Why is it important that highly infectious pathogens are studied, and how does this impact future healthcare?

Abstract

Author: Bax AJ
Affiliations: Bolton School Girls’ Division, Bolton

Background:

In light of the current pandemic, it is essential to understand whether prevention measures can reduce the negative effects of highly infectious pathogens on the population, with regards to morbidity, mortality, social and financial repercussions. This vital research highlights whether this would be possible primarily through scientific study and the implementation of findings by public health.

Objectives:

The primary objectives are to assess the importance of studying highly infectious pathogens and their outcomes for healthcare.

Methodology:

To successfully evaluate the impact of studying such pathogens, it was important that research was undertaken to explore both the beneficial and adverse effects. The critical appraisal of grey literature (such as government policies, guidelines and data), academic research journals with graphs to support conclusions (which were obtained by performing a PubMed search from the year 2000 to present) and lectures, were essential in ensuring the reputability of information.

Conclusion:

Having conducted thorough research on a variety of different pathogens, it was evident that there are two sides of the argument which must be considered when studying pathogens. The long-term benefits for healthcare in terms of cost-efficiency and an overall reduction in morbidity and mortality rates are compromised by the short-term financial investments for governments, and challenges faced by society when adhering to prevention measures.

Introduction

In-depth knowledge of highly infectious pathogens can allow for a better understanding of the way they infect human hosts, the diseases they cause and interventions which can disrupt their effects. The current COVID-19 pandemic has highlighted how a lack of detailed understanding of such factors can result in widespread disease, mortality and socio-economic detriment.
The aims of this article are to outline the benefits of studying such pathogens for healthcare, in addition to the challenges they pose in relation to Antimicrobial Resistance (AMR), vaccination and treatment development, public health and healthcare providers.

The importance of studying highly infectious pathogens

Highly infectious pathogens such as Human Immunodeficiency Virus (HIV) can have significant antigenic variability leading to difficulty in effective vaccine development and achievement of herd immunity. Therefore, these pathogens need to be studied even after treatments are developed to allow for more refined and targeted treatments with fewer side effects.
The study of HIV has allowed development and dissemination of antiretroviral therapies (ART) resulting in a 96% decrease in HIV transmission, leading to HIV levels transforming from pandemic (in the 1980s) to low endemic from 2014.^[1] Studying behaviours of pathogens such as viral replication can allow intervention by ART.^[2]
However, ARTs are fraught with the increasing prevalence of AMR. Continuous study of HIV and other pathogens susceptible to mutations is therefore important to address this issue as well as the rise of new pathogen strains. ^[3] It is estimated that at least 700000 people die every year from AMR globally with the potential of one person dying because of AMR every three seconds if not tackled by 2050. ^[4] The healthcare costs of AMR are also high, as infections caused by these pathogens have associated complications and long in-patient hospital stay.
Another example of a drug-resistant pathogen is Multi-Drug Resistant Tuberculosis (MDR-TB), with global cases in 2017 reaching 558 000. ^[5] There are currently attempts to overcome this threat through the study of MDR-TB strains. Drug resistance can be detected using laboratory tests which analyse bacteria for drug sensitivity and resistance patterns. Such tests ensure that all those diagnosed with MDR-TB are provided with alternative treatments. ^[6]
AMR can thus make established treatments ineffective, and new diagnostic tools, vaccinations and drugs for emerging pathogen strains will need trialling to assist healthcare workers on the frontline.
Additionally, the study of pathogens, especially those capable of transmission via a non-human host, is important, as these are difficult to eradicate and have the potential to cause outbreaks. ^[7] This can also enable a better understanding of their evolution and transmission cycle, allowing for more targeted treatments for the diseases they cause as well as public health education and prevention strategies.
For instance, the coronavirus responsible for Severe Acute Respiratory Syndrome (SARS-CoV) can be sustained outside of human populations and has emerged as COVID-19 (SARS-CoV-2). ^{[8] [9]} Clinical research and collaboration are thus needed to produce effective vaccinations. However, due to the mutation frequency, even an effective vaccine may be insufficient to prevent disease. In the meantime, curative treatments are being developed together with public health infection control measures to address the effects of the virus. ^[10]

