Acute Infection Research Articles

An Overview on Disease Burden and Management of Respiratory Syncytial Virus Infections in Older Adults in the Asia-Pacific Region.

Respiratory syncytial virus (RSV) represents a significant burden on older adults (aged ≥ 50years) globally and can lead to acute respiratory tract infections with substantial morbidity and mortality. However, there is a significant gap in knowledge regarding RSV infection in older adults, particularly in the Asia-Pacific region. This knowledge gap underscores the need for targeted and comprehensive studies to fully understand the nuanced epidemiology of RSV in ageing populations. This review synthesises data from various countries, emphasising the impact of RSV on older populations in the Asia-Pacific region. The overall proportions of RSV-related ARIs among older patients ranged from 0.2% to 5.6%. Among older adult patients with CAP, RSV accounted for 1.1%-10.3% of cases. However, it is crucial to note that the diversity in reported percentages highlights the influence of factors such as geographic location, health care settings and diagnostic practices. The most common symptoms observed in older adults with RSV infection were cough, sputum production and fever, followed by dyspnoea, sore throat and rhinorrhoea. Most of the old adults with RSV infection had underlying diseases, and RSV can cause significant morbidity and mortality in old adults. Treatment of RSV infections predominantly involve supportive care, with aerosolised ribavirin reserved for severe cases, especially immunocompromised patients. Emerging antiviral agents, including fusion and nucleoprotein inhibitors, offer promising avenues for future therapeutics. The recent approval of the bivalent RSV prefusion F protein-based vaccine for individuals aged 60 and older represents a milestone in preventive strategies. In conclusion, RSV infection remains a significant threat to older adults in the Asia-Pacific region, necessitating ongoing research and surveillance efforts. The recent vaccine approval marks a positive milestone, but further studies are crucial for refining prevention and treatment approaches.

Herpes zoster in an immunocompetent adolescent – A case of rare occurrence

ABSTRACT Herpes zoster is an acute viral infection caused by the reactivation of the varicella zoster virus. It occurs commonly in immunocompromised adults. Odontalgia may be an early prodromal symptom when herpes zoster involves the oral and maxillofacial region, which lays significant emphasis on the role of a dentist in early diagnosis and treatment of the infection. Herpes zoster infection commonly affects adult and elderly patients and is very rare in children. This article shows cases of herpes zoster infection in a 14-year-old immunocompetent boy who presented with dental pain as a prodromal sign. Herpes zoster may occur in children and thus should be considered in the differential diagnosis of acute multiple ulcers occurring in that population.

Treatment Failure Rates Significantly Decrease at One and Five Years After Debridement, Antibiotics, and Implant Retention for Acute Periprosthetic Joint Infection in Total Knee Arthroplasty: A 10 Year Cohort Study

Treatment Failure Rates Significantly Decrease at One and Five Years After Debridement, Antibiotics, and Implant Retention for Acute Periprosthetic Joint Infection in Total Knee Arthroplasty: A 10 Year Cohort Study

Evaluating omadacycline dosing regimens against drug-resistant pathogens including Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae in adults: a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation.

The objective of this study was to evaluate the efficacy of various dosing regimens of omadacycline against main drug-resistant pathogens in the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). Monte Carlo simulations were conducted using pharmacokinetic parameters and pharmacodynamic data to calculate cumulative fractions of response (CFRs) in terms of drug area under the concentration curve/minimum inhibition concentration targets.CFR ≥ 90% was considered optimal for a dosage regimen. CFR of any approved oral/intravenous regimen with loading-dose was ≥ 90% against methicillin-resistant Staphylococcus aureus (MRSA) for ABSSSI and penicillin-resistant Streptococcus pneumonia, tetracycline-resistant Streptococcus pneumonia, MRSA and β-lactamase positive Haemophilus influenzae for CABP. In conclusion, approved oral/intravenous loading and maintenance doses of omadacycline showed enough efficacy in the treatment of ABSSI and CABP caused by the main drug-resistant pathogens.

