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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.