Performance Evaluation of VIDAS® Diagnostic Assays Detecting Anti-Chikungunya Virus IgM and IgG Antibodies: An International Study.

Chikungunya (CHIK) is a debilitating mosquito-borne disease with an epidemiology and early clinical symptoms similar to those of other arboviruses-triggered diseases such as dengue or Zika. Accurate and rapid diagnosis of CHIK virus (CHIKV) infection is therefore challenging. This international study evaluated the performance of the automated VIDAS® anti-CHIKV IgM and IgG assays compared to that of manual competitor IgM and IgG ELISA for the detection of anti-CHIKV IgM and IgG antibodies in 660 patients with suspected CHIKV infection. Positive and negative agreements of the VIDAS® CHIKV assays with ELISA ranged from 97.5% to 100.0%. The sensitivity of the VIDAS® CHIKV assays evaluated in patients with a proven CHIKV infection confirmed reported kinetics of anti-CHIKV IgM and IgG response, with a positive detection of 88.2-100.0% for IgM ≥ 5 days post symptom onset and of 100.0% for IgG ≥ 11 days post symptom onset. Our study also demonstrated the superiority of ELISA and VIDAS® assays over rapid diagnostic IgM/IgG tests. The analytical performance of VIDAS® anti-CHIKV IgM and IgG assays was excellent, with a high precision (coefficients of variation ≤ 7.4%) and high specificity (cross-reactivity rate ≤ 2.9%). This study demonstrates the suitability of the automated VIDAS® anti-CHIKV IgM and IgG assays to diagnose CHIKV infections and supports its applicability for epidemiological surveillance and differential diagnosis in regions endemic for CHIKV.

In-hospital mortality risk stratification in children aged under 5 years with pneumonia with or without pulse oximetry: A secondary analysis of the Pneumonia REsearch Partnership to Assess WHO REcommendations (PREPARE) dataset.

OBJECTIVES: We determined the pulse oximetry benefit in pediatric pneumonia mortality risk stratification and chest-indrawing pneumonia in-hospital mortality risk factors. METHODS: We report the characteristics and in-hospital pneumonia-related mortality of children aged 2-59 months who were included in the Pneumonia Research Partnership to Assess WHO Recommendations dataset. We developed multivariable logistic regression models of chest-indrawing pneumonia to identify mortality risk factors. RESULTS: Among 285,839 children, 164,244 (57.5%) from hospital-based studies were included. Pneumonia case fatality risk (CFR) without pulse oximetry measurement was higher than with measurement (5.8%, 95% confidence interval [CI] 5.6-5.9% vs 2.1%, 95% CI 1.9-2.4%). One in five children with chest-indrawing pneumonia was hypoxemic (19.7%, 95% CI 19.0-20.4%), and the hypoxemic CFR was 10.3% (95% CI 9.1-11.5%). Other mortality risk factors were younger age (either 2-5 months [adjusted odds ratio (aOR) 9.94, 95% CI 6.67-14.84] or 6-11 months [aOR 2.67, 95% CI 1.71-4.16]), moderate malnutrition (aOR 2.41, 95% CI 1.87-3.09), and female sex (aOR 1.82, 95% CI 1.43-2.32). CONCLUSION: Children with a pulse oximetry measurement had a lower CFR. Many children hospitalized with chest-indrawing pneumonia were hypoxemic and one in 10 died. Young age and moderate malnutrition were risk factors for in-hospital chest-indrawing pneumonia-related mortality. Pulse oximetry should be integrated in pneumonia hospital care for children under 5 years.

Clinical markers of post-Chikungunya chronic inflammatory joint disease: A Brazilian cohort.

