In the last century, advances in medical sciences, access to healthcare, and improved sanitation have reduced the mortality and morbidity of infectious diseases globally and regionally. This is particularly true for respiratory and diarrhoeal infections.
However, the last 100 years have also been characterised by outbreaks, epidemics, and pandemics caused by emerging and re-emerging pathogens, most of which have been zoonotic in origin. Typically, these new pathogens have first appeared in a small section of humans, established a foothold in the local population, and then become trans-border pathogens of concern. Pathogens that have gone on to cause significant mortality at a global level are characterised by a set of attributes. Such pathogens often have long latent periods during which the infected person stays asymptomatic but actively spreads the infection to other individuals. Difficult to detect because of late onset of symptoms, such diseases can spread at an accelerated rate before large-scale trends can be picked up by surveillance systems. This has been the case with two standout viruses amongst others: COVID-19 and HIV.
Some such pathogens also possess strong immune escape features that have enabled them to deploy mechanisms to thwart the immune system’s attack. Pathogens such as HIV, Mycobacterium tuberculosis, Mycobacterium leprae, Treponema pallidum, and Listeria monocytogenes amongst others not only have immune escape features, but have also caused significant mortality and morbidity globally. Many of the emergent pathogens of concern have been so novel that medical counter measures to prevent, detect, or treat them did not initially exist; resulting in epidemics or pandemics and severe loss of life. This point is exemplified by H1N1 (influenza A virus), Ebola virus, HIV, and COVID-19.
Emerging pathogens of significance
In its latest R&D Blueprint for Epidemics, WHO prioritises 34 priority pathogens across 16 families that have the potential to cause epidemics or pandemics. In order to optimise R&D efforts, WHO further lists priority diseases caused by these pathogens for funding allocation including COVID-19, Crimean-Congo haemorrhagic fever, Ebola virus disease and Marburg virus disease, Lassa fever, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS), Monkeypox, Nipah and henipaviral diseases, Plague, Rift Valley fever, Zika, and ‘Disease X’ – this last one being an as-yet-unknown disease that will inevitably cause an epidemic or a pandemic. WHO has prioritised these diseases based on their transmission potential; case fatality, severity, high vulnerability of specific populations; and insufficiency of prophylactic and therapeutic counter measures against them.
Many biological and environmental pathways of pathogen mutation and evolution have existed since the beginning of life on Earth and over eons, resulted in new species emerging and applying natural selective pressures on hosts. This process of host-pathogen interactions will go on as part of life processes. However, here we focus on pathogen emergence anchored in human action and population trends that are rapidly rising in scale and impact. The virulence of some of these pathogens could be curbed by managing these actions and trends.
The impact of economic forces and climate change
Continuing rapid population and economic growth, rising urbanisation and population density in Low- and Middle-Income Countries (LMICs), agriculture and animal husbandry intensification, and human-caused climate change events are resulting in increasing environmental risk factors and the intensity of human-animal contact. This takes the form of human displacement into previously forested or wild areas, increased contact between domesticated animals and husbandry handlers, increased contact between domesticated and wild animals, and consumption of previously not consumed meats from wild areas. Animal husbandry has become the dominant pathway for zoonotic virus spillovers from wild animals to humans. Urbanisation is helping mosquito vectors for Zika and Chikungunya proliferate because they are well adapted to thriving in urban spaces with high population densities, which also lend themselves well to higher rates of transmission and mutation.
Climate change can expose humans to new pathogen in a myriad of ways other than the aforementioned climate-event displacement pathway. The impact of climate events on infectious disease dynamics can be pathogen-specific and varied. Increasing rates of hydro-met events can sharpen the reach of pathogens into human populations in newer regions and to newer vectors, or of existing vectors into newer regions, or increase the transmission window itself; resulting in cases of diseases novel to these regions. With rising mean temperatures and precipitation, an increasing number of dams, and the spread of mosquito vectors in the Himalayas, malaria and dengue are on the rise in these areas; even in higher regions such as Bhutan and the Hindu Kush Himalayas – illustrating the role of climate change in the spread of pathogen and disease.
Climate change is also affecting patterns in different latitudinal zones. Rising humidity and temperature could lead to more outbreaks of enteric diseases such as typhoid, cholera, and rotavirus-caused diarrhoea in zones which now routinely experience tropical weather for extended periods. However, much of the association of climate change with diseases caused by enteric and airborne pathogens remains statistical. The effect of climate change on influenza and other airborne diseases is imprecisely established. Climate change also has indirect effects on human susceptibility to pathogens by decimating infrastructure, compromising food and water security, disrupting health services, impacting livelihoods, and increasing the need for resources for climate mitigation and non-health adaptation thereby drastically reducing the envelope for healthcare research and implementation.
