Need for a robust public health response to seasonal influenza in India

While advocating a public health strategy for control of any disease, one needs to ensure that a sufficiently good case is made for it. While not always possible, it requires evidence supporting high and preferably increasing (if not addressed) burden of disease of concern, identification of at-risk groups, availability of effective interventions, operational and financial feasibility of the interventions, a sound investment case, feasible mechanisms for evaluation and surveillance to reassess the burden of disease to gauge the impact of control initiatives1.

The Global Influenza Strategy (2019-2030) aims to mitigate pandemic impact, minimize zoonotic risk and reduce seasonal influenza burden through strategies of surveillance and monitoring, pandemic preparedness, seasonal influenza prevention and research and innovation2. India has drafted a national influenza pandemic preparedness plan3. The COVID-19 pandemic has raised both national and global preparedness to new levels, and we should be able to manage future pandemics better4. While the preparedness of pandemic and seasonal influenza are interlinked, they are not the same. For example, pandemic would require vaccinating in a campaign mode, whereas seasonal influenza would need it in a routine mode, and both have very different health system implications.

Seasonal influenza infections happen in India throughout the year, with bimodal peaks during the monsoon and winter seasons. India, with its large latitudinal expanse, has varied seasonality of influenza and does not conform to temperate north hemisphere recommendations5. The changing strains, types and subtypes across years result in different levels of infections with one type or subtype predominating that year and causing seasonal outbreaks. This necessitates annual vaccinations of the nationally defined target groups with vaccine composition depending on the current circulating strains6.

Every year influenza causes substantial disease and deaths, but estimating the number of deaths due to influenza is challenging as routine testing for influenza is not done in clinical settings and influenza is rarely certified as a cause of death. The mortality is, therefore, estimated indirectly by modelling ‘excess’ deaths, especially as it has distinct seasonality and can be used to measure excess respiratory, circulatory or all-cause deaths. Using this approach in India, it has been estimated from Sample Registration System and viral surveillance data for 2010-2013 that 56,503 (6178-111,869) respiratory and 70,589 circulatory (5283-144,681) totalling to 127,092 (64,046-190,139) excess deaths were attributable to influenza per year, even in the non-pandemic period. Majority (65%) of deaths occurred among older persons above 65 yr and 15-20 per cent were among under fives7.

In a hospital-based surveillance, influenza virus was most commonly detected among acute respiratory infections (ARIs, 15.4%) as well as severe acute respiratory infections (SARIs, 12.7%)8. A two-site study aimed at estimating the influenza hospitalization burden by a hospital surveillance and linked health utilization survey in a defined community in 2010-2012, reported 5-20 per cent positivity among hospitalized medical patients. Varying annual influenza-associated hospitalization rates were recorded at 20.3-51.6 per 10,000 in Vadu and 4.4-6.3 per 10,000 in Ballabgarh9. This translates into 1 to 5 million admissions per year nationally. Robust data on case fatality rates (CFR) are not available, though a CFR of 5.5 per cent during the pandemic and 29 per cent during the post-pandemic period for hospitalized H1N1 influenza cases has been reported10,11. These studies suffer from serious selection bias.

A meta-analysis estimated that 16-18 million cases of influenza infections occurred in under-fives12. Unpublished results of the multi-site cohort of older adults estimated that 5-7 million symptomatic ARI occurred annually, resulting in about 2.5 million pneumonias13. Information on the cost of influenza management is not available in India. The cost of pneumonia among community-dwelling older adults was estimated to be about $ 181 (interquartile range [IQR]: 105-327) in public and $ 1,118 (IQR: 376-1775) in private hospitals14. As the use of antivirals is very low, one can assume that the current cost of influenza will be similar to the cost of treatment of pneumonia.

It is surprising that despite healthcare workers being at the highest risk for contacting influenza and potential spreaders of infection, there are no data on burden among them from India. There is little evidence on the burden among high risk children from India. A prospective cohort study among pregnant women of India, Peru and Thailand estimated influenza incidence between 69.6 and 88.7 per 10,000 pregnant woman-months during the 2017/2018 seasons15. Influenza positivity among respiratory infections among pregnant women has been reported in the range of 18-21 per cent16. Influenza infection has been reported to be associated with poor pregnancy outcomes, higher need for hospitalization, lower birth weight and maternal mortality17.

Critical evidence on the burden of influenza, even among groups prioritized by the Government of India, is quite patchy and hinders advocacy for adoption of a public health approach. The major public health strategies for addressing seasonal influenza are surveillance, better access to diagnostics, standardized management of influenza cases to reduce mortality and the use of the vaccine to prevent infections.

Surveillance for influenza in India occurs as part of the Integrated Disease Surveillance Programme (IDSP) whose key features are the submission of weekly disease surveillance data from public facilities of all levels (subcentre, primary health centre, community health centre and hospitals) from all over India and outbreak identification (serving as warning signal) being coordinated by the National Centre for Disease Control.

A systematic review of cases of influenza A (H1N1) in India from 2010-2020 showed that the actual reported cases were far below the estimated cases18. However, with the introduction of the Integrated Health Information Portal (IHIP) and the strengthening of the Integrated Public Health Laboratory capacity, there is an opportunity to generate surveillance data useful for action. This is also now supported by a network of influenza-like illnesses (ILIs)/SARI surveillance network of the Viral Research and Diagnostic Laboratories (VRDL) of the Indian Council of Medical Research (ICMR), which provides influenza positivity rates in them and is also linked to genomic surveillance19. Thus, while the surveillance system has been strengthened and may be adequate to identify virus strains and seasonality, it is not sufficient for the estimation of burden as it is not linked to appropriate denominators to generate community incidence and healthcare utilization figures. There is a need to differentiate between surveillance needs, which require testing only a representative sample and not all SARIs for influenza; and case management needs, where the evidence-supported testing algorithm can be followed for all SARI/ILI cases.