BACKGROUND: Chikungunya-fever (CHIKF) remains a public health major issue. It is clinically divided into three phases: acute, post-acute and chronic. Chronic cases correspond to 25-40% individuals and, though most of them are characterized by long-lasting arthralgia alone, many of them exhibit persistent or recurrent inflammatory signs that define post-Chikungunya chronic inflammatory joint disease (pCHIKV-CIJD). We aimed to identify early clinical markers of evolution to pCHIKV-CIJD during acute and post-acute phases. METHODOLOGY/PRINCIPAL FINDINGS: We studied a prospective cohort of CHIKF-confirmed volunteers with longitudinal clinical data collection from symptoms onset up to 90 days, including a 21-day visit (D21). Of 169 patients with CHIKF, 86 (50.9%) completed the follow-up, from whom 39 met clinical criteria for pCHIKV-CIJD (45.3%). The relative risk of chronification was higher in women compared to men (RR = 1.52; 95% CI = 1.15-1.99; FDR = 0.03). None of the symptoms or signs presented at D0 behaved as an early predictor of pCHIKV-CIJD, while being symptomatic at D21 was a risk factor for chronification (RR = 1.31; 95% CI = 1.09-1.55; FDR = 0.03). Significance was also observed for joint pain (RR = 1.35; 95% CI = 1.12-1.61; FDR = 0.02), reported edema (RR = 3.61; 95% CI = 1.44-9.06; FDR = 0.03), reported hand and/or feet small joints edema (RR = 4.22; 95% CI = 1.51-11.78; FDR = 0.02), and peri-articular edema observed during physical examination (RR = 2.89; 95% CI = 1.58-5.28; FDR = 0.002). Furthermore, patients with no findings in physical examination at D21 were at lower risk of chronic evolution (RR = 0.41, 95% CI = 0.24-0.70, FDR = 0.01). Twenty-nine pCHIKV-CIJD patients had abnormal articular ultrasonography (90.6% of the examined). The most common findings were synovitis (65.5%) and joint effusion (58.6%). CONCLUSION: This cohort has provided important insights into the prognostic evaluation of CHIKF. Symptomatic sub-acute disease is a relevant predictor of evolution to chronic arthritis with synovitis, drawing attention to joint pain, edema, multiple articular involvement including small hand and feet joints as risk factors for chronification beyond three months, especially in women. Future studies are needed to accomplish the identification of accurate and early biomarkers of poor clinical prognosis, which would allow better understanding of the disease's evolution and improve patients' management, modifying CHIKF burden on global public health.

The Relationship between DUGBE Virus Infection and Autophagy in Epithelial Cells.

Dugbe orthonairovirus (DUGV) is a tick-borne arbovirus within the order Bunyavirales. Although displaying mild pathogenic potential, DUGV is genetically related to the Crimean-Congo hemorrhagic fever virus (CCHFV), another orthonairovirus that causes severe liver dysfunction and hemorrhagic fever with a high mortality rate in humans. As we previously observed that CCHFV infection could massively recruit and lipidate MAP1LC3 (LC3), a core factor involved in the autophagic degradation of cytosolic components, we asked whether DUGV infection also substantially impacts the autophagy machinery in epithelial cells. We observed that DUGV infection does impose LC3 lipidation in cultured hepatocytes. DUGV infection also caused an upregulation of the MAP1LC3 and SQSTM1/p62 transcript levels, which were, however, more moderate than those seen during CCHFV infection. In contrast, unlike during CCHFV infection, the modulation of core autophagy factors could influence both LC3 lipidation and viral particle production: the silencing of ATG5 and/or ATG7 diminished the induction of LC3 lipidation and slightly upregulated the level of infectious DUGV particle production. Overall, the results are compatible with the notion that in epithelial cells infected with DUGV in vitro, the autophagy machinery may be recruited to exert a certain level of restriction on viral replication. Thus, the relationship between DUGV infection and autophagy in epithelial cells appears to present both similarities and distinctions with that seen during CCHFV infection.

Derivation and validation of a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality in 20 countries.