One of the leading causes of death, indoor and outdoor air pollution can create a more conducive environment for respiratory pathogens to thrive and proliferate; particularly in urban settings in LMICs and for more vulnerable population segments such as women, children, and the poor.
Medical successes, abuse and demographics
Some pathogens and diseases seem to be surfacing and expanding because of the unintended effects of medical successes and the abuse of medical tools. It is posited that once smallpox vaccination was stopped because of the vaccine’s success in eliminating the disease, monkeypox incidence started to increase. Abuse of antibiotics in humans and animals is fuelling Antimicrobial Resistance (AMR) which has become one of the leading causes of mortality globally.
Demographic shifts can also result in similar outcomes; an ageing population’s waning immunity opens the door to many opportunistic infections at scale while an increasing birth rate can expand the number of individuals susceptible to pathogens for which effective vaccines are not accessible, or increase the age of infection from such pathogens.
Acting as a powerful catalyst, global dynamics rapidly take localised emergence to the world scale, helping pathogens that establish a toehold in one corner of the world to swiftly capture new suitable vectors in other regions or infect people across countries. With the exponential growth of international air travel, travellers nowadays can transmit infections across continents at blistering speed, far outpacing surveillance detection levels. The world witnessed this phenomenon to devastating effect during the unprecedented spread of the COVID-19 pandemic, the fastest in recorded history. Similarly, the ever-increasing international trade of plant and animal products has increased epidemic risks through the export of pathogens in these products to new geographies. This is illustrated by the case of African Swine Flu which was found only in Sub-Saharan Africa until 2007 but since then has expanded into Europe through the introduction of contaminated meat from Eastern Africa and now is prevalent in parts of Asia as well.
Strategies for the management of emerging pathogens
Strategies for managing emerging pathogens must be devised with the perspective of their potential for causing epidemics and pandemics and be anchored in the principles and praxis of One Health; recognising that human health is intertwined with the health of animals and plants globally. Further, eschewing the reactive approach, strategies must proactively prepare for addressing the disease impact of emerging pathogens by premising action on the inevitability of new epidemics and possibly a pandemic. Additionally, the approach must consider the priority pathogen families rather than isolated pathogens for faster-acting and wider responses to known and unknown threats. Collaboration across disciplines, countries, and interested parties will be key for pathogen discovery, countermeasures, and equitable access. Finally, success will hinge on the highest order of political will for significantly ramping up investments in the management of emerging pathogens. The following broad strategic areas should be considered.
Surveillance: Enhancing global surveillance systems for emerging infectious diseases, particularly at human-animal interfaces, is crucial. This can be achieved by leveraging advanced genomic technologies and strengthening sequencing capacities, serological surveillance, water surveillance, digital/AI detection, and risk modelling – including climate change and urbanisation effects; monitoring animal reservoirs; and developing and deploying appropriate and multiplex diagnostic tools. Surveillance of sewage from ships and aircraft at ports of entries – such as airports and seaports – can go a long way in strengthening early warning alerts. Highly efficient surveillance data sharing and integration of data streams at the global, national, and sub-national levels will be instrumental for action.
During the first wave of COVID-19, India expanded the scope of the existing Virus Research and Diagnostic Laboratories (VRDLs) for RT-PCR testing of samples in a short span of time and subsequently also set up the pan-country Indian SARS-CoV-2 Genomics Consortium (INSACOG) of 67 laboratories. The Government of India has released guidelines for Indian Public Health Labs at the district and block level and is funding the setting up of this network across the country through the Ayushman Bharat Health Infrastructure Mission. The Government of India also runs a sentinel AMR surveillance programme covering seven pathogens. Tata Institute for Genetics and Society (TIGS) runs an environmental surveillance programme anchored in wastewater-based epidemiology, air surveillance, and seroprevalence for prioritised pathogens. Through more than a score members, the Alliance for Pathogen Surveillance Innovations (APSI-India) hosts a large wastewater surveillance programme in Bengaluru and Hyderabad with plans for expanding into other cities. These networks will, over time, become prime for deploying against emerging pathogens in the country. WHO’s International Pathogen Surveillance Network (IPSN) has recently awarded its first set of grants for LMICs to strengthen global surveillance of pathogens for mitigating their epidemic and pandemic potential.
Basic research: It is critical to comprehensively and quickly invest in basic research on prioritised pathogen families and diseases that surface through surveillance of humans and animals. Basic research will open the doors of knowledge to mechanisms by which new pathogens affect humans and cause disease; the immune system’s response to these pathogens and potential medical counter measures for prevention, protection, rapid detection, and treatment.
