Influenza Global Health & Disasters Course October 19, 2016 Wayne Sullender, MD Center for Global Health Department of Pediatrics University of Colorado Anschutz Medical Campus wayne.sullender@ucdenver.edu
Disclosure Slide No relevant financial relationships to report.
Learning Objectives Understand the mechanisms by which antigenic shift and antigenic drift occur in influenza viruses and the epidemiologic implications of these changes. Recognize the burden of disease due to influenza in developing countries and among displaced populations. Describe the options for the prevention of influenza virus infections and planning for influenza pandemics.
Pneumonia forgotten killer World Pneumonia Day November 12, 2016 http://www.worldpneumoniaday.org
Pneumonia killed 965,000 in 2013: more than AIDS, malaria, and measles combined. 2013 Pneumonia Liu 2014 Lancet, Global, regional, and national causes of child mortality in 2000 13
Global burden of disease due to influenza in children < 5 years is substantial 90 million cases of influenza 20 million influenza acute lower respiratory infections (13% of all ALRI) 1 million influenza-associated severe ALRI (7% of cases of all severe ALRI) 28,000 111,500 deaths in children, influenzaassociated ALRI 99% of these deaths in developing countries. Estimates for 2008, Lancet 2011 (0140-6736), 378 (9807), p 1917
Influenza Virion Segmented RNA genome Hemagglutinin (HA): Cell attachment, membrane fusion Neutralizing antibodies block attachment and fusion Neuraminidase (NA): Cleaves sialic acid, prevents virion clumping Antibodies block virion release Influenza A: H1N1, H3N2, etc Katz, CDC www.preventinfluenza.org/nivs_2011/2-katz_vaccine_technologies www.cdc.gov/flu/images
quasispecies Antigenic drift Individual genetic changes, RNA polymerase lacks proof-reading/editing Error prone replication RNA viruses: swarm of non-identical but closely related genomes or quasispecies Selective pressure: mutants with growth advantages become predominant. [Curr Top Microbiol Immunol. 1992;176:1-20]
Influenza Antigenic Changes Influenza Reassortment: Reassortment of genomic segments creates hybrid virus: antigenic shift, pandemics Antigenic Drift: Minor antigenic changes in HA and NA Causes local outbreaks, requires vaccine changes. Murray Medical Microbiology
2013: Most Recent H7N9 Flu Deadlier Than H1N1 H7N9 emerged by reassortment (antigenic shift). May have occurred in habitats shared by wild and domestic birds. Most of those infected had contact with infected poultry or contaminated environments. 665 cases and 229 deaths reported globally from March 2013 through May 9, 2015, most from mainland China Alexandra Sifferlin June 24,2013 healthland.time.com/2013/06/24/most recent h7n9 flu deadlier than h1n1 http://wwwnc.cdc.gov/travel/notices/watch/avian flu h7n9 china
Influenza in resource limited settings
UNHCR: highest levels of displacement on record, ½ are children. 34,000 people are forcibly displaced every day http://www.unhcr.org/images/infographics/figuresataglance 16JUN2016.png downloaded 10.5.2016
Communicable diseases, alone or with malnutrition, account for most deaths in complex emergencies Preventive measure Impact on spread of Site planning Clean water Good sanitation Adequate nutrition Vaccination Vector control Personal protection Personal hygiene Health education Case management Diarrhea, acute respiratory infection (ARI) Diarrhea, typhoid, guinea worm Diarrhea, vector borne diseases, scabies Tuberculosis, measles, ARI Measles, meningitis, yellow fever, Japanese encephalitis, diphtheria, influenza Malaria, leishmaniasis, plague, dengue, Japanese encephalitis, yellow fever, etc Malaria, leishmaniasis (insecticide treated nets) Louse borne diseases (also ARI) STDs, HIV/AIDS, Diarrhoea ARI, diarrhea, tuberculosis, meningitis, vector borne diseases Lancet 2004, 364:1974 1983
Respiratory viral infections in two long term refugee camps in Kenya, 2007 2010: high rates of illness among children 10 90% specimens (+) for at least one virus among children < 5 yrs with severe ARI BMC Infect Dis. 2012 Jan 17;12:7
Influenza in Refugees on the Thailand Myanmar Border, May October 2009 URI and ALRI common Influenza in 20% influenzalike illnesses, 23% of pneumonias Monthly Incidence (per 1,000 population) (A) URI and (B) ALRI Emerg Infect Dis. 2010 Sep;16(9):1366 72
Burden of acute respiratory infections in crisis affected populations Systematic review on the burden of ARI. ARI always within the top four causes of hospitalization. ARI the first or second most frequent cause of outpatient consultation. ARI among the top three causes of death in all but one study, irrespective of age group. Very high excess morbidity and mortality (20 35% mortality) due to ARI Confl Health. 2010 Feb 11;4:3. doi: 10.1186/1752 1505 4 3
Risk factors morbidity and mortality from pandemic influenza in refugee/displaced populations overcrowding poor access to basic health care services malnutrition communicable diseases logistic challenges, remote locations or ongoing conflict lack of adequate surveillance to detect cases poor links to national disease surveillance systems possible exclusion from national influenza preparedness activities lack of staff to investigate outbreaks and manage ill persons. Pandemic influenza preparedness and mitigation in refugee and displaced populations WHO 2008
Influenza Planning Improved influenza surveillance with global coordination International/national/regional/local planning and development of surge capacity Plans for vaccine development, production, and administration Antiviral susceptibility testing and consideration of antiviral stockpiling/dispensation Pandemic influenza preparedness and mitigation in refugee and displaced populations WHO 2008
WHO provides surveillance data % samples (+) and influenza type 30Sept, 2016 Shading of countries shows % (+) for influenza Pie charts give virus type WHO 5Oct2016 http://www.who.int/influenza/surveillance_monitoring/updates/2016_10_03_influenza_update_273.jpg?ua=1