This is not only true of coronaviruses. Pathogen evolution in influenza, for example, can identify whether they are seasonal or pandemic strains. Studying behaviours of these strains can highlight if there is a need to increase vaccine production for more pathogenic variants with low immunogenicity, reinforcing public health decisions for healthcare professionals on vaccine dosage or the number of doses required to offer an adequate response.^[11]
Another reason for studying pathogens even after treatments have been developed is to gain a better understanding of how pathogens interact in different populations. In this way, risk groups can be identified and protected through public health guidelines, policies and treatments.
For example, the current COVID-19 government guidelines provide advice on ‘shielding’ high-risk groups. ^[12] Study of the lifecycle and behaviour of SARS-CoV-2 has allowed mathematical modelling to produce epidemiological data so that governments can advise public health measures such as social distancing. ^[13]
Study of Influenza has allowed the categorisation of pregnant women as a risk group because of adverse pregnancy outcomes and vertical transmission. The UK Antenatal Influenza Vaccination programme has decreased infant hospitalisations by 50%.^[14]

Elderly populations are also at high risk of influenza complications and show poor responses to vaccination. Knowing the latter enables refinement of vaccinations by adding novel adjuvants to improve immunogenicity, which is useful as smaller doses are used, more people are vaccinated and there is faster herd immunity. ^[15]
Further, through the ongoing study of pathogens, healthcare systems can be better prepared for emerging high-risk strains. This allows links to be made between different pathogens and the resulting clinical presentations and responses to existing treatment. Studying highly infectious pathogens with similar microbiology can allow existing treatments to be initiated to prevent disease progression. For instance, existing ARTs can be effective when given soon after symptom onset in Influenza and SARS-COV-2, when viral replication is high. ^[16] Existing drugs including Remdesivir (previously used for Ebola), are being trialled to treat COVID-19. ^[17]
Diagnosis and differentiation between different infectious diseases can be challenging due to similar clinical presentations. For example, malaria diagnosis can be difficult due to the overlap of symptoms with typhoid and dengue fever. Studying pathogens causing these respective diseases can allow the development of rapid diagnostic tests with high sensitivity and specificity to avoid misdiagnosis. ^[18]
However, just studying pathogens in isolation is unlikely to have a significant impact on healthcare. Its benefit would only be realised if pathogen research is part of an overall public health strategy, including health education, policy development, disease surveillance, accurate diagnostic tools and other health protection measures. ^[19]
Public Health awareness programmes and guidelines aim to target social awareness and stigma. In HIV, policies have been considered to address cultural stigmas and education to improve uptake of testing in vulnerable populations with the highest infection rates. This would then allow targeted treatment to those with the asymptomatic disease as well as preventative measures, such as Pre-Exposure Prophylaxis (PrEP) for others.^{[20] [21]} Taking measles as another example, a public health approach was necessary to counteract the erroneous autism association which triggered a decrease in uptake of the Measles, Mumps and Rubella (MMR) vaccine. ^[22]

Further, the eradication of smallpox in 1980 highlighted the importance of understanding cultural norms to promote vaccination uptake. ^[23] Such government-instigated measures work alongside the scientific study of pathogens, protecting populations and lessening the burden on healthcare systems.
Governments are also in a position to pass public health legislation addressing environmental issues which affect the emergence of highly infectious pathogens. For example, coronaviruses’ association with non-human hosts necessitates habitat destruction as well as animal exportation. ^{[24] [25]}

