, patient with previously diagnosed HIV infection) most recent viral load was less than 1000 copies per mL. However, interpretation of both cases was complicated by long intervals (ie, 50 days and 53 days) between the transmission date and the most recent index viral load result.
INTERPRETATION
There is almost zero risk of sexual transmission of HIV with viral loads of less than 1000 copies per mL. These data provide a powerful opportunity to destigmatise HIV and promote adherence to ART through dissemination of this positive public health message. These findings can also promote access to viral load testing in resource-limited settings for all people living with HIV by facilitating uptake of alternative sample types and technologies.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Humans; HIV Infections; Anti-HIV Agents; Prospective Studies; Viremia; Viral Load
PubMed: 37490935
DOI: 10.1016/S0140-6736(23)00877-2 -
Journal of Obstetrics and Gynaecology :... Dec 2023Pregnant women are one of the endangered groups who need special attention in the COVID-19 epidemic. We conducted a systematic review and summarised the studies that... (Meta-Analysis)
Meta-Analysis
Pregnant women are one of the endangered groups who need special attention in the COVID-19 epidemic. We conducted a systematic review and summarised the studies that reported adverse pregnancy outcomes in pregnant women with COVID-19 infection. A literature search was performed in PubMed and Scopus up to 1 September 2022, for retrieving original articles published in the English language assessing the association between COVID-19 infection and adverse pregnancy outcomes. Finally, in this review study, of 1790 articles obtained in the initial search, 141 eligible studies including 1,843,278 pregnant women were reviewed. We also performed a meta-analysis of a total of 74 cohort and case-control studies. In this meta-analysis, both fixed and random effect models were used. Publication bias was also assessed by Egger's test and the trim and fill method was conducted in case of a significant result, to adjust the bias. The result of the meta-analysis showed that the pooled prevalence of preterm delivery, maternal mortality, NICU admission and neonatal death in the group with COVID-19 infection was significantly more than those without COVID-19 infection (<.01). A meta-regression was conducted using the income level of countries. COVID-19 infection during pregnancy may cause adverse pregnancy outcomes including of preterm delivery, maternal mortality, NICU admission and neonatal death. Pregnancy loss and SARS-CoV2 positive neonates in Lower middle income are higher than in High income. Vertical transmission from mother to foetus may occur, but its immediate and long-term effects on the newborn are unclear.
Topics: Female; Humans; Infant, Newborn; Pregnancy; COVID-19; Infectious Disease Transmission, Vertical; Perinatal Death; Pregnancy Complications, Infectious; Pregnancy Outcome; Premature Birth; SARS-CoV-2; Maternal Mortality; Intensive Care Units, Neonatal; Patient Admission
PubMed: 36651606
DOI: 10.1080/01443615.2022.2162867 -
Journal of Travel Medicine Sep 2023Viral load dynamics and shedding kinetics are critical factors for studying infectious diseases. However, evidence on the viral dynamics of mpox remains limited and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Viral load dynamics and shedding kinetics are critical factors for studying infectious diseases. However, evidence on the viral dynamics of mpox remains limited and inconclusive. Thus, we aimed to provide a comprehensive understanding of the viral load and viability of the re-emerged mpox virus since 2022.
METHODS
For this systematic review and meta-analysis, we searched PubMed/MEDLINE, Embase and Google Scholar for published articles that are related to mpox viral dynamics up to April 2023.
RESULTS
From 19 studies, 880 samples and 1477 specimens were collected. The pooled median Ct values appeared in the following order: skin lesion [Ct value 21.7 (IQR 17.8-25.5)], anorectal [22.3 (16.9-27.6)], saliva [25.9 (22.5-31.1)], oral [29.0 (24.5-32.8)], semen [29.6 (25.9-33.4)], urine [30.5 (24.6-36.4)], pharyngeal [31.9 (26.5-37.3)], urethra [33.0 (28.0-35.0)] and blood [33.2 (30.4-36.1)]. People living with human immunodeficiency virus (HIV) have a lower Ct value in the skin [skin HIV+, 19.2 (18.3-20.0) vs skin HIV-, 25.4 (21.2-29.0)]. From the Ct values and test day since symptom onset, we identified temporal trends of viral load for each specimen type. Changes in the trend were observed at 4 days in saliva, 5 days in blood, 6 days in skin, 7 days in anorectal, urine, semen and pharyngeal and 8 days in the urethra. We determined optimal Ct cutoff values for anorectal (34.0), saliva (27.7) and urethra (33.0) specimens, where a Ct value above each cutoff suggests minimal viral viability. Using these cutoff values, we derived the duration of viable viral isolation in each specific specimen type (anorectal 19 days, saliva 14 days and urethra 14 days).
