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Objectives We assessed the effect of inactivated COVID-19 vaccine boosting immunization on the viral shedding time for patients infected with the Omicron variant BA.2.Methods We performed a real-world study by analyzing outbreak data of patients infected with the COVID-19 Omicron variant BA.2 from March to May 2022 in Shanghai, China. Patients were categorized into three groups, including not fully vaccinated (0 and 1 dose), fully vaccinated (2 doses), and booster-vaccinated (3 doses).Results A total of 4443 patients infected with COVID-19 were included in the analysis.

Puumala virus (PUUV) is a hantavirus causing haemorrhagic fever with renal syndrome. Studies showing an increased risk of lymphoid malignancies following hantavirus infection, together with the observation that PUUV infects B cells motivated us to study the risk of lymphoid malignancies following PUUV infection.

This winter is particularly noteworthy, as common viruses are making a resurgence and spreading at an alarming rate, with an unprecedented outbreak of Respiratory Syncytial Virus (RSV) currently ongoing. It is important to remember that RSV can also pose a significant threat to the elderly and those with underlying health conditions [1], which is often overlooked given the focus on bronchiolitis in healthy children and the associated risk of hospitalization [2]. This is particularly concerning, as RSV is believed to be responsible for 14,000 deaths per year in the USA for people aged 65 and over; and it is estimated to cause the deaths of approximately 100,000 children worldwide annually.

The World Health Organization (WHO) estimated that about 10.6 million people fell ill with tuberculosis (TB) worldwide in 2021, equivalent to 134 cases per 100,000 inhabitants [1-3]. Children aged under 15 years account for about 11% of TB cases, meaning >1 million new pediatric cases in 2021 [1, 3]. There were an estimated 1.6 million deaths due to TB in 2021, of which 14% involved children [1, 3]. Up to 80% of deaths occurred in children aged under 5 years [4].

Coronavirus Disease-19 (COVID 19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) are the two leading causes of death in the world [1–3].

fHbp is a virulence factor expressed by the human-specific pathogen N. meningitidis, a leading cause of meningitis and sepsis worldwide which frequently asymptomatically colonizes the human upper airway. fHbp binds human CFH, a negative regulator of the complement system, and has multiple roles during meningococcal infection. fHbp was initially identified as a vaccine antigen, named GNA1870 [1] or LP2086 [2]. It was then shown that the meningococcus binds CFH to its surface via an ~33 kDa protein, promoting bacterial survival in serum [3].

There is a scarcity of data on outcomes and predictors of therapeutic failure of mAbs in frail COVID-19 patients.

AbstractBackgroundALPK1 agonist has recently been reported to demonstrate anti-HBV efficacy via activating NF-κB signaling, which is crucial for maximizing interferon responses. Here, we investigated the impact of ALPK1 on HBV replication, and explored ALPK1 variants for predicting PegIFNα treatment response.MethodsThe potential anti-HBV effect of ALPK1 was evaluated in HBV-integrated and HBV-infected hepatoma cells. The potentially functional genetic variants of ALPK1 were screened out and their correlations with PegIFNα treatment response were assessed in 945 HBeAg-positive chronic hepatitis B (CHB) patients.ResultsWe revealed that ALPK1 inhibited HBV replication in hepatocytes via activating the JAK-STAT pathway. ALPK1 overexpression improved the anti-HBV effect of IFNα in cell models. A missense variant, rs35389530 (P660L), of ALPK1 was strongly associated with combined response (CR, namely HBeAg seroconversion and HBV DNA level <3.3log10IU/ml) to PegIFNα treatment in CHB patients (P = 2.12 × 10−6). Moreover, a polygenic score (PGS) integrating ALPK1_rs35389530 and two additional genetic variants was further significantly associated with CR (Ptrend = 9.28 × 10−7), HBsAg level (Ptrend = 0.0002), and HBsAg loss (Ptrend = 0.025).ConclusionsThe anti-HBV effects of ALPK1 through activating JAK-STAT pathway provides a new perspective for CHB therapy. ALPK1_rs35389530 and PGS are potential biomarkers to predict PegIFNα treatment response and may be utilized for optimizing CHB treatment.

AbstractInfection with intestinal whipworms (Trichuris spp.) causes widespread morbidity and may alter responses to enteric and extraintestinal co-infections. Here, we show that Trichuris muris infection in mice increases co-infection with two evolutionary divergent enteric pathogens, the bacterium Citrobacter rodentium and the helminth Heligmosomoides polygyrus. Co-infection caused reduced weight gain and promoted type-1-biased inflammation. In contrast, T. muris-infected mice were more resistant to migrating Ascaris suum larvae in the lungs. Our results highlight the divergent nature of pathogen interactions, and suggest that whipworm infection is a risk-factor for co-infections with other pathogens within the gastrointestinal tract.

AbstractInpatient direct oral challenge programs are increasingly deployed as part of antimicrobial stewardship (AMS) initiatives to reduce the burden and impacts of penicillin allergy labels on antibiotic prescribing. Using data from a prospective multicentre cohort inpatient penicillin allergy program, we identify the key targets for delabeling to aid health service implementation.