Clinical characteristics and in-hospital outcomes associated with RSV-ALRI compared to other viral ALRI in hospitalised children under two years old.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections (ALRIs) associated hospitalisations in children. It is unclear if hospitalized RSV-ALRI differs in clinically from other viral ALRIs. We aimed to compare the disease impact of hospitalised RSV with other viral ALRI in children under 2 years. We conducted a retrospective study using electronic medical records of children under 2 hospitalized with ALRIs at Sydney Children's Hospitals Network from 2020-2022. We compared demographics and clinical features between RSV-positive and RSV-negative (positive for other viruses) cases. Poisson quasi-likelihood regression was used to estimate adjusted prevalence ratios (aPRs) for three in-hospital outcomes: length of stay, need for respiratory support and intensive care. We examined 330 children under 2 years hospitalized with RSV-positive ALRIs and 330 with RSV-negative ALRIs (positive for other viruses). RSV-positive cases were older (12 vs. 8 months, p<0.001) and more often presented with cough (99% vs. 92%), fever (80% vs. 58%), crackles (89% vs. 76%), hypoxia (50% vs. 36%), and lethargy (36% vs. 20%). They were also more likely to undergo chest x-rays (74% vs. 49%) and receive antibiotics (65% vs. 35%). Adjusted analysis showed RSV-positive children had a higher likelihood of LOS > 2 days (aPR 1.95, 95% CI 1.14-3.36).). However, there were no differences in the need for intensive care or respiratory support. Children with RSV-ALRI exhibited more severe symptoms, received more antibiotics, and had longer hospital stays compared to those with other viral ALRIs, underscoring the need for effective prevention and treatment strategies for RSV.

GENERAL CHARACTERISTICS OF CHILDREN WITH NON-RHEUMATIC MYOCARDITIS IN THE SAMARKAND REGION FROM 2022-2023

In the Cardio-Rheumatology Department of the Samarkand Regional Multidisciplinary Pediatric Clinical Center, we examined clinical and electrocardiographic analyses of 50 young children diagnosed with non-rheumatic myocarditis (NM) over the years 2022-2023. Results show that 86% of these young patients had a history of acute respiratory infections.

An Outbreak of Respiratory Viral Infections in a Professional Ice Hockey Team.

Viral acute respiratory infections (ARIs) are an important cause of illness in athletes. However, their impact on ice hockey players is unclear. We describe an outbreak of ARIs in a professional ice hockey team. Contrary to expected influenza, the 40-day outbreak was caused by 8 different respiratory viruses, that is, 2 different influenza A viruses, human coronavirus-NL63 (HCoV-NL63), respiratory syncytial viruses (RSV) A and B, 2 different rhinoviruses, enterovirus D68, and parainfluenza type 2 virus. Only influenza A and HCoV-NL63 were possibly spread within the team thus suggesting an important contraction from the community. The burden of illness was substantial.

Emerging Lineages A2.2.1 and A2.2.2 of Human Metapneumovirus (hMPV) in Paediatric Respiratory Infections: Insights from India"

ObjectiveHuman metapneumovirus (hMPV) is recognized as a significant cause of acute respiratory infections (ARI) among infants under 5 years of age. MethodNasal swabs collected from January 2021 to June 2024 were screened to detect hMPV using RT-qPCR. Further, representative positive samples were sequenced and subjected to phylogenetic analysis. ResultsOut of 4,519 samples tested, 113 were positive for hMPV. Notably, an outbreak occurred between November 2022 and March 2023, where 56 out of 583 patients (9.6%) tested positive. Analysis of the outbreak samples revealed that majority (6.3%) of cases occurred in December and January. hMPV infection was more prevalent in less than 1 year, with clinical manifestations of 29 (67%) patients had a history of wheezing and 3 (6.9%) experienced seizures. On genetic analysis of F protein, 37 samples identified two genotypes as A and B, with sub clusters of 29 (85.29%) samples to A2.1, 1 (2.94%) to A2.2.1and 4 (11.76%) to A2.2.2 within genotype A, and 1 sample clustered with B1 and 2 samples to B2 within genotype B. ConclusionsThe study underscores the significant prevalence and genetic diversity of hMPV among children in Puducherry, India. Notably, the identification of novel A2.2.1 and A2.2.2 lineages highlights the evolving nature of hMPV.

