Characteristics of Hospitalized COVID-19 Patients at Admission and Factors Associated with Clinical Severity in Low- and Middle-Income Countries: An Observational Study.

Despite the numerous articles published on the clinical characteristics and outcomes of COVID-19 with regard to high-income countries, little is known about patients in low- and middle-income countries (LMIC) in this context. The objective of this observational, prospective, hospital-based multicentric study was to describe clinical features and outcomes of laboratory-confirmed COVID-19 patients hospitalized in each of the participating centers in Bangladesh, Guinea, Ivory Coast, Lebanon, Madagascar, and Mali during the first year of the pandemic (March 5, 2020 to May 4, 2021). The study outcome was the clinical severity of COVID-19, defined as hospitalization in intensive care unit or death. Multivariate logistic regression models were performed to identify independent variables associated with disease severity. Overall, 1,096 patients were included. The median age was 49.0 years, ranging from 38.0 in Mali to 63.0 years in Guinea. The overall clinical severity of COVID-19 was 12.3%, ranging from 6.4% in Mali to 18.8% in Guinea. In both groups of patients <60 and ≥60 years old, cardiovascular diseases (adjusted odds ratio [aOR]: 1.99; 95% CI: 1.13-3.50, P = 0.02; aOR: 2.47; 95% CI: 1.33-4.57, P = 0.004) were independently associated with clinical severity, whereas in patients <60 years, diabetes (aOR: 2.13; 95% CI: 1.11-4.10, P = 0.02) was also associated with clinical severity. Our findings suggest that COVID-19-related severity and death in LMICs are mainly driven by older age. However, the presence of chronic diseases can also increase the risk of severity especially in younger patients.

Epidemiology of community-acquired pneumonia caused by S treptococcus pneumoniae in older adults: a narrative review.

PURPOSE OF REVIEW: This review covers updated perspectives on different aspects of pneumococcal community-acquired pneumonia (pCAP), including the epidemiology, clinical presentation, risk factors, antibiotic treatment, and existing preventive strategies in older adults. RECENT FINDINGS: pCAP remains the most prevalent condition among lower respiratory tract infections in the older adults according to Global Burden of Diseases 2019. Older adults can display atypical symptoms such as confusion, general clinical deterioration, new onset of and exacerbation of underlying illness that might trigger clinical suspicion of pCAP. Older adults with pCAP often experience increased disease severity and a higher risk of pulmonary complications compared with younger individuals, owing to age-related changes in immunity and a higher prevalence of comorbidities. Vaccination stands fundamental for prevention, emphasizing the need for effective immunization strategies, specifically tailored for older adults. There is a pressing need to reinforce efforts aimed at boosting pneumococcal vaccination rates. SUMMARY: Despite a high morbidity and mortality, the burden of pCAP, in particular hospital admission and occurrence of invasive infections, among the elderly population is not sufficiently documented. This review findings emphasize the substantial burden of pCAP in this vulnerable population, driven by factors such as advancing age and underlying comorbidities. The emergence of antibiotic-resistant pneumococcal strains further complicates treatment decisions and highlights the importance of tailored approaches for managing pCAP in older adults.

Factors Associated with Long COVID-19 in a French Multicentric Prospective Cohort Study.

(1) Background: A substantial proportion of COVID-19 patients continue to experience long-lasting effects that hamper their quality of life. The objectives of this study were (1) to report the prevalence of persistent clinical symptoms 6-12 months after the onset of COVID-19 and (2) to identify potential factors at admission associated with the occurrence of long COVID. (2) Methods: A prospective study was conducted among COVID-19 adult patients, hospitalized in four French university hospitals. Patients were invited to two ambulatory follow-up medical visits, 6-8 months (visit #1) and one year (visit #2) after the onset of their COVID-19. A multivariate logistic regression was performed to assess factors associated with long COVID. (3) Results: In total, 189 patients participated in this study (mean age of 63.4 years). BMI > 30 kg/m2 (aOR 3.52), AST levels between 31 and 42 U/L (aOR 8.68), and AST levels > 42 U/L (aOR 3.69) were associated with persistent clinical symptoms at visit #1. Anosmia (aOR 13.34), AST levels between 31 and 42 U/L (aOR 10.27), stay in ICU (aOR 5.43), pain (aOR 4.31), and longer time before hospitalization (aOR 1.14) were significantly associated with persistent clinical symptoms at visit #2. Patients with ageusia (aOR 0.17) had a lower risk of long COVID. (4) Conclusions: This study showed that some patients experienced persistent clinical symptoms one year after COVID-19 onset that were associated with some determinants at the acute phase/stage.

