Infectious Respiratory Disease

Content

Overview of Pathogens

Microbes, also known as microorganisms, are too small to see with the unaided eye, ubiquitous, and unavoidable. Throughout the insides and outside of human bodies (and other living organisms) live bacteria, viruses, protozoa, and fungi that collectively we call the “human microbiota”.⁴ Of the many microbes that live on or inside of us, many of them are involved in biological processes that are beneficial for us. This includes microbes found in and on human mouths, skin, urinary tracts, and gastrointestinal tracts. Bacillus subtilis is a species of bacteria that lives on the skin and releases a substance called bacitracin, which has antibacterial properties.⁵ Scientists have studied microbes that are beneficial to humans to exploit their therapeutic properties. Bacteriophages are types of viruses that infect and kill bacteria, and could be used to develop a specific bacteriophage that would target a harmful bacterial species like Escherichia coli as a medical treatment.⁶ While some of these microbes can be perfectly harmless, or even beneficial to human health, some make us sick, which we call pathogens. Our understanding of microbes and their interactions with humans and other living organisms is dynamic, and COVID-19 has only highlighted how much more we have to learn.

Although many contributed to our understanding of microorganisms, the first discoveries made regarding microbes were made by Robert Hooke and Anton van Leeuwenhoek in the 17^th century. Despite Hooke not completing undergraduate school at Oxford and Leeuwenhoek not having much formal schooling, both of these individuals provided the foundation for our understanding of cells and microscopy.⁷ During this time, disease outbreaks like smallpox and the black plague occurred. Still, the association between a disease and a specific pathogenic microorganism would not be made until the late 19^th century. Up until discoveries made by John Snow and Robert Koch, the link between a particular microbe and its associated disease had not yet been made. Throughout much of the 19^th century, cholera exploded in urbanized areas, was transported by ships in bilge water, and thrived due to unsanitary conditions brought on by high population density and dumping human excrement into London’s Thames River.⁸ Even though progress had been made concerning understanding microbes since the work of Hooke and Leeuwenhoek, the leading theory of pathogenesis of cholera and other diseases was the Miasma Theory, which speculated that diseases like cholera were caused by breathing in “foul smells due to poor sanitation.”⁹ Snow investigated and traced cholera deaths to observe a larger concentration of deaths from people who lived on or near Broad Street and received their water supply from the cholera-contaminated Broad Street pump, compared with populations that received their water supply from wells that were isolated from contamination. Snow’s subsequent investigations of cholera throughout districts in London involved two water companies and found populations supplied by Southwark and Vauxhall had cholera death rates that were almost ten times those of the populations provided by Lambeth; 315 deaths per 10,000 houses and 37 deaths per 10,000 houses, respectively.¹⁰

Additionally, discoveries made by Robert Koch provided definitive proof that specific microbes cause specific diseases. Koch investigated anthrax and discovered a causal relationship between the disease anthrax and the bacteria Bacillus anthracis.¹¹ Determining the particular pathogen that causes a disease was a huge step in controlling pathogens. Snow and Koch’s epidemiology work provided the causal association of a disease and specific microbes, which provided evidence for Germ Theory to replace Miasma Theory as the explanation for why diseases occur and how they spread.

Armed with a better understanding of how diseases spread through the contamination of pathogens, advances were made concerning sanitation (e.g., water and waste effluence) and hygiene (e.g., handwashing) that drastically decreased the amount of disease and deaths from water and foodborne illnesses and kept new cases and deaths under control, particularly in urban environments. Waterborne diseases like cholera persist in countries that are less economically developed and can be prevalent in regions involved in war due to water supply contamination or impact on sanitation. While diarrheal diseases are still a significant cause of death, especially with younger populations, annual deaths from diarrheal diseases have dropped from 3.5 million people in 1980 to 1.17 million people in 2021. The discoveries of Hooke, Leeuwenhoek, Snow, and Koch all contributed to a better understanding of how to control water and foodborne illnesses.