Leptospira Leptolysin Contributes to Serum Resistance but Is Not Essential for Acute Infection.

Previous invitro works focusing on virulence determinants of the spirochete Leptospira implicated metalloproteinases as putative contributing factors to the pathogenicity of these bacteria. Those proteins have the capacity to degrade extracellular matrix components (ECM) and proteins of host's innate immunity, notably effectors of the complement system. In this study, we gained further knowledge on the role of leptolysin, one of the leptospiral-secreted metalloproteinases, previously described as having a broad substrate specificity. We demonstrated that a proportion of human patients with mild leptospirosis evaluated in the current study produced antibodies that recognize leptolysin, thus indicating that the protease is expressed during host infection. Using recombinant protein and a knockout mutant strain, Manilae leptolysin-, we determined that leptolysin contributes to Leptospira interrogans serum resistance invitro, likely by proteolysis of complement molecules of the alternative, the classical, the lectin, and the terminal pathways. Furthermore, in a hamster model of infection, the mutant strain retained virulence; however, infected animals had lower bacterial loads in their kidneys. Further studies are necessary to better understand the role and potential redundancy of metalloproteinases on the pathogenicity of this important neglected disease.

Cost-effectiveness of ceftazidime/avibactam for infections due to carbapenem-resistant bacteria: analysis in Ecuadorian context

Abstract Aim To analyze the cost-effectiveness of ceftazidime/avibactam-based therapy (CAZ/AVI) versus colistin-based therapy (COL) for pneumonia/bacteremia caused by carbapenem-resistant enterobacterales adjusted to the Ecuador context. Methods A Markov decision model was extrapolated from literature. The analysis had a 5-year time horizon from the Ecuadorian Ministry of Health (MoH) perspective. The model is composed of five health states: (i) Pneumonia/bacteriemia, (ii) Home discharge (iii) Long-term care discharge (LTC), (iv) LTC with chronic dialysis, and (v) Death. The entire hypothetical cohort starts the Markov process in the pneumonia/bacteriemia state; then it can transit through the other health states according to transition probabilities. Patients who survive the acute infection state may develop nephrotoxicity, which could need renal replacement therapy for short- or long-term. Results The base case estimated for CAZ/AVI treatment an incremental cost-effectiveness ratio (ICER) of 10 273 USD per QALY gained, with an average incremental cost of USD 5489 and 0.5343 incremental QALYs for each patient during the 5-year time horizon. This deterministic ICER is equivalent to 1.5 the value of 1 GDP per capita in Ecuador. Conclusions CAZ/AVI showed a 92% probability of being cost-effective compared to treatment with COL, considering a maximum payment availability of USD 13 000 in the Ecuadorian context.

Direct and indirect effects of hepatitis B vaccination in four low- and middle-income countries

Population-level vaccination effects of the hepatitis B vaccine were investigated in four low- and middle-income countries with different levels of vertical and horizontal transmission. Indirect vaccination effects constitute a large proportion of overall vaccination effects of the vaccination programmes in all four countries (over 70% by 2030 in all four countries). However, countries with higher levels of vertical transmission benefit less from indirect vaccination effects from the infant hepatitis B vaccine series during the first decades of the vaccination programme, making the birth dose vaccine more important in these countries. Vaccination, even at levels that do not fully control transmission, has a great effect on the development of disease as it also increases the average age of infection, thereby causing a decrease in the number of chronic infections relative to the number of acute infections.