Patient influenza vaccination reduces the risk of hospital-acquired influenza: An incident test negative-case control study in Lyon university hospital, France (2004-2020).

BACKGROUND: Literature is limited on the impact of patient vaccination on the risk of hospital-acquired influenza (HAI). This test negative case-control study nested in a surveillance program aimed at evaluating the effectiveness of influenza vaccination in reducing the risk of HAI in hospitalized patients during 15 influenza seasons (2004-05 to 2019-20). METHODS: HAI cases were those who developed influenza like illness (ILI) symptoms at least 72 h after hospitalization and had a positive reverse transcriptase-polymerase chain reaction (RT-PCR). Controls were those with ILI symptoms and a negative RT-PCR test. A nasal swab as well as socio-demographic, clinical data and information on influenza vaccination were collected. RESULTS: Of the 296 patients included, 67 were confirmed HAI cases. Influenza vaccine coverage was significantly higher among controls compared to HAI cases (p = 0.002). The risk of HAI was reduced by almost 60 % in vaccinated patients. CONCLUSIONS: A better control of HAI can be achieved by vaccinating hospitalized patients.

Epidemiology and serotype distribution of Streptococcus pneumoniae carriage among influenza-like illness cases in metropolitan Vientiane, Lao PDR: a community-based cohort study.

Background: Data on the epidemiology of Streptococcus pneumoniae among influenza-like illness (ILI) cases, particularly in low- and middle-income countries are scarce. This study assessed the prevalence, risk factors and serotype distribution of S. pneumoniae carriage among ILI cases in metropolitan Vientiane, Lao People's Democratic Republic. The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced among infants in October 2013. Methods: Active ILI surveillance was conducted through weekly phone calls in an open community-based cohort study (April 2015-February 2019), involving 5,690 participants from 1,142 randomly selected households. Participants reporting ILI symptoms provided a nasopharyngeal swab and answered a questionnaire. S. pneumoniae and serotype pneumococcal-positive samples were screened by Multiplex PCR assays. Chi-squared tests and generalized linear mixed models were used to test for variables associated with pneumococcal positivity. Results: Among 1,621 ILI episodes, 269 (16.6%) tested positive for nasopharyngeal pneumococcal carriage, with the highest prevalence (55.4%) in children under 5 years. Pneumococcal carriage was significantly associated with concurrent detection of Hemophilus influenzae (adjusted odds ratio [aOR]: 6.93; 95% CI: 2.10-22.9) and exposure to household cigarette smoke (aOR: 1.65; 95% CI: 1.07-2.54). PCV13 serotypes accounted for 37.8% of all pneumococcal isolates. Detection of PCV13 serotypes among ILI cases aged under 5 years declined significantly between 2015/16 and 2018/19. Conclusions: Community-based surveillance of S. pneumoniae among ILI cases complement surveillance at healthcare facilities to provide a more complete picture of pneumococcal carriage. Our findings contribute also to the growing body of evidence on the effects of PCV13 introduction on circulating serotypes and their potential replacement.

Minerals and Antioxidant Micronutrients Levels and Clinical Outcome in Older Patients Hospitalized for COVID-19 during the First Wave of the Pandemic.

Excessive inflammatory response has been implicated in severe respiratory forms of coronavirus disease 2019 (COVID-19). Trace elements such as zinc, selenium, and copper are known to modulate inflammation and immunity. This study aimed to assess the relationships between antioxidant vitamins and mineral trace elements levels as well as COVID-19 severity in older adults hospitalized. In this observational retrospective cohort study, the levels of zinc, selenium, copper, vitamin A, ß-carotene, and vitamin E were measured in 94 patients within the first 15 days of hospitalization. The outcomes were in-hospital mortality secondary to COVID-19 or severe COVID-19. A logistic regression analysis was conducted to test whether the levels of vitamins and minerals were independently associated with severity. In this cohort (average age of 78 years), severe forms (46%) were associated with lower zinc (p = 0.012) and ß-carotene (p < 0.001) concentrations, and in-hospital mortality (15%) was associated with lower zinc (p = 0.009), selenium (p = 0.014), vitamin A (p = 0.001), and ß-carotene (p = 0.002) concentrations. In regression analysis, severe forms remained independently associated with lower zinc (aOR 2.13, p = 0.018) concentrations, and death was associated with lower vitamin A (aOR = 0.165, p = 0.021) concentrations. Low plasma concentrations of zinc and vitamin A were associated with poor prognosis in older people hospitalized with COVID-19.