INTRODUCTION: Existing risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality across various settings. METHODS: We used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries. Patients with complete data were included in a logistic regression model to assess the association of candidate variables with the outcome hospitalised pneumonia-related mortality. Adjusted log coefficients were calculated for each candidate variable and assigned weighted points to derive the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) risk assessment tool. We used bootstrapped selection with 200 repetitions to internally validate the PREPARE risk assessment tool. RESULTS: A total of 27 388 children were included in the analysis (mean age 14.0 months, pneumonia-related case fatality ratio 3.1%). The PREPARE risk assessment tool included patient age, sex, weight-for-age z-score, body temperature, respiratory rate, unconsciousness or decreased level of consciousness, convulsions, cyanosis and hypoxaemia at baseline. The PREPARE risk assessment tool had good discriminatory value when internally validated (area under the curve 0.83, 95% CI 0.81 to 0.84). CONCLUSIONS: The PREPARE risk assessment tool had good discriminatory ability for identifying children at risk of hospitalised pneumonia-related mortality in a large, geographically diverse dataset. After external validation, this tool may be implemented in various settings to identify children at risk of hospitalised pneumonia-related mortality.

Nasopharyngeal Viral and Bacterial Co-Detection among Children from Low- and Middle-Income Countries with and without Pneumonia.

The role of microbial coinfection in the pathogenesis of pneumonia in children is not well known. The aim of this work was to describe the prevalence of microorganism co-detection in nasopharyngeal samples (NPS) of pneumonia cases and control subjects and to study the potential association between nasopharyngeal microorganism co-detection and pneumonia. A case-control study was carried out from 2010 to 2014 in nine study sites located in low- or middle-income countries. The data from 888 children under 5 years of age with pneumonia (cases) and 870 children under 5 without pneumonia (controls) were analyzed. Nasopharyngeal samples were collected; reverse transcription polymerase chain reaction (RT-PCR) enabled the detection of five bacteria and 19 viruses. Multiple, mixed-effects logistic regression modeling was undertaken to evaluate the association between microorganism co-detection and pneumonia. A single Streptococcus pneumoniae colonization was observed in 15.2% of the controls and 10.1% of the cases (P = 0.001), whereas S. pneumoniae and a single virus co-detection was observed in 33.3% of the cases and in 14.6% of the controls (P < 0.001). Co-detections with rhinovirus, respiratory syncytial virus, parainfluenza virus, human metapneumovirus, and influenza virus were more frequent in the cases compared with the controls (P < 0.001) and were significantly associated with pneumonia in multiple regression analysis. The proportion of single virus detection without bacterial co-detection was not different between cases and controls (13.6% versus 11.3%, P = 0.13). This study suggests that coinfection of S. pneumoniae and certain viruses may play a role in the pathophysiology of pneumonia in children.

External validation of the RISC, RISC-Malawi, and PERCH clinical prediction rules to identify risk of death in children hospitalized with pneumonia.

BACKGROUND: Existing scores to identify children at risk of hospitalized pneumonia-related mortality lack broad external validation. Our objective was to externally validate three such risk scores. METHODS: We applied the Respiratory Index of Severity in Children (RISC) for HIV-negative children, the RISC-Malawi, and the Pneumonia Etiology Research for Child Health (PERCH) scores to hospitalized children in the Pneumonia REsearch Partnerships to Assess WHO REcommendations (PREPARE) data set. The PREPARE data set includes pooled data from 41 studies on pediatric pneumonia from across the world. We calculated test characteristics and the area under the curve (AUC) for each of these clinical prediction rules. RESULTS: The RISC score for HIV-negative children was applied to 3574 children 0-24 months and demonstrated poor discriminatory ability (AUC = 0.66, 95% confidence interval (CI) = 0.58-0.73) in the identification of children at risk of hospitalized pneumonia-related mortality. The RISC-Malawi score had fair discriminatory value (AUC = 0.75, 95% CI = 0.74-0.77) among 17 864 children 2-59 months. The PERCH score was applied to 732 children 1-59 months and also demonstrated poor discriminatory value (AUC = 0.55, 95% CI = 0.37-0.73). CONCLUSIONS: In a large external application of the RISC, RISC-Malawi, and PERCH scores, a substantial number of children were misclassified for their risk of hospitalized pneumonia-related mortality. Although pneumonia risk scores have performed well among the cohorts in which they were derived, their performance diminished when externally applied. A generalizable risk assessment tool with higher sensitivity and specificity to identify children at risk of hospitalized pneumonia-related mortality may be needed. Such a generalizable risk assessment tool would need context-specific validation prior to implementation in that setting.