Protective role of TRPV1+ nociceptive neurons communication to macrophages against T. cruzi infection in mice

Chagas’ disease is a life-threatening condition caused by Trypanosoma cruzi. Patients with chronic disease may develop gastrointestinal, neurological, or associated neuro-digestive dysfunctions. CNS invasion by T. cruzi can occur in the acute phase, and its presence in the brain and cerebrospinal fluid was reported. T. cruzi induces nociceptor neuron activation and pain. Nociceptive neurons and macrophage interact in diseases, and this neuroimmune communication has a pivotal role in disease outcome. We investigated, the role of TRPV1+ neurons in experimental T. cruzi infection in mice. T. cruzi forms were observed in the DRG and spinal cord in early stages of acute infection, and intrathecal administration of T. cruzi antigens into spinal cord induced pain. Trpv1 mRNA expression was increased in the DRG of infected mice and targeting TRPV1 reduced T. cruzi-induced pain. TRPV1 nociceptor ablation increased blood parasitemia while TRPV1 knockout mice presented 50% mortality upon infection in a normally non-lethal model. TRPV1 knockout also worsened clinical outcomes (hepatomegaly and megacecum), increased plasmatic Th2 cytokines and nitrite in cardiac tissue, and reduced heart leukocyte infiltration. Conditioned media of capsaicin-stimulated DRG neurons decreased macrophage internalization of T. cruzi, and CGRP receptor antagonism in infected mice reduced pain, increased early parasitemia and promoted 18% mortality. This indicates that soluble mediators released upon nociceptor activation such as CGRP increase macrophage ability to control disease outcome. These data unveil TRPV1+ neurons release CGRP to limit macrophage internalization of T. cruzi, triggering protective mechanisms against T. cruzi infection.

Post-COVID in healthcare workers and its consequences on quality of life, activities, participation, need for rehabilitation and care experiences: protocol of a cohort study

IntroductionHealthcare workers (HCWs) have been of particular relevance for overcoming the SARS-CoV-2 pandemic. At the same time they have been affected by SARS-CoV-2 infections with above average probability. Around 6.5% of the overall infected persons are likely to develop persistent symptoms resulting from the infection, known as long-COVID or post-COVID syndrome (PCS). The aim of this study is (1) to investigate the prevalence, course and characteristics of PCS in German HCWs, (2) to examine its effects on psychosocial variables, (3) to identify rehabilitation and healthcare needs and (4) to analyse treatment experiences.Methods and analysisIn a cohort study with a randomised selection of participants (N=20 000) from the Employer’s Liability Insurance Association for Health and Welfare Care, the health status of HCWs, who had COVID-19 in their professional context will be examined. There will be two measurement points: baseline (T1) and a 12-month follow-up (T2). The outcome measures are the health status with a particular focus on persistent or newly occurring symptoms after a SARS-CoV-2 infection, health-related quality of life, functional capacity, the subjective need for and utilisation of healthcare services. Pre-existing conditions, the course of the acute infection and sociodemographic factors are considered as predictors. An advisory board made up of affected HCWs supports the study by contributing to the surveys’ contents.Ethics and disseminationThe study has been approved by the Local Ethics Committee of the Center for Psychosocial Medicine at the University Hospital Hamburg-Eppendorf (LPEK-0518). For dissemination, the results will be published in peer-reviewed journals, presented at conferences and communicated to relevant stakeholders in general and rehabilitation medicine.Trail registration numberhttps://drks.de/search/de/trial/DRKS00029314

From acute to persistent infection: revealing phylogenomic variations in Salmonella Agona.

Salmonella enterica serovar Agona (S. Agona) has been increasingly recognised as a prominent cause of gastroenteritis. This serovar is a strong biofilm former that can undergo genome rearrangement and enter a viable but non-culturable state whilst remaining metabolically active. Similar strategies are employed by S. Typhi, the cause of typhoid fever, during human infection, which are believed to assist with the transition from acute infection to chronic carriage. Here we report S. Agona's ability to persist in people and examine factors that might be contributing to chronic carriage. A review of 2233 S. Agona isolates from UK infections (2004-2020) and associated carriage was undertaken, in which 1155 had short-read sequencing data available. A subset of 207 isolates was selected from different stages of acute and persistent infections within individual patients. The subset underwent long-read sequencing and genome structure (GS) analysis, as well as phenotyping assays including carbon source utilisation and biofilm formation. Associations between genotypes and phenotypes were investigated to compare acute infections to those which progress to chronic. GS analysis revealed the conserved arrangement GS1.0 in 195 isolates, and 8 additional GSs in 12 isolates. These rearranged isolates were typically associated with early, convalescent carriage (3 weeks- 3 months). We also identified an increase in SNP variation during this period of infection. We believe this increase in genome-scale and SNP variation reflects a population expansion after acute S. Agona infection, potentially reflecting an immune evasion mechanism which enables persistent infection to become established.

