SARInet Meeting Proceedings

The Severe Acute Respiratory Infection Network (SARInet) is a network of Member States of the Americas that conduct SARI surveillance and was established in 2013 to facilitate sharing of ideas, access to resources, and to strategically address SARI surveillance. Since 2013 an annual regional network meeting has taken place in order to strengthen the collaboration and quality of work performed by the network members. The most recent meeting was held in Punta Cana, Dominican Republic in May 2017, uniting over 100 participants from 28 countries, 20 national influenza centers (NICs), nine national laboratories, and several collaborating institutions.

During the three day meeting, a variety of topics was addressed through oral presentations, posters, and workshops, including updates on SARI surveillance guidance and policies, integrating human and animal influenza surveillance, influenza vaccination, application of surveillance tools and data uses, and emerging issues in influenza and surveillance. Country and regional surveillance staff and technical influenza experts shared their experiences, challenges, updates, and recommendations for strengthening influenza surveillance.

The objectives of the meeting were to:

  • Identify regional gaps in influenza surveillance, and
  • Share advances in regional influenza and other respiratory virus surveillance

Meeting Presentation Summaries

Block 1: Integrating human and animal influenza surveillance

The increasing interactions between populations of poultry, pigs, and people worldwide have led to an increasing threat of the emergence of novel influenza viruses. While much has been learned about controlling avian influenza in animals and people over the past decades, significant gaps remain in the knowledge of modes of transmission, occupational risks, baseline exposure rates, and thesustainable implementation of control measures. The need for animal and human health sectors to coordinate and collaborate in the areas of disease control, prevention, and research in a more formal manner was highlighted by presenters during this block.

Global updates on avian influenza and tools to assess pandemic potential,Dr Julia Fitzner, WHO

Advance planning and preparedness are critical to help mitigate the impact of a pandemic. Pandemic influenza risk management (PIRM) takes an emergency risk management for health approach which aligns more closely with the disaster risk management structures already in place in many countries.

Various guidance documents exist to assist in the tracking and management of influenza; these include the TIPRA guidance to assess the pandemic potential of non-seasonal influenza viruses, PISA guidance to support the assessment of influenza severity, and aprotocol to investigate non-seasonal influenza and other emerging acute respiratory diseases (in clearance).

Virus information for all human infections with a non-seasonal influenza virus is reportable under the IHR.

Within the Americas, Canada, Mexico, and the USA have recorded 295 original viruses viathe influenza virus traceability mechanism (IVTM). This included the documentation of Influenza A/Mexico/7218/2012 (H7N3) isolated from a human and detected in Mexico in 2012 which was recorded in IVTM by CDC Atlanta.

Global updates of avian and other novel influenza sub-types:

  • From 2003 through 12 May 2017, 859 laboratory-confirmed human cases of avian influenza A(H5N1) virus infection have been officially reported to WHO from 16 countries; of these cases, 453 have died. Since May 2016 there has been a dramatic decline of reported human cases worldwide
  • From 2014 through 12 May 2017, 16 lab-confirmed human cases of avian influenza A(H5N6) virus infection have been reported to WHO from China; most cases had exposure to live poultry or live poultry markets; 6 cases were fatal
  • From 2013 through 16 May 2017, 1486 lab-confirmed human cases of avian influenza A(H7N9) virus infection have been reported to WHO from 3 countries; of these cases, at least 373 have died

Only by sharing data and viruses can the global situation be understood.

Emergence and changes in swine and avian influenza viruses globally, Dr Stephen Lindstrom, CDC

Avian H5Nx continues to spread to many countries although numbers of human infections are low. Updated CDC H5 assays detect recently circulating viruses.

Avian H7N9 continues to spread more widely in poultry populations in China and causes high numbers of human infection and death. Detection has spread throughout China including provinces near the country’s border. CDC EuH7 assay detects recently circulating H7N9 viruses from China.

Other viruses causing human infection include, by origin: swine H3N2v, H1N1v, and H1N2v; Asian avian H9N2; and Feline (N. Am. avian origin) H7N2.