AbstractBackgroundLaboratory tests to diagnose neurosyphilis using cerebrospinal fluid (CSF) are currently disadvantageous as a lumbar puncture is required, which may result in patients with neurosyphilis missing an opportunity for early diagnosis. Thus, blood biomarker candidates that are more convenient and minimally invasive to collect for diagnosing neurosyphilis is urgently needed.MethodsThis observational study aimed to analyze serum ubiquitin C-terminal hydrolase-L1 (UCH-L1), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NF-L) levels in 153 patients without HIV and to evaluate their diagnostic performance in neurosyphilis compared with CSF.ResultsSerum UCH-L1, GFAP, and NF-L levels were significantly higher in patients with neurosyphilis compared with patients with uncomplicated syphilis or non-syphilis. For the diagnosis of neurosyphilis, serum UCH-L1, GFAP, and NF-L revealed sensitivities of 90.20%, 80.40%, and 88.24%, and specificities of 92.16%, 78.43%, and 80.39%, respectively, at cut-off levels of 814.50 pg/mL, 442.70 pg/mL, and 45.19 pg/mL, respectively. In patients with syphilis, serum UCH-L1, GFAP, and NF-L levels correlated strongly or moderately with those in the CSF, with similar or better diagnostic performance than those in the CSF. The testing algorithms’ sensitivity and specificity increased to 98.04% and 96.08%, respectively, when subjected to parallel and combination testing, respectively.ConclusionTo avoid lumbar puncture, each serum UCH-L1, GFAP, and NF-L is a good entry point and biomarker candidate for the diagnosis of neurosyphilis among patients without HIV. These proteins used in concerto can further improve the diagnostic sensitivity and specificity.

AbstractThe human gut harbors native microbial communities, forming a highly complex ecosystem. Synthetic microbial communities (SynComs) of the human gut are an assembly of microorganisms isolated from human mucosa or fecal samples. In recent decades, the ever-expanding culturing capacity and affordable sequencing, together with advanced computational modeling, started a ‘‘golden age’’ for harnessing the beneficial potential of SynComs to fight gastrointestinal disorders, such as infections and chronic inflammatory bowel diseases. As simplified and completely defined microbiota, SynComs offer a promising reductionist approach to understanding the multi-species and multi-kingdom interactions in the microbe-host-immune axis. However, there are still many challenges to overcome before we can precisely construct SynComs of designed function and efficacy that allow the translation of scientific findings to patients' treatments. Here we discussed the strategies used to design, assemble, and test a SynCom, and address the significant challenges, which are of microbiological, engineering, and translational nature, that stand in the way of using SynComs as live bacterial therapeutics.

Chora and colleagues show that infection of the liver by Plasmodium modulates severity of disease in the experimental cerebral malaria (ECM) model by generating gamma delta (ɣδ) T cells that produce IL-17. This work calls into question the long-standing assumption that liver infection does not modulate severity of malaria.

Parasite worms or helminths (see Glossary) are parasites of almost all vertebrates, including humans as well as wild and domestic mammals. Globally, helminths affect nearly a quarter of the human population, essentially infecting individuals living under poor hygienic conditions in low- and middle-income countries [1]. Such an epidemiologic situation explains the large geographic overlap between regions where helminth infections are endemic and areas where diseases caused by heterologous agents such as tuberculosis, malaria, or infection by HIV are prevalent.

Microbial communities that degrade natural polysaccharides are thought to have a hierarchical organization and one-way positive interactions from higher to lower trophic levels. Daniels et al. have recently shown that reciprocal interactions between trophic levels can occur and that these interactions change over the duration of a batch culture.

Abstract Purpose Overweight and obesity have increased in people living with HIV (PLH). Our study evaluated weight, body-mass-index (BMI), and waist-to-hip ratio (WHR) change over 5 years of follow-up in PLH compared to the general population. Methods HIV-positive participants in the HIV Heart Aging (HIVH) study were matched 1:2 by age and sex with HIV-negative controls of the population-based Heinz Nixdorf Recall (HNR) study. Both studies were recruited in the German Ruhr area. The association between HIV and weight, BMI, and WHR changes was examined using linear regression. Regression models were adjusted for parameters potentially affecting weight gain. Results The matched HIVH and HNR participants (N = 585 and N = 1170, respectively; 14.7% females) had a mean age of 55 years at baseline. Despite the lower baseline weight (− 6 kg, 95% CI − 7.46 to − 4.59), the linear regression showed greater absolute and relative weight and BMI increases after 5 years in HIVH compared to HNR. Adjusting the linear regression models for smoking amplified that HIVH had a higher absolute and relative weight difference of 0.7 kg or ~ 1% compared to HNR after 5 years (95% Cl 0.1 to 1.3 and 0.2 to 1.6, respectively). Adjusting for HDL, LDL, systolic blood pressure, and diabetes mellitus did not affect the results. Conclusions PLH had lower weight than the general population at baseline and after 5 years, but experienced greater increases in body weight after 5 years. WHR change after 5 years was lower in PLH compared to the general population, despite a higher WHR at baseline. …