Cost-effectiveness of an online supervised group physical and mental health rehabilitation programme for adults with post-COVID-19 condition after hospitalisation for COVID-19: the REGAIN RCT

BackgroundFollowing the COVID-19 pandemic, millions of people continue to experience ongoing physical and mental health sequelae after recovery from acute infection. There is currently no specific treatment for the diverse symptoms associated with post-COVID-19 condition. Physical and mental health rehabilitation may help improve quality of life in such patients. This study reports the cost-effectiveness of a programme of physical and mental health rehabilitation compared to best practice usual care in people with post-COVID-19 condition who were previously hospitalised.MethodsWe conducted an economic evaluation within a randomised controlled trial from the perspective of the UK national health service (NHS) and personnel social services perspective (PSS). Resource used and health-related quality of life were collected using bespoke questionnaire and the EQ-5D-5 L questionnaire at three, six, and 12 months. Incremental costs and quality adjusted life years accrued over the follow-up period were estimated and reported as the incremental cost-effectiveness ratio. Estimate uncertainty was managed by multiple imputation and bootstrapping cost-effectiveness estimates; and displayed graphically on the cost-effectiveness plane.ResultsOver a 12-month time horizon, incremental costs and QALYs were £305 (95% CI: -123 to 732) and 0.026 (95% CI: -0.005 to 0.052) respectively. The ICER was £11,941 per QALY indicating cost-effective care. Sensitivity analyses supported the base case findings. The probability of the intervention being cost-effective at a £30,000 per QALY willingness-to-pay threshold was 84%.ConclusionThe within-trial economic evaluation suggested that people with post-COVID-19 condition after hospitalisation should be offered a programme of physical and mental health rehabilitation as it likely reflects a cost-effective use of NHS resources. Hospitalisation for COVID-19 has become less commonplace: further evaluation in non-hospitalised patients may be worthwhile.Trial registrationISRCTN registry ISRCTN11466448 23rd November 2020.

Influenza and non-influenza ARVI in children. A relationship between cytokine profile, parameters of the “lipid peroxidation – antioxidant defense system” as well as clinical and laboratory indicators

Influenza and acute respiratory viral infections (ARVI) impose a substantial damage to the population health in the Russian Federation due to their seasonal circulation and predominantly affect young children. A very few data on the cytokine profile, the nonspecific LPO — AOD system and their relationships with clinical characteristics in such diseases in preschool children are available. The aim of this study was to assess the cytokine profile, LPO — AOD system parameters and their relationship with the clinical and laboratory characteristics of diseases in preschool children with influenza and other ARVI. 86 preschool children (3–6 years old) were examined: with an established diagnosis of influenza (n = 31), non-influenza ARVI (n = 28), apparently healthy children (control group (n = 27). All pediatric samples were analyzed by enzyme-linked immunosorbent assay assessing blood serum concentrations of C-reactive protein and cytokines IL-1β, IL-4, IL-6, IL-8, TNFα, IFNα, IFNγ. Spectrophotometric, fluorometric and enzyme immunoassay methods to assess the state of the “LPO — AOD” system were used. In the group of children with influenza vs other ARVI, a higher incidence of intoxication syndrome was revealed. Cytokine profile in children from both clinical groups compared with control cohort was featured with higher indicators of both pro-inflammatory and anti-inflammatory origin. Children with non-influenza ARVI, had increased magnitude of LPO final products in the nonspecific LPO — AOD system along with lowered concentration of fat-soluble vitamins, general antioxidant activity, GSH level, and SOD activity. In the group with influenza, the level of primary and final lipid peroxidation products was increased, whereas that of for retinol,α-tocopherol, and total antioxidant activity was decreased paralleled with higher GSSG and SOD levels. Numerous correlations were noted in the group of children with ARVI: IL-1β/ketones, IL-6/ketones, IL-8/ketones, TNFα/ketones, IL-4/ketones, IFNg/shortness of breath, IFNα/cough, double bonds/fever, double bonds/AST, SO/intoxication, retinol/fever, GSSG/cough. The influenza group differed in the following relationships: IL-4/ketones, IL-4/fever, IFNα/ketones, CDs/AST. It can be concluded that in preschool children with ARVI and influenza, changes in the cytokine profile are accompanied by increased pro- and anti-inflammatory cytokine levels, increased intensity of lipid peroxidation reactions along with reduced magnitude of antioxidant factors. In the group with ARVI, there was a relationship between the final toxic products of lipid peroxidation — Schiff bases — and the intoxication index, as well as the presence of protective mechanisms in the form of connections between interferons and disease clinical manifestations. The group with influenza was distinguished by the presence of protective relations, which may have a beneficial effect in the context of developing pathological process. The data obtained will help expand the understanding of the pathogenetic mechanisms related to immune reactivity and nonspecific lipid peroxidation reactions in preschool patients and formulate appropriate measures for correction.

