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Background Herpes zoster (HZ) is the clinical syndrome associated with reactivation of latent varicella-zoster virus (VZV). Several factors have been implicated to promote VZV reactivation; these include immunosuppression, older age, mechanical trauma, physiologic stress, lymphopenia, and more recently, infection with severe acute respiratory syndrome coronavirus-2 (SARS- CoV-2). Recent reports suggest an increase in the number of HZ cases in the general population during the global COVID-19 pandemic. However, it is unknown what proportion of HZ during the pandemic is due to reactivation of wild-type or vaccine-strain VZV. Case Here we report the first known case of HZ concomitant with SARS-CoV2 infection in a 20-month-old female who was treated with a single dose of dexamethasone, due to reactivation of the vaccine-type strain of VZV after presenting with a worsening vesicular rash. Conclusion In this case, we were able to show vaccine-strain VZV reactivation in the context of a mild acute symptomatic COVID-19 infection in a toddler. Being able to recognize HZ quickly and effectively in a pediatric patient can help stave off the significant morbidity and mortality associated with disease process.

The COVID-19 pandemic has been marked by continuous emergence of novel SARS-CoV-2 variants. Questions remain about the mechanisms with which those variants establish themselves in new geographic areas. We performed a discrete phylogeographic analysis on 18,529 sequences of the SARS-CoV-2 Omicron BA.5 sublineage sampled during February-June 2022 to elucidate emergence of that sublineage in different regions of the United States. The earliest BA.5 sublineage introductions came from Africa, the putative variant origin, but most were from Europe, matching a high volume of air travelers. In addition, we discovered extensive domestic transmission between different US regions, driven by population size and cross-country transmission between key hotspots. We found most BA.5 virus transmission within the United States occurred between 3 regions in the southwestern, southeastern, and northeastern parts of the country. Our results form a framework for analyzing emergence of novel SARS-CoV-2 variants and other pathogens in the United States.

Background: Fluticasone furoate (drug code GW685698) is an enhanced-affinity glucocorticoid that has been developed for the treatment of allergic rhinitis. Objectives: The objectives of this study were to estimate the absolute bioavailability of fluticasone furoate nasal spray and to describe the intranasal (IN) and IV pharmacokinetics of fluticasone furoate in healthy subjects. Methods: This was a single-center, randomized, open label, 2-period crossover study. Healthy male and female subjects were randomized to receive supra-therapeutic doses of fluticasone furoate 880 μg IN qSh for 10 doses in 1 treatment period, and a single IV dose of 250 pg fluticasone furoate given as an infusion over 20 minutes in the other treatment period. Each treatment period was separated by a 4- to 5-day washout period. Blood sampling was carried out over 8 hours following the final IN dose and 24 hours following the IV dose to determine plasma fluticasone furoate concentrations. Plasma samples were analyzed for fluticasone furoate using online solid-phase extraction with high-performance liquid chromatography with tandem mass-spectrometric detection. The lower limit of quantification was 10 pg/mL. The sample size was based primarily on logistical considerations. Sample-size sensitivity was assessed by estimating the 90% CI for the absolute bioavailability of IN fluticasone furoate, based on different estimated bioavailabilities and within-subject SDs. The following pharmacokinetic parameters were derived: IN administration: AUC from time 0 to the end of the dosing interval (AUC 0−τ), AUC 0−t, C max, and T max; IV administration: AUC 0−∞, AUC 0−t, t 1/2, C max, T max, total systemic clearance, and volume of distribution at steady state. Results: A total of 16 subjects were included in the study. Their mean age was 27.8 years (range, 19–45 years), and their mean body weight was 72.84 kg (range, 55.3–97.2 kg). The geometric mean AUC 0−τ for 880 μg IN was 74.9 pg · mL/h and geometric mean AUC 0−∞ for 250 μg IV was 4259 pg · mL/h. The geometric mean of the absolute bioavailability of fluticasone furoate nasal spray in these healthy subjects was 0.50% (90% CI, 0.34%–0.74%). The administration of large doses by the IN route did not elicit clinical concern. Three (19%) of 16 subjects reported adverse events (AEs) during the IN administration period, with 2 subjects experiencing dizziness and 1, toothache. Five (31%) subjects reported AEs during the IV administration period, with 3 subjects experiencing infusion-site or IV catheter-related events; 1 subject, dizziness; and 1 subject, headache. Conclusions: The geometric mean of the absolute bioavailability of fluticasone furoate 880 μg IN qSh for 10 doses in these healthy subjects was low—0.50%.