Various types of pathogens cause a variety of illnesses and are transmitted in different ways. The specific pathogens mentioned above, Vibrio cholerae and Bacillus anthracis, are both bacteria. To control cholera and other waterborne diseases, the use of chlorine for water sanitation gained popularity near the start of the 20^th century.¹² Once the source of contamination was discovered, water for consumption was treated to kill pathogens, and people were educated on the means and importance of sanitation; cholera was getting under control. Aside from waterborne illnesses like cholera, other diseases can arise when pathogens are transmitted in various ways. This curriculum will focus on the types of pathogens that affect the respiratory system and are collectively called infectious respiratory diseases.

Bacteria and viruses have some similarities (they are both microbes and both can cause disease); however, there are some significant differences between them. First, a bacterium is a unicellular organism that can replicate on its own, while a virus is not a cell and needs a host to replicate.¹³ Bacterial cells are larger and have far more genes, at around 5,000 to 10,000 (for smaller bacteria), than a virus like the herpes virus, which only has around 200 to 400 genes.¹⁴ The genetic material for bacteria is DNA, while the genetic material for viruses could be either DNA or RNA.¹⁵ Bacteria are treated with antibiotics, and viruses are treated with antivirals. Many types of pathogens are included in the category of respiratory diseases, but the focus here will be on viral diseases.

Respiratory Disease Transmission

Infectious agents like cholera are diseases that are spread through populations – cholera spread through European cities during the 18^th century due to contaminated water sources like the Broad Street pump. However, respiratory diseases spread in ways that make it harder to control the source of infection. One major infectious respiratory disease is influenza, commonly known as the flu, and is caused by the Influenza virus. Typical flu symptoms include fever, chills, cough, sore throat, aches, and sometimes vomiting and diarrhea; it can be mild to severe and life-threatening.¹⁶ Influenza is a disease caused by several types, including influenza A, B, C, and D. Influenza type A is the flu type seen in annual seasonal outbreaks and has been involved in influenza pandemics, notably the 1918 flu.¹⁷ Different names for disease spread differ by how much the disease has spread from its origin. When an outbreak of a disease spreads over a greater region, it is called an epidemic, and when it spreads globally, it is called a pandemic.¹⁸ Modern transportation and globalization in recent years have only improved the ability for disease to spread further throughout the world. The 1918 influenza pandemic, also called the “Spanish flu”, impacted about a third of the world’s population and killed an estimated 50 million people – the largest estimated death toll for all viral pandemics.¹⁹ The movement of troops in World War I during the 1918 pandemic provided the uncontrolled means for the virus to spread between people from distant places. Densely populated urban areas also provide agreeable conditions for the spread of a virus, particularly if the disease has asymptomatic carriers who are unaware of infection. The COVID-19 pandemic caused by the SARS-CoV-2 virus killed an estimated 14.9 million people directly and indirectly.²⁰ In recent years, it had seemed like measles, a respiratory disease caused by the morbillivirus, was all but eradicated from the U.S. Data from the U.S. shows 179,829 new cases in 1919 to 285 new cases in 2024 of measles.²¹ Vaccine hesitation has allowed some limited outbreaks to become more out of control, as the US has hit an all-time high in 2025 with over 1,300 cases and three deaths; 92% of the victims were either not vaccinated, or their vaccination status was unknown.²² Not only can respiratory diseases be deadly, but the number of cases and deaths can rapidly increase. A disease’s reproductive number is the new cases that could be produced “in a completely susceptible population.”²³

