First Attempt to Implement Ophthalmia Neonatorum Prophylaxis in Angola: Microorganisms, Efficacy, and Obstacles

Purpose. To determine the efficacy of povidone-iodine (P-I) prophylaxis for ophthalmia neonatorum (ON) in Angola and to document maternal prevalence and mother-to-child transmission rates. Methods. Endocervical samples from mothers n=317 and newborn conjunctival smears n=245 were analysed by multiplex polymerase chain reaction (PCR) for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Mycoplasma genitalium (MG). Newborns were randomized into a noninterventional group and an interventional group that received a drop of P-I 2.5% bilaterally after conjunctival smear collection. Mothers were trained to identify signs of ON and attend a follow-up visit. Results. Forty-two newborns had ocular pathology, and 11 (4.4%) had clinical signs of ON at the time of delivery. Maternal PCR was positive for MG n=19, CT n=8, and NG n=2. Six newborns were positive for CT n=4, MG n=2, and NG n=1. Mother-to-child transmission rates were 50% for CT and NG and 10.5% for MG. Only 16 newborns returned for follow-up. Conclusions. Lack of maternal compliance prevented successful testing of prophylactic P-I efficacy in ON prevention. Nevertheless, we documented the prevalence and mother-to-child transmission rates for CT, NG, and MG. These results emphasize the need to develop an effective Angolan educational and prophylactic ON program

Clinical Study First Attempt to Implement Ophthalmia Neonatorum Prophylaxis in Angola: Microorganisms, Efficacy, and Obstacles

properly cited. Purpose. To determine the efficacy of povidone-iodine (P-I) prophylaxis for ophthalmia neonatorum (ON) in Angola and to document maternal prevalence and mother-to-child transmission rates. Methods. Endocervical samples from mothers ( = 317) and newborn conjunctival smears ( = 245) were analysed by multiplex polymerase chain reaction (PCR) for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Mycoplasma genitalium (MG). Newborns were randomized into a noninterventional group and an interventional group that received a drop of P-I 2.5% bilaterally after conjunctival smear collection. Mothers were trained to identify signs of ON and attend a follow-up visit. Results. Forty-two newborns had ocular pathology, and 11 (4.4%) had clinical signs of ON at the time of delivery. Maternal PCR was positive for MG ( = 19), CT ( = 8), and NG ( = 2). Six newborns were positive for CT ( = 4), MG ( = 2), and NG ( = 1). Mother-to-child transmission rates were 50% for CT and NG and 10.5% for MG. Only 16 newborns returned for follow-up. Conclusions. Lack of maternal compliance prevented successful testing of prophylactic P-I efficacy in ON prevention. Nevertheless, we documented the prevalence and mother-to-child transmission rates for CT, NG, and MG. These results emphasize the need to develop an effective Angolan educational and prophylactic ON program

Estimation of Reduction in Influenza Vaccine Effectiveness Due to Egg-Adaptation Changes—Systematic Literature Review and Expert Consensus

Background: Influenza vaccines are the main tool to prevent morbidity and mortality of the disease; however, egg adaptations associated with the choice of the manufacturing process may reduce their effectiveness. This study aimed to estimate the impact of egg adaptations and antigenic drift on the effectiveness of trivalent (TIV) and quadrivalent (QIV) influenza vaccines. Methods: Nine experts in influenza virology were recruited into a Delphi-style exercise. In the first round, the experts were asked to answer questions on the impact of antigenic drift and egg adaptations on vaccine match (VM) and influenza vaccine effectiveness (IVE). In the second round, the experts were presented with the data from a systematic literature review on the same subject and aggregated experts’ responses to round one questions. The experts were asked to review and confirm or amend their responses before the final summary statistics were calculated. Results: The experts estimated that, across Europe, the egg adaptations reduce, on average, VM to circulating viruses by 7–21% and reduce IVE by 4–16%. According to the experts, antigenic drift results in a similar impact on VM (8–24%) and IVE (5–20%). The highest reduction in IVE was estimated for the influenza virus A(H3N2) subtype for the under 65 age group. When asked about the frequency of the phenomena, the experts indicated that, on average, between the 2014 and 19 seasons, egg adaptation and antigenic drift were significant enough to impact IVE that occurred in two and three out of five seasons, respectively. They also agreed that this pattern is likely to reoccur in future seasons. Conclusions: Expert estimates suggest there is a potential for 9% on average (weighted average of “All strains” over three age groups adjusted by population size) and up to a 16% increase in IVE (against A(H3N2), the <65 age group) if egg adaptations that arise when employing the traditional egg-based manufacturing process are avoided

HTLV infection in HCV-antibody positive patients in Spain.

