key: cord-0968420-fgrh2mg2 authors: Gupta, Swati; Gupta, Tejas; Gupt, Nivedita title: Global Respiratory Virus Surveillance: Strengths, Gaps and Way Forward date: 2022-05-15 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2022.05.032 sha: 43e0f4d630c70db25289a67e61ecba5828712607 doc_id: 968420 cord_uid: fgrh2mg2 Current situation : Global Influenza Surveillance and Response System (GISRS), coordinated by the World Health Organization (WHO) is a global framework for surveillance of Influenza and other respiratory viruses, data collection, laboratory capacity building, genomic data submission and archival, standardization and calibration of reagents and vaccine strains, production of seasonal influenza vaccines and creating a facilitatory regulatory environment for the same. Gaps : WHO designated National Influenza Centres (NICs) are entrusted with establishing surveillance in their respective countries. National and sub-national surveillance remains weak in most parts of the world due to varying capacities of the NICs, lack of funds, poor human and veterinary surveillance mechanisms, lack of intersectoral coordination and varying commitments of the local government. Way forward : As Influenza viruses have a wide variety of non-human hosts, it is critical to strengthen surveillance at local levels for timely detection of untypable or novel strains with potential to cause epidemics or pandemics. In this article, we have proposed possible strategies to strengthen and expand local capacities for respiratory virus surveillance through the designated NIC of the WHO. Abbreviations : Avian influenza virus (AIV); Acute respiratory illness (ARI); Influenza A virus (IAV); Coronaviruses (CoVs); Coronavirus disease 2019 (COVID-19); Centers for Disease Control and Prevention (CDC); External Quality Assurance Program (EQAP); Global Influenza Surveillance and Response System (GISRS); Global Influenza Program (GIP); Global Initiative on Sharing Avian Influenza Data (GISAID); Influenza-like illness (ILI); Inter-Laboratory-Quality Control (ILQC); Respiratory Syncytial Virus (RSV); Real-time reverse transcription-polymerase chain reaction (rRT-PCR); Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2); Severe acute respiratory syndrome (SARI); National Influenza Centres (NIC); World Health Organization (WHO); WHO-Coordinating Centres (WHO-CCs); WHO-H5 Reference Laboratories (WHO H5 RLs); World organization for animal health (OIE); WHO-Essential Regulatory Laboratories (WHO ERLs) Gaps: WHO designated National Influenza Centres (NICs) are entrusted with establishing surveillance in their respective countries. National and sub-national surveillance remains weak in most parts of the world due to varying capacities of the NICs, lack of funds, poor human and veterinary surveillance mechanisms, lack of intersectoral coordination and varying commitments of the local government. As Influenza viruses have a wide variety of non-human hosts, it is critical to strengthen surveillance at local levels for timely detection of untypable or novel strains with potential to cause epidemics or pandemics. In this article, we have proposed possible strategies to strengthen and expand local capacities for respiratory virus surveillance through the designated NIC of the WHO. Coronaviruses have been witnessed across the world (Baber, 2020) . Global history of pandemics over the past century indicates maximum potential of influenza viruses to mutate, reassort and evolve to cause outbreaks. This is exemplified by repeated Influenza A virus (IAV) outbreaks starting from H1N1 Spanish Flu in 1918 , H2N2 Asian Flu in 1957 , H3N2 Hong Kong Flu in 1968 and H1N1 swine flu in 2009 (Peteranderl et al., 2016 . Intermittent focal outbreaks of avian influenza virus (AIV) in Asian countries have affected poultry, migratory and wild birds (Shao et al., 2017) with reported human infections in poultry handlers or their close contacts. Coronaviruses (CoVs) are also known to evolve gradually and cause zoonotic outbreaks of respiratory infections. So far three coronavirus outbreaks have been reported of which the 2019 Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) outbreak in China rapidly spread across the world and was declared a pandemic within a few months (Louca, 2021) . Overall, repeated outbreaks of respiratory viral infections have adversely impacted the health of people all across the world, health care systems, frontline workers, global community, economy and development. In view of the prolonged devastating impact of the coronavirus disease 2019 (COVID-19) pandemic, it is now critical to strengthen public health surveillance for early detection and control of emerging outbreaks of Influenza and other respiratory viruses. As per the global recommendations, COVID-19 and Influenza surveillance should be integrated through ILI/SARI (Influenza Like Illness/Severe Acute Respiratory Illness) surveillance platforms (Global influenza strategy 2019-2030, n.d.) . In this article, we have described the existing global and regional networks for surveillance of circulating and emerging strains of respiratory viruses, highlighted gaps and proposed strategies to strengthen and expand respiratory virus surveillance 7 through the designated National Influenza Centres (NIC) of the World Health Organization (WHO). Global Influenza Program (GIP) was established in 1947, expanded with the establishment of WHO and renamed as Global Influenza Surveillance and Response System (GISRS) (Ziegler et al., 2018) . WHO-GISRS framework includes four Essential Regulatory Laboratories (WHO ERLs), seven Coordinating Centres (WHO-CCs) and 13 H5 Reference Laboratories (WHO H5 RLs) at the global level and 148 National Influenza Centres (NICs) in 124 WHO Member States at the national level (World Health Organization, 2022a). All WHO network laboratories are mandated to regularly submit sequencing data to the Global Initiative on Sharing Avian Influenza Data (GISAID) (Hay and McCauley, 2018) . Figure 1 describes the roles and responsibilities of WHO-GISRS laboratory network. NICs are the national reference laboratories and serve as a backbone for influenza testing, provision of vaccine strains/clinical samples, surveillance and outbreak response in accordance with WHO protocols. They undertake influenza-like illness (ILI), acute respiratory illness (ARI) and severe acute respiratory syndrome (SARI) surveillance for detecting circulating strains of influenza and other respiratory viruses. Training for real-time reverse transcription-polymerase chain reaction (rRT-PCR), cell culture-based virus isolation and genome sequencing is also provided to NICs by WHO. The laboratory and epidemiological data is required to be submitted to WHO-FluNet and WHO FluID databases respectively. Untypable influenza strains are to be referred to WHO-CCs for characterization. WHO ERLs undertake influenza vaccine strain selection, calibration of reagents and provide strains and reagents to vaccine manufacturers and relevant stakeholders. WHO-H5 reference laboratories work on Influenza A(H5N1) and other avian/animal influenza viruses which may cause poultry outbreaks and human infections. They are involved in surveillance, virus isolation, antigenic and genetic characterization, antiviral susceptibility testing, conducting laboratory studies, providing technical and laboratory support to partner institutions and also offer required support to WHO for formulating and revising guidelines periodically. NICs are entrusted with the task of conducting national surveillance. However, the national and subnational framework for surveillance of Influenza and other respiratory viruses remains weak in most parts of the world due to varying capacities of NICs (El Guerche-Séblain et al., 2021), manpower constraints , inadequate human and veterinary surveillance 9 (Bailey et al., 2018; Rabinowitz et al., 2012) , poor intersectoral coordination (Buse et al., 2022; Perez Arredondo et al., 2021) , funding constraints and low commitments of the local governments (World Health Organization, 2014). Since Influenza viruses have the capacity to mutate and evolve rapidly, it is critical to strengthen surveillance at local levels for improving vaccine strain selection and timely detection of untypable or novel human or avian influenza viruses which may lead to outbreaks. The WHO NICs are positioned well to establish and run the sub-national respiratory virus surveillance programs in the field. The NICs should be strengthened and leveraged fully to establish a robust subnational respiratory virus surveillance network for quick detection of novel influenza virus strains and signals of impending outbreaks. Following steps are recommended for strengthening the existing influenza surveillance networks at the national level through the NICs: At National Level: (Polansky et al., 2016; World Health Organization, 2014) . Strengthening the infrastructure and expertise of NICs will help in their efficient functioning and will enable expedited availability of local data to guide policy decisions. During the COVID-19 pandemic, many countries have significantly ramped up their capacity for molecular testing and next-generation sequencing, which must be repurposed and utilized now to fulfil the larger surveillance gaps. employee friendly policies to reduce attrition for maintaining high-quality surveillance. and transport samples to NICs for further characterization and quality control purposes. In Figure 2 , we have suggested a broad framework for sub-national surveillance which can be established under the NICs. (Ziegler et al., 2018) . In 2022, WHO has reported the presence of 148 NICs in 124 countries (World Health Organization, 2022a). However, more than 70 countries in the world still do not have designated NICs. Each country should make attempts to establish at least one NIC for instituting systematic mechanisms of collaboration and support from WHO. In large and densely populated countries one NIC may not be able to effectively coordinate and manage surveillance for the whole country. In such circumstances, it may be appropriate to establish more than one NIC, depending upon the population of the country, its size, availability of resources and equipped laboratories. Funding is a key factor for establishing and sustaining surveillance, laboratory testing, maintaining desired data quality and retaining trained manpower. Self-assessment of the GISRS was undertaken as per 15 recommendations of the WHO Advisory Group. Findings revealed that many NICs suffer due to poor fund allocation and low commitment of the local governments (World Health Organization, 2014). Polansky et al. in their survey of 35 countries supported by CDC for developing influenza surveillance found that 29 (81%) countries identified funding as the most critical requirement to sustain surveillance followed by staff training and technical advice (Polansky et al., 2016) . Often developing countries face challenges to fund and maintain public health surveillance, thus making them vulnerable to large outbreaks and economic losses. It is pivotal for the local governments to establish mechanisms for funding surveillance by collaboration with relevant international stakeholders and partners. CDC continues to undertake such capacity building in under-represented areas (Polansky et al., 2016) . However, more international support and collaborations must be fostered for keeping the word safe by early detection and effective containment of pathogens of pandemic potential and appropriate selection of Influenza vaccine strains. The local policymakers should also be proactive in seeking International financial and technical support for strengthening public health surveillance of their countries. Timely response in any outbreak is of utmost importance as early alert will help in quick contact tracing and disease containment. Besides, successful virus isolation early in the outbreak will enable the development of diagnostic tests for implementing preventive and therapeutic strategies to contain virus transmission. Commitment and support of the international 18 stakeholders, increased international funding and handholding of local governments by WHO will be instrumental in achieving this goal. Training and capacity building in various domains related to field epidemiological surveillance; laboratory testing, biosafety and biosecurity and quality adherence; data collection, proper archival, analysis and timely reporting are of crucial importance. Orientation of the local government authorities and prioritization of respiratory virus surveillance as one of the top public health priorities need to be undertaken by UN agencies for protecting the world against devastating pandemics in future. Learning from the experiences of the COVID-19 pandemic and to timely avert such threats in future, we must aim at early detection, prevention and control at local levels for preventing future epidemics and pandemics. No funding was provided to support the manuscript. Authors confirm no conflict of interest. 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