Mode of Transmission

Diseases spread when people susceptible to a particular disease are exposed to a source. Sources of infection might be from water, food, surfaces, an animal, or another person. The infectious agent must leave from a “portal of exit” to infect another host; for respiratory diseases, this might be the mouth or nose during coughing, sneezing, or talking.²⁴ How pathogens like viruses are spread from one host to another host is called the mode of transmission. The mode of transmission might be from direct contact, as is the case with kissing and sexual contact, or when a respiratory droplet makes contact with a susceptible person’s eyes, nose, or mouth; however, droplets are generally larger and fall to the ground relatively quickly.²⁵ Cases where the mode of transmission is direct tend to have more obvious ways of prevention. Kissing and sexual contact can be avoided, and social distancing of more than 6 feet prevents the direct transmission of larger droplets since they fall so quickly. When an infectious agent’s mode of transportation is indirectly spread by airborne particles called aerosols, the aerosols are so small that they can remain suspended in the air for long periods and can infect someone after the host has left the area.²⁶ Disinfecting something solid (food) or liquid (water) is much easier than dealing with contamination in the air we breathe. Eating and drinking are intentional; breathing is unintentional. Public officials and scientists have historically disagreed about making proclamations that a particular disease is airborne. In 2020, despite scientists pleading with the World Health Organization that the SARS-CoV-2 virus was airborne, the organization maintained for months that droplets were the primary mode of transmission; admission of airborne transmission for measles and influenza has produced the same controversies and initial denial of airborne transmission.²⁷ Getting accurate information is crucial for controlling outbreaks and minimizing cases and deaths; however, the slow response to communicate accurate information to the public likely cost lives and resulted in new cases soaring out of control.

Prevention Strategies

Prevention of infectious respiratory diseases can take many forms, but it is challenging due to the nature of a virus being airborne. A multilayered approach to infection prevention can work best to reduce the risk of exposure to airborne pathogens. While not comprehensive, this unit will explore five prevention strategies to reduce the likelihood of infection. Table 1 below provides a brief evaluation of their strengths, weaknesses, and limitations.

Table 1: Description and evaluation of prevention strategies to reduce the risk of infection from respiratory diseases.

Vaccines are a way to gain some immunity from the virus before infection and provide some control of transmission, provided a large enough percentage of the population receives the vaccine to form herd immunity. Vaccines can be developed by inactivating a virus through attenuation, chemical applications, breaking a virus into subunits, or exposing a host to viral proteins.³⁶ This pre-infection exposure allows the body to generate a rapid response by the immune system.

Increasing the ventilation of indoor air spacing lowers the concentration of viruses, pathogens, and other particles in a room and thus decreases the risk of transmission of airborne viruses. Likewise, the use of masks in indoor spaces also reduces the amount of virus that can be transmitted. The American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE) sets a standard minimum of 0.35 air changes per hour (ACH) for living areas in residential locations.³⁷ Due to higher occupancy in public spaces and the need to minimize infections within healthcare settings, different standards are recommended for spaces like classrooms and hospitals. The CDC recommends a minimum of 5 air changes per hour to prevent respiratory disease transmission in the workplace. A study measuring the efficiency of masking and ventilation in medical settings found that an air change rate of 9 changes per hour was more effective in reducing the percentage of virus remaining in a room than other air change rate values.³⁸ Additionally, wearing three-layer masks was found to reduce the probability of infection significantly.³⁹ Ventilation systems with higher ACH may incur higher costs with limited effectiveness.

Social distancing and masking provide methods to put distance and barriers between pathogens and susceptible individuals. Neither can provide complete protection against infection, but each can further reduce the risk of transmission, particularly for indoor spaces. The initial recommendations of social distancing of more than 1-2 meters were shown to be insufficient due to aerosols that remain suspended in the air longer than initially believed. While masking does not provide complete protection and is dependent on mask type and condition, it is another means to reduce indoor viral concentrations and risk of transmission.