Plasmodium falciparum transmission by Anopheles gambiae mosquitoes is remarkably efficient, resulting in a very high prevalence of human malaria infection in sub-Saharan Africa. A combination of genetic mapping, linkage group selection, and functional genomics was used to identify Pfs47 as a P. faldparum gene that allows the parasite to infect A. gambiae without activating the mosquito immune system. Disruption of Pfs47 greatly reduced parasite survival in the mosquito, and this phenotype could be reverted by genetic complementation of the parasite or by disruption of the mosquito complement-like system. Pfs47 suppresses midgut nitration responses that are critical to activate the complement-like system. We provide direct experimental evidence that immune evasion mediated by Pfs47 is critical for efficient human malaria transmission by A. gambiae.

Dengue is the most prevalent mosquito-borne viral disease in humans, and cases are continuing to rise globally. In particular, islands in the Caribbean have experienced more frequent outbreaks, and all four dengue virus (DENV) serotypes have been reported in the region, leading to hyperendemicity and increased rates of severe disease. However, there is significant variability regarding virus surveillance and reporting between islands, making it difficult to obtain an accurate understanding of the epidemiological patterns in the Caribbean. To investigate this, we used travel surveillance and genomic epidemiology to reconstruct outbreak dynamics, DENV serotype turnover, and patterns of spread within the region from 2009-2022. We uncovered two recent DENV-3 introductions from Asia, one of which resulted in a large outbreak in Cuba, which was previously under-reported. We also show that while outbreaks can be synchronized between islands, they are often caused by different serotypes. Our study highlights the importance of surveillance of infected travelers to provide a snapshot of local introductions and transmission in areas with limited local surveillance and suggests that the recent DENV-3 introductions may pose a major public health threat in the region. Dengue is a major public health concern in the Americas, and the Caribbean can be a source for reintroduction and spread. Here, the authors use travel surveillance data and genomic epidemiology to reconstruct Dengue epidemic dynamics in the Caribbean from 2009-2022.

During May 2022-April 2023, dengue virus serotype 3 was identified among 601 travel-associated and 61 locally acquired dengue cases in Florida, USA. All 203 sequenced genomes belonged to the same genotype III lineage and revealed potential transmission chains in which most locally acquired cases occurred shortly after introduction, with little sustained transmission.

Background The increasing burden of dengue virus on public health due to more explosive and frequent outbreaks highlights the need for improved surveillance and control. Genomic surveillance of dengue virus not only provides important insights into the emergence and spread of genetically diverse serotypes and genotypes, but it is also critical to monitor the effectiveness of newly implemented control strategies. Here, we present DengueSeq, an amplicon sequencing protocol, which enables whole-genome sequencing of all four dengue virus serotypes. Results We developed primer schemes for the four dengue virus serotypes, which can be combined into a pan-serotype approach. We validated both approaches using genetically diverse virus stocks and clinical specimens that contained a range of virus copies. High genome coverage (>95%) was achieved for all genotypes, except DENV2 (genotype VI) and DENV 4 (genotype IV) sylvatics, with similar performance of the serotype-specific and pan-serotype approaches. The limit of detection to reach 70% coverage was 10-100 RNA copies/μL for all four serotypes, which is similar to other commonly used primer schemes. DengueSeq facilitates the sequencing of samples without known serotypes, allows the detection of multiple serotypes in the same sample, and can be used with a variety of library prep kits and sequencing instruments. Conclusions DengueSeq was systematically evaluated with virus stocks and clinical specimens spanning the genetic diversity within each of the four dengue virus serotypes. The primer schemes can be plugged into existing amplicon sequencing workflows to facilitate the global need for expanded dengue virus genomic surveillance.