Sharpening basic research will entail creating and selecting suitable animal models, refined understanding of the correlates of protection, deep knowledge of disease aetiology and pathogenesis overall and for various levels of severity and comorbidities; and exploring novel ex vivo models. AI, particularly, machine learning could prove useful for these applications.
Medical counter measures: Using insights from existing and new basic research, medical counter measures for priority pathogen families can be developed. These counter measures will help prevent, detect, and treat diseases caused by these pathogens. Tools will include vaccines, diagnostics, and therapeutics for priority diseases. New pathogens and new serotypes of existing pathogens could blunt the effectiveness of existing vaccines. Hence research on universal/pan-virus vaccines that protect against related viruses and multiple strains should be prioritised. mRNA technology can help accelerate new vaccine development by potentially serving the ambition of having a vaccine against new pandemics ready in 100 days. Low-cost diagnostics that can be used in community settings and multi-pathogen in-lab diagnostics will be instrumental in rapid detection. AI has quickly established itself to play a highly critical role in the development of such tools in recent years.
Implementation and environmental research: Investing in Non-pharmaceutical Interventions (NPIs) – such as masking, social distancing, and lockdowns for COVID-19 – will be crucial for reducing transmission and buying time early on to develop and deploy tools against the next pandemic. Also known as public health and social measures, NPIs need more research investments to better understand their efficacy and cost-effectiveness against different priority pathogen families, unintended negative consequences, and implementation approaches.
It will be imperative for countries to generate evidence on the context-fit and impact of medical counter measures and surveillance systems for modulating innovations and ensuring cost-effective deployment. Priority must be accorded to research on mechanistic models of climate change with pathogens, vectors, and enteric and airborne diseases to investigate and better understand multi-factorial causes, complex interactions, and mitigation opportunities.
Access, equity, and stewardship: Countries will necessarily have to develop pandemic preparedness frameworks and comprehensive preparedness roadmaps that align with the legally binding International Health Regulations. Guidelines and SOPs will have to be developed with roles and response timelines. Countries will have to expand access to vaccines by introducing vaccines for priority pathogens in their public immunisation programmes, including vaccines against endemic pathogens in those regions, and tweaking the due age if indicated by shifting epidemiology and vaccine science. Misuse of antibiotics and their inferior and variable quality will have to be tackled on a war-footing to reduce the incidence of AMR. Harmonised and accelerated clinical trial and regulatory processes will help rapidly deploy counter measures across geographies and reduce access barriers. Simultaneously, building and strengthening regional clinical trial and manufacturing infrastructure will aid these objectives.
The Government of India in conjunction with States runs a multitude of infectious disease prevention and treatment, control, and elimination programmes. The government also runs the National AMR Plan, AMR surveillance, and the Integrated Disease Surveillance Programme. The government has recently launched the One Health Mission focussing on surveillance, research, data management, and pandemic preparedness in the country. Further, the government has also released a Niti Aayog report on framework for proactive pandemic preparedness in the country that recommends enacting a new Public Health Emergency Act, creating an empowered group at the highest level chaired by the Cabinet Secretary, dedicated fund for preparedness, harmonising infectious disease surveillance, modelling, expanding the network of BSL 3 and 4 facilities, investing in research of priority pathogens and counter measures, setting up an institute of innovation for new platform technologies for vaccines, strengthening health systems including supply chains and human resources, and focussing on risk communication and international collaborations.
Partnerships: Finally, various interested parties must work in close collaboration with each other to ensure success. While private academia and researchers can accelerate research and innovation; manufacturers, global consortia, and governments can help with rapid regulatory approvals, commercialisation, and stockpiling of tools. However, historically high risks and poor visibility into demand have held back such actions in the past. By placing the agenda high on their lists and in concert with philanthropy, governments must take on the primary role of steering, financing, and derisking these partnerships through publicly funded programmes that prioritise the fight against emerging pathogens.
Conclusion
Novel pathogens have been a part of human history over thousands of years. They will continue to appear and upgrade in the arms race that is infectious disease through biological and anthropogenic processes and wreak havoc. For the first time in our history, we have the wherewithal and tools to combat these emerging pathogens and nullify their impact. However, our response must become proactive, evidence-informed, and equity oriented. Most importantly, we must invest vast sums of money and expertise in researching and rolling out mitigation measures that will help keep us ready for the next pandemic well in time, for which unified political commitment over the long term is essential. Coupled with the addressing of social, behavioural, environmental, and economic determinants of health, these measures can ensure that our future is secure from the large-scale destructive power of pathogens.
(Dr. Soumya Swaminathan, MD, is Principal Advisor, NTEP, MoHFW, Government of India, and Chairperson, M.S. Swaminathan Research Foundation, Chennai. Harkabir Singh Jandu is an independent consultant.)
Published – February 17, 2025 03:00 pm IST