While handwashing and not touching one’s face do not control the transmission of suspended aerosols, they can reduce the risk of transmission due to droplets and indirect vehicle-borne transmission. No one strategy for prevention will completely control transmission of infectious respiratory diseases, but using several different strategies can provide more protection from infection. The CDC recommends using multiple protection strategies together, as they are more effective when combined (e.g., keeping vaccinations up to date, increasing ventilation, masking, using social distancing, and practicing good hygiene).⁴⁰

Immune System

Suppose the chain of infection is not interrupted and the virus successfully reaches the skin or a portal of entry (e.g., eyes, nose, or mouth). In that case, the immune system aims to provide the body with protection and eliminate the disease agent. There are two lines of defense in the immune system: the innate and the adaptive immune system. The innate immune system is a generalized response to foreign invaders; this includes barriers like the skin and mucous membrane to stop pathogens at entry, causes inflammation surrounding the site of infection, and identifies or tags pathogens and abnormal cells to be destroyed by white blood cells or natural killer cells.⁴¹ The benefit of this being a generalized system is a quick reaction to any foreign invader. When the innate immune system is not enough to eliminate the threat, the adaptive immune system takes over with a more targeted approach, with T cells, B cells, and antibodies. Pathogens and cells alike have molecules called antigens on their outsides that act as ID tags. T cells can activate helper cells and destroy infected or tumor cells, B cells develop specific antibodies that match a pathogen’s antibody and will “remember” any pathogens that reinfect the body, and antibodies are specialized proteins that can recognize and attach to a specific antigen on a pathogen for a quick response by inactivating them.⁴² Should the immune system fail to eradicate the virus from the body before body systems are overwhelmed, medical intervention and therapeutics would be needed to support recovery.

Vaccines provide the ability to prepare the adaptive immune system in advance of being infected by a specific pathogen. Vaccines in the future may focus on methods that involve T cell immunity, since many viruses can evade recognition by the antibody.⁴³ New mRNA vaccines for COVID-19 have demonstrated safety and effectiveness over time. In contrast, other vaccines introduce a part of a virus, priming the immune system in case of infection with that specific pathogen.⁴⁴ Vaccines may be controversial because of side effects, misinformation, and mistrust, but they do protect the individual and the community against disease. The concept of herd immunity means that once a certain percentage of a population is immune, either from vaccines or from a prior infection, transmission of the disease can no longer persist – this is about 50 – 75% for COVID-19 at a range of R_o values from 2 – 5 and about 93% for measles with a R_o value at 15.⁴⁵ There is a positive correlation between the R_o value and the percentage of a population required to reach “herd immunity”.

Therapeutics

Therapeutics for a novel disease pose a challenge since a new disease would likely require a new therapy. During the COVID-19 pandemic, when treatments were being tested on patients in clinical trials, there wasn’t any standout medication that worked well. Some trials used during the COVID-19 pandemic included drugs that affected immune system activity, treatments that provide antibodies, and several existing antivirals. Still, these treatments were either too costly, too harmful, or not effective enough.⁴⁶ The severity of some COVID-19 cases and the resulting deaths warranted the innovation of treatment to save lives. The drug Paxlovid was developed by combining antiviral medications nirmatrelvir and ritonavir, and a 28-day clinical trial resulted in 88% fewer deaths and a 75% lower hospital admission rate. This can be particularly impactful for older adults or people who are immunocompromised and are ineligible for a vaccine. Other therapeutics relied on treatments that would impact the immune system and its response. During the COVID-19 pandemic, reports of overactive immune system responses occurred; drugs that provide immunomodulation can regulate the immune response so it does not damage the host.⁴⁷ Additionally, antibodies can be synthesized within a lab for a specific pathogen and used as a target for treatment. Monoclonal antibodies are generated to interact with the spike protein on SARS-CoV-2 to inactivate it and tag it to be destroyed.⁴⁸

