Containment - lecture 5 - Pandemic preparedness

pandemics of the last century

• 1918 spanish flu (influenza)

  • 50 million death

  • A(H1N1)

• 1958 Asian flu

  • 2 million deaths

  • A(H2N2)

• 1968 hong kong flu

  • 1 million deaths

  • A(H3N2)

• 2009 Mexican flu

  • 200 000 deaths

  • A(H1N1)

• 650 000 fatalities in seasonal epidemics

things that affect the risk of a viral outbreak (pandemic)

• traveling

• high density population

• farming (high amount of animals together)

• climate change

importance in tackling a pandemic

• different disciplines are needed to prevent pandemics

(public) health research questions related to an outbreak or viral introduction into a population

• viral mutation rate

• host immune response

• risk factors 

• progression of symptoms

• transmission route

• cause of the outbreak

• viral shedding kinetics

• how to diagnose

• infectious per iod

• pathogenesis

• pre-existing immunity

research during a pandemic (covid)

• start 2020 cohorts with infected individuals (health care workers)

• start 2021; cohorts with vaccinated individuals

• 20201 > cohorts with booster vaccination

• >1000 inclusion health care workers

  • rapid interaction with ethical committee was essential

  • sampling pre and post infection

  • sampling pre and post vaccination.

urgent questions during pandemic

• do novel virus variants escape the immune system

  • use of neutralization assay to look into specific immune responses.

• for covid there was a new variant (omicron). the immune system did not recognize new variant well → booster vaccine was advised. (booster vaccines were adjusted to the novel variants)

SENTINAL study

• surveillance and immunology among HCW and animal workers

• highly pathogenic avian influenza

  • comes from birds (highest risk poultry)

  • mammals (cattle) have been infected

  • some human to human transmissions

highly pathogenic avian influenza (HPAI) 

• influenza comes from bird (sometimes mammals infected) 

• no transmission from human to human 

• in the netherlands people get it from poultry. 

• humans are frequently exposed to seasonal influenza viruses

  • natural infections (H1N1, H3N3, B) 

  • seasonal vaccinations 

pre eisting immunity to HPAI

• H5 is highly pathogenic → humans have very rare (H5 specific antibody) responses because

  • limited binding to the HA1 / RBD

  • limited HI

  • some stem specific neutralisation of H5N1 (clade 2.3.4.4B detected)

• cross reactive T cell responses have been reported

  • small studies systemic data for H5N1

population immunity to H5Nx

• Study objective: To understand why population immunity to H5Nx avian influenza viruses by performing newly developed immunological assays

• could H5Nx disease severity be blunted due to pre-existing immunity to HPAI 

• design → antibody and T cell assays on blood obtained from health care workers prior to the 2024/2025 respiratory season. 

• cohort characteristics

  • predominantly female

  • seasonal influenza vaccine uptake (71%)

  • age distribution 49

• low recognition of HA1 subunits (H5 and H7). potentially stem specific antibodies → no idea how well protection is. needs to bind to the spike protein

• neutralizing antibodies (we might have few antibodies binding to the influenza but if the antibodies that due bind have a very high neutralizing affinity this could be okay). 

  • however, there was no neutralizing antibodies at all 

measles

• respiratory virus for humans

• decreasing vaccination rate in Nl

• most infectious virus for the human population

  • R=18 (the number that 1 sick person will infect)

• incubation period 9-19 days (can already spread the virus earlier)

• exanthema, fever, cough, conjunctivitis, koplik spots in mouth.

• measles leads to immune suppression → opportunistic infections happen → superinfection

• very rare → severe neurological complications→ 100% lethal. → antibodies will be found in CSF when this is the case

  • can happen years after someone is infected with measles because the virus can stay in the brain for years

• mortality 150 000 - 200 000 children (worldwide)

lessons learned when refusing vaccination

• understand motives and concerns

• work with trusted messenger

• communicate in a tailored way

• bring the vaccine to the people

• engage in respectful dialogue, not coercion

• use social media and targeted campaigns.

measles affect immune system

• depletion / destruction lymphoid tissue → memory immune cells destroyed 

• B lymphocyte depletion

• decrease of CD4/CD8 T cells after measles infection

study design for measles

• study population;

  • unvaccinated adults (18 years or older) who will be vaccinated or become infected during the upcoming measles outbreak

  • unvaccinated adults enrolled in the study who do not contract measles will be included as controls

  • additionally, we will include adults who were vaccinated or naturally infected during the previous outbreak in 2013.

• study design

  • observational cohort study

  • phenotyping and functional analysis of B and T cell (sub) populations in blood of individuals.

EXAM !!! lessons learned today

• what are risk factors for a new outbreak

• think of examples of viruses that might cause next outbreak → measles, west nile virus (usutu)

• what are essential questions

• what are essential measures to take in an outbreak