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Background As the societal value of vaccines is increasingly recognized, there is a need to examine methodological approaches that could be used to integrate these various benefits in the economic evaluation of a vaccine.Research design and methods A literature review and two expert panel meetings explored methodologies to value herd immunity, health spillover effects (beyond herd immunity), impact on antimicrobial resistance, productivity, and equity implications of vaccines.Results The consideration of broader benefits of vaccines in economic evaluation is complicated and necessitates technical expertise. Whereas methodologies to account for herd immunity and work productivity are relatively well established, approaches to investigate equity implications are developing and less frequently applied. Modeling the potential impact on antimicrobial resistance not only depends on the multi-faceted causal relationship between vaccination and resistance but also on data availability.Conclusions Different methods are available to value the broad impact of vaccines, and it is important that analysts are aware of their strengths and limitations and justify their choice of method. In the future, we expect that an increasing number of economic evaluations will consider the broader benefits of vaccines as part of their base-case analysis or in sensitivity analyses.

IntroductionThe literature establishes a clear social gradient in health for transmissible respiratory diseases. However, this gradient’s extent remains largely unexplored in the context of COVID-19, and it is uncertain whether the pandemic has exacerbated this gradient. The study aims to compare the socio-economic profiles and comorbidities during the COVID-19 pandemic with a control population affected by viral pneumonia/respiratory disease in 2019.MethodsThis case-control study analyzed linked data from all patients hospitalized for COVID-19 in 2020 (n = 22,087) and for respiratory diseases in 2019 (n = 7,586). Socio-economic data from the social security database were linked to clinical data from the hospital registry. We analyzed the socio-demographic and clinical factors associated with COVID-19 hospitalization (control group, wave 1, and wave 2) using multinomial regressions and logistic regression models and the length of stay during hospitalization using binomial negative regressions.ResultsA social health gradient was observed in both the COVID-19 and control groups, with a significant increase across waves for COVID-19 (p-trend < 0.0001). Men, people over the age of 45, those with comorbidities, high population density, lower income, lower socio-economic status, and people living in Brussels capital were at higher risk of COVID-19 hospitalization and longer length of stay compared to the control group. Except for sub-Saharan Africans, all patients of foreign nationality had a significantly increased risk of hospitalization (p

Background: Blood culture-negative endocarditis (BCNE) is a diagnostic challenge, therefore our objective was to pinpoint high-risk cohorts for BCNE. Methods: The study included adult patients with definite endocarditis. Data were collected via the Infectious Diseases International Research Initiative (ID-IRI). The study analysing one of the largest case series ever reported was conducted across 41 centers in 13 countries. We analysed the database to determine the predictors of BCNE using univariate and logistic regression analyses. Results: Blood cultures were negative in 101 (11.65 %) of 867 patients. We disclosed that as patients age, the likelihood of a negative blood culture significantly decreases (OR 0.975, 95 % CI 0.963–0.987, p

Summary: Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.