Since hepatitis C virus (HCV) and human T-lymphotropic virus (HTLV) share transmission routes, dual infection could be frequent. In Spain, HTLV underdiagnosis is highlighted by the high proportion of patients presenting either with tropical spastic paraparesis or adult T cell leukemia at first diagnosis. We examined whether the renewed efforts for expanding HCV testing may provide a sentinel population that might selectively be targeted to unveil asymptomatic HTLV carriers. The presence of anti-HTLV antibodies was examined in 3,838 consecutive individuals with reactive HCV serology attended during the last 3 years at 13 hospitals distributed across the Spanish geography. Overall 71% were male, and the median age was 41 years old. Foreigners represented 9% of the study population. A total of 50 individuals (1.3%) were seroreactive for HTLV, being 30 confirmed as HTLV-2 and 2 as HTLV-1 (0.12%). The remaining 18 had indeterminate Western blot patterns. Most individuals with HTLV-2 and HTLV indeterminate serology were human immunodeficiency virus positive, former injection drug users, and native Spaniards. In contrast, the two HTLV-1 infections were found in men coming from Brazil and the Dominican Republic, respectively. In summary, the overall prevalence of HTLV infection in individuals living in Spain seropositive for HCV is 1.3%, more than 10-fold greater than in general outclinics in Spain. However, immigrants from HTLV-1 endemic regions and former injection drug users with HTLV-2 infection are by far the major contributory groups in HCV patients. Therefore, testing for HTLV in newly diagnosed HCV individuals would not contribute much to improve late HTLV diagnosis in Spain

Executive summary. diagnosis, treatment and prophylaxis of influenza virus infection. Consensus statement of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Pediatric Infectious Diseases (SEIP), the Spanish Association of Vaccinology (AEV), the Spanish Society of Family and Community Medicine (SEMFYC) and the Spanish Society of Preventive Medicine, Public Health and Health Management (SEMPSPGS)

[spa] El virus de la gripe ha acompañado al ser humano desde tiempo inmemorial, en forma de epidemias anuales y pandemias ocasionales. Se trata de una infección respiratoria con múltiples repercusiones sobre la vida de las personas a nivel individual y social, así como una importante sobrecarga para el sistema sanitario. El presente documento de consenso surge de la colaboración de diversas sociedades científicas españolas implicadas en la atención de la infección por virus de la gripe. Las conclusiones extraídas se han fundamentado en las evidencias de mayor calidad disponibles en la literatura científica y, en su defecto, en la opinión de los expertos convocados. En el documento de consenso se abordan los aspectos clínicos, microbiológicos, terapéuticos y preventivos (respecto de la prevención de la transmisión y en relación con la vacunación) de la gripe, tanto para población pediátrica como para adultos. Este documento de consenso pretende ayudar a facilitar el abordaje clínico, microbiológico y preventivo de la infección por virus de la gripe y, consecuentemente, a disminuir sus importantes consecuencias sobre la morbimortalidad de la población.[eng]The influenza virus has accompanied humans since time immemorial, in the form of annual epidemics and occasional pandemics. It is a respiratory infection with multiple repercussions on people's lives at an individual and social level, as well as representing a significant burden on the health system. This Consensus Document arises from the collaboration of various Spanish scientific societies involved in influenza virus infection. The conclusions drawn are based on the highest quality evidence available in the scientific literature and, failing that, on the opinion of the experts convened. The Consensus Document addresses the clinical, microbiological, therapeutic, and preventive aspects (with respect to the prevention of transmission and in relation to vaccination) of influenza, for both adult and pediatric populations. This Consensus Document aims to help facilitate the clinical, microbiological, and preventive approach to influenza virus infection and, consequently, to reduce its important consequences on the morbidity and mortality of the population

Host adaptive immunity deficiency in severe pandemic influenza

INTRODUCTION: Pandemic A/H1N1/2009 influenza causes severe lower respiratory complications in rare cases. The association between host immune responses and clinical outcome in severe cases is unknown. METHODS: We utilized gene expression, cytokine profiles and generation of antibody responses following hospitalization in 19 critically ill patients with primary pandemic A/H1N1/2009 influenza pneumonia for identifying host immune responses associated with clinical outcome. Ingenuity pathway analysis 8.5 (IPA) (Ingenuity Systems, Redwood City, CA) was used to select, annotate and visualize genes by function and pathway (gene ontology). IPA analysis identified those canonical pathways differentially expressed (P < 0.05) between comparison groups. Hierarchical clustering of those genes differentially expressed between groups by IPA analysis was performed using BRB-Array Tools v.3.8.1. RESULTS: The majority of patients were characterized by the presence of comorbidities and the absence of immunosuppressive conditions. pH1N1 specific antibody production was observed around day 9 from disease onset and defined an early period of innate immune response and a late period of adaptive immune response to the virus. The most severe patients (n = 12) showed persistence of viral secretion. Seven of the most severe patients died. During the late phase, the most severe patient group had impaired expression of a number of genes participating in adaptive immune responses when compared to less severe patients. These genes were involved in antigen presentation, B-cell development, T-helper cell differentiation, CD28, granzyme B signaling, apoptosis and protein ubiquitination. Patients with the poorest outcomes were characterized by proinflammatory hypercytokinemia, along with elevated levels of immunosuppressory cytokines (interleukin (IL)-10 and IL-1ra) in serum. CONCLUSIONS: Our findings suggest an impaired development of adaptive immunity in the most severe cases of pandemic influenza, leading to an unremitting cycle of viral replication and innate cytokine-chemokine release. Interruption of this deleterious cycle may improve disease outcome.The study was scientifically sponsored by the Spanish Society for Critical Care Medicine (SEMICYUC). Funding: MICCIN-FIS/JCYL-IECSCYL-SACYL (Spain): Programa de Investigación Comisionada en Gripe, GR09/0021-EMER07/050- PI081236-RD07/0067. CIHR-NIH-Sardinia Recherché-LKSF Canada support DJK.S

Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza

Abstract Introduction Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic cytokine and antibody levels in evaluating differences in early immune response in both mild and severe patients infected with nvH1N1. Methods We profiled 29 cytokines and chemokines and evaluated the haemagglutination inhibition activity as quantitative and qualitative measurements of host immune responses in serum obtained during the first five days after symptoms onset, in two cohorts of nvH1N1 infected patients. Severe patients required hospitalization (n = 20), due to respiratory insufficiency (10 of them were admitted to the intensive care unit), while mild patients had exclusively flu-like symptoms (n = 15). A group of healthy donors was included as control (n = 15). Differences in levels of mediators between groups were assessed by using the non parametric U-Mann Whitney test. Association between variables was determined by calculating the Spearman correlation coefficient. Viral load was performed in serum by using real-time PCR targeting the neuraminidase gene. Results Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1β), and the absence of anti-nvH1N1 antibodies, characterized the early response to nvH1N1 infection in both hospitalized and mild patients. High systemic levels of type-II interferon (IFN-γ) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17, IL-6) and T-helper 1 (TNF-α, IL-15, IL-12p70) responses were exclusively found in hospitalized patients. IL-15, IL-12p70, IL-6 constituted a hallmark of critical illness in our study. A significant inverse association was found between IL-6, IL-8 and PaO2 in critical patients. Conclusions While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. The exact role of Th1 and Th17 mediators in the evolution of nvH1N1 mild and severe disease merits further investigation as to the detrimental or beneficial role these cytokines play in severe illness

Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection

Pandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cytokine IL-6 has been implicated in both seasonal and severe pandemic H1N1 influenza A (H1N1pdm) infection. Here, we investigated the role of IL-6 in severe H1N1pdm infection. We found IL-6 to be an important feature of the host response in both humans and mice infected with H1N1pdm. Elevated levels of IL-6 were associated with severe disease in patients hospitalized with H1N1pdm infection. Notably, serum IL-6 levels associated strongly with the requirement of critical care admission and were predictive of fatal outcome. In C57BL/6J, BALB/cJ, and B6129SF2/J mice, infection with A/Mexico/4108/2009 (H1N1pdm) consistently triggered severe disease and increased IL-6 levels in both lung and serum. Furthermore, in our lethal C57BL/6J mouse model of H1N1pdm infection, global gene expression analysis indicated a pronounced IL-6 associated inflammatory response. Subsequently, we examined disease and outcome in IL-6 deficient mice infected with H1N1pdm. No significant differences in survival, weight loss, viral load, or pathology were observed between IL-6 deficient and wild-type mice following infection. Taken together, our findings suggest IL-6 may be a potential disease severity biomarker, but may not be a suitable therapeutic target in cases of severe H1N1pdm infection due to our mouse data

Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza

<p>Abstract</p> <p>Background</p> <p>Severe disease caused by 2009 pandemic influenza A/H1N1virus is characterized by the presence of hypercytokinemia. The origin of the exacerbated cytokine response is unclear. As observed previously, uncontrolled influenza virus replication could strongly influence cytokine production. The objective of the present study was to evaluate the relationship between host cytokine responses and viral levels in pandemic influenza critically ill patients.</p> <p>Methods</p> <p>Twenty three patients admitted to the ICU with primary viral pneumonia were included in this study. A quantitative PCR based method targeting the M1 influenza gene was developed to quantify pharyngeal viral load. In addition, by using a multiplex based assay, we systematically evaluated host cytokine responses to the viral infection at admission to the ICU. Correlation studies between cytokine levels and viral load were done by calculating the Spearman correlation coefficient.</p> <p>Results</p> <p>Fifteen patients needed of intubation and ventilation, while eight did not need of mechanical ventilation during ICU hospitalization. Viral load in pharyngeal swabs was 300 fold higher in the group of patients with the worst respiratory condition at admission to the ICU. Pharyngeal viral load directly correlated with plasma levels of the pro-inflammatory cytokines IL-6, IL-12p70, IFN-γ, the chemotactic factors MIP-1β, GM-CSF, the angiogenic mediator VEGF and also of the immuno-modulatory cytokine IL-1ra (p < 0.05). Correlation studies demonstrated also the existence of a significant positive association between the levels of these mediators, evidencing that they are simultaneously regulated in response to the virus.</p> <p>Conclusions</p> <p>Severe respiratory disease caused by the 2009 pandemic influenza virus is characterized by the existence of a direct association between viral replication and host cytokine response, revealing a potential pathogenic link with the severe disease caused by other influenza subtypes such as H5N1.</p