Prior SARS-CoV-2 infection enhances and reshapes spike protein-specific memory induced by vaccination.

The diversity of vaccination modalities and infection history are both variables that have an impact on the immune memory of individuals vaccinated against SARS-CoV-2. To gain more accurate knowledge of how these parameters imprint on immune memory, we conducted a long-term follow-up of SARS-CoV-2 spike protein-specific immune memory in unvaccinated and vaccinated COVID-19 convalescent individuals as well as in infection-naïve vaccinated individuals. Here, we report that individuals from the convalescent vaccinated (hybrid immunity) group have the highest concentrations of spike protein-specific antibodies at 6 months after vaccination. As compared with infection-naïve vaccinated individuals, they also display increased frequencies of an atypical mucosa-targeted memory B cell subset. These individuals also exhibited enhanced TH1 polarization of their SARS-CoV-2 spike protein-specific follicular T helper cell pool. Together, our data suggest that prior SARS-CoV-2 infection increases the titers of SARS-CoV-2 spike protein-specific antibody responses elicited by subsequent vaccination and induces modifications in the composition of the spike protein-specific memory B cell pool that are compatible with enhanced functional protection at mucosal sites.

Addressing the COVID-19 pandemic challenges for operational adaptations of a cluster randomized controlled trial on dengue vector control in Malaysia.

INTRODUCTION: The COVID-19 pandemic placed an unprecedented overload on healthcare system globally. With all medical resources being dedicated to contain the spread of the disease, the pandemic may have impacted the burden of other infectious diseases such as dengue, particularly in countries endemic for dengue fever. Indeed, the co-occurrence of COVID-19 made dengue diagnosis challenging because of some shared clinical manifestations between the two pathogens. Furthermore, the sudden emergence and novelty of this global public health crisis has forced the suspension or slow-down of several research trials due to the lack of sufficient knowledge on how to handle the continuity of research trials during the pandemic. We report on challenges we have faced during the COVID-19 pandemic and measures that were implemented to continue the iDEM project (intervention for Dengue Epidemiology in Malaysia). METHODS: This randomized controlled trial aims to assess the effectiveness of Integrated Vector Management (IVM) on the incidence of dengue in urban Malaysia by combining: targeted outdoor residual spraying (TORS), deployment of auto-dissemination devices (ADDs), and active community engagement (CE). Our operational activities started on February 10, 2020, a few weeks before the implementation of non-pharmaceutical interventions to contain the spread of COVID-19 in Malaysia. RESULTS: The three main issues affecting the continuity of the trial were: ensuring the safety of field workers during the interventions; ensuring the planned turnover of TORS application and ADD deployment and services; and maintaining the CE activities as far as possible. CONCLUSIONS: Even though the pandemic has created monumental challenges, we ensured the safety of field workers by providing complete personal protective equipment and regular COVID-19 testing. Albeit with delay, we maintained the planned interval time between TORS application and ADDs services by overlapping the intervention cycles instead of having them in a sequential scheme. CE activities continued remotely through several channels (e.g., phone calls and text messages). Sustained efforts of the management team, significant involvement of the Malaysian Ministry of Health and a quick and smart adaptation of the trial organisation according to the pandemic situation were the main factors that allowed the successful continuation of our research. TRIAL REGISTRATION: Trial registration number: ISRCTN-81915073 . Date of registration: 17/04/2020, 'Retrospectively registered'.

T cell response against SARS-CoV-2 persists after one year in patients surviving severe COVID-19.