H1N2v notes from the field, BRA

A novel human influenza A(H1N2) variant virus was identified by genomic characterization in a specimen from a pig farmer in the southern Brazilian region who presented with influenza-like illness.

The virus was a triple reassortant virus containing gene segments from subtypes H1N2 (hemagglutinin), H3N2 (neuraminidase), and pandemic H1N1 (remaining genes), closely resembling a swine virus detected in Brazil in 2011.

The patient did not have antibodies against the virus circulating in the swine population.

Lessons learned include the need to improve the integration of the animal and human health sectors and the need to fortify human and animal influenza surveillance networks in Brazil.

H7N6 notes from the field, CHI

Experience in the investigation of the avian influenza outbreak H7N6, December 2016-January 2017, Valparaíso region, Chile

12/30/2016: The Agricultural and Livestock Service (SAG) reported to the Ministry of Health the findingof avianinfluenza in turkeys in two poultry farms in ComunaQuilpué. Influenza A virus(H7) was detected by ELISA technique.

Immediate activation of control methods according to SAG protocol were implemented, including the slaughter and destruction of affected birds, isolation of the affected area, restriction of access to the affected site, virologic study of the poultry, increasing biosecurity measures to prevent the spread of the virus to other levels, and reportingof the event to the World Organization for Animal Health (OIE).

Avian influenza research was conducted to detect in a timely manner the presence of respiratory symptoms in exposed persons and establish control measures to prevent illness propagation. A retrospective study of direct or indirect exposures in those working from December 11, 2016 through January 3, 2017 (14 days before the initial detection of infected poultry) was conducted.

Results:

  • Two affected foci were found in fattening turkeys, with 7 of 10 sectors affected
  • 132 (of 136)exposed workers interviewed, 99% male
  • Nopositive cases in exposed workers, however, influenza vaccination is below 70% in the at-risk population
  • Most cases experienced mild respiratory symptoms, and tested negative for avian influenza (H7)
  • Diverse use of biosecurity measuresreported among workers

It is hypothesized that the influenza outbreaks in poultry were caused by: (a) indirect transmission from migratory birds found near to the tanks located on both farms, (b) indirect transmission through fomites,as both outbreaks had the same causal agent, or (c)increased risk due to using the same vehicles to transport birds.

Country experience with integrated surveillance, USA

Variant influenza A virus infections are defined as human infection with influenza A virus subtypes different from currently circulating human subtypes (A/H1 and A/H3). Influenza viruses that are known to circulate in pigs are called “influenza viruses—swine” when isolated from pigs, but are called “variant viruses” when isolated from humans.

Prevention of variant influenza includes: getting seasonal influenza vaccination, avoiding contact with sick animals, minimizing unnecessary contact with animals at fairs, staying away from animals when sick, and washing hands after contact with animals, contaminated equipment, or surfaces, etc.

CDC and APHIS developed a monitoring plan for responders involved in outbreaks of HPAI H5 avian influenza in the United States. This plan supports increased engagement of state and local health departments in the monitoring of responders for illness consistent with influenza.

CDC recommends that all persons exposed to infected birds or virus-contaminated environments be monitored for illness for 10 days after their last exposure. State health departments should notify CDC immediately when testing any patient under investigation for HPAI H5 virus infection.

Country experience with integrated surveillance, MEX

60% of human pathogens are of animal origin, 75% of emerging animal diseases can be transmitted to humans.

Mexico utilizes active and passive surveillance for tracking of animal diseases.

Strengthening of the intersectoral response is achieved through the continuous exchange of information, the sharing of protocols and advances in diagnosis, routinely holding meetings, and carrying out collaborative projects between the animal and health sectors.

Country experience with integrated surveillance, COL

On 12/09/2016, the National Institute of Health received a report of the death of a 49-year-old female resident from a rural community. The patient presented with symptoms of headache, fever, and general malaise following the handling of a diseased hen which quickly evolved to clinical and neurological deterioration and death.