Problems and challenges involved

Studying pathogens even after treatments have been developed requires investment in research programmes, which pharmaceutical companies or academics may find little incentive to undertake. Not only do antimicrobials take significant time to develop, but are given in courses, meaning they may provide a lesser return in profit, than for instance an anti-diabetic medication taken indefinitely. This may explain why a new class of antibiotic has not been discovered for more than a quarter of a century. ^{[26] [27]}
However, in relation to preventative therapies, the study of pathogens can bring financial benefits to healthcare systems, which was seen with the smallpox vaccination programme. An entire 58 million pounds was recouped just 26 days after the eradication of the virus, from avoidance of complications of disease and cost-saving to healthcare providers. ^[28]
However, there may be a point when it is no longer cost-effective to study a particular pathogen if the disease it causes is minimally prevalent. There is an economic argument to divert resources away from studying the variola virus now that smallpox is eradicated. ^[29] On the other hand, as was illustrated by the UK losing its ‘measles free’ status in 2019, outbreaks of infectious disease can still occur after periods of insignificant prevalence. ^[30]
There is an argument to prioritise the study of pathogens for which no effective treatment exists rather than those pathogens which have available treatment options. Even so, in the midst of the COVID-19 pandemic, the WHO still recommended proceeding with malaria testing and research with the Regional Artemisinin Initiative to Elimination (RIA2E) malaria eradication programme. ^[31]
Focus just on pathogen study diverts healthcare investment from other areas of research such as chronic non-infectious diseases. For this reason, equal importance must be placed on the study of prevalent non-communicable diseases. The UK burden of healthcare cost is still skewed towards chronic non-infectious diseases. Yet, trials such as the Response to Optimal Selection of neo-adjuvant Chemotherapy in Operable breast cancer (ROSCO) have stalled in the current pandemic with the UK government focusing resources towards the study of SARS-CoV-2.^[32] It is paradoxical that a lack of available treatment for cancer can exacerbate the impact of COVID-19, as observed in Wuhan, China, in which a study showed that cancer patients had higher risks of all severe outcomes of COVID-19. ^{[33] [34]}

Conclusion

In summary, the ongoing study of pathogens is important in the struggle against infectious diseases. Significant investment in research and development is needed at least initially, but which healthcare systems will benefit from in the future by cost-effective preventative and curative treatments. Even after treatments have been developed for highly infectious pathogens, the ongoing study allows adjustments and refinements to reduce side-effect profiles.
However, in order to transform public and global healthcare innovation, the study of such pathogens must be part of a coordinated approach with other evidence-based public health measures such as infection control, disease surveillance and preventative guidelines, all whilst balancing the needs for non-communicable disease research.
_________________________

Address for Correspondence

Aaliyah J Bax
[email protected]

About the Author

As an aspiring Academic Doctor with a passion for Biology, she was driven to explore this topic, with the aim to further understand the interactions between clinical practice, academic research, public health and future healthcare outcomes.
Glossary of terminology
Adjuvants a substance which improves the body’s immune system response
Antibody a protein which is released by plasma cells in an immune response to destroy an antigen
Antigen foreign substance found on pathogens which stimulate an immune response
Antigenic variability ability for a pathogen to mutate its antigen randomly as to avoid a targeted immune response
Antimicrobial Resistance ability for emerging strains pathogens to become resistant to antimicrobials due to mutations leading to directional natural selection
Antiretroviral Therapy (ART) medication which is used to target the replication of certain retroviruses such as HIV
Communicable disease diseases which can be transmitted from person to person
Cross-protective immunity when antibodies already present in the immune system following immunity of a specific pathogen also provide immunity to another pathogen (on first exposure) which is complementary to the antibody
Doxycycline type of antibiotic used to treat respiratory infections, for example
Endemic a disease found in a specific geographical area or demographic
Epidemiology the study of diseases, how they emerge and patterns within populations
Herd Immunity an epidemiological concept describing when the majority of a population is sufficiently immune to a pathogen
Immunogenicity ability of an antigen to stimulate an immune response
Morbidity a measure of disease within a population
Mortality a measure of death within a population
Mutation a random process which occurs in the DNA during replication, changing its base sequence which can lead to a change in the shape of an antigen for example.
Non-communicable disease diseases which are mainly associated with lifestyle or genetics, and cannot spread from person to person
Pathogen a disease-causing microorganism
Pandemic highest infectious level wherein the disease is highly prevalent in multiple countries or the world
Pre-Exposure Prophylaxis a preventative drug given before exposure of HIV to block its entry into the body
Public health a branch of medicine seeking to improve the overall health of the population
Regional Artemisinin Initiative 2 Elimination (RAI2E) programme a global organisation which seeks to overcome the effects of resistant antimalarials (mainly Artemisinins) on the eradication of malaria
Response to Optimal Selection of neo-adjuvant Chemotherapy in Operable breast cancer (ROSCO) a trial looking into tests which can help select chemotherapy before surgery on breast-cancer patients
Socio-economic the combined impact of social and financial factors
Vertical Transmission passage of a pathogen from a mother directly to her baby after birth