Abstract Purpose Lung transplant (LTx) recipients are at risk for poor outcomes from coronavirus disease 2019 (COVID-19). The aim of the study was to assess the outcome of patients receiving pre-exposure prophylaxis (PrEP) with tixagevimab and cilgavimab after LTx. Methods All LTx recipients with outpatient visits from February 28th to October 31st, 2022 at two German centers were included. Baseline characteristics were recorded and patients followed until November 30rd, 2022. Infections with SARS-CoV-2, disease severity, and COVID-19-associated death were compared between patients with and without PrEP. Results In total, 1438 patients were included in the analysis, and 419 (29%) received PrEP. Patients receiving PrEP were older and earlier after transplantation, had lower glomerular filtration rates, and lower levels of SARS-CoV-2-S antibodies. In total, 535 patients (37%) developed SARS-CoV-2 infection during a follow-up of median of 209 days. Fewer infections occurred in patients with PrEP during the study period (31% vs. 40%, p = 0.004). Breakthrough SARS-CoV-2 infections after PrEP occurred in 77 patients (19%). In total, 37 infections (8%) were severe or critical. No difference in severity of COVID-19 was observed between patients with and without PrEP. There were 15 COVID-19-associated deaths (n = 1 after PrEP). Compared to matched controls, there was a non-significant difference towards a lower risk for moderate to critical COVID-19 (p 0.184). Conclusion The number of SARS-CoV-2 infections was lower in LTx recipients with PrEP. Despite being at higher risk for worse outcome severity of COVID-19 and associated mortality were similar in patients with and without PrEP. …

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Abstract HIV-1 remains a global health concern and to date, nearly 38 million people are living with HIV. The complexity of HIV-1 pathogenesis and its subsequent prevalence is influenced by several factors including the HIV-1 subtype. HIV-1 subtype variation extends to sequence variation in the amino acids of the HIV-1 viral proteins. Of particular interest is the transactivation of transcription (Tat) protein due to its key function in viral transcription. The Tat protein predominantly functions by binding to the transactivation response (TAR) RNA element to activate HIV-1 transcriptional elongation. Subtype-specific Tat protein sequence variation influences Tat-TAR binding affinity. Despite several studies investigating Tat-TAR binding, it is not clear which regions of the Tat protein and/or individual Tat amino acid residues may contribute to TAR binding affinity. We, therefore, conducted a scoping review on studies investigating Tat-TAR binding. We aimed to synthesize the published data to determine (1) the regions of the Tat protein that may be involved in TAR binding, (2) key Tat amino acids involved in TAR binding and (3) if Tat subtype-specific variation influences TAR binding. A total of thirteen studies met our inclusion criteria and the key findings were that (1) both N-terminal and C-terminal amino acids outside the basic domain (47–59) may be important in increasing Tat-TAR binding affinity, (2) substitution of the amino acids Lysine and Arginine (47–59) resulted in a reduction in binding affinity to TAR, and (3) none of the included studies have investigated Tat subtype-specific substitutions and therefore no commentary could be made regarding which subtype may have a higher Tat-TAR binding affinity. Future studies investigating Tat-TAR binding should therefore use full-length Tat proteins and compare subtype-specific variations. Studies of such a nature may help explain why we see differential pathogenesis and prevalence when comparing HIV-1 subtypes.…

Abstract Background In yellow fever (YF) endemic areas, measles, mumps, and rubella (MMR), and YF vaccines are often co-administered in childhood vaccination schedules. Because these are live vaccines, we assessed potential immune interference that could result from co-administration. Methods We conducted an open-label, randomized non-inferiority trial among healthy 1-year-olds in Misiones Province, Argentina. Children were randomized to one of three groups (1:1:1): Co-administration of MMR and YF vaccines (MMR1YF1), MMR followed by YF vaccine four weeks later (MMR1YF2), or YF followed by MMR vaccine four weeks later (YF1MMR2). Blood samples obtained pre-vaccination and 28 days post-vaccination were tested for immunoglobulin G antibodies against measles, mumps, and rubella, and for YF virus-specific neutralizing antibodies. Non-inferiority in seroconversion was assessed using a -5% non-inferiority margin. Antibody concentrations were compared with Kruskal-Wallis tests. Results Of 851 randomized children, 738 were correctly vaccinated, had ≥ 1 follow-up sample, and were included in the intention-to-treat population. Non-inferior seroconversion was observed for all antigens (measles seroconversion: 97.9% in the MMR1YF1 group versus 96.3% in the MMR1YF2 group, a difference of 1.6% [90% CI -1.5, 4.7]; rubella: 97.9% MMR1YF1 versus 94.7% MMR1YF2, a difference of 3.3% [-0.1, 6.7]; mumps: 96.7% MMR1YF1 versus 97.9% MMR1YF2, a difference of -1.3% [-4.1, 1.5]; and YF: 96.3% MMR1YF1 versus 97.5% YF1MMR2, a difference of -1.2% [-4.2, 1.7]). Rubella antibody concentrations and YF titers were significantly lower following co-administration; measles and mumps concentrations were not impacted. Conclusion Effective seroconversion was achieved and was not impacted by the co-administration, although antibody levels for two antigens were lower. The impact of lower antibody levels needs to be weighed against missed opportunities for vaccination to determine optimal timing for MMR and YF vaccine administration. Trial Registration The study was retrospectively registered in ClinicalTrials.gov (NCT03368495) on 11/12/2017. …