BACKGROUND: In critically ill COVID-19 patients, the initial response to SARS-CoV-2 infection is characterized by major immune dysfunctions. The capacity of these severe patients to mount a robust and persistent SARS-CoV-2 specific T cell response despite the presence of severe immune alterations during the ICU stay is unknown. METHODS: Critically ill COVID-19 patients were sampled five times during the ICU stay and 9 and 13 months afterwards. Immune monitoring included counts of lymphocyte subpopulations, HLA-DR expression on monocytes, plasma IL-6 and IL-10 concentrations, anti-SARS-CoV-2 IgG levels and T cell proliferation in response to three SARS-CoV-2 antigens. FINDINGS: Despite the presence of major lymphopenia and decreased monocyte HLA-DR expression during the ICU stay, convalescent critically ill COVID-19 patients consistently generated adaptive and humoral immune responses against SARS-CoV-2 maintained for more than one year after hospital discharge. Patients with long hospital stays presented with stronger anti-SARS-CoV-2 specific T cell response but no difference in anti-SARS-CoV2 IgG levels. INTERPRETATION: Convalescent critically ill COVID-19 patients consistently generated a memory immune response against SARS-CoV-2 maintained for more than one year after hospital discharge. In recovered individuals, the intensity of SARS-CoV-2 specific T cell response was dependent on length of hospital stay. FUNDING: This observational study was supported by funds from the Hospices Civils de Lyon, Fondation HCL, Claude Bernard Lyon 1 University and Région Auvergne Rhône-Alpes and by partial funding by REACTing (Research and ACTion targeting emerging infectious diseases) INSERM, France and a donation from Fondation AnBer (http://fondationanber.fr/).

Efficacy of careHPV™ human papillomavirus screening versus conventional cytology tests for the detection of precancerous and cancerous cervical lesions among women living with HIV-1 in Lao People's Democratic Republic.

BACKGROUND: In the Lao People's Democratic Republic (Lao PDR), cervical cancer is the third leading cause of women cancer. AIMS: The objective of this cross-sectional study was to compare the efficacy of careHPV™ test versus conventional Pap smear or Siriraj liquid-based cytology in the detection of cervical cancer in women living with human immunodeficiency virus type 1 (HIV-1). MATERIALS & METHODS: Overall, 631 women consented to participate. Four cervical specimens were taken for the purpose of conventional Pap smear, Siriraj liquid-based cytology, careHPV™ test, and HPV-16 genotyping. The exact McNemar test was used to compare the efficacy and diagnostic performance of the tests. RESULTS: Of the 631 women with follow-up, 331 were human papillomavirus (HPV) negative. High-grade squamous intraepithelial lesions were found in 37 women, biopsy-proven high-grade cervical intraepithelial neoplasia in 50 women, and invasive carcinoma in seven women. The proportion of women with high-grade cervical lesion or carcinoma detected after abnormal careHPV™ test was higher (6.02%; 95% confidence interval [CI]: 4.4-8.1) than that detected by conventional Pap smear (4.59%; 95% CI: 3.2-6.5). careHPV™ and HPV-16 genotyping had, respectively, the highest sensitivity (80.8%; 95% CI: 67.4-89.5) and specificity (92.2%; 95% CI: 89.8-94.2). HPV-16 was the most frequently detected genotype. CONCLUSIONS: careHPV™ test represents a screening option in Lao PDR, particularly in women living with HIV-1 because of higher prevalence of chronic HPV in this population.

Baseline clinical features of COVID-19 patients, delay of hospital admission and clinical outcome: A complex relationship.

INTRODUCTION: Delay between symptom onset and access to care is essential to prevent clinical worsening for different infectious diseases. For COVID-19, this delay might be associated with the clinical prognosis, but also with the different characteristics of patients. The objective was to describe characteristics and symptoms of community-acquired (CA) COVID-19 patients at hospital admission according to the delay between symptom onset and hospital admission, and to identify determinants associated with delay of admission. METHODS: The present work was based on prospective NOSO-COR cohort data, and restricted to patients with laboratory confirmed CA SARS-CoV-2 infection admitted to Lyon hospitals between February 8 and June 30, 2020. Long delay of hospital admission was defined as ≥6 days between symptom onset and hospital admission. Determinants of the delay between symptom onset and hospital admission were identified by univariate and multiple logistic regression analysis. RESULTS: Data from 827 patients were analysed. Patients with a long delay between symptom onset and hospital admission were younger (p<0.01), had higher body mass index (p<0.01), and were more frequently admitted to intensive care unit (p<0.01). Their plasma levels of C-reactive protein were also significantly higher (p<0.01). The crude in-hospital fatality rate was lower in this group (13.3% versus 27.6%), p<0.01. Multiple analysis with correction for multiple testing showed that age ≥75 years was associated with a short delay between symptom onset and hospital admission (≤5 days) (aOR: 0.47 95% CI (0.34-0.66)) and CRP>100 mg/L at admission was associated with a long delay (aOR: 1.84 95% CI (1.32-2.55)). DISCUSSION: Delay between symptom onset and hospital admission is a major issue regarding prognosis of COVID-19 but can be related to multiple factors such as individual characteristics, organization of care and severe pathogenic processes. Age seems to play a key role in the delay of access to care and the disease prognosis.