CONCLUSION
Skin lesion, anorectal and saliva samples contained the highest viral load. The peak viral load manifests within 4-8 days after symptom onset, and viable virus detection was presumed to cease within 14-19 days from symptom onset in anorectal, saliva and urethral samples.
Topics: Humans; Viral Load; Kinetics; Mpox (monkeypox); Semen; HIV Infections
PubMed: 37581603
DOI: 10.1093/jtm/taad111 -
Viruses Aug 2023Co-infection is an underappreciated phenomenon in contemporary disease ecology despite its ubiquity and importance in nature. Viruses, and other co-infecting agents, can... (Review)
Review
Co-infection is an underappreciated phenomenon in contemporary disease ecology despite its ubiquity and importance in nature. Viruses, and other co-infecting agents, can interact in ways that shape host and agent communities, influence infection dynamics, and drive evolutionary selective pressures. Bats are host to many viruses of zoonotic potential and have drawn increasing attention in their role as wildlife reservoirs for human spillover. However, the role of co-infection in driving viral transmission dynamics within bats is unknown. Here, we systematically review peer-reviewed literature reporting viral co-infections in bats. We show that viral co-infection is common in bats but is often only reported as an incidental finding. Biases identified in our study database related to virus and host species were pre-existing in virus studies of bats generally. Studies largely speculated on the role co-infection plays in viral recombination and few investigated potential drivers or impacts of co-infection. Our results demonstrate that current knowledge of co-infection in bats is an ad hoc by-product of viral discovery efforts, and that future targeted co-infection studies will improve our understanding of the role it plays. Adding to the broader context of co-infection studies in other wildlife species, we anticipate our review will inform future co-infection study design and reporting in bats. Consideration of detection strategy, including potential viral targets, and appropriate analysis methodology will provide more robust results and facilitate further investigation of the role of viral co-infection in bat reservoirs.
Topics: Animals; Animals, Wild; Biological Evolution; Chiroptera; Coinfection; Virus Diseases
PubMed: 37766267
DOI: 10.3390/v15091860 -
Frontiers in Microbiology 2023Human cytomegalovirus (HCMV) is one of the main causes of serious complications in immunocompromised patients and after congenital infection. There are currently drugs... (Review)
Review
Human cytomegalovirus (HCMV) is one of the main causes of serious complications in immunocompromised patients and after congenital infection. There are currently drugs available to treat HCMV infection, targeting viral polymerase, whose use is complicated by toxicity and the emergence of resistance. Maribavir and letermovir are the latest antivirals to have been developed with other targets. The approval of letermovir represents an important innovation for CMV prevention in hematopoietic stem cell transplant recipients, whereas maribavir allowed improving the management of refractory or resistant infections in transplant recipients. However, in case of multidrug resistance or for the prevention and treatment of congenital CMV infection, finding new antivirals or molecules able to inhibit CMV replication with the lowest toxicity remains a critical need. This review presents a range of molecules known to be effective against HCMV. Molecules with a direct action against HCMV include brincidofovir, cyclopropavir and anti-terminase benzimidazole analogs. Artemisinin derivatives, quercetin and baicalein, and anti-cyclooxygenase-2 are derived from natural molecules and are generally used for different indications. Although they have demonstrated indirect anti-CMV activity, few clinical studies were performed with these compounds. Immunomodulating molecules such as leflunomide and everolimus have also demonstrated indirect antiviral activity against HCMV and could be an interesting complement to antiviral therapy. The efficacy of anti-CMV immunoglobulins are discussed in CMV congenital infection and in association with direct antiviral therapy in heart transplanted patients. All molecules are described, with their mode of action against HCMV, preclinical tests, clinical studies and possible resistance. All these molecules have shown anti-HCMV potential as monotherapy or in combination with others. These new approaches could be interesting to validate in clinical trials.
PubMed: 38053548
DOI: 10.3389/fmicb.2023.1321116