Summary: Background: Maternal pertussis vaccination with Tdap vaccine is recommended to protect newborns from severe postnatal infection. HIV-exposed uninfected (HEU) infants have a higher incidence of pertussis infection and may particularly benefit from maternal immunization. The impact of HIV infection on the quality of IgG and memory B cell (MBC) responses to Tdap vaccination in pregnant women (PW) living with HIV (PWH) is unknown. Methods: In this observational study, humoral immune responses to Tdap vaccination, including IgG levels, Fc-dependent effector functions, and MBC frequencies, were measured before and after vaccination in 40 PWH and 42 HIV-uninfected PW. Placental transfer of IgG and avidity were assessed in cord blood (CB). Soluble and cellular immune activation markers were quantified at baseline. Findings: One month after vaccination, PWH had lower frequencies of MBC compared with HIV-uninfected PW. At delivery, PWH had attenuated pertussis-specific IgG levels and Fc-dependent effector functions. Reduced levels of maternal vaccine polyfunctional IgG and IgG avidity were transferred to HEU as compared to HIV-unexposed newborns. After adjustment with ethnicity, maternal antibody levels and gestational age at vaccination, HIV infection was independently associated with decreased levels of PT specific-IgG in CB. Both maternal and neonatal pertussis-specific IgG responses as well as PT-specific IgG avidity were inversely correlated with maternal sCD14 levels before vaccination among PWH. Interpretation: Maternal HIV infection is associated with attenuated humoral immune responses to Tdap vaccination that correlate with sCD14. Suboptimal transfer of maternal immunity may further increase the risk of severe pertussis infection in HEU infants. Funding: This work was supported by IRIS Fund managed by the Foundation Roi Baudouin [2017J1820690206902], Association Vésale pour la Recherche Médicale and the Medical Council of CHU Saint-Pierre and has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, US Department of Health and Human Services, under Award No. U19AI145825. N.D. is a clinical researcher and A.M. is Research Director at the Fonds de la Recherche Scientifique (F.R.S.-FNRS), Belgium. M.E.A. was partially supported by NIH NIAID 1U19AI14825. This article is published with the support of the Fondation Universitaire of Belgium.

Background All European countries have national immunization programs (NIPs) to protect gainst infectious diseases. We aimed to estimate the individual lifetime cost of vaccination in 23 European countries, assuming full compliance with NIP schedules. Research design and methods We used publicly available data to estimate the individual lifetime cost of vaccination with the vaccines that are currently recommended and funded in each country for healthy individuals and for individuals with underlying medical conditions. We included a scenario analysis for healthy individuals in which all currently recommended vaccines were universally funded, and compared the annual costs per person of vaccination to the annual per-capita costs of all-cause hospitalization and anti-infective medications. Results The individual lifetime cost of vaccination was €592–3,504 for healthy individuals (median: €1,663; 13–20 diseases), €744–9,081 for individuals with underlying conditions (median: €2,992; 13–21 diseases), and €1,225–4,832 (median: €2,565; 21–22 diseases) in the scenario analysis, with median values for vaccine acquisition of €1,203, €1,731, and €1,788, respectively. Conclusions Our estimates show that the maximum potential cost of vaccination requires a relatively low level of investment assuming full compliance. These data could be useful for policymakers in future financial planning and evaluation of NIPs.

Background Between 2015 and 2019, when 62% of Belgian adults aged ≥65 years were vaccinated with standard quadrivalent influenza vaccines, influenza caused an average of 3,905 hospitalizations and 347 premature deaths per year in older adults. The objective of the present analysis was to estimate the cost-effectiveness of the adjuvanted quadrivalent influenza vaccine (aQIV) compared to the standard (SD-QIV) and high-dose (HD-QIV) vaccines in elderly Belgians. Research Design and Methods The analysis was based on a static cost-effectiveness model that captured the evolution of patients infected with influenza and was customized with available national data. Results Vaccinating adults aged ≥65 years with aQIV instead of SD-QIV would decrease the number of hospitalizations by 530 and the number of deaths by 66 in the 2023–2024 influenza season. aQIV was cost-effective compared to SD-QIV with an incremental cost of €15,227/quality-adjusted life year (QALY). aQIV is cost-saving when compared to HD-QIV in the subgroup of institutionalized elderly adults who were granted reimbursement for this vaccine. Conclusion In a health care system striving to improve the prevention of infectious diseases, a cost-effective vaccine such as aQIV is a key asset to reduce the number of influenza-related hospitalizations and premature deaths in older adults.