Testing and Monitoring

When SARS-CoV-2 was discovered, it was a novel disease, which meant it was new, and new diagnostic tests needed to be developed. Not only did everyone need new tests, but they needed them fast and in huge amounts. Testing at the start of the pandemic was challenging due to these reasons and likely contributed to more outbreaks getting out of control. Additionally, distributing tests to the public and addressing errors with new tests posed even more challenges. Slovakia set out to test its entire population on October 31^st, 2020, using COVID-19 antigen tests. Although it is challenging to determine the specific contributions of testing or other interventions, the country saw a significant reduction in cases in the weeks following the massive testing event.⁴⁹ In November, Liverpool attempted to execute a large-scale testing of 100,000 people; however, the tests were not as sensitive for antigens as they should have been, and one-third of testers received false negatives.⁵⁰ Producing large-scale diagnostics and engineering tests that are accurate is not insurmountable, but certainly makes data collection problematic, not to mention the time lag in reporting. Wastewater monitoring, employed in previous epidemiology investigations, has occurred before and was used during the COVID-19 pandemic to provide accurate tracking of SARS-CoV-2 concentrations and can be used to control interventions when and where they are needed with more advanced notice than could be provided with individual diagnostic tests.⁵¹ Much like prevention, using a variety of testing methods provides a more comprehensive view of infections at any particular time and location.

National and International Response

There were varied responses to the COVID-19 pandemic from different regions and countries. Local communities provided outreach, and communities found other ways of interacting. Economic programs helped when jobs were lost or businesses shuttered. Many countries made policies to keep their constituents safe. Countries like South Korea initially saw a rapid outbreak, but put measures into place to control the spread. This includes expedited development and approval of diagnostic tests, starting an aggressive self-quarantine program, and repurposing government officials to run a contact tracing program.⁵² Other factors involved in Korea’s rapid response were challenges with a large number of deaths and economic losses during the 2015 MERS outbreak that might have “increased the willingness of the population to listen to and adhere to the advice of the government and public health officials.”⁵³ The initial response of countries varied greatly, with some countries acting to contain after the date of the first case, while other countries put containment measures in place sooner than when the first case occurred. The US, Germany, and Japan implemented their first containment after the date of the first case. In contrast, Indonesia and Mongolia implemented their initial containment measures before the date of the first case.⁵⁴ These countries had different health outcomes for case and death rates; however, it is possible that the late start for action in the US contributed to the high number of total deaths.⁵⁵ It is difficult to determine the effect that national policies had on COVID-19 deaths. One analysis looking at death rates for several countries compared that data to a Stringency index (a measure of restrictions based on nine indicators, including school closures and travel bans), found some countries that imposed fewer restrictions, such as Sweden, recorded fewer deaths per population than many high-income countries that had stricter lockdown measures.⁵⁶ While the Stringency index takes into account several pandemic mitigation strategies, it does not measure how they were executed or the impact of each measure.

Framework for Controlling the Virus

Infectious respiratory diseases are challenging to control. In part because the transmission for some is airborne, but there are many challenges. There are control measures that can be set in place proactively, some more effective than others, and some more feasible than others. For instance, transmission during an outbreak would decrease if everyone social distanced, had vaccines, and wore the most heavy-duty masks, cases would drop. However, there will never be 100% compliance for one strategy, and not one approach will work 100%. Some good practices for controlling the spread include layering disease prevention strategies, reducing personal and community risk, increasing the air changes per minute, and using far-UVC to reduce the viral concentration in an indoor space.⁵⁷ In thinking about the control of a pandemic, methods and strategies that are the most effective are important for reducing the spread. The concept of engineering controls for reducing the transmission of COVID-19 indoors can be described as a hierarchy.⁵⁸ The most effective control is to eliminate the pathogen – to remove it from the space or building physically.⁵⁹ Cleaning the air involves several key strategies: increasing ventilation and air flow, increasing air changes per minute for an HVAC system, opening windows for natural ventilation, using HEPA filters to remove small pathogens like viruses from the circulated air, and minimizing the number of people sharing the same indoor space.⁶⁰ The next most efficient are engineering controls that isolate people from the pathogens: social distancing, isolating when symptomatic, and avoiding large groups of people, particularly during an outbreak.⁶¹ Following in reduced efficiency is communicating to the public on what to do, which can be particularly important at the city and state level, since there were contrasting regional differences in the number of infections. Using personal protective equipment (PPE) at the individual level would be the final and least efficient means of control.