Procalcitonin as a biomarker for ventilator associated pneumonia in COVID-19 patients: Is it an useful stewardship tool?

Ventilator associated pneumonia(VAP) is a severe complication that can lead to high mortality when not early identified or when therapy is delayed. The aim of this study was to evaluate procalcitonin(PCT) as a biomarker for VAP development. In total, 73 hospitalized patients with COVID-19 were analyzed. PCT levels greater than 0.975ng/mL were more related to VAP. No association was found for C-reactive protein (CRP). The results show that procalcitonin may be a pertinent biomarker for VAP diagnosis and can be a helpful tool for antibiotic withdrawal.

Evaluation of loop-mediated isothermal amplification assay for detection of Clostridioides difficile infection: A prospective diagnostic performance study.

A novel Loop-mediated isothermal amplification (LAMP) assay, HiberGene's CD was evaluated with 82 unformed stools from patients suspected of C. difficile infection (CDI). Compared to glutamate dehydrogenase (GDH) toxins A/B test (C.diff Quik Chek®), HiberGene's LAMP showed 100% of sensitivity and 95,8% of specificity; and compared to FilmArray™ GI panel ® (BioFire), a sensitivity of 81,2% and a specificity of 100%, with 96.38% of agreement.

Bacterial and Viral Infection in Patients Hospitalized for Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Implication for Antimicrobial Management and Clinical Outcome.

Patients with chronic obstructive pulmonary disease (COPD) exhibit frequent acute exacerbations (AE). The objectives of this study were first to evaluate the prevalence of pathogens associated to these episodes by combining conventional bacteriology and multiplex viral and bacterial PCR assays in sputum specimens, and second to determine whether C-reactive protein (CRP) value and clinical outcome could be influenced by the type of microbial agent(s) recovered from these samples. A cohort of 84 Tunisian patients hospitalized at the emergency room for AECOPD was investigated prospectively for the semi-quantitative detection of bacteria by conventional culture (the threshold of positivity was of 107 CFU/ml) and for the detection of viral genome and DNA of atypical bacteria by quantitative PCR using two commercial multiplex respiratory kits (Seegene and Fast-track). The two kits exhibited very similar performances although the Seegene assay was a bit more sensitive. A large number and variety of pathogens were recovered from the sputum samples of these 84 patients, including 15 conventional bacteria, one Chlamydia pneumoniae and 63 respiratory viruses, the most prevalent being rhinoviruses (n = 33) and influenza viruses (n = 13). From complete results available for 74 patients, the presence of bacteria was significantly associated with risk of recurrence at 6 and 12 months post-infection. The combination of these different markers appears useful for delineating correctly the antimicrobial treatment and for initiating a long-term surveillance in those patients with high risk of recurrent exacerbation episodes. A prospective study is required for confirming the benefits of this strategy aimed at improving the stewardship of antibiotics.