WHO Global Early Warning and Response System (EWARS) Brings together expertise in disease outbreaks and humanitarian emergencies to strengthen early warning, alert and response in emergency settings technical guidance, training and field based tools EWARS in a box: kit of ruggedized, field ready equipment needed to establish and manage surveillance and response activities in field settings without reliable internet or electricity (mobile phones, laptops, solar generators). www.who.int/features/2016/disease early warning response/en/
Build capacity to cope with a pandemic Implement public health measures Implement communication plans minimize shortages of essential services such as health care (including for usual burden of disease), access to food, safe water, sanitation, power, communications and security/protection; minimize social disruption; prioritize vulnerable countries strengthen partnerships with governments to ensure the coordination of activities Pandemic influenza preparedness and mitigation in refugee and displaced populations WHO 2008
Pandemic response lessons from influenza H1N1 2009 in Asia Despite warm words and pledges, efforts to engage the international community to ensure equitable sharing of limited resources such as antivirals and vaccines fell short and stockpiles in the main remained in the rich world. Respirology. 2011 Aug;16(6):876 82
Public Health Measures Social distancing Respiratory etiquette Cover coughs and sneezes Do not spit in public If using masks, dispose of them or wash them Wash hands Wash hands with soap and clean water carefully and often (and clean surfaces). Pandemic influenza preparedness and mitigation in refugee and displaced populations WHO 2008
Family/Household Level: measures to mitigate pandemic influenza in low resource settings Prevention Keep your distance. Wash your hands, cover your coughs and sneezes. Isolate your ill Care Fluids, nutrition Fever Rest Medications, care seeking Influenza Other Respir Viruses. 2013 Nov;7(6):909 13
Community/District Level: measures to mitigate pandemic influenza in low resource settings Prevention Educate on prevention. Limit public crowding, gathering, mixing, and contacts Care Educate on home care, assist the neediest (including care, food, and water). Community case management Influenza Other Respir Viruses. 2013 Nov;7(6):909 13
Estimated number of persons affected by pandemic influenza in a population of 10,000 in a crowded, low resource setting Description rates # persons/day Ill influenza 15-60% up to 100 outpatients 30 50%* up to 50 inpatients Up to 10% * up to 10 Deaths 4% or more * up to 4 or more *of those ill Pandemic influenza preparedness and mitigation in refugee and displaced populations WHO 2008
Hospital Surge Planning Screening, surveillance, and tracking of exposed individuals Controlled access to facility Prevention strategies (next slide) Disease specific admission criteria Enable continuity of clinical operations Sustained increase in patients (staff/space) Additional triage areas Increased ventilator/icu needs and support Pediatric Education in Disasters Manual, Influenza, Nyquist and Berman
Prevention strategies in hospital surge planning Isolation and cohorting Personal protective equipment (PPE: masks, gloves, gowns) Vaccination Antiviral prophylaxis Environmental controls (separate areas ill/non ill patients) Visitation and ill staff policies Pediatric Education in Disasters Manual, Influenza, Nyquist and Berman
Prioritization for vaccine and antivirals Group Rationale Health care workers HCWs are the highest risk group for infection (also 1st responders: EMTs, police, fire) HCWs may transmit illness to vulnerable patients. Essential staff Maintain essential services in health facilities High risk Risk of severe disease: pregnant women, conditions young, elderly, underlying medical conditions Pandemic influenza preparedness and mitigation in refugee and displaced populations WHO 2008 Pediatric Education in Disasters Manual, Influenza, Nyquist and Berman CDC 4Nov2013: http://www.cdc.gov/flu/about/disease/index.htm
Supportive care Influenza Management Antivirals: Neuraminidase inhibitors (oseltamivir and zanamivir) for prophylaxis and treatment. Uncertain availability and efficacy in low resource settings. Efforts centred on maintaining and increasing vaccine production, and ensuring access to pharmaceuticals responses that remain unattainable for many low and middle income countries... reflects a particular view of biomedicine that pays inadequate attention to the weak capacity of many health systems. Glob Public Health. 2012;7 Suppl 2:S111 26 O2 delivery in 12 African countries: 44% with uninterrupted access to an oxygen source J Infect Dev Ctries. 2010 Aug 4;4(7):419 24
Influenza vaccines
Current influenza vaccines Safe Effectiveness is variable and depends on: antigenic match and immunogenicity host factors such as age and immune status May require annual reformulation due to antigenic changes. Egg-based technologies limit rapid response and surge capacity for pandemics. Katz, CDC http://www.preventinfluenza.org/nivs_2011/2 katz_vaccine_technologies
Influenza Virus Vaccine for the 2016 2017 Season, northern hemisphere Both inactivated and live attenuated vaccines (only inactivated recommended in USA 2016) Trivalent: A/California/7/2009 (H1N1)pdm09 like virus; A/Hong Kong/4801/2014 (H3N2) like virus; B/Brisbane/60/2008 like virus (Yamagata lineage). Quadrivalent influenza vaccines add the following additional B strain to the above trivalent vaccine: a B/Phuket/3073/2013 like virus (Victoria lineage) www.who.int/influenza/vaccines/virus/recommendations/2016_17_north/en/
Summary Influenza viruses change constantly on the basis of antigenic drift and shift, requiring reformulation of vaccines and leading to pandemics. Influenza virus infections in resource limited settings, including among refugees/displaced persons, cause significant disease in children and adults. Control measures include universal hygiene behaviors and social distancing. Influenza vaccines and antivirals may be employed if available.