We explored the self-reported antibiotic stewardship (AS), and infection prevention and control (IPC) activities in intensive care units (ICUs) of different income settings. A cross-sectional study was conducted using an online questionnaire to collect data about IPC and AS measures in participating ICUs. The study participants were Infectious Diseases–International Research Initiative (IDI-IR) members, committed as per their institutional agreement form. We analyzed responses from 57 ICUs in 24 countries (Lower-middle income (LMI), n = 13; Upper-middle income (UMI), n = 33; High-income (HI), n = 11). This represented (~5%) of centers represented in the ID-IRI. Surveillance programs were implemented in (76.9%−90.9%) of ICUs with fewer contact precaution measures in LMI ones (p = 0.02); (LMI:69.2%, UMI:97%, HI:100%). Participation in regional antimicrobial resistance programs was more significantly applied in HI (p = 0.02) (LMI:38.4%,UMI:81.8%,HI:72.2%). AS programs are implemented in 77.2% of institutions with AS champions in 66.7%. Infectious diseases physicians and microbiologists are members of many AS teams (59%&50%) respectively. Unqualified healthcare professionals(42.1%), and deficient incentives(28.1%) are the main barriers to implementing AS. We underscore the existing differences in IPC and AS programs’ implementation, team composition, and faced barriers. Continuous collaboration and sharing best practices on APM is needed. The role of regional and international organizations should be encouraged. Global support for capacity building of healthcare practitioners is warranted.

Objective Belgium has been hit harder by COVID-19 than other countries in Europe. While clinical risk factors are well studied, socioeconomic risk factors remained underexplored. This study’s objective was to analyse the social and clinical profile of patients hospitalised for COVID-19 during the two waves of 2020, compared with a control population in 2019 in two hospitals located in Brussels’ most deprived area.Design and methods We did a case–control study by using the minimal clinical data set in two Brussels hospitals. All patients hospitalised for COVID-19 in 2020, divided into two waves (n=3220), were compared with all patients hospitalised for viral pneumonia and respiratory diseases in 2019 (control population n=2950). Multinomial regression models were used to estimate the relative risk ratios of the association between the COVID-19 hospitalised populations (waves 1 and 2) and risk factors (social and clinical) stratified by age.Results Patients under 65 years of age and hospitalised for COVID-19 presented significantly higher rates (relative rate ratio (95% CI)), especially for the first wave, of obesity 1.6 (1.2–2.2), African nationalities 1.4 (1.0–1.8), lack of health insurance 1.6 (1.3–2.1), living in high-density population areas 1.6 (1.3–2.1) and low incomes 1.7 (1.4–2.1), compared with the control population For patients over 65 years of age, we did not observe significant excess of COVID-19 hospitalisations for any risk factors, except diabetes during for the second wave but we have a significant excess mortality rate than the control population for both waves (p

ObjectiveWe evaluated the public health impact and return on investment of Belgium’s pediatric immunization program (PIP) from both healthcare-sector and societal perspectives.MethodsWe developed a decision analytic model for 6 vaccines routinely administered in Belgium for children aged 0–10 years: DTaP-IPV-HepB-Hib, DTaP-IPV, MMR, PCV, rotavirus, and meningococcal type C. We used separate decision trees to model each of the 11 vaccine-preventable pathogens: diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type b, measles, mumps, rubella, Streptococcus pneumoniae, rotavirus, and meningococcal type C; hepatitis B was excluded because of surveillance limitations. The 2018 birth cohort was followed over its lifetime. The model projected and compared health outcomes and costs with and without immunization (based on vaccine-era and pre–vaccine era disease incidence estimates, respectively), assuming that observed reductions in disease incidence were fully attributable to vaccination. For the societal perspective, the model included productivity loss costs associated with immunization and disease in addition to direct medical costs. The model estimated discounted cases averted, disease-related deaths averted, life-years gained, quality-adjusted life-years gained, costs (2020 euros), and an overall benefit–cost ratio. Scenario analyses considered alternate assumptions for key model inputs.ResultsAcross all 11 pathogens, we estimated that the PIP prevented 226,000 cases of infections and 200 deaths, as well as the loss of 7,000 life-years and 8,000 quality-adjusted life-years over the lifetime of a birth cohort of 118,000 children. The PIP was associated with discounted vaccination costs of €91 million from the healthcare-sector perspective and €122 million from the societal perspective. However, vaccination costs were more than fully offset by disease-related costs averted, with the latter amounting to a discounted €126 million and €390 million from the healthcare-sector and societal perspectives, respectively. As a result, pediatric immunization was associated with overall discounted savings of €35 million and €268 million from the healthcare-sector and societal perspectives, respectively; every €1 invested in childhood immunization resulted in approximately €1.4 in disease-related cost savings to the health system and €3.2 in cost savings from a societal perspective for Belgium’s PIP. Estimates of the value of the PIP were most sensitive to changes in input assumptions for disease incidence, productivity losses due to disease-related mortality, and direct medical disease costs.ConclusionBelgium’s PIP, which previously had not been systematically assessed, provides large-scale prevention of disease-related morbidity and premature mortality, and is associated with net savings to health system and society. Continued investment in the PIP is warranted to sustain its positive public health and financial impact.