Abstract Background Several studies have shown different effects of telehealth interventions on adherence to Antiretroviral therapy (ART) among people living with HIV. This study conducted a meta-analysis of Randomized Controlled Trials (RCTs) to estimate the pooled effect of telehealth interventions on the treatment adherence of HIV patients. Methods The researchers conducted literature searches in Scopus, PubMed, Web of Science, Google Scholar, and Cochrane Central Register of Controlled Trials databases. In addition, open grey was systematically searched until January 2022 for RCTs around the effects of telehealth on adherence to treatment ART among patients with HIV. Each study’s methodological quality was assessed using the Cochrane Collaboration tool. Pooled Standard Mean Differences (SMD) and Risk Ratio (RR) with 95% CI were calculated using the random effects model. Results In total, 12 eligible articles were considered in the present systematic review. A random-effects meta-analysis using 5 RCTs yielded the pooled RR estimate of 1.18 (95% CI: 1.03 to 1.35, p < 0.05); I2 = 0, suggesting the adherence to treatment among patients with HIV who received telehealth intervention was significantly 18% upper than control groups. Moreover, the random effects analysis of SMD showed a positive effect for telehealth with SMR = 0.36 (95% CI: 0.22 to 0.49, p < 0.05); I2 = 91.9%, indicating that telehealth intervention increased ART adherence to the treatment group compared to the control group. Conclusion Telehealth intervention as a new modality of health care service delivery could be a valuable strategy to improve ART adherence among patients with HIV. It can strengthen the capacity of HIV care services. On a large scale, telehealth can be utilized as a supplementary component for ART delivery and retention toward successful adherence to the therapy. …

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) usually demonstrates multi-organ injury with a high mortality rate. This study aimed to investigate associations of serum aspartate/alanine aminotransferase (AST)/ALT, cytosolic AST (cAST)/ALT and mitochondrial AST (mAST)/ALT ratios with the prognosis of SFTS patients. Methods A total of 355 confirmed SFTS patients were included. Clinical and laboratory data were compared between survivors and nonsurvivors. Logistic regression analysis was used to assess the independent risk factors for fatality in all patients and those admitted to the intensive care unit (ICU). The predictive values of the risk factors and constructed risk models were evaluated. Results Mean age and biochemical parameters were significantly greater in nonsurvivors than in survivors. In ICU patients, the three ratios, high-sensitivity troponin I (hsTnI), creatine kinase (CK), lactate dehydrogenase (LDH) and α-hydroxybutyrate dehydrogenase (α-HBDH) were elevated markedly in nonsurvivors than in survivors. Multivariate logistic regression analysis showed that age, three ratios and α-HBDH were independent risk factors for mortality in all patients. Only the three ratios were independent risk factors for death in ICU patients. Risk Models (M1, M2 and M3) and simplified models (sMs) containing the three ratios respectively had comparatively high predictive values for fatality in all patients with area under ROC curves (AUCs) > 0.85. In ICU patients, mAST/ALT ratio had the highest predictive value, sensitivity and odds ratio (OR) for mortality among three ratios. Conclusion AST/ALT, cAST/ALT and mAST/ALT ratios were associated with unfavorable clinical outcome of SFTS. The prognostic value of mAST/ALT ratio was higher in severe cases. …

Abstract Brucellosis is highly contagious zoonotic bacterial disease caused by gram-negative genus. It has a wide spectrum of clinical manifestations and due to variety and nonspecificity of clinical signs the diagnostics can be very complicated. We present a clinical case of severe chronic brucellosis in a 5-years old boy with long-term course of disease and multiorgan involvement. A different complication of brucellosis including severe syndrome of inappropriate ADH secretion (SIADH) are discussed. Despite severe course of disease patient achieved significant clinical improvement due to multidisciplinary approach and optimal etiotropic and pathogenetic treatment.…

Abstract Background Anthrax is a zoonotic disease caused by the Bacillus anthracis bacteria, which is one of the top five important livestock diseases and the second top priority zoonotic disease, next to rabies, in Ethiopia, which remains a major problem for animals and public health in Ethiopia. This study was conducted to verify the existence of the outbreak, determine risk factors, and implement measures to control the anthrax outbreak in Farta woreda, South Gondar zone, Northwest Ethiopia in 2019. Methods A community-based case-control study was conducted from March 25 to April 1, 2019. A structured questionnaire was used to collect data and for review of documents and discussion with livestock and health office staff. The collected data were analyzed by SPSS and presented in tables and graphs. Results A total of 20 human anthrax cases with an attack rate of 2.5 per 1000 population were reported from the affected kebele. The age of the cases ranged from 1 month to 65 years (median age = 37.5 years). Of the total cases, 66.7% were male and 77.8% were 15 and older. The probability of developing anthrax among people who had unvaccinated animals was higher than in those who didn’t have unvaccinated animals with an AOR = 8.113 (95% CI 1.685–39.056) and the probability of getting anthrax in relation to people’s awareness of anthrax was AOR = 0.114 (95% CI 0.025–0.524). Conclusion An anthrax outbreak occurred in Wawa Mengera Kebele of Farta woreda. The presence of unvaccinated animals in a household was found to be a risk factor for anthrax cases. Timely animal vaccination and strengthening health education on the vaccination of animals, mode of transmission, and disposal of dead animals are essential for preventing anthrax cases. …

