The next influenza pandemic: will we be ready to care for our children?
Ontology highlight
ABSTRACT:
SUBMITTER: Woods CR
PROVIDER: S-EPMC7118918 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:People living with HIV (PWH) often exhibit poor responses to influenza vaccination despite effective combination anti-retroviral (ART) mediated viral suppression. There exists a paucity of data in identifying immune correlates of influenza vaccine response in context of HIV infection that would be useful in improving its efficacy in PWH, especially in younger individuals. Transcriptomic data were obtained by microarray from whole blood isolated from aviremic pediatric and adolescent HIV-infected individuals (4-25 yrs) given two doses of Novartis/H1N1 09 vaccine during the pandemic H1N1 influenza outbreak. Supervised clustering and gene set enrichment identified contrasts between individuals exhibiting high and low antibody responses to vaccination. High responders exhibited hemagglutination inhibition antibody titers >1:40 post-first dose and 4-fold increase over baseline. Baseline molecular profiles indicated increased gene expression in metabolic stress pathways in low responders compared to high responders. Inflammation-related and interferon-inducible gene expression pathways were higher in low responders 3 wks post-vaccination. The broad age range and developmental stage of participants in this study prompted additional analysis by age group (e.g. <13yrs and >13yrs). This analysis revealed differential enrichment of gene pathways before and after vaccination in the two age groups. Notably, CXCR5, a homing marker expressed on T follicular helper (Tfh) cells, was enriched in high responders (>13yrs) following vaccination which was accompanied by peripheral Tfh expansion. Our results comprise a valuable resource of immune correlates of vaccine response to pandemic influenza in HIV infected children that may be used to identify favorable targets for improved vaccine design in different age groups.
2021-03-18 | GSE167893 | GEO
Project description:The 2009 H1N1 influenza A virus that has targeted not only those with chronic medical illness, the very young and old, but also a large segment of the patient population that has previously been afforded relative protection - those who are young, generally healthy, and immune naive. The illness is mild in most, but results in hospitalization and severe ARDS in an important minority. Among those who become critically ill, 20-40% will die, predominantly of severe hypoxic respiratory failure. However, and potentially in part due to the young age of those affected, intensive care with aggressive oxygenation support will allow most people to recover. The volume of patients infected and with critical illness placed substantial strain on the capacity of the health care system and critical care most specifically. Despite this, the 2009 pandemic has engaged our specialty and highlighted its importance like no other. Thus far, the national and global critical care response has been brisk, collaborative and helpful - not only for this pandemic, but for subsequent challenges in years ahead.
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Project description:Outside Asia, Egypt is considered to be an influenza H5N1 epicentre and presents a far greater pandemic risk than other countries. The long-term endemicity of H5N1 and the recent emergence of H9N2 in poultry call attention to the need for unravelling the epidemiology, ecology and highly diverse gene pool of influenza A virus (IAV) in Egypt which is the aim of this review. Isolation of a considerable number of IAV subtypes from several avian and mammalian hosts was described. Co-infections of poultry with H5N1 and H9N2 and subclinical infections of pigs and humans with H1N1 and H5N1 may raise the potential for the reassortment of these viruses. Moreover, the adjustment of IAV genomes, particularly H5N1, to optimize their evolution toward efficient transmission in human is progressing in Egypt. Understanding the present situation of influenza viruses in Egypt will help in the control of the disease and can potentially prevent a possible pandemic.
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Project description:The 2009 pandemic influenza A (H1N1) (pH1N1) virus continues to circulate worldwide. Determining the roles of chronic conditions and bacterial coinfection in mortality is difficult because of the limited data for children with pH1N1-related critical illness.We identified children (<21 years old) with confirmed or probable pH1N1 admitted to 35 US PICUs from April 15, 2009, through April 15, 2010. We collected data on demographics, baseline health, laboratory results, treatments, and outcomes.Of 838 children with pH1N1 admitted to a PICU, the median age was 6 years, 58% were male, 70% had ?1 chronic health condition, and 88.2% received oseltamivir (5.8% started before PICU admission). Most patients had respiratory failure with 564 (67.3%) receiving mechanical ventilation; 162 (19.3%) received vasopressors, and 75 (8.9%) died. Overall, 71 (8.5%) of the patients had a presumed diagnosis of early (within 72 hours after PICU admission) Staphylococcus aureus coinfection of the lung with 48% methicillin-resistant S aureus (MRSA). In multivariable analyses, preexisting neurologic conditions or immunosuppression, encephalitis (1.7% of cases), myocarditis (1.4% of cases), early presumed MRSA lung coinfection, and female gender were mortality risk factors. Among 251 previously healthy children, only early presumed MRSA coinfection of the lung (relative risk: 8 [95% confidence interval: 3.1-20.6]; P < .0001) remained a mortality risk factor.Children with preexisting neurologic conditions and immune compromise were at increased risk of pH1N1-associated death after PICU admission. Secondary complications of pH1N1, including myocarditis, encephalitis, and clinical diagnosis of early presumed MRSA coinfection of the lung, were mortality risk factors.