Abstract Background Clarithromycin may act as immune-regulating treatment in sepsis and acute respiratory dysfunction syndrome. However, clinical evidence remains inconclusive. We aimed to evaluate whether clarithromycin improves 28-day mortality among patients with sepsis, respiratory and multiple organ dysfunction syndrome. Methods We conducted a multicenter, randomized, clinical trial in patients with sepsis. Participants with ratio of partial oxygen pressure to fraction of inspired oxygen less than 200 and more than 3 SOFA points from systems other than the respiratory function were enrolled between December 2017 and September 2019. Patients were randomized to receive 1 gr of clarithromycin or placebo intravenously once daily for 4 consecutive days. The primary endpoint was 28-day all-cause mortality. Secondary outcomes were 90-day mortality; sepsis response (defined as at least 25% decrease in SOFA score by day 7); sepsis recurrence; and differences in peripheral blood cell populations and leukocyte transcriptomics. Results Fifty-five patients were allocated to each arm. By day 28, 27 (49.1%) patients in the clarithromycin and 25 (45.5%) in the placebo group died (risk difference 3.6% [95% confidence interval (CI) − 15.7 to 22.7]; P = 0.703, adjusted OR 1.03 [95%CI 0.35–3.06]; P = 0.959). There were no statistical differences in 90-day mortality and sepsis response. Clarithromycin was associated with lower incidence of sepsis recurrence (OR 0.21 [95%CI 0.06–0.68]; P = 0.012); significant increase in monocyte HLA-DR expression; expansion of non-classical monocytes; and upregulation of genes involved in cholesterol homeostasis. Serious and non-serious adverse events were equally distributed. Conclusions Clarithromycin did not reduce mortality among patients with sepsis with respiratory and multiple organ dysfunction. Clarithromycin was associated with lower sepsis recurrence, possibly through a mechanism of immune restoration. Clinical trial registration clinicaltrials.gov identifier NCT03345992 registered 17 November 2017; EudraCT 2017-001056-55.

In utero exposure to maternally-derived antigens following chronic infection is associated with modulation of infants ‘immune response, differential susceptibility to post-natal infections and immune response toward vaccines. The maternal environment, both internal (microbiota) and external (exposure to environmental microbes) also modulates infant's immune response but also the clinical phenotype after birth. Vertical transmission of ubiquitous respiratory pathogens such as influenza and COVID-19 is uncommon. Evidence suggest that in utero exposure to maternal influenza and SARS-CoV-2 infections may have a significant impact on the developing immune system with activation of both innate and adaptive responses, possibly related to placental inflammation. Here in, we review how maternal respiratory infections, associated with airway, systemic and placental inflammation but also changes in maternal microbiota might impact infant's immune responses after birth. The clinical impact of immune modifications observed following maternal respiratory infections remains unexplored. Given the high frequencies of respiratory infections during pregnancy (COVID-19, influenza but also RSV and HMPV), the impact on global child health could be important.