Longitudinal Fecal Microbiota Profiles in A Cohort of Non-Hospitalized Adolescents and Young Adults with COVID-19: Associations with SARS-CoV-2 Status and Long-Term Fatigue

Adolescents most often experience mild acute COVID-19, but may still face fatigue and persistent symptoms such as post-COVID-19 condition (PCC) and post-infective fatigue syndrome (PIFS). We explored the fecal microbiota of SARS-CoV-2 positive and negative non-hospitalized adolescents and young adults (12–25 years of age) in the “Long-Term Effects of COVID-19 in Adolescents” (LoTECA) project, a longitudinal observational cohort study. With a targeted qPCR approach, the quantities of 100 fecal bacterial taxa were measured at baseline (early convalescent stage) in 145 SARS-CoV-2-positive and 32 SARS-CoV-2 negative participants and after six months in 107 of the SARS-CoV-2-positive and 19 of the SARS-CoV-2 negative participants. Results: Faecalibacterium prausnitzii M21.2 and Gemmiger formicilis (both p &lt; 0.001) were enriched in the SARS-CoV-2-positive participants compared to negative controls at baseline. In SARS-CoV-2-positive participants, lower baseline abundance of Faecalibacterium prausnitzii M21/2 (p = 0.013) and higher abundance of Clostridium spiroforme (p = 0.006), Sutterella wadsworthensis (p &lt; 0.001), and Streptococcus thermophilus (p = 0.039) were associated with six-month fatigue. Sutterella wadsworthensis and Streptococcus thermophilus enrichment was additionally associated with PCC in the SARS-CoV-2-positive group (p &lt; 0.001 and 0.042 respectively). Conclusions: Adolescents and young adults with mild acute COVID-19 infection had increased fecal abundance of the beneficial Faecalibacterium prausnitzii M21/2 and Gemmiger formicilis compared to SARS-CoV-2 negative controls in the early convalescent stage. Additionally, the abundance of both known (Faecalibacterium prausnitzii, Streptococcus thermophilus) and new (Clostridium spiroforme, Sutterella wadsworthensis) bacteria were associated with persistent symptoms such as fatigue in the COVID-19 infected group, warranting further exploration of the role of these bacteria in COVID-19 disease and PCC pathophysiology.

An analysis of virtual triage utilization by pregnant women prior to and during the COVID-19 pandemic.