The current Standard Treatment Workflow (STW) of ICMR for management of ARI in adults does not consider viral infections at all and is oriented towards Streptococcus pneumoniae only20. There is currently no consensus on the standard diagnostic and treatment approaches for SARI admitted in hospitals. Despite oseltamivir being available in the public sector system, its use is quite low. One of the paradoxes is that the test for influenza is advised only if the illness does not resolve within a few days21, whereas the antivirals are most effective if used within 48 h of onset22. Notably, a point-of-care test has been shown to improve the use of antivirals and reduce the use of antibiotics23.

As for vaccination, the effectiveness of vaccines (nasal and intramuscular) has been established in the Indian population, especially amongst children24,25. Most professional bodies, such as paediatricians, pulmonologists, physicians or obstetricians, do recommend vaccination of their respective speciality groups,26-29. Currently, the Indian government recommends influenza vaccination among priority groups of healthcare workers, pregnant women and adults and children with specific comorbidities and considers it desirable for children belonging to six months to eight year age group and the elderly30. However, it is not incorporated in the routine immunization programme for children. The National Programme for Health Care of the Elderly does not provide vaccines as part of its hospital-based services. Data on vaccine coverage of influenza vaccine are not available regularly; among older adults, population level coverage of influenza vaccine was reported to be 1.5 per cent in the year 2017-1831.

In an influenza vaccination campaign among healthcare workers, the vaccine compliance was only 30 per cent. This study found that deficiency in knowledge, misconceptions and concerns regarding vaccine were important factors leading to decreased uptake32. Even during the 2009 H1N1 pandemic, the acceptance of pandemic influenza vaccine was only 26 per cent in Maharashtra despite free vaccination33. Poor sensitization of the care providers was identified as a major barrier to influenza vaccination in pregnant women in India34,35. It has also been shown that engaging clinicians reduce the missed opportunities for vaccination during antenatal period36. This hesitancy of healthcare providers to take and recommend influenza vaccine needs to be understood better and addressed through development of an effective multidimensional interventions37.

If a vaccine is not used in low- and middle-income countries (LMICs) due to lack of evidence of cost-effectiveness, it becomes difficult to generate reliable cost-effectiveness estimates. However, in an analysis from Lao PDR, providing influenza vaccination to health workers, deemed cost beneficial while vaccinating pregnant women and adults above 60 yr was assessed to be cost-effective and highly cost-effective respectively38. However, caution needs to be exercised to extrapolate such cost-effectiveness estimates to India as these are very contextual.

An assessment of the operational feasibility of influenza vaccination programmes targeting risk groups in the South-East Asian Region concluded that targeting healthcare workers had little operational impact39. However, addressing other risk groups would require considerable augmentation of production, doses per vaccinator and cold storage capacity39. Some of the major barriers, in order of frequency, to initiation of influenza vaccination programmes identified in a survey amongst LMICs were lack of local cost-effectiveness estimates of influenza vaccination (87%), lack of local data on burden due to influenza (84%), competing health priorities (80%), low perceived risk from influenza amongst the public (79%), lack of good risk communication tools (77%), lack of financial support for influenza vaccine programmes (75%) and vaccine-related concerns40.

However, preparedness for seasonal peaks of influenza helps in being prepared for pandemics by using the same tools - improved surveillance, established laboratory testing processes, regulatory approval of influenza vaccines and use of non-pharmacological interventions (NPIs). The availability of pre-existing platforms such as adult vaccination enables a faster response in case of a pandemic. Countries, which had an existing seasonal influenza vaccine programme were more likely to vaccinate their people during a pandemic41. Countries with regulatory delays received vaccines later, thus failing to avert a higher number of cases and losing more lives42.

The lack of evidence on burden and cost-effectiveness in the Indian context and identification of it as a significant barrier to a vaccination programme points towards what needs to be done. There has been no sustained and comprehensive approach to measure the seasonal influenza disease burden in India. The limited data from India are still focused on influenza H1N1pdm09 strain reflecting a lack of recognition of the burden due to other types and subtypes of influenza. Most publications revolve around the positivity rate in admitted patients, clinical features and laboratory typing of strains. Public health-related research on burden, risk groups or factors, transmission dynamics, the effectiveness of therapeutic/pharmacological and non-pharmacologic interventions (NPIs) etc., are sparse. There appears to be a disconnect between public health research needs and whatever research that is currently being conducted in the country. This results in a narrow base of evidence that limits advocacy efforts, a vicious cycle of underfunded research and a lack of evidence for advocacy. The immediate needs in this regard are summarized in Box.

Presently, neither a universal influenza immunization programme nor a vertical national programme on influenza is justified. What is needed is to integrate influenza prevention and control measures in existing national public health platforms/initiatives. Immunization for the elderly, adults and children with comorbidities is already being contemplated and advocated not only for influenza but for other infections as well44,45. Reducing child mortality further in India would need consideration of integrated approaches.

Such an inclusive public health response to influenza will facilitate a stronger and faster response to future pandemics as well as to other respiratory viruses like a respiratory syncytial virus. A case for forging a robust public health response to seasonal influenza was never stronger as the demand of the present day .