BackgroundChemerin is an extracellular protein with chemotactic activities and its expression is increased in various diseases such as metabolic syndrome and inflammatory conditions. Its role in lung pathology has not yet been extensively studied but both known pro- and anti-inflammatory properties have been observed. The aim of our study was to evaluate the involvement of the chemerin/ChemR23 system in the physiopathology of COVID-19 with a particular focus on its prognostic value.MethodsBlood samples from confirmed COVID-19 patients were collected at day 1, 5 and 14 from admission to Erasme Hospital (Brussels – Belgium). Chemerin concentrations and inflammatory biomarkers were analyzed in the plasma. Blood cells subtypes and their expression of ChemR23 were determined by flow cytometry. The expression of chemerin and ChemR23 was evaluated on lung tissue from autopsied COVID-19 patients by immunohistochemistry (IHC).Results21 healthy controls (HC) and 88 COVID-19 patients, including 40 in intensive care unit (ICU) were included. Plasma chemerin concentration were significantly higher in ICU patients than in HC at all time-points analyzed (p

Objectives: We aimed to explore cytokine profile in patients as it relates to Coronavirus Disease 2019 (COVID-19) severity, and to establish a predictive cytokine score to discriminate severe from non-severe cases and provide a prognosis parameter for patients that will require intensive care unit (ICU) transfer. Methods: Serum samples of 63 patients diagnosed with SARS-CoV-2 infection were collected early after hospital admission (day 0–3). Patients were categorized in five groups based on the clinical presentation, the PaO2/FiO2 ratio and the requirement of mechanical ventilation. Results: Three cytokines, IL-6, IL-8 and IL-10, were markedly higher in severe forms (n = 44) than in non-severe forms (n = 19) (p < 0.005). A score combining levels of these three cytokines (IL-6*IL-8*IL-10) had the highest performance to predict severity: sensitivity of 86.4% (95% CI, 72.4–94.8) and specificity of 94.7% (95% CI, 74.0–99.9) for a cutoff value of 2068 pg/mL. Elevated levels of IL-6, IL-8 and IL-10 were also found in critically ill patients. The combination of IL-6*IL-10 serum levels allowed the highest predictability for ICU transfer: AUC of 0.898 (p < 0.0001). Conclusion: The combinatorial IL-6*IL-8*IL-10 score at presentation was highly predictive of the progression to a severe form of the disease, and could contribute to improve patient triage and to adapt therapeutic strategy within clinical trials more accurately and efficiently.

Severe COVID-19 disease is associated with dysregulation of the myeloid compartment during acute infection. Survivors frequently experience long-lasting sequelae, but little is known about the eventual persistence of this immune alteration. Herein, we evaluated TLR-induced cytokine responses in a cohort of mild to critical patients during acute or convalescent phases (n = 97). In the acute phase, we observed impaired cytokine production by monocytes in the patients with the most severe COVID-19. This capacity was globally restored in convalescent patients. However, we observed increased responsiveness to TLR1/2 ligation in patients who recovered from severe disease, indicating that these cells display distinct functional properties at the different stages of the disease. In patients with acute severe COVID-19, we identified a specific transcriptomic and epigenomic state in monocytes that can account for their functional refractoriness. The molecular profile of monocytes from recovering patients was distinct and characterized by increased chromatin accessibility at activating protein 1 (AP1) and MAF loci. These results demonstrate that severe COVID-19 infection has a profound impact on the differentiation status and function of circulating monocytes, during both the acute and the convalescent phases, in a completely distinct manner. This could have important implications for our understanding of short- and long-term COVID-19–related morbidity.