ABSTRACT Objective: The Vienna Challenge Chamber (VCC) offers a controlled and controllable paradigm in which to reproducibly evaluate the efficacy of anti-allergic treatment. The aim of this study was to assess the efficacy of the novel intranasal corticosteroid fluticasone furoate (FF) in the VCC. Methods: The single-centre, randomised, double-blind, placebo-controlled, two-period crossover study was conducted in 59 adult males with grass pollen allergic rhinitis (AR). Patients received either Fluticasone furoate 200 mcg once-daily, or placebo intranasally for 8 days. AR symptoms were induced during 4-hour allergen challenges with grass pollen in the VCC at the end of each 8-day treatment period. A first challenge was conducted at 1–5 hours post-dose, followed by a second challenge at 22–26 hours post-dose. The primary endpoint was total nasal symptom score (TNSS; sum of itch, sneeze, rhinorrhoea, obstruction symptoms assessed on a categorical scale of 0–3) weighted mean over 2–5 hours post-dose. Secondary endpoints included: TNSS weighted mean over 23–26 hours post-dose and global symptom score, eye symptom score, nasal secretions and nasal airflow weighted means over 2–5 and 23–26 hours post-dose. Results: Fluticasone furoate showed consistent attenuation of AR symptoms in both the early and late challenges. Compared with placebo, weighted mean of TNSS was reduced on average by 4.14 point-scores at 2–5 hours post-dose and 3.63 point scores at 23–26 hours post-dose. These positive effects were also seen across all secondary endpoints. Conclusion: An 8-day treatment course of intranasal FF 200 mcg given once-daily statistically significantly reduced symptoms of AR including associated eye symptoms. Statistical significance was declared where the relevant two-sided 95 % confidence interval did not contain zero. This positive effect was sustained over 24 hours suggesting that fluticasone furoate could be efficacious as a once daily steroid.

Objective: To assess the effectiveness of nurse led follow up in the management of patients with lung cancer. Design:Randomised controlled trial. Setting:Specialist cancer hospital and three cancer units in southeastern England Participants: 203 patients with lung cancer who had completed their initial treatment and were expected to survive for at least 3 months. Intervention: Nurse led follow up of outpatients compared with conventional medical follow up. Outcome measures: Quality of life, patients' satisfaction, general practitioners' satisfaction, survival, symptom-free survival, progression-free survival, use of resources, and comparison of costs. Results: Patient acceptability of nurse led follow up was high: 75% (203/271) of eligible patients consented to participate. Patients who received the intervention had less severe dyspnoea at 3 months (P=0.03) and had better scores for emotional functioning (P=0.03) and less peripheral neuropathy (P=0.05) at 12 months. Intervention group patients scored significantly better in most satisfaction subscales at 3, 6, and 12 months (P<0.01 for all subscales at 3 months). No significant differences in general practitioners' overall satisfaction were seen between the two groups. No differences were seen in survival or rates of objective progression, although nurses recorded progression of symptoms sooner than doctors (P=0.01). Intervention patients were more likely to die at home rather than in a hospital or hospice (P=0.04), attended fewer consultations with a hospital doctor during the first 3 months (P=0.004), had fewer radiographs during the first 6 months (P=0.04), and had more radiotherapy within the first 3 months (P=0.01). No other differences were seen between the two groups in terms of the use of resources. Conclusion: Nurse led follow up was acceptable to lung cancer patients and general practitioners and led to positive outcomes.