Leprosy or Hansen's Disease: Bacteria and Nerve Damage
A Potentially Serious Bacterial Infection
Leprosy is a disease that has been feared since ancient times due to its effects on the body. It’s caused by a bacterial infection and can produce debilitating and disfiguring symptoms. A lack of understanding of the disease has resulted in ostracization and sometimes cruel treatment of patients.
Doctors now know that it’s not easy to catch leprosy and that the disease progresses slowly. In addition, they can treat the infection effectively if it does develop. If someone becomes infected and doesn’t get treatment, however, serious nerve damage can result.
Leprosy is also known as Hansen's disease. In 1873, a Norwegian doctor named Gerhard Henrik Armauer Hansen discovered that a bacterium was the cause of the disease. The bacterium was eventually named Mycobacterium leprae. Though leprosy is the more common term for the illness, Hansen's disease is sometimes preferred today because it reduces the stigma attached to the illness. Some interesting discoveries have been made in relation to exactly how M. leprae causes nerve damage.
There are two main types of leprosy. Paucibacillary or tuberculoid leprosy is much milder than the multibacillary or lepromatous form of the disease. Some people have a disorder that is on the borderline between the two forms.
Possible Symptoms of Leprosy
The list below contains some common symptoms of leprosy. A patient may not have all of them. In addition, having one or more of the symptoms doesn't necessarily mean that a person has leprosy. Different diseases often share some of their symptoms. A doctor should be consulted for a diagnosis.
The symptoms of leprosy take an average of five years to appear after the initial infection but may take as long as twenty years. The milder symptoms generally develop first. The disease is rarely fatal but may be so due to a secondary effect such as kidney failure. Symptoms may include:
- skin lesions (patches with an altered appearance) that are white or red in colour
- numbness in the lesions due to nerve damage in the skin
- skin lumps and bumps, especially on the face
- loss of eyebrows and eyelashes
- muscle weakness or paralysis
- enlarged nerves under the skin that can often be seen from outside the body
- eye and vision problems, including blindness in severe cases
- nose problems, such as nosebleeds. a stuffy nose, and disfigurement
- chronic ulcers on the soles of the feet
- paralysis and clubbing of hands and feet
- reabsorption of the cartilage in fingers or toes, making them shorter
- damage to the male reproductive organs
- kidney damage
Additional problems may develop because the patient may develop injuries in the areas without sensation. The nerve damage may stop them from feeling pain and realizing that their body is being hurt.
It's important to get treatment for leprosy as early as possible in the progression of the disease. The sooner treatment is begun, the less likely that symptoms will be severe or permanent. Early attention is necessary because doctors may be unable to correct some of the effects of the disease even when the bacteria are destroyed.
Leprosy bacteria may be transmitted from person to person in droplets of moisture released when an infected person sneezes or coughs. Most people don't become infected when this happens, however. Long-term exposure to a contagious person is needed. In addition