Active tuberculosis (aTB) remains a major killer from infectious disease, partially due to delayed diagnosis and hence treatment. Classical microbiological methods are slow and lack sensitivity, molecular techniques are costly and often unavailable. Moreover, available immuno-diagnostic tests lack sensitivity and do not differentiate between aTB and latent TB infection (LTBI). Here, we evaluated the performance of the combined measurement of different chemokines/cytokines induced by two different stage-specific mycobacterial antigens, Early-secreted-antigenic target-6 (ESAT-6) and Heparin-binding-haemagglutinin (HBHA), after a short in vitro incubation of either peripheral blood mononuclear cells (PBMC) or whole blood (WB). Blood samples were collected from a training cohort comprising 22 aTB patients, 22 LTBI subjects and 17 non-infected controls. The concentrations of 13 cytokines were measured in the supernatants. Random forest analysis identified the best markers to differentiate M. tuberculosis-infected from non-infected subjects, and the most appropriate markers to differentiate aTB from LTBI. Logistic regression defined predictive abilities of selected combinations of cytokines, first on the training and then on a validation cohort (17 aTB, 27 LTBI, 25 controls). Combining HBHA- and ESAT-6-induced IFN-γ concentrations produced by PBMC was optimal to differentiate infected from non-infected individuals in the training cohort (100% correct classification), but 2/16 (13%) patients with aTB were misclassified in the validation cohort. ESAT-6-induced-IP-10 combined with HBHA-induced-IFN-γ concentrations was selected to differentiate aTB from LTBI, and correctly classified 82%/77% of infected subjects as aTB or LTBI in the training/validation cohorts, respectively. Results obtained on WB also selected ESAT-6- and HBHA-induced IFN-γ concentrations to provided discrimination between infected and non-infected subjects (89%/90% correct classification in the training/validation cohorts). Further identification of aTB patients among infected subjects was best achieved by combining ESAT-6-induced IP-10 with HBHA-induced IL-2 and GM-CSF. Among infected subjects, 90%/93% of the aTB patients were correctly identified in the training/validation cohorts. We therefore propose a two steps strategy performed on 1 mL WB for a rapid identification of patients with aTB. After elimination of most non-infected subjects by combining ESAT-6 and HBHA-induced IFN-γ, the combination of IP-10, IL-2 and GM-CSF released by either ESAT-6 or HBHA correctly identifies most patients with aTB.

Abstract Background The COVID-19 pandemic has imposed an enormous burden on health care systems around the world. In the past, the administration of convalescent plasma of patients having recovered from SARS and severe influenza to patients actively having the disease showed promising effects on mortality and appeared safe. Whether or not this also holds true for the novel SARS-CoV-2 virus is currently unknown. Methods DAWn-Plasma is a multicentre nation-wide, randomized, open-label, phase II proof-of-concept clinical trial, evaluating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19 in Belgium. Patients hospitalized with a confirmed diagnosis of COVID-19 are eligible when they are symptomatic (i.e. clinical or radiological signs) and have been diagnosed with COVID-19 in the 72 h before study inclusion through a PCR (nasal/nasopharyngeal swab or bronchoalveolar lavage) or a chest-CT scan showing features compatible with COVID-19 in the absence of an alternative diagnosis. Patients are randomized in a 2:1 ratio to either standard of care and convalescent plasma (active treatment group) or standard of care only. The active treatment group receives 2 units of 200 to 250 mL of convalescent plasma within 12 h after randomization, with a second administration of 2 units 24 to 36 h after ending the first administration. The trial aims to include 483 patients and will recruit from 25 centres across Belgium. The primary endpoint is the proportion of patients that require mechanical ventilation or have died at day 15. The main secondary endpoints are clinical status on day 15 and day 30 after randomization, as defined by the WHO Progression 10-point ordinal scale, and safety of the administration of convalescent plasma. Discussion This trial will either provide support or discourage the use of convalescent plasma as an early intervention for the treatment of hospitalized patients with COVID-19 infection. Trial registration ClinicalTrials.gov NCT04429854 . Registered on 12 June 2020 - Retrospectively registered.

We report a case of Argentine hemorrhagic fever diagnosed in a woman in Belgium who traveled from a disease-endemic area. Patient management included supportive care and combination therapy with ribavirin and favipiravir. Of 137 potential contacts, including friends, relatives, and healthcare and laboratory workers, none showed development of clinical symptoms of this disease.