Abstract Background Exposure during pregnancy to malaria and sexually-transmitted infections is associated with adverse birth outcomes including low birth weight (LBW). This study aimed at assessing if the adjunction of two doses of azithromycin to sulfadoxine-pyrimethamine for the intermittent preventive treatment of malaria in pregnancy can reduce LBW. Methods A two parallel-groups, open-label randomized controlled trial involving pregnant women (16 to 35 years of age and 12 to 24 weeks of gestation as confirmed by last menstrual period or fundal height) was conducted in rural Burkina Faso. Women were assigned in a 1:1 ratio either to use azithromycin (1 g daily for 2 days) during the second and third trimesters of pregnancy plus monthly sulfadoxine-pyrimethamine (1500/75 mg) (SPAZ) (intervention) or to continue using a monthly sulfadoxine-pyrimethamine (1500/75 mg) (SP) (control). Primary outcome was a LBW (birth weight measured within 24 h after birth < 2500 g). Secondary outcomes including stillbirth, preterm birth or miscarriage are reported together with safety data. Results A total of 992 pregnant women underwent randomization (496 per group) and 898 (90.5%) valid birth weights were available (450 in SPAZ and 448 in SP). LBW incidence was 8.7% (39/450) in SPAZ and 9.4% (42/448) in controls (p-value = 0.79). Compared with controls, pregnant women with SPAZ showed a risk ratio (RR) of 1.16 (95% confidence interval (CI 0.64–2.08]) for preterm births, 0.75 (95% CI 0.17–3.35) for miscarriage and 0.64 (95% CI 0.25–1.64) for stillbirths. No treatment-related serious adverse events (SAEs) have been observed, and there was no significant difference in the number of SAEs (13.5% [67/496] in SPAZ, 16.7% [83/496] in SP, p-value = 0.18) or AEs (17.1% [85/496] in SPAZ, 18.8% [93/496] in SP, p-value = 0.56). Conclusion Adequate prevention regimen with monthly sulfadoxine-pyrimethamine given to all pregnant women has been proved to reduce the risk of LBW in malaria endemic areas. Adding azithromycin to the regimen does not offer further benefits, as far as women receive a malaria prevention regimen early enough during pregnancy. Trial registration Pan African Clinical Trial Registry (https://pactr.samrc.ac.za/Search.aspx): PACTR201808177464681. Registered 21 August 2018. …

The nirsevimab binding site was highly conserved between 1956 and 2021. Nirsevimab escape variants were rare and have not increased over time.

ObjectivesThe COVID-19 pandemic has highlighted insufficiencies and gaps within healthcare systems globally. In most countries, including high-income countries, healthcare facilities were over-run and occupied with too few resources beyond capacity. We carried out a systematic review with a primary aim to identify the influence of the COVID-19 pandemic on the presentation and treatment of stroke globally in populations≥65 years of age.DesignA systematic review was completed. In total, 38 papers were included following full-text screening.Data sourcesPubMed, MEDLINE and Embase.Eligibility criteriaEligible studies included observational and real-world evidence publications with a population who have experienced stroke treatment during the COVID-19 pandemic. Exclusion criteria included studies comparing the effect of the COVID-19 infection on stroke treatment and outcomes.Data extraction and synthesisPrimary outcome measures extracted were the number of admissions, treatment times and patient outcome. Secondary outcomes were severity on admission, population risk factors and destination on discharge. No meta-analysis was performed.ResultsThis review demonstrated that 84% of studies reported decreased admissions rates during the COVID-19 pandemic. However, among those admitted, on average, had higher severity of stroke. Additionally, in-hospital stroke treatment pathways were affected by the implementation of COVID-19 protocols, which resulted in increased treatment times in 60% of studies and increased in-hospital mortality in 82% of studies by 100% on average. The prevalence of stroke subtype (ischaemic or haemorrhagic) and primary treatment methods (thrombectomy or thrombolysis) did not vary due to the COVID-19 pandemic.ConclusionsDuring the COVID-19 pandemic, many populations hesitated to seek medical attention, decreasing hospital admissions for less severe strokes and increasing hospitalisation of more severe cases and mortality. The effect of the pandemic on society and healthcare systems needs to be addressed to improve stroke treatment pathways and prepare for potential future epidemics.PROSPERO registration numberCRD42021248564.…

IntroductionRecently, the improvement of chronic hyperglycaemia-related damage of type 2 diabetes mellitus (T2DM) through functional food consumption has attracted the attention of many clinicians. This study aims to determine the effectiveness of date seed powder (DSP) as a functional food (prebiotic) on the cardiometabolic risk factors, oxidative stress, anti-/inflammatory biomarkers, metabolic endotoxaemia (gut microbiota), adipokines, hypothalamic–pituitary–adrenal axis biomarkers, immune system, anthropometric indices and mental health in patients with T2DM.MethodsThis study protocol will be conducted as randomised, triple-blind, placebo-controlled trial with the inclusion of 48 patients with T2DM. The participants will be randomly assigned into two equal groups of intervention (n=24) and placebo (n=24) and receive 5 g/day of DSP or placebo for 8 weeks, respectively. At baseline and post-intervention, fasting blood samples will be collected to assess the serum levels of lipid profile, glycaemic indices, antioxidant and oxidative stress, anti-/inflammatory biomarkers, lipopolysaccharide, 8-hydroxy-guanine, adipokines, hypothalamic–pituitary–adrenal axis biomarkers, immune system and mental health. Data will be analysed using the SPSS software (V.16.0). To compare the quantitative variables, paired and unpaired Student’s t-tests and covariance analyses will be used.DiscussionIn this study, the potential effects of DSP on patients with T2DM will be evaluated for the first time. It is hoped that the results would increase the body of scientific knowledge about DSP supplementation on the cardiometabolic risk factors, oxidative stress, anti-/inflammatory biomarkers, metabolic endotoxaemia, adipokines, hypothalamic–pituitary–adrenal axis biomarkers, immune system, anthropometric indices and mental health in patients with T2DM.Ethics and disseminationThe study protocol was approved by the Ethical Committee of the Tabriz University of Medical Sciences, Tabriz, Iran (code: IR.TBZMED.REC.1400.752).Trial registration numberIranian Registry of Clinical Trials (www.irct.ir/IRCT20150205020965N10).…