1. Jones, Alexandra, Ide Cremin, Fareed Abdullah, John Idoko, Peter Cherutich, Nduku Kilonzo, Helen Rees, et al. “Transformation of HIV from Pandemic to Low-Endemic Levels: A Public Health Approach to Combination Prevention.” The Lancet 384, no. 9939 (2014): 272–79. ↑
2. Cohen, Myron S, Ying Q Chen, Marybeth McCauley, Theresa Gamble, Mina C Hosseinipour, Nagalingeswaran Kumarasamy, James G Hakim, et al. “Prevention of HIV-1 Infection with Early Antiretroviral Therapy.” The New England Journal of Medicine 365, no. 6 (2011): 493–505. ↑
3. Clavel, François, and Allan J. Hance. “HIV Drug Resistance.” New England Journal of Medicine 350, no.10 (2004): 1023–1035. ↑
4. TEDx Talks “The Drugs Don’t Work: Sally Davies at TEDxAlbertopolis.” TEDx Talks (2013) ↑
5. World Health Organisation. “Drug-Resistant Tuberculosis.” World Health Organization (2019). https://doi.org//entity/tb/areas-of-work/drug-resistant-tb/en/index.html. ↑
6. World Health Organisation “What Is Multidrug-Resistant Tuberculosis (MDR-TB) and How Do We Control It?” World Health Organisation (2018) https://www.who.int/news-room/q-a-detail/what-is-multidrug-resistant-tuberculosis-%28mdr-tb%29-and-how-do-we-control-it.
   ‌ ↑
7. Aylward, R Bruce, and Maureen Birmingham. “The Human Story.” BMJ 331, no.7527 (2005): 1261–1262. https://doi.org/10.1136/bmj.331.7527.1261. ↑
8. Zhong, Nanshan. 2004. “Management and Prevention of SARS in China.” Edited by R. M. May, A. R. McLean, J. Pattison, and R. A. Weiss. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 359, no.1447 (2004): 1115–1116. https://doi.org/10.1098/rstb.2004.1491. ↑
9. Adnan Shereen, Muhammad, Suliman Khan, Abeer Kazmi, Nadia Bashir, and Rabeea Siddique. “COVID-19 Infection: Origin, Transmission, and Characteristics of Human Coronaviruses.” Journal of Advanced Research 24, (2020): 91-98.
   ↑
10. Public Health England “COVID-19: Guidance for Health Professionals.” GOV.UK (2020). https://www.gov.uk/government/collections/wuhan-novel-coronavirus#infection-prevention-and-control.
    ‌ ↑
11. Jong, M. D d., and R. W Sanders. “The Future of Influenza Vaccines.” BMJ 339, no.7725 (2009): b4014–b4014. https://doi.org/10.1136/bmj.b4014. ↑
12. Public Health England “Guidance on Shielding and Protecting People Defined on Medical Grounds as Extremely Vulnerable from COVID-19.” GOV.UK. (2020). https://www.gov.uk/government/publications/guidance-on-shielding-and-protecting-extremely-vulnerable-persons-from-covid-19/guidance-on-shielding-and-protecting-extremely-vulnerable-persons-from-covid-19. ↑
13. Lewnard, Joseph A, and Nathan C Lo. “Scientific and Ethical Basis for Social-Distancing Interventions against COVID-19.” The Lancet Infectious Diseases 20, no. 6 (2020). https://doi.org/10.1016/s1473-3099(20)30190-0. ↑
14. Wilcox, Christopher R, Rebecca Rowe, Deborah C Mobley, Merlin Willcox, and Christine E Jones. “Routine Vaccinations during Pregnancy: An Update.” British Journal of General Practice 70, no. 692 (2020): 142–143. https://doi.org/10.3399/bjgp20x708089.