Biological samples from the poultry farm and nearby areas were collected. The biological samples tested negative for New Castle and avian influenza infection. Samples testednegative for influenza and positive for Streptococcus pneumonia by hemocultureassays.

In Colombia, all cases complying with the case definition of antecedent exposure to sick birds or travelers from areas with avian influenza circulation should be reported and investigated in a timely manner.

Field research and laboratory results must be obtained for all reported cases.

The sensitivity of the early warning system depends on the proper integration and joint work of all levels and actors involved in both human and animal surveillance.

Animal influenza surveillance strengthening activities in Latin America, Dr Shultz-Cherry, St Judes/WHO CC

Surveillance was conducted in South America to determine the prevalence and diversity of influenza viruses in Colombia and Chile. The study was initiated in 2010 and 2015, respectively, with four sites in Colombia (Santa Marta, Medellin, Bogota, Los Llanos) and 15 sites in Chile around Santiago.

Wild birds (environmental samples), swine, and domestic birds (live animal markets, backyard, industry, and captive) were examined, using a risk assessment algorithm (CDC IRAT) to determine the risk of influenza viruses to humans, poultry, and swine.

Results:

  • Avian influenza virus and swine influenza virus are present in South America
  • Limited avian influenza found in Colombia, however swine influenza is prevalent; virus prevalence by species is determined by RT-qPCR. In Chile, diverse strains of avian influenza and swine influenza viruses were detected, influenza is prevalent
  • Studies linking avian influenza viruses in the Americas continue and need to be done in more countries
  • Latitudinal segment diversity is found between South American and North American avian influenza viruses

What’s next in the animal-human interface?

  • Serosurvey studies of disease surveillance in Colombia
  • Investigation of high-risk influenza virus subtypes and occurrence of spill-over events
  • Lots of opportunities for collaboration
  • Expand within South America
  • Training
  • Capacity building

Human-animal interface survey results in the Americas, Dr Rakhee Palekar, PAHO

PAHO administered a 41-question survey to n=17 Ministries of Health (MoH) and n=12 Ministries of Agriculture (MoAg) in the Americas to assess inter-sectoral influenza surveillance and response.

Survey results suggest the following: most MoH have limited influenza surveillance of farmers/farm inhabitants and are not collecting information about exposure to animals from SARI and ILI cases; most MoAg have active avian influenza surveillance and have a national laboratory to test for influenza; and MoH and MoAg agree that it would be feasible to establish inter-sectoral information sharing.

Recommendations for the strengthening of inter-sectoral influenza surveillance and response include: improve ascertainment of high-risk exposures among SARI and ILI cases, increase information sharing between MoH and MoAg, and provide inter-sectoral preparation/training of clinicians and workers to recognize and respond to high-risk events.

Reporting unusual and unexpected events to PAHO/WHO, Dr Angel Rodriguez, PAHO

Unusual events include findings of: novel influenza viruses not circulating widely in the human population, unsubtypeable influenza viruses, and exposure history to unusual pathogens combined with respiratory disease (e.g. respiratory disease plus travel to the Middle East (MERS-CoV)or exposure to sick animals).

Human infection caused by a confirmed or suspected novel influenza virus with pandemic potential, including a variant virus, should be reported immediately to the WHO IHR Regional Contact Point (via the IHR National Focal Point) and the Global Influenza Surveillance and Response System (GISRS) (via ).

Block 2: Influenza seasonality and virus sharing

Twice per year, the World Health Organization (WHO) convenes a group of experts to determine the seasonal influenza vaccine composition for the Northern and Southern Hemispheres. The group analyzes global surveillance and vaccine effectiveness data to make an informed decision. Effective surveillance is necessary for understanding influenza seasonality and for determining the best strategies for influenza control, which include anoptimal choice of influenza vaccine formulation and timing of vaccination campaigns.

During this blockpresenters’ highlighted approaches to determining the seasonality of influenza and the importance of shipping samples to the WHO Collaborating Centers for antigentic and genetic characterization as part of routine surveillance.