ObjectiveCOVID-19 pandemic remains one of the most significant public health challenges ever faced globally. Vaccines are key to ending the pandemic as well as minimise its consequences. This study determined the uptake of COVID-19 vaccines and associated factors among adults in Uganda.Design, setting and participantsWe conducted a cross-sectional mobile phone survey among adults in Uganda.Main outcome variableParticipants reported their uptake of COVID-19 vaccines.ResultsOf the participants contacted, 94% (1173) completed the survey. Overall, 49.7% had received COVID-19 vaccines with 19.2% having obtained a full dose and 30.5% an incomplete dose. Among the unvaccinated, 91.0% indicated intention to vaccinate. Major reasons for vaccine uptake were protection of self from COVID-19 (86.8%) and a high perceived risk of getting the virus (19.6%). On the other hand, non-uptake was related to vaccine unavailability (42.4%), lack of time (24.1%) and perceived safety (12.5%) and effectiveness concerns (6.9%). The factors associated with receiving COVID-19 vaccines were older age (≥65 years) (Adjusted Prevalence Ratio (APR)=1.32 (95% CI: 1.08 to 1.61)), secondary (APR=1.36 (95% CI: 1.12 to 1.65)) or tertiary education (APR=1.62 (95% CI: 1.31 to 2.00)) and health workers as a source of information on COVID-19 (APR=1.26 (95% CI: 1.10 to 1.45)). Also, reporting a medium-income (APR=1.24 (95% CI: 1.02 to 1.52)) and residence in Northern (APR=1.55, 95% CI: 1.18 to 2.02) and Central regions (APR=1.48, 95% CI: 1.16 to 1.89) were associated with vaccine uptake.ConclusionsUptake of COVID-19 vaccines was moderate in this sample and was associated with older age, secondary and tertiary education, medium-income, region of residence and health workers as a source of COVID-19 information. Efforts are needed to increase access to vaccines and should use health workers as champions to enhance uptake.…

ObjectiveUnderstanding the determinants of adolescent pregnancy and how they have changed over time is essential for measuring progress and developing strategies to improve adolescent reproductive health. This study examined changes over time in the prevalence and determinants of adolescent pregnancy in Ghana.MethodsA total of 11 nationally representative surveys from the Ghana Demographic and Health Survey (1988, 1993, 1998, 2003, 2008, 2014), Multiple Indicator Cluster Survey (2006, 2011, 2017–2018) and Malaria Indicator Survey (2016 and 2019) provided data on 14 556 adolescent girls aged 15–19 for this analysis. A random-effect meta-analysis, time trends and multivariable logistic regression models were used to track the prevalence and determinants of adolescent pregnancy.ResultsThe pooled prevalence of adolescent pregnancy in Ghana was 15.4% (95% CI=13.49% to 17.30%). Rural areas (19.5%) had a higher prevalence of adolescent pregnancy than urban areas (10.6%). In the overall sample, middle adolescents (15–17 years) (aOR=0.30, 95% CI=0.23 to 0.39), adolescents in urban areas (aOR=0.56, 95% CI=0.43 to 0.74), large households (aOR=0.62, 95% CI=0.49 to 0.78), not working (aOR=0.62, 95% CI=0.43 to 0.90) and those unaware of contraceptive methods (aOR=0.49, 95% CI=0.27 to 0.90) were less likely to become pregnant. Adolescents from middle-income (aOR=0.91, 95% CI=0.67 to 1.24) or high-income (aOR=0.59, 95%CI=0.36 to 0.94) households, those who were semiliterate (aOR=0.56, 95%CI=0.39 to 0.82) or literate (aOR=0.28, 95%CI=0.21 to 0.37) and those with fewer previous sex partners were less likely to become pregnant. Not all determinants in the overall sample were consistently associated with adolescent pregnancy in the last three decades. Between 1988 and 1998, determinants of adolescent pregnancy were age, literacy, employment, household size and whether the mother was alive. Between 2003 and 2008, age, literacy, household size, income, age of last sexual partner, number of previous partners and contraception knowledge determined adolescent pregnancy. From 2011 to 2019, age, residence, literacy and menstrual cycle knowledge were determinants of adolescent pregnancy.ConclusionInterventions and policies to prevent adolescent pregnancy should prioritise adolescents from disadvantaged backgrounds.…