This analysis describes the use patterns of web-based virtual triage (VT) by pregnant patients before and during the first two years of the COVID-19 pandemic, and how the pandemic influenced frequency of VT use, nature of symptoms reported, and the associated implications for maternal healthcare delivery. An online survey of 36,910 patients who reported pregnancy was completed between January 1, 2019 and June 30, 2022. The data were segmented into six month periods to allow comparative analyses of usage frequency and changes in initial complaints over the study period, with particular emphasis on the early months of the COVID-19 pandemic. Descriptive statistics and trend analyses were used to identify significant shifts in symptom reporting and user demographics. A marked increase in the utilization of VT by pregnant women during the pandemic occurred. The percentage of pregnant users grew from 0.32% in the first half of 2019 to 0.85% in late 2021, with the greatest rise (213%) in the first six months of 2020. The most common symptoms reported were abdominal pain, headache, nausea, back pain, fatigue and cough. Pre-pandemic, VT use focused on prospective mothers learning about the potential causes of typical symptoms occurring during pregnancy, but during the pandemic there was a substantial increase in reporting symptoms associated with acute respiratory infections such as cough, nasal congestion, and dyspnea. The COVID-19 pandemic significantly influenced the use of VT by pregnant women, with a shift towards addressing concerns related to respiratory symptoms and potential COVID-19 exposure. These findings underline the significant role of digital health tools in maintaining access to health information during times of crisis and highlight the evolving needs of pregnant patients in such settings.

Enteroviruses, Respiratory Syncytial Virus and Seasonal Coronaviruses in Influenza-like Illness Cases in Nepal

Acute respiratory infection is one of the leading causes of morbidity and mortality among children in low- and middle-income countries. Due to limited diagnostic capability, many respiratory pathogens causing influenza-like illness go undetected. This study aims to detect enterovirus, respiratory syncytial virus, seasonal coronavirus and respiratory pathogens other than influenza in patients with influenza-like illness. A total of 997 (54.3%) respiratory samples (collected in the years 2016–2018) were randomly selected from 1835 influenza-negative samples. The xTAG Respiratory Viral Panel (RVP) FAST v2 panel was used to detect respiratory pathogens including enterovirus/rhinovirus (EV/RV), respiratory syncytial virus (RSV) and seasonal coronavirus (HKU1, OC43, NL63 and 229E). A total of 78.7% (785/997) were positive for respiratory viruses. Of these viruses, EV/RV was detected in 36.3% (362/997), which is the highest number, followed by RSV in 13.7% (137/997). The seasonal coronaviruses HKU1 and OC43 (1.5%, 15/997), NL63 (1.2%, 12/997) and 229E (1%, 10/997) were also detected. The EV/RV-positive samples were sequenced, of which 16.7% (5/30) were confirmed as EVs and were identified as coxsackievirus (CV) types CVB5, CVB3, CV21 and CVB2. The findings of this study highlight the importance of strengthening influenza-like illness surveillance programs in the region by including other respiratory viruses in their scope besides seasonal human influenza viruses.

B cell receptor dependent enhancement of dengue virus infection.

Dengue virus (DENV) is the causative agent of dengue, a mosquito-borne disease that represents a significant and growing public health burden around the world. A unique pathophysiological feature of dengue is immune-mediated enhancement, wherein preexisting immunity elicited by a primary infection can enhance the severity of a subsequent infection by a heterologous DENV serotype. A leading mechanistic explanation for this phenomenon is antibody dependent enhancement (ADE), where sub-neutralizing concentrations of DENV-specific IgG antibodies facilitate entry of DENV into FcγR expressing cells such as monocytes, macrophages, and dendritic cells. Accordingly, this model posits that phagocytic mononuclear cells are the primary reservoir of DENV. However, analysis of samples from individuals experiencing acute DENV infection reveals that B cells are the largest reservoir of infected circulating cells, representing a disconnect in our understanding of immune-mediated DENV tropism. In this study, we demonstrate that the expression of a DENV-specific B cell receptor (BCR) renders cells highly susceptible to DENV infection, with the infection-enhancing activity of the membrane-restricted BCR correlating with the ADE potential of the IgG version of the antibody. In addition, we observed that the frequency of DENV-infectible B cells increases in previously flavivirus-naïve volunteers after a primary DENV infection. These findings suggest that BCR-dependent infection of B cells is a novel mechanism immune-mediated enhancement of DENV-infection.