Human pathogens: infectious diseases
As you learnt earlier in the course, pathogens are microbes that harm their host and cause the particular symptoms we recognise as an infectious disease. Pathogens come from four of the five groups of microbes: viruses, bacteria, fungi and protists. We are not really sure why there are no pathogenic archaea, especially given that some archaea live in association with hosts (including humans).
Whilst we may consider pathogens as “bad” microbes, they are really just trying to replicate. Pathogens affect every living organism, but in this Step we will focus on the ways human pathogens cause infectious diseases and how they are spread within the community.
In order to cause an infection, pathogens have to overcome the host immune response and be able to replicate within a specific tissue(s) or cell type(s). Some pathogens produce virulence factors such as toxins to get access to nutrients or to overcome the immune response. The disease anthrax is caused by the endospore- and toxin-producing Gram positive bacterium Bacillus anthracis (Figure 1: Left). The symptoms and prognosis depend on the portal of entry, although all forms are often fatal if they are not treated with antibiotics. Cutaneous anthrax (Figure 1: Right) is caused when bacterial endospores enter via a wound in the skin. Inhalation of the spores into the lungs causes pulmonary anthrax and ingestion of the spores, usually via consumption of contaminated meat, leads to gastrointestinal anthrax. It cannot be transmitted from person to person, but it is considered a potential bioterrorist threat.
Figure 1: Left: Light microscope image of Gram-stained Bacillus anthracis cells © CDC/ Dr. Brodsky. Right: Skin lesion, located on the dorsum of a right hand caused by Bacillus anthracis © CDC/ F. Marc LaForce, M.D.
In many cases, disease symptoms are due to the activation of the immune response rather than direct damage caused by the pathogen. Ebola virus directly infects immune cells (Figure 2: left) and triggers the uncontrolled release of immune signalling molecules called cytokines. This “cytokine storm” damages the lining of blood vessels and other tissues, leading to internal bleeding and multiple organ failure. The novel human coronavirus SARS-CoV-2 responsible for the current global pandemic causes a disease called Covid-19. Scientists are still trying to understand exactly why infection with this virus leads to such a wide range of outcomes; in many cases the infection is asymptomatic or results in a mild respiratory illness, whereas in some cases it progresses to a severe illness that can be fatal. The severe symptoms are thought to be the result of a cytokine storm, with uncontrolled inflammation causing damage to the lungs and other internal organs. This can also stimulate the liver to produce excessive clotting factors, making the blood extremely sticky and causing blood clots to form around the body. Covid-19 patients are therefore at a higher risk of developing complications including deep vein thrombosis, pulmonary embolisms, heart attacks, and strokes.
Figure 2: Left: Digitally colourised scanning electron microscope (SEM) image of Ebola virus particles (coloured blue) being released from an infected monkey cell (yellow) © NIAID. Right: Digitally colourised transmission electron microscope (TEM) image of SARS-CoV-2 virus particles (coloured blue). © CDC/ Hannah A Bullock; Azaibi Tamin
The bacterium Mycobacterium tuberculosis (Figure 3) is a human pathogen that frequently establishes a latent infection. It only causes the symptoms of the disease Tuberculosis (TB) in around 5% of cases, but this does not mean we should not be concerned about this disease. Approximately ¼ of the world population are infected with TB and it is one of the top 10 leading causes of death worldwide, predominantly in lower-income countries, and it is the leading cause of death in patients with HIV. Drug-resistant TB (MDR/RR-TB) is a global health crisis with the WHO estimating 558,000 in 2017.
Figure 3: Digitally colourised scanning electron microscopic (SEM) image of rod shaped Mycobacterium tuberculosis bacterial cells, the pathogen that causes tuberculosis (TB) © NIAID
Some symptoms of infectious disease are directly related to the transmission of the pathogen from host to host. Cold sore blisters and genital warts are an effective way to spread HSV-1 between people via direct contact. Coughs and sneezes spread respiratory infections through communities via the airborne route. Diarrhoeal diseases are spread via water-borne or food-borne (also known as faecal-oral) transmission. Some pathogens are vector-borne, where they are transmitted between human hosts by another living organism such as a mosquito or tick.
Borrelia burgdorferi is a Gram negative spiral-shaped bacterium (Figure 4: Left) that causes Lyme disease. This organism has developed a unique mechanism for overcoming the host’s iron-withdraw immune response (see Step 1.13) – it has completely dispensed with the need for iron and uses manganese instead. This is an example of a vector-borne disease because this pathogen is transmitted to humans by Ixodes ticks (Figure 4: Middle) after they bite infected animals such as squirrels or mice. The main symptoms are fever, fatigue and headache. In ~80% of cases it causes a characteristic “bull’s eye” rash at the bite site (Figure 4: Right). If left untreated the infection can spread to the heart, joints and nervous system leading to serious complications.