Crimean-Congo hemorrhagic fever virus replication imposes hyper-lipidation of MAP1LC3 in epithelial cells.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a virus that causes severe liver dysfunctions and hemorrhagic fever, with high mortality rate. Here, we show that CCHFV infection caused a massive lipidation of LC3 in hepatocytes. This lipidation was not dependent on ATG5, ATG7 or BECN1, and no signs for recruitment of the alternative ATG12-ATG3 pathway for lipidation was found. Both virus replication and protein synthesis were required for the lipidation of LC3. Despite an augmented transcription of SQSTM1, the amount of proteins did not show a massive and sustained increase in infected cells, indicating that degradation of SQSTM1 by macroautophagy/autophagy was still occurring. The genetic alteration of autophagy did not influence the production of CCHFV particles demonstrating that autophagy was not required for CCHFV replication. Thus, the results indicate that CCHFV multiplication imposes an overtly elevated level of LC3 mobilization that involves a possibly novel type of non-canonical lipidation. Abbreviations: BECN1: Beclin 1; CCHF: Crimean-Congo hemorrhagic fever; CCHFV: Crimean-Congo hemorrhagic fever virus; CHX: cycloheximide; ER: endoplasmic reticulum; GFP: green fluorescent protein; GP: glycoproteins; MAP1LC3: microtubule associated protein 1 light chain 3; MOI: multiplicity of infection; n.i.: non-infected; NP: nucleoprotein; p.i.: post-infection; SQSTM1: sequestosome 1.

Serotypes of Streptococcus pneumoniae in Children Aged <5 Years Hospitalized With or Without Pneumonia in Developing and Emerging Countries: A Descriptive, Multicenter Study.

BACKGROUND: Improving knowledge regarding Streptococcus pneumoniae distribution in pneumonia cases is important to better target preventive and curative measures. The objective was to describe S. pneumoniae serotypes in children with or without pneumonia. METHODS: It was a case-control study carried out in 8 developing and emerging countries between 2010 and 2014. Cases were children aged <5 years admitted to the hospital for pneumonia. Controls were children admitted for surgery or routine outpatient care. RESULTS: In nasopharyngeal samples, S. pneumoniae were detected in 68.2% of the cases and 47.5% of the controls (P < .001). Nasopharyngeal carriage was associated with a higher risk of being a case in 6/8 study sites (adjusted odds ratio ranged from 0.71 [95% confidence interval [CI], .39-1.29; P = .26] in India [Pune/Vadu] to 11.86 [95% CI, 5.77-24.41; P < .001] in Mongolia). The 13-valent pneumococcal conjugate vaccine (PCV13) serotypes were more frequently detected in cases with nasopharyngeal carriage (67.1%) than in controls with nasopharyngeal carriage (54.6%), P < .001. Streptococcus pneumoniae was detected in blood by polymerase chain reaction in 8.3% of the cases. Of 34 cases with an S. pneumoniae serotype detected in blood, 27 (79%) had the same serotype in the nasopharyngeal sample. CONCLUSIONS: The results confirm the assumption that the isolate carrying or causing disease in an individual is of the same serotype. Most serotypes independently associated with nasopharyngeal carriage or pneumonia are covered by PCV13, suggesting that increased PCV coverage would reduce the burden of S. pneumoniae-related pneumonia.

First insights into the genetic characteristics and drug resistance of Mycobacterium tuberculosis population collected during the first national tuberculosis prevalence survey of Lao PDR (2010-2011).