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Project description:It is widely believed that protecting health care facilities against outbreaks of pandemic influenza requires pharmaceutical resources such as antivirals and vaccines. However, early in a pandemic, vaccines will not likely be available and antivirals will probably be of limited supply. The containment of pandemic influenza within acute-care hospitals anywhere is problematic because of open connections with communities. However, other health care institutions, especially those providing care for the disabled, can potentially control community access. We modeled a residential care facility by using a stochastic compartmental model to address the question of whether conditions exist under which nonpharmaceutical interventions (NPIs) alone might prevent the introduction of a pandemic virus. The model projected that with currently recommended staff-visitor interactions and social distancing practices, virus introductions are inevitable in all pandemics, accompanied by rapid internal propagation. The model identified staff reentry as the critical pathway of contagion, and provided estimates of the reduction in risk required to minimize the probability of a virus introduction. By using information on latency for historical and candidate pandemic viruses, we developed NPIs that simulated notions of protective isolation for staff away from the facility that reduced the probability of bringing the pandemic infection back to the facility to levels providing protection over a large range of projected pandemic severities. The proposed form of protective isolation was evaluated for social plausibility by collaborators who operate residential facilities. It appears unavoidable that NPI combinations effective against pandemics more severe than mild imply social disruption that increases with severity.
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Project description:In The Netherlands a major part of preparedness planning for an epidemic or pandemic consists of maintaining essential public services, e.g., by the police, fire departments, army personnel, and healthcare workers. We provide estimates for peak demand for healthcare workers, factoring in healthcare worker absenteeism and using estimates from published epidemiologic models on the expected evolution of pandemic influenza in relation to the impact on peak surge capacity of healthcare facilities and intensive care units (ICUs). Using various published scenarios, we estimate their effect in increasing the availability of healthcare workers for duty during a pandemic. We show that even during the peak of the pandemic, all patients requiring hospital and ICU admission can be served, including those who have non-influenza-related conditions. For this rigorous task differentiation, clear hierarchical management, unambiguous communication, and discipline are essential and we recommend informing and training non-ICU healthcare workers for duties in the ICU.
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Project description:The recent outbreaks of influenza A/H5N1 and 'swine influenza' A/H1N1 have caused global concern over the potential for a new influenza pandemic. Although it is impossible to predict when the next pandemic will occur, appropriate planning is still needed to maximize efficient use of resources and to minimize loss of life and productivity. Many tools now exist to assist countries in evaluating their plans but there is little to aid in writing of the plans. This study discusses the process of drafting a pandemic influenza preparedness plan for developing countries that conforms to the International Health Regulations of 2005 and recommendations of the World Health Organization. Stakeholders from many sectors should be involved in drafting a comprehensive pandemic influenza plan that addresses all levels of preparedness.
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Project description:Despite the best efforts of influenza scientists, companies and health officials to prepare for the next pandemic, most of the world's people will not have access to affordable supplies of vaccines and antiviral agents. They will have to rely on 19th century public health 'technologies' to see them through. In the 21st century, science ought to be able to provide something better. Influenza scientists study the molecular characteristics of influenza viruses and their signaling effects in cell culture and animal models of infection. While these studies have been enormously informative, they have been unable to explain the system-wide effects of influenza on the host, the increased mortality of younger adults in the 1918 influenza pandemic and the much lower mortality rates in children who were more commonly infected with the 1918 virus. Experiments by non-influenza scientists have defined common cell signaling pathways for acute lung injury caused by different agents, including inactivated H5N1 influenza virus. These pathways include several molecular targets that are up-regulated in acute lung injury and down-regulated by anti-inflammatory and immunomodulatory agents, including statins, fibrates, and glitazones. These agents also help reverse the mitochondrial dysfunction that accompanies multi-organ failure, something often seen in fatal Influenza. Observational studies suggest that statins are beneficial in treating patients with pneumonia (there are no such studies for fibrates and glitazones). Other studies suggest that these agents might be able to 'roll back' the self-damaging host response of young adults to the less damaging response of children and thus save lives. Research is urgently needed to determine whether these and other agents that modify the host response might be useful in managing H5N1 influenza and the next pandemic.
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Project description:Challenges facing seasonal and pandemic influenza vaccination include: increasing the immunogenicity of seasonal vaccines for the most vulnerable, increasing vaccination coverage against seasonal influenza, and developing vaccines against pandemic strains that are immunogenic with very low quantities of antigen to maximize the number of people who can be vaccinated with a finite production capacity. We review Sanofi Pasteur's epidemic and pandemic influenza research and development programmes with emphasis on two key projects: intradermal influenza vaccine for seasonal vaccination of both elderly and younger adults, and pandemic influenza vaccine.
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