Figure 4: Left: Digitally colourised scanning electron microscope (SEM) image of Borrelia burgdorferi bacteria, the cause of Lyme disease ©CDC/ Claudia Molins. Middle: a blacklegged Ixodes tick, the vector that transmits Borrelia burgdorferi © CDC/ James Gathany; William L. Nicholson, Ph.D. Right: Pathognomonic erythematous rash in the pattern of a “bull’s-eye” characteristic of Lyme disease caused by Borrelia burgdorferi © CDC/ James Gathany
In this additional resource PDF, you can see a summary table of transmission routes with examples of infectious human diseases and the pathogens that cause them. It is in a pathogen’s best interests to transmit the infection to as many new hosts as possible, so it is not beneficial for a pathogen to kill its host.
Why are some infectious diseases deadly?
The most dangerous infectious diseases in the world today are transmitted to humans from other animal hosts (such infections are termed zoonoses). For example, it is likely that fruit bats are the primary hosts of Ebola virus and it can spread from bats to primates such as chimpanzees and gorillas. If a person handles an infected animal during the preparation or consumption of bush meat, they can become infected. The virus is then transmitted between people via direct contact with infected bodily fluids leading to EVD outbreaks. Ebola survivors can also transmit the virus via sexual transmission for many weeks/months after they recover. It is possible to control EVD outbreaks using proper containment and decontamination measures, largely because it is not airborne. You may like to watch this video on the sciencemag website about the hunt for Ebola virus in African fruit bats.
The HIV/AIDS pandemic is also zoonotic in origin. Simian immunodeficiency virus (SIV) has entered the human population from primates (mainly chimpanzees) on several occasions. Each time it did this it acquired mutations whilst replicating in human cells that transformed it into distinct types of HIV. The most successful type of HIV is called HIV-1 group M, which is responsible for 95%+ of infections worldwide. It can be transmitted from person to person by several transmission routes, including sexual transmission, vertical transmission (mother to child via the placenta, during delivery or breastfeeding), needle sharing, or medical procedures e.g. blood transfusions (iatrogenic transmission). HIV infects white blood cells and can integrate its genome into the chromosome of the host cell where it can remain latent for many months / years. Every time the host cell replicates the daughter cells receive a copy of the virus. Later in the infection, the virus actively replicates and eventually kills the white blood cell (Figure 5). If left untreated, the white blood cell count falls leading to the disease AIDS. AIDS patients typically die from other infections (eg TB) because their immune system is not working properly.
Figure 5: Digitally colourised scanning electron micrograph (SEM) image of human immunodeficiency virus, HIV-1 (green) budding from cultured lymphocyte (blue) grown in tissue culture © CDC/ C. Goldsmith, P. Feorino, E. L. Palmer, W. R. McManus
Several coronaviruses have made the leap from animals into the human population over the past few decades. You can learn more about these outbreaks and pandemics in the next Step.
The distinction between an infection and a disease
The above article discusses some of the more deadly diseases, but did you know that you’re almost certainly infected with at least one virus even if you have no symptoms of a disease?
You may find it surprising that almost 100% of healthy non-symptomatic adults are infected with at least one type of virus, probably more. If you have ever had chickenpox (Figure 7: Left) or a cold sore (Figure 7: Right) you’ll have noticed the characteristic blisters caused by these viruses. Whilst the symptoms of the infection may have disappeared many years ago, the viruses are probably still with you today. This is because these viruses are able to enter cells of the nervous system and establish a latent infection, where they stop replicating (or replicate very slowly) and hide from the immune system.
Figure 7: Left: Chickenpox blisters caused by a herpesvirus called varicella zoster virus (VZV) © CDC/ Dr. K.L. Hermann. Right: This photograph depicts a close-up of the lips of a patient with a herpes simplex lesion on the lower lip, due to the herpes simples virus-1 (HSV-1) © CDC/ Dr. Herrmann
Dormant (non-replicating) microbes may be reactivated in healthy individuals or if the immune system is suppressed eg when taking immunosuppressant drugs after an organ transplant or due to co-infection with HIV. The reactivation of a latent VZV infection, known as shingles or zoster, causes a localised burning sensation and skin rash with painful blisters; produced when the chickenpox viruses leave the nerve cells and start replicating again.
You may also be infected with a circovirus called torque teno virus (TTV), also known as transfusion transmitted virus, which replicates very slowly. It was first detected in 1997 in a Japanese patient suffering with post-transfusion hepatitis (liver infection) but later studies revealed TTV is not the causative agent of any known disease. It’s thought to cause little or no damage to host tissues and replicates so slowly, it avoids detection by the immune surveillance system. This slow, stealthy approach may be a deliberate tactic, with people unknowingly transmitting the virus to others, as the virus is found all over the world. In some communities over 90% of adults are infected with TTV!
Does this surprise you? Share your thoughts in the comment area below.
In the next Step, you can explore a timeline of some of the most notable outbreaks of infectious diseases that have occurred throughout history, including the current pandemic caused by SARS-CoV-2.
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