BACKGROUND: In Lao People's Democratic Republic (PDR), tuberculosis (TB) prevalence was estimated at 540/100,000 in 2011. Nevertheless, little is known about the genetic characteristics and anti-TB drug resistance of the Mycobacterium tuberculosis population. The main objective of this work was to study the genetic characteristics and drug resistance of M. tuberculosis population collected during the first National TB Prevalence Survey (TBPS) of Lao PDR (2010-2011). METHODS: Two hundred and twenty two isolates collected during TBPS (2010-2011) were analyzed with the GenoType MTBDRplus test for M. tuberculosis identification and drug resistance detection. Then, 206 of the 222 isolates were characterized by spoligotyping and MIRU-VNTR typing. RESULTS: Among the 222 M. tuberculosis isolates, 11 were mono-resistant to isoniazid and 2 were resistant to isoniazid and rifampicin (MDR-TB), using the GenoType MTBDRplus test. Among the 202 genetically characterized isolates, the East African-Indian (EAI) family was predominant (76.7%) followed by the Beijing (14.4%) and T (5.5%) families. EAI isolates came from all the country provinces, whereas Beijing isolates were found mainly in the northern and central provinces. A higher proportion of Beijing isolates was observed in people younger than 35 years compared to EAI. Moreover, the percentage of drug resistance was higher among Beijing (17.2%) than EAI (5.2%) isolates, and the two MDR-TB isolates belonged to the Beijing family. Combined analysis of the MIRU-VNTR and spoligotyping results (n = 202 isolates) revealed an estimated clustering rate of 11% and the occurrence of mini-outbreaks of drug-resistant TB caused by Beijing genotypes. CONCLUSIONS: The EAI family, the ancient and endemic family in Asia, is predominant in Lao PDR whereas the prevalence of Beijing, the most harmful M. tuberculosis family for humans, is still low, differently from neighboring countries. However, its association with drug resistance, its presence in young patients and its potential association with recent transmission suggest that the Beijing family could change TB epidemiological pattern in Lao PDR. Therefore, efficient TB control and surveillance systems must be maintained and reinforced to prevent the emergence of highly transmissible and drug-resistant strains in Lao PDR, as observed in neighboring countries.

Correction: "Epidemiology and aetiology of influenza-like illness among households in metropolitan Vientiane, Lao PDR": A prospective, community-based cohort study.

[This corrects the article DOI: 10.1371/journal.pone.0214207.].

Zika virus infection among symptomatic patients from two healthcare centers in Sao Paulo State, Brazil: prevalence, clinical characteristics, viral detection in body fluids and serodynamics.

Zika virus (ZIKV) clinical presentation and frequency/duration of shedding need further clarification. Symptomatic ZIKV-infected individuals identified in two hospitals in Sao Paulo State, Brazil, were investigated regarding clinical characteristics, shedding in body fluids, and serodynamics. Ninety-four of 235 symptomatic patients (Site A: 58%; Site B: 16%) had Real-Time PCR-confirmed ZIKV infection; fever, headache and gastrointestinal symptoms were less frequent, and rash was more frequent compared to ZIKV-negative patients. Real-Time PCR in serum had worse performance compared to plasma, while urine had the highest sensitivity. Shedding in genital fluids and saliva was rare. IgM positivity was the highest <14 days after the symptoms onset (86%), decreasing >28 days (24%); IgG positivity increased >14 days (96%) remaining positive in 94% of patients >28 days. ZIKV prevalence varied importantly in two neighboring cities during the same transmission season. Urine Real-Time PCR can improve diagnostic sensitivity; serum testing is less useful. Accurate serological tests are needed to improve diagnosis and surveillance.

"Epidemiology and aetiology of influenza-like illness among households in metropolitan Vientiane, Lao PDR": A prospective, community-based cohort study.

Respiratory diseases are a major contributor to morbidity and mortality in many tropical countries, including Lao PDR. However, little has been published regarding viral or bacterial pathogens that can contribute to influenza-like illness (ILI) in a community setting. We report on the results of a community-based surveillance that prospectively monitored the incidence of ILI and its causative pathogens in Vientiane capital in Lao PDR. A cohort of 995 households, including 4885 study participants, were followed-up between May 2015 and May 2016. Nasopharyngeal swabs, throat swabs, and sputum specimens were collected from ILI cases identified through active case-finding. Real-Time PCR was used to test nasopharyngeal swabs for 21 respiratory pathogens, while throat and sputum samples were subjected to bacterial culture. Generalized linear mixed models were used to assess potential risk factors for associations with ILI. In total, 548 episodes of ILI were reported among 476 (9.7%) of the study participants and 330 (33.2%) of the study households. The adjusted estimated incidence of ILI within the study area was 10.7 (95%CI: 9.4-11.9) episodes per 100 person-years. ILI was significantly associated with age group (p<0.001), sex (p<0.001), and number of bedrooms (p = 0.04) in multivariate analysis. In 548 nasopharyngeal swabs, the most commonly detected potential pathogens were Streptococcus pneumoniae (17.0%), Staphylococcus aureus (11.3%), influenza A (11.1%; mostly subtype H3N2), rhinovirus (7.5%), and influenza B (8.0%). Streptococci were isolated from 42 (8.6%) of 536 throat swabs, most (27) of which were Lancefield Group G. Co-infections were observed in 132 (24.1%) of the 548 ILI episodes. Our study generated valuable data on respiratory disease burden and patterns of etiologies associated with community-acquired acute respiratory illness Laos. Establishment of a surveillance strategy in Laos to monitor trends in the epidemiology and burden of acute respiratory infections is required to minimize their impact on human health.