We report 4 cases of Fusobacterium nucleatum bacteremia associated with coronavirus disease (COVID-19). Three cases occurred concomitantly with COVID-19 diagnosis; 1 occurred on day 15 of intensive care. None of the patients had known risk factors for F. nucleatum bacteremia. F. nucleatum infection could represent a possible complication of COVID-19.

Objectives: The aim was to characterize the clinical features, outcomes, and strain diversity of laboratory-confirmed Streptococcus pyogenes (group A Streptococcus, GAS) infections among inpatients hospitalized at a tertiary level hospital in Brussels, Belgium, according to the patients’ housing status (homeless vs. not homeless). Methods: Between August 2016 and January 2018, all patients hospitalized with a laboratory-confirmed GAS infection were prospectively enrolled and risk factors were recorded. GAS strains were characterized using emm-typing and emm-clustering in both inpatients and outpatients. Analyses were performed according to homelessness status. Results: During the study period, 48% (28/58) of adults hospitalized with a GAS infection at the tertiary hospital were homeless. The estimated incidence rate was 100 times higher for homeless persons. Skin abscesses were more frequent in the homeless group (21.4% vs. 3.3%) and mortality was high (10.7%). Limited emm-type diversity was found in this group, with four emm-types (64, 77, 83, and 101) accounting for 76.1% of the infections, and the majority of these emm-types belonged to the D4 emm-cluster. Pooled analyses of inpatient and outpatient strains indicated lower diversity in the homeless group. Conclusions: The homeless are disproportionately affected by GAS and have a higher rate of abscesses and high mortality. The lower emm-type diversity and preferential infection with four emm-types likely reflects endemic circulation of GAS in this population. Preventive strategies are warranted in this fragile population. Keywords: Streptococcus pyogenes, Epidemiology, Streptococcal m protein, Skin infections, Homeless persons

Purpose. To report multimodal imaging findings in two cases of AIDS-related cryptococcal chorioretinitis associated with uveitis and vasculitis. Methods. Findings on clinical examination, color fundus photography, fluorescein and indocyanine green angiographies, and optical coherence tomography. Patients. Both patients were diagnosed with Cryptococcus neoformans meningitis in the setting of untreated HIV infection with CD4+ T cell count

Background Cancer seems to have an independent adverse prognostic effect on COVID-19-related mortality, but uncertainty exists regarding its effect across different patient subgroups. We report a population-based analysis of patients hospitalised with COVID-19 with prior or current solid cancer versus those without cancer.Methods We analysed data of adult patients registered until 24 May 2020 in the Belgian nationwide database of Sciensano. The primary objective was in-hospital mortality within 30 days of COVID-19 diagnosis among patients with solid cancer versus patients without cancer. Severe event occurrence, a composite of intensive care unit admission, invasive ventilation and/or death, was a secondary objective. These endpoints were analysed across different patient subgroups. Multivariable logistic regression models were used to analyse the association between cancer and clinical characteristics (baseline analysis) and the effect of cancer on in-hospital mortality and on severe event occurrence, adjusting for clinical characteristics (in-hospital analysis).Results A total of 13 594 patients (of whom 1187 with solid cancer (8.7%)) were evaluable for the baseline analysis and 10 486 (892 with solid cancer (8.5%)) for the in-hospital analysis. Patients with cancer were older and presented with less symptoms/signs and lung imaging alterations. The 30-day in-hospital mortality was higher in patients with solid cancer compared with patients without cancer (31.7% vs 20.0%, respectively; adjusted OR (aOR) 1.34; 95% CI 1.13 to 1.58). The aOR was 3.84 (95% CI 1.94 to 7.59) among younger patients (