Tobacco smoking and severity of COVID-19: Experience from a hospital-based prospective cohort study in Lyon, France.

Information gathered so far from published studies attest the existence of a complex relationship between tobacco smoking and the severity of COVID-19. We investigated the association between smoking habits and the severity of COVID-19 in patients hospitalized in university-affiliated hospitals in Lyon, France. Baseline sociodemographic, clinical and biological characteristics of adult COVID-19 hospitalized patients presenting from the community were prospectively collected and analyzed. Tobacco exposure was documented at admission. Characteristics of patients hospitalized in medical wards to those admitted or transferred to intensive care units (ICUs) were compared using Mann-Whitney and Χ2 or Fisher's exact test. A composite endpoint including admission or transfer to ICU or death was created as a proxy for severe outcome. Adjusted odds ratio (aOR) and 95% confidence interval (95% CI) were calculated to identify variables independently associated with a severe outcome. Of the 645 patients with documented information on smoking habits, 62.6% were never-smokers, 32.1% ex-smokers, and 5.3% active smokers. Past tobacco use was independently associated with an increased risk of severe outcome (aOR: 1.71; 95% CI: 1.12-2.63), whereas a nonsignificant protective trend was found for active smoking. The results suggest that past smoking is associated with enhanced risk of progressing toward severe COVID-19 disease in hospitalized patients.

Measuring the effectiveness of integrated vector management with targeted outdoor residual spraying and autodissemination devices on the incidence of dengue in urban Malaysia in the iDEM trial (intervention for Dengue Epidemiology in Malaysia): study protocol for a cluster randomized controlled trial.

BACKGROUND: In common with many South East Asian countries, Malaysia is endemic for dengue. Dengue control in Malaysia is currently based on reactive vector management within 24 h of a dengue case being reported. Preventive rather than reactive vector control approaches, with combined interventions, are expected to improve the cost-effectiveness of dengue control programs. The principal objective of this cluster randomized controlled trial is to quantify the effectiveness of a preventive integrated vector management (IVM) strategy on the incidence of dengue as compared to routine vector control efforts. METHODS: The trial is conducted in randomly allocated clusters of low- and medium-cost housing located in the Federal Territory of Kuala Lumpur and Putrajaya. The IVM approach combines: targeted outdoor residual spraying with K-Othrine Polyzone, deployment of mosquito traps as auto-dissemination devices, and community engagement activities. The trial includes 300 clusters randomly allocated in a 1:1 ratio. The clusters receive either the preventive IVM in addition to the routine vector control activities or the routine vector control activities only. Epidemiological data from monthly confirmed dengue cases during the study period will be obtained from the Vector Borne Disease Sector, Malaysian Ministry of Health e-Dengue surveillance system. Entomological surveillance data will be collected in 12 clusters randomly selected from each arm. To measure the effectiveness of the IVM approach on dengue incidence, a negative binomial regression model will be used to compare the incidence between control and intervention clusters. To quantify the effect of the interventions on the main entomological outcome, ovitrap index, a modified ordinary least squares regression model using a robust standard error estimator will be used. DISCUSSION: Considering the ongoing expansion of dengue burden in Malaysia, setting up proactive control strategies is critical. Despite some limitations of the trial such as the use of passive surveillance to identify cases, the results will be informative for a better understanding of effectiveness of proactive IVM approach in the control of dengue. Evidence from this trial may help justify investment in preventive IVM approaches as preferred to reactive case management strategies. TRIAL REGISTRATION: ISRCTN ISRCTN81915073 . Retrospectively registered on 17 April 2020.

Prognostic factors of severe community-acquired staphylococcal pneumonia in France.