Burden of Influenza in Less Than 5-Year-Old Children Admitted to Hospital with Pneumonia in Developing and Emerging Countries: A Descriptive, Multicenter Study.

This descriptive 4-year study reports the proportion of detection of influenza viruses in less than 5-year-old children hospitalized for pneumonia in eight developing and emerging countries and describes clinical and microbiological characteristics of influenza-related pneumonia cases. Hospitalized children presenting radiologically confirmed pneumonia aged 2-60 months were prospectively enrolled in this observational standardized study. Mean proportion of isolated influenza virus was 9.7% (95% confidence interval: 7.9-11.8%) among 888 pneumonia children analyzed, with moderate heterogeneity between countries-ranging from 6.2% in Cambodia to 18.8% in Haiti. The clinical characteristics of children with influenza-related pneumonia were not substantially different from those of other pneumonia cases. Influenza A H1N1-related pneumonia cases appeared as more severe than pneumonia cases related to other strains of influenza. Streptococcus pneumoniae was detected more often in blood samples from influenza-related cases than in those without detected influenza viruses (19.7% versus 9.5%, P = 0.018). Influenza-related pneumonia is frequent among children less than 5 years old with pneumonia, living in developing and emerging countries. Influenza might be a frequent etiologic agent responsible for pneumonia or a predisposing status factor for pneumococcal-related pneumonia in this population.

Role of p53/NF-κB functional balance in respiratory syncytial virus-induced inflammation response.

The interplay between respiratory syncytial virus (RSV) and the p53 pathway has only been reported in a limited number of studies, yet the underlying abrogation mechanisms of p53 activity during the time course of infection, possibly involving viral proteins, remained unclear. Here, we demonstrate that RSV infection impairs global p53 transcriptional activity, notably via its proteasome-dependent degradation at late stages of infection. We also demonstrate that NS1 and NS2 contribute to the abrogation of p53 activity, and used different experimental strategies (e.g. siRNA, small molecules) to underline the antiviral contribution of p53 in the context of RSV infection. Notably, our study highlights a strong RSV-induced disequilibrium of the p53/NF-κB functional balance, which appears to contribute to the up-regulation of the expression of several proinflammatory cytokines and chemokines.

RSV Infection in Human Macrophages Promotes CXCL10/IP-10 Expression during Bacterial Co-Infection.

Respiratory syncytial virus (RSV), a major etiologic agent of acute lower respiratory infection constitutes the most important cause of death in young children worldwide. Viral/bacterial mixed infections are related to severity of respiratory inflammatory diseases, but the underlying mechanisms remain poorly understood. We have previously investigated the intracellular mechanisms that mediate the immune response in the context of influenza virus/Streptococcus pneumoniae (Sp) co-infection using a model of human monocyte-derived macrophages (MDMs). Here, we set up and characterized a similar model of MDMs to investigate different scenarios of RSV infection and co-infection with Sp. Our results suggest that Sp contributes to a faster and possibly higher level of CXCL10/IP-10 expression induced by RSV infection in human MDMs.