The COVID-19 pandemic has significantly impacted on the delivery of clinical trials in the UK, posing complicated organisational challenges and requiring adaptations, especially to exercise intervention studies based in the community. We aim to identify the challenges of public involvement, recruitment, consent, follow-up, intervention and the healthcare professional delivery aspects of a feasibility study of exercise in hypertensive primary care patients during the COVID-19 pandemic. While these challenges elicited many reactive changes which were specific to, and only relevant in the context of ‘lockdown’ requirements, some of the protocol developments that came about during this unprecedented period have great potential to inform more permanent practices for carrying out this type of research. To this end, we detail the necessary adaptations to many elements of the feasibility study and critically reflect on our approach to redesigning and amending this ongoing project in order to maintain its viability to date. Some of the more major protocol adaptations, such as moving the study to remote means wherever possible, had further unforeseen and undesirable outcomes (eg, additional appointments) with regards to extra resources required to deliver the study. However, other changes improved the efficiency of the study, such as the remote informed consent and the direct advertising with prescreening survey. The adaptations to the study have clear links to the UK Plan for the future of research delivery. It is intended that this specific documentation and critical evaluation will help those planning or delivering similar studies to do so in a more resource efficient and effective way. In conclusion, it is essential to reflect and respond with protocol changes in the current climate in order to deliver clinical research successfully, as in the case of this particular study.…

PurposeThe Swedish InfCareHIV cohort was established in 2003 to ensure equal and effective care of people living with HIV (PLHIV) and enable long-term follow-up. InfCareHIV functions equally as a decision support system as a quality registry, ensuring up-to-date data reported in real time.ParticipantsInfCareHIV includes data on >99% of all people with diagnosed HIV in Sweden and up to now 13 029 have been included in the cohort. InfCareHIV includes data on HIV-related biomarkers and antiretroviral therapies (ART) and also on demographics, patient-reported outcome measures and patient-reported experience measures.Findings to dateSweden was in 2015 the first country to reach the UNAIDS (United Nations Programme on HIV/AIDS)/WHO’s 90-90-90 goals. Late diagnosis of HIV infection was identified as a key problem in the Swedish HIV-epidemic, and low-level HIV viraemia while on ART associated with all-cause mortality. Increased HIV RNA load in the cerebrospinal fluid (CSF) despite suppression of the plasma viral load was found in 5% of PLHIV, a phenomenon referred to as ‘CSF viral escape’. Dolutegravir-based treatment in PLHIV with pre-existing nucleoside reverse transcriptase inhibitor-mutations was non-inferior to protease inhibitor-based regimens. An increase of transmitted drug resistance was observed in the InfCareHIV cohort. Lower efficacy for protease inhibitors was not due to lower adherence to treatment. Incidence of type 2 diabetes and insulin resistance was high in the ageing HIV population. Despite ART, the risk of infection-related cancer as well as lung cancer was increased in PLHIV compared with HIV-negative. PLHIV were less likely successfully treated for cervical precancer and more likely to have human papillomavirus types not included in current HPV vaccines. Self-reported sexual satisfaction in PLHIV is improving and is higher in women than men.Future plansInfCareHIV provides a unique base to study and further improve long-term treatment outcomes, comorbidity management and health-related quality of life in people with HIV in Sweden.…

Abstract Purpose Overweight and obesity have increased in people living with HIV (PLH). Our study evaluated weight, body-mass-index (BMI), and waist-to-hip ratio (WHR) change over 5 years of follow-up in PLH compared to the general population. Methods HIV-positive participants in the HIV Heart Aging (HIVH) study were matched 1:2 by age and sex with HIV-negative controls of the population-based Heinz Nixdorf Recall (HNR) study. Both studies were recruited in the German Ruhr area. The association between HIV and weight, BMI, and WHR changes was examined using linear regression. Regression models were adjusted for parameters potentially affecting weight gain. Results The matched HIVH and HNR participants (N = 585 and N = 1170, respectively; 14.7% females) had a mean age of 55 years at baseline. Despite the lower baseline weight (− 6 kg, 95% CI − 7.46 to − 4.59), the linear regression showed greater absolute and relative weight and BMI increases after 5 years in HIVH compared to HNR. Adjusting the linear regression models for smoking amplified that HIVH had a higher absolute and relative weight difference of 0.7 kg or ~ 1% compared to HNR after 5 years (95% Cl 0.1 to 1.3 and 0.2 to 1.6, respectively). Adjusting for HDL, LDL, systolic blood pressure, and diabetes mellitus did not affect the results. Conclusions PLH had lower weight than the general population at baseline and after 5 years, but experienced greater increases in body weight after 5 years. WHR change after 5 years was lower in PLH compared to the general population, despite a higher WHR at baseline. …

by Malin-Theres Seffer, Martin Weinert, Gabriella Molinari, Manfred Rohde, Lothar Gröbe, Jan T. Kielstein, Susanne EngelmannIntroduction Extracorporeal blood purification systems represent a promising alternative for treatment of blood stream infections with multiresistant bacteria. Objectives The aim of this study was to analyse the binding activity of S. aureus to Seraph affinity filters based on heparin coated beads and to identify effectors influencing this binding activity. Results To test the binding activity, we used gfp-expressing S. aureus Newman strains inoculated either in 0.9% NaCl or in blood plasma and determined the number of unbound bacteria by FACS analyses after passing through Seraph affinity filters. The binding activity of S. aureus was clearly impaired in human plasma: while a percent removal of 42% was observed in 0.9% NaCl (p-value 0.0472) using Seraph mini columns, a percent removal of only 10% was achieved in human plasma (p-value 0.0934). The different composition of surface proteins in S. aureus caused by the loss of SarA, SigB, Lgt, and SaeS had no significant influence on its binding activity. In a clinically relevant approach using the Seraph® 100 Microbind® Affinity Filter and 1000 ml of human blood plasma from four different donors, the duration of treatment was shown to have a critical effect on the rate of bacterial reduction. Within the first four hours, the number of bacteria decreased continuously and the reduction in bacteria reached statistical significance after two hours of treatment (percentage reduction 64%, p-value 0.01165). The final reduction after four hours of treatment was close to 90% and is dependent on donor. The capacity of Seraph® 100 for S. aureus in human plasma was approximately 5 x 108 cells. Conclusions The Seraph affinity filter, based on heparin-coated beads, is a highly efficient method for reducing S. aureus in human blood plasma, with efficiency dependent on blood plasma composition and treatment duration.…