PURPOSE: Staphylococcus aureus causes severe forms of community-acquired pneumonia (CAP), namely staphylococcal pleuropneumonia in young children and staphylococcal necrotising pneumonia in older patients. Methicillin resistance and the Panton-Valentine leukocidin (PVL) toxin, as well as less specific factors, have been associated with poor outcome in severe CAP, but their roles are unclear. METHODS: A prospective multicentre cohort study of severe staphylococcal CAP was conducted in 77 paediatric and adult intensive care units in France between January 2011 and December 2016. After age-clustering, risk factors for mortality, including pre-existing conditions, clinical presentation, laboratory features, strain genetic lineage, PVL, other virulence factors and methicillin resistance were assessed using univariate and multivariable Cox and LASSO (least absolute shrinkage and selection operator) regressions. RESULTS: Out of 163 included patients, aged 1 month to 87 years, 85 (52.1%) had PVL-positive CAP; there were 20 (12.3%) patients aged <3 years (hereafter "toddlers"), among whom 19 (95%) had PVL-positive CAP. The features of PVL-positive CAP in toddlers matched with the historical description of staphylococcal pleuropneumonia, with a lower mortality (three (15%) out of 19) compared to PVL-positive CAP in older patients (31 (47%) out of 66). Mortality in older patients was predicted by PVL-positivity (hazard ratio (HR) 1.81, 95% CI 1.03-3.17) and methicillin resistance (HR 2.37, 95% CI 1.29-4.34) independently from S. aureus lineages and the presence of other determinants of virulence. CONCLUSION: PVL was associated with staphylococcal pleuropneumonia in toddlers and was a risk factor for mortality in older patients with severe CAP, independently of methicillin resistance, S. aureus genetic background and other virulence factors.

Factors associated with admission to intensive care units in COVID-19 patients in Lyon-France.

INTRODUCTION: A new respiratory virus, SARS-CoV-2, has emerged and spread worldwide since late 2019. This study aims at analysing clinical presentation on admission and the determinants associated with admission in intensive care units (ICUs) in hospitalized COVID-19 patients. PATIENTS AND METHODS: In this prospective hospital-based study, socio-demographic, clinical and biological characteristics, on admission, of adult COVID-19 hospitalized patients presenting from the community for their first admission were prospectively collected and analysed. Characteristics of patients hospitalized in medical ward to those admitted in ICU were compared using Mann-Whitney and Chi-square or Fisher exact test when appropriate. Univariate logistic regression was first used to identify variables on admission that were associated with the outcome i.e. admission to an ICU versus total hospital stay in a medical ward. Forward selection was then applied beginning with sex, age and temperature in the multivariable logistic regression model. RESULTS: Of the 412 patients included, 325 were discharged and 87 died in hospital. Multivariable regression showed increasing odds of ICU hospitalization with temperature (OR, 1.56 [95% CI, 1.06-2.28] per degree Celsius increase), oxygen saturation <90% (OR, 12.45 [95% CI, 5.27-29.4]), abnormal lung auscultation on admission (OR, 3.58 [95% CI, 1.58-8.11]), elevated level of CRP (OR, 2.7 [95% CI, 1.29-5.66for CRP>100mg/L vs CRP<10mg/L). and monocytopenia (OR, 3.28 [95% CI, 1.4-7.68]) were also associated with increasing odds of ICU hospitalization. Older patients were less likely to be hospitalized in ICU (OR, 0.17 [95%CI, 0.05-0.51]. CONCLUSIONS: Age and delay between onset of symptoms and hospital admission were associated with the risk of hospitalisation in ICU. Age being a fixed variable, interventions that shorten this delay would improve the prognosis of Covid-19 patients.

Incidence of Asymptomatic and Symptomatic Influenza Among Healthcare Workers: A Multicenter Prospective Cohort Study.