How to establish influenza seasonality, Dr Paula Couto, PAHO

Analysis of seasonality allows for an understanding of what is usual and preparation for increased influenza activity periods.

A variety of statistical methods are available to estimate influenza seasonality (based on the weekly proportion of influenza positive samples, % of SARI or ILI cases):

  • Averaging methodology: aligns all annual curves into a single average epidemic curve based on the median epidemiologic week
  • Binomial negative method: a logistic regression model which assumes a negative binomial distribution to predict monthly influenza activity
  • Moving epidemic methodology (MEM): calculated with the R package,determines the arithmetic mean of pre- and post-epidemic rates for historical seasons, with defined intensity thresholds

A combination of methods is required to ascertain influenza seasonality, particularly in tropical countries, as there is no gold standard.

Using the MEM method for influenza seasonality determination, Dr Tomas Vega, MoH Spain

Objectives: To detect the start of epidemics and to compare the intensity (transmissibility, seriousness and impact) of seasonal epidemic waves in a territory over time and between different territories.

Method: The Moving Epidemic Method identifies and locates the epidemics, aligns the epidemic waves, establishes a baseline and estimates the intensity thresholds.

The MEM can be used with any influenza surveillance parameter, with different performances, usefulness, and limits.

A Web application is being developed to facilitate the use of the MEM modeling process at the local/country level. A version can be downloaded from Modelling guidelines and a technical manual complete the MEM documents.

New approaches for modelling influenza data in tropical countries are under investigation. An international collaborative project is being designed.

Importance of viral genetic and antigenic characterization and human serology for influenza vaccine strain selection, Dr Xiyan Xu, CDC/WHO CC

Information regarding the WHO vaccine strain selection for the Northern Hemisphere 2017-18 season was reviewed.

Next generation sequencing (NGS) has improved throughput of genomic sequencing.

However, the complexity, cost factors, and need for NGS must be considered before implementing NGS.

Block 3: Influenza vaccination

Knowledge of influenza-seasonality is important to determine the appropriate timing for influenza vaccine campaigns. Trivalent influenza vaccines contain three influenza viruses: two influenza A viruses and an influenza B virus; while quadrivalent vaccines contain four influenza viruses-the same viruses as the trivalent vaccine plus an additional influenza B virus.

During this block, experts discussed the use of trivalent versus quadrivalent influenza vaccines, measures of influenza vaccine effectiveness, and ways to improve influenza vaccine coverage.

Updates on REVELAC-inetwork and current vaccine recommendations, Ms Alba Maria Ropero, PAHO

The presenter discussed advances in influenza vaccination in the Americas, the progress made in generating evidence for vaccination programs in Latin America and the Caribbean, the status of Revelac in Chile, and opportunities for intra- and inter-institutional collaboration.

SAGE/TAG recommendations for seasonal influenza vaccination 2004-2015 were reviewed:

  • All countries should strengthen their surveillance system to determine:
  • disease burden due to influenza
  • cost-effectiveness of introducing the vaccine, and
  • seasonality in order to identify the best vaccination strategy, formulation and vaccination period in tropical countries
  • All countries should establish a vaccination policy against seasonal influenza in:
  • Pregnant women
  • children <5 years (6-23 months)
  • older adults, and
  • health workers and people with risk conditions

Evidence needed by influenza vaccination programs in LAC

  • Epidemiological information to guide influenza vaccination programs
  • know the burden of disease by influenza
  • seasonality, when to vaccinate in countries of the tropic
  • what formulation of the vaccine to use
  • Evidence of vaccine performance (effectiveness)
  • support investment in the vaccine (free vaccine to target groups)
  • keep or extend to high-risk groups
  • guide complementary measures in seasons of low concordance between vaccine and circulating virus
  • Evidence of Impact
  • insert disease burden, effectiveness, and coverage data to assess the impact of the vaccine
  • Evidence of program performance
  • coverage, maternal immunization, health workers
  • economic studies

Requirements for participation in the multicenter evaluation of REVELAC-iare presented