    ‌ ↑
15. Jong, M. D d., and R. W Sanders. “The Future of Influenza Vaccines.” BMJ 339, no.7725 (2009): b4014–b4014. ↑
16. Lipsitch, Marc, Stanley Perlman, and Matthew K Waldor. “Testing COVID-19 Therapies to Prevent Progression of Mild Disease.” The Lancet Infectious Diseases, (2020). https://doi.org/10.1016/s1473-3099(20)30372-8. ↑
17. Grein, Jonathan, Norio Ohmagari, Daniel Shin, George Diaz, Erika Asperges, Antonella Castagna, Torsten Feldt, et al. “Compassionate Use of Remdesivir for Patients with Severe Covid-19.” New England Journal of Medicine, (2020). https://doi.org/10.1056/nejmoa2007016. ↑
18. Shrestha, P., T. Roberts, A. Homsana, T.O. Myat, J.A. Crump, Y. Lubell, and P.N. Newton. “Febrile Illness in Asia: Gaps in Epidemiology, Diagnosis and Management for Informing Health Policy.” Clinical Microbiology and Infection 24, no.8 (2018): 815–826. https://doi.org/10.1016/j.cmi.2018.03.028. ↑
19. Dittrich, Sabine, Marie Lamy, Shreehari Acharya, Htin Kyaw Thu, Rittika Datta, Stuart D Blacksell, Phone Si Hein, Chris Erwin G Mercado, Xavier C Ding, and Amita Chebbi. “Diagnosing Malaria and Other Febrile Illnesses during the COVID-19 Pandemic.” The Lancet Global Health 8, no.7 (2020): e879–880. https://doi.org/10.1016/s2214-109x(20)30210-2.
    ‌ ↑
20. Calabrese, Sarah K., and Kristen Underhill. “How Stigma Surrounding the Use of HIV Preexposure Prophylaxis Undermines Prevention and Pleasure: A Call to Destigmatize ‘Truvada Whores.’” American Journal of Public Health 105, no.10 (2015) : 1960–1964. https://doi.org/10.2105/ajph.2015.302816. ↑
21. “Transformation of HIV from Pandemic to Low-Endemic Levels: A Public Health Approach to Combination Prevention.” The Lancet 384, no.9939 (2014): 272–279. https://doi.org/10.1016/s0140-6736(13)62230-8. ↑
22. Morgan, O. W., M. Meltzer, D. Muir, H. Hogan, C. Seng, J. Hill, and J. Beckford. “Specialist Vaccination Advice and Pockets of Resistance to MMR Vaccination: Lessons from an Outbreak of Measles.” Communicable Disease and Public Health 6, no.4 (2003): 330–333. https://pubmed.ncbi.nlm.nih.gov/15067861/. ↑
23. Foege WH. ‘‘House on fire: the fight to eradicate smallpox.’’ University of California Press, Berkeley (2011)
    ‌ ↑
24. Wolfe, Nathan D., Claire Panosian Dunavan, and Jared Diamond. “Origins of Major Human Infectious Diseases.” Nature 447, no. 7142 (2007): 279–283. https://doi.org/10.1038/nature05775. ↑
25. Power, Alison G., and Charles E. Mitchell. “Pathogen Spillover in Disease Epidemics.” The American Naturalist 164, no. S5 (2004): S79–S89. https://doi.org/10.1086/424610. ↑
26. Singh, Sheo B., Katherine Young, and Lynn L. Silver. “What Is an ‘Ideal’ Antibiotic? Discovery Challenges and Path Forward.” Biochemical pharmacology 133 (2017): 63–73. https://doi.org/10.1016/j.bcp.2017.01.003. ↑