BACKGROUND: Influenza is an important cause of viral hospital-acquired infection involving patients, healthcare workers (HCW), and visitors. The frequency of asymptomatic influenza among HCW with possible subsequent transmission is poorly described. The objective is to determine the cumulative incidence of asymptomatic, paucisymptomatic, and symptomatic influenza among HCW. METHOD: A multicenter prospective cohort study was done in 5 French university hospitals, including 289 HCW during the 2016-2017 influenza season. HCW had 3 physical examinations (time [T] 0, before epidemic onset; T.1, before epidemic peak; T.2, T.3, after epidemic peak). A blood sample was taken each time for influenza serology and a nasal swab was collected at T1 and T2 for influenza detection by polymerase chain reaction (PCR). Positive influenza was defined as either a positive influenza PCR, and/or virus-specific seroconversion against influenza A, the only circulating virus, with no vaccination record during follow-up. Symptoms were self-reported daily between T1 and T2. Cumulative incidence of influenza was stratified by clinical presentation per 100 HCW. RESULTS: Of the 289 HCW included, 278 (96%) completed the entire follow-up. Overall, 62 HCW had evidence of influenza of whom 46.8% were asymptomatic, 41.9% were paucisymptomatic, and 11.3% were symptomatic. Cumulative influenza incidence was 22.3% (95% confidence interval [CI]: 17.4%-27.2%). Cumulative incidence of asymptomatic influenza was 5.8% (95% CI: 3.3%-9.2%), 13.7% (95% CI: 9.9%-18.2%) for paucisymptomatic influenza, and 2.9% (95% CI: 1.3%-5.5%) for symptomatic influenza. CONCLUSIONS: Asymptomatic and paucisymptomatic influenza were frequent among HCW, representing 47% and 42% of the influenza burden, respectively. These findings highlight the importance of systematic implementation of infection control measures among HCW regardless of respiratory symptoms from preventing nosocomial transmission of influenza. CLINICAL TRIALS REGISTRATION: NCT02868658.

Protocol for a prospective, observational, hospital-based multicentre study of nosocomial SARS-CoV-2 transmission: NOSO-COR Project.

INTRODUCTION: The newly identified SARS-CoV-2 can cause serious acute respiratory infections such as pneumonia. In France, mortality rate in the general population was approximately 10% and could reach higher levels at the hospital. In the current context of high incidence rates of SARS-CoV-2 in the community, a significant increase in the rate of nosocomial transmission is expected. The risk of nosocomial transmission could even be higher in low-income countries that have fragile healthcare systems. This protocol is intended to estimate the prevalence and incidence of suspected or confirmed cases of nosocomial SARS-CoV-2 infection, the clinical spectrum and the determinants (risk factors/protective) at participating hospitals. METHODS AND ANALYSIS: This will be an international multicentre prospective, observational, hospital-based study in adults and children. It will include volunteer patients and healthcare professionals in France and hospitals affiliated with the GABRIEL network. Demographic and clinical data will be collected using case report forms designed especially for the purpose of the project. A nasopharyngeal swab will be collected and tested for SARS-CoV-2 by reverse-transcriptase PCR. Characteristics of the study participants, the proportion of confirmed nosocomial SARS-CoV-2 infections relative to all patients with syndromes suggestive of SARS-CoV-2 infection, will be analysed. Appropriate multivariate modelling will be used to identify the determinants associated with nosocomial onset. ETHICS AND DISSEMINATION: This study was approved by the clinical research and committee of all participating countries. The findings will be submitted to peer-reviewed journal for publication and shared with national health authorities. TRIAL REGISTRATION NUMBER: NCT04290780.

Targeted outdoor residual spraying, autodissemination devices and their combination against Aedes mosquitoes: field implementation in a Malaysian urban setting.

Currently, dengue control relies largely on reactive vector control programmes. Proactive vector-control using a rational, well-balanced integrated vector management approach may prove more successful for dengue control. As part of the development of a cluster randomized controlled epidemiological trial, a study was conducted in Johor Bahru, Malaysia. The study included one control site (three buildings) and three intervention sites which were treated as follows: targeted outdoor residual spraying only (TORS site, two buildings); deployment of autodissemination devices only (ADD site, four buildings); and the previous two treatments combined (TORS + ADD site, three buildings). The primary entomological measurement was per cent of positive ovitraps-ovitrap index (OI). The effect of each intervention on OI was analyzed by a modified ordinary least squares regression model. Relative to the control site, the TORS and ADD sites showed a reduction in the Aedes OI (-6.5%, P = 0.04 and -8.3%, P = 0.10, respectively). Analysis by species showed that, relative to control, the Ae. aegypti OI was lower in ADD (-8.9%, P = 0.03) and in TORS (-10.4%, P = 0.02). No such effect was evident in the TORS + ADD site. The present study provides insights into the methods to be used for the main trial. The combination of multiple insecticides with different modes of action in one package is innovative, although we could not demonstrate the additive effect of TORS + ADD. Further work is required to strengthen our understanding of how these interventions impact dengue vector populations and dengue transmission.