by Christina Gjerlev Poulsen, Daniel G. K. Rasmussen, Federica Genovese, Tine W. Hansen, Signe Holm Nielsen, Henrik Reinhard, Bernt Johan von Scholten, Peter K. Jacobsen, Hans-Henrik Parving, Morten Asser Karsdal, Peter Rossing, Marie Frimodt-MøllerBackground Diabetic kidney disease is a major cause of morbidity and mortality. Dysregulated turnover of collagen type III is associated with development of kidney fibrosis. We investigated whether a degradation product of collagen type III (C3M) was a risk marker for progression of chronic kidney disease (CKD), occurrence of cardiovascular disease (CVD), and mortality during follow up in people with type 2 diabetes (T2D) and microalbuminuria. Moreover, we investigated whether C3M was correlated with markers of inflammation and endothelial dysfunction at baseline. Methods C3M was measured in serum (sC3M) and urine (uC3M) in 200 participants with T2D and microalbuminuria included in an observational, prospective study at Steno Diabetes Center Copenhagen in Denmark from 2007–2008. Baseline measurements included 12 markers of inflammation and endothelial dysfunction. The endpoints were CVD, mortality, and CKD progression (>30% decline in eGFR). Results Mean (SD) age was 59 (9) years, eGFR 90 (17) ml/min/1.73m2 and median (IQR) urine albumin excretion rate 102 (39–229) mg/24-h. At baseline all markers for inflammation were positively correlated with sC3M (p≤0.034). Some, but not all, markers for endothelial dysfunction were correlated with C3M. Median follow-up ranged from 4.9 to 6.3 years. Higher sC3M was associated with CKD progression (with mortality as competing risk) with a hazard ratio (per doubling) of 2.98 (95% CI: 1.41–6.26; p = 0.004) adjusted for traditional risk factors. uC3M was not associated with CKD progression. Neither sC3M or uC3M were associated with risk of CVD or mortality. Conclusions Higher sC3M was a risk factor for chronic kidney disease progression and was correlated with markers of inflammation.…

by Soyeon Kim, Anneke C. Hesseling, Xingye Wu, Michael D. Hughes, N. Sarita Shah, Sanjay Gaikwad, Nishi Kumarasamy, Erika Mitchell, Mey Leon, Pedro Gonzales, Sharlaa Badal-Faesen, Madeleine Lourens, Sandy Nerette, Justin Shenje, Petra de Koker, Supalert Nedsuwan, Lerato Mohapi, Unoda A. Chakalisa, Rosie Mngqbisa, Rodrigo Otávio da Silva Escada, Samuel Ouma, Barbara Heckman, Linda Naini, Amita Gupta, Susan Swindells, Gavin Churchyard, on behalf of the ACTG A5300/IMPAACT 2003 PHOENIx Feasibility Study Team Background Understanding factors associated with prevalent Mycobacterium tuberculosis infection and prevalent TB disease in household contacts of patients with drug-resistant tuberculosis (TB) may be useful for TB program staff conducting contact investigations. Methods Using data from a cross-sectional study that enrolled index participants with rifampin-resistant pulmonary TB and their household contacts (HHCs), we evaluated HHCs age ≥15 years for factors associated with two outcomes: Mycobacterium tuberculosis infection and TB disease. Among HHCs who were not already diagnosed with current active TB disease by the TB program, Mycobacterium tuberculosis infection was determined by interferon-gamma release assay (IGRA). TB disease was adjudicated centrally. We fitted logistic regression models using generalized estimating equations. Results Seven hundred twelve HHCs age ≥15 years enrolled from 279 households in eight high-TB burden countries were a median age of 34 years, 63% female, 22% current smokers and 8% previous smokers, 8% HIV-positive, and 11% previously treated for TB. Of 686 with determinate IGRA results, 471 tested IGRA positive (prevalence 68.8% (95% Confidence Interval: 64.6%, 72.8%)). Multivariable modeling showed IGRA positivity was more common in HHCs aged 25–49 years; reporting prior TB treatment; reporting incarceration, substance use, and/or a period of daily alcohol use in the past 12 months; sharing a sleeping room or more evenings spent with the index participant; living with smokers; or living in a home of materials typical of low socioeconomic status.Forty-six (6.5% (95% Confidence Interval: 4.6%, 9.0%)) HHCs age ≥15 years had prevalent TB disease. Multivariable modeling showed higher prevalence of TB disease among HHCs aged ≥50 years; reporting current or previous smoking; reporting a period of daily alcohol use in the past 12 months; and reporting prior TB treatment. Conclusion We identified overlapping and distinct characteristics associated with Mycobacterium tuberculosis infection and TB disease that may be useful for those conducting household TB investigations.…