27. TEDx Talks. “The Drugs Don’t Work: Sally Davies at TEDxAlbertopolis.” TEDx Talks (2013) ↑
28. Barrett, Scott. “Eradication versus Control: The Economics of Global Infectious Disease Policies.” Bulletin of the World Health Organization 82, no.9 (2004): 683–688. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2622975/.
    ‌ ↑
29. Fenner, Frank. “Global Eradication of Smallpox.” Clinical Infectious Diseases 4, no. 5 (1982): 916–930. https://doi.org/10.1093/clinids/4.5.916. ↑
30. Venkatesh, Ashwin, Daphne Theresa Chia, Anthony Tang, and William Waldock “Efficacy of Text Message Intervention for Increasing MMR Uptake in Light of the Recent Loss of UK’s Measles-Free Status.” British Journal of General Practice 70, no.692 (2020): 110.1-110. https://doi.org/10.3399/bjgp20x708401. ↑
31. Dittrich, Sabine, Marie Lamy, Shreehari Acharya, Htin Kyaw Thu, Rittika Datta, Stuart D. Blacksell, Phone Si Hein, Chris Erwin G. Mercado, Xavier C. Ding, and Amita Chebbi. \”Diagnosing malaria and other febrile illnesses during the COVID-19 pandemic.\” The Lancet Global Health 8, no.7 (2020): e879-880. https://doi.org/10.1016/s2214-109x(20)30210-2. ↑
32. Thornton, Jacqui. \”Clinical trials suspended in the UK to prioritise covid-19 studies and free up staff.\” BMJ 368 (2020): m1172. https://doi.org/10.1136/bmj.m1172.
    ‌ ↑
33. Dai, M., D. Liu, M. Liu, F. Zhou, G. Li, Z. Chen, Z. Zhang et al. Patients with cancer appear more vulnerable to SARS-COV-2: a multi-center study during the COVID-19 outbreak. Cancer Discovery. (2020). CD-20-0422. https://doi. org/10.1158/2159-8290. cd-20-0422. ↑
34. Liang, Wenhua, Weijie Guan, Ruchong Chen, Wei Wang, Jianfu Li, Ke Xu, Caichen Li, et al. “Cancer Patients in SARS-CoV-2 Infection: A Nationwide Analysis in China.” The Lancet Oncology 21, no.3 (2020): 335–337. https://doi.org/10.1016/S1470-2045(20)30096-6.
    Figure 1:
    Public Health England “Health Matters: Antimicrobial Resistance.” GOV.UK. (2016). https://www.gov.uk/government/publications/health-matters-antimicrobial-resistance/health-matters-antimicrobial-resistance.
    Figure 2:
    Adnan Shereen, Muhammad, Suliman Khan, Abeer Kazmi, Nadia Bashir, and Rabeea Siddique. “COVID-19 Infection: Origin, Transmission, and Characteristics of Human Coronaviruses.” Journal of Advanced Research 24, (2020): 91-98. https://doi.org/10.1016/j.jare.2020.03.005.
    Figure 3:
    Sammon, Cormac J., Julia Snowball, Anita McGrogan, and Corinne S. de Vries. “Evaluating the Hazard of Foetal Death Following H1N1 Influenza Vaccination; A Population Based Cohort Study in the UK GPRD.” PLOS One 7, no.12 (2012): e51734. https://doi.org/10.1371/journal.pone.0051734.
    Figure 4:
    Public Health England “Cover of Vaccination Evaluated Rapidly (COVER) Programme 2019 to 2020: Quarterly Data.” GOV.UK (2019) https://www.gov.uk/government/statistics/cover-of-vaccination-evaluated-rapidly-cover-programme-2019-to-2020-quarterly-data.
    ‌ ↑