General practitioners (GPs) play a critical role in patient acceptance of vaccination. Vaccine hesitancy (VH) is a growing phenomenon in the general population but also affects GPs. Few data exist on VH among GPs. The objectives of this analysis of a population of GPs in the Belgian Wallonia-Brussels Federation (WBF) were to: (1) determine the prevalence and the features of VH, (2) identify the correlates, and (3) estimate the discrepancy in vaccination’s behaviors between the GPs’ children and the recommendations made to their patients. An online survey was carried out among the population of general practitioners practicing in the WBF between 7 January and 18 March 2020. A hierarchical cluster analysis was carried out based on various dimensions of vaccine hesitancy: perception of the risks and the usefulness of vaccines as well as vaccine recommendations for their patients. A total of 251 GPs answered the survey. The average percentage of moderate to high vaccine hesitancy was 50.6%. Three factors were independently associated with increased risk of vaccine hesitancy: an age

An amendment to this paper has been published and can be accessed via the original article.

Group B streptococcus (GBS) is a major cause of neonatal sepsis and mortality worldwide. Studies from both developed and developing countries have shown that HIV exposed but uninfected (HEU) infants are at increased risk of infectious morbidity, as compared to HIV unexposed uninfected infants (HUU). A higher susceptibility to GBS infections has been reported in HEU infants, particularly late-onset diseases (LOD) and more severe manifestations of GBS diseases. We review here the possible explanations for increased susceptibility to GBS infection. Maternal GBS colonization during pregnancy is a major risk factor for early-onset GBS invasive disease but colonization rates are not higher in HIV-infected compared to HIV-uninfected pregnant women, while selective colonization with more virulent strains in HIV-infected women is suggested in some studies. Lower serotype specific GBS maternal antibody transfer and quantitative and qualitative defects of innate immune responses in HEU infants may play a role in the increased risk of GBS invasive disease. The impact of maternal antiretroviral treatment and its consequences on immune activation in HEU newborns is important to study. Maternal immunization presents a promising intervention to reduce GBS burden in the growing HEU population.

BACKGROUND: We previously showed that newborns congenitally infected with Trypanosoma cruzi (M+B+) display a strong type 1 parasite-specific T cell immune response, whereas uninfected newborns from T. cruzi-infected mothers (M+B-) are prone to produce higher levels of proinflammatory cytokines than control neonates (M-B-). The purpose of the present study was to determine if such fetal/neonatal immunological environments could alter the response to standard vaccines administered in early life. METHODOLOGY: Infants (6-7 months old) living in Bolivia, an area highly endemic for T. cruzi infection, and having received Bacillus Calmette Guerin (BCG), hepatitis B virus (HBV), diphtheria and tetanus vaccines, were enrolled into the M+B+, M+B-, M-B- groups mentioned above. The production of IFN-gamma and IL-13, as markers of Th1 and Th2 responses respectively, by peripherical blood mononuclear cells stimulated with tuberculin purified protein derivative of Mycobacterium tuberculosis (PPD) or the vaccinal antigens HBs, diphtheria toxoid (DT) or tetanus toxoid (TT), as well as circulating levels of IgG antibodies against HBsAg, DT and TT were analyzed in infants. Cellular responses to the superantigen SEB were also monitored in M+B+, M+B-, M-B-infants and newborns. PRINCIPAL FINDINGS: M+B+ infants developed a stronger IFN-gamma response to hepatitis B, diphtheria and tetanus vaccines than did M+B- and M-B- groups. They also displayed an enhanced antibody production to HBsAg. This was associated with a type 1-biased immune environment at birth, since cells of M+B+ newborns produced higher IFN-gamma levels in response to SEB. M+B- infants produced more IFN-gamma in response to PPD than the other groups. IL-13 production remained low and similar in all the three groups, whatever the subject's ages or vaccine status. CONCLUSION: These results show that: i) both maternal infection with T. cruzi and congenital Chagas disease do not interfere with responses to BCG, hepatitis B, diphtheria and tetanus vaccines in the neonatal period, and ii) the overcoming of immunological immaturity by T. cruzi infection in early life is not limited to the development of parasite-specific immune responses, but also tends to favour type 1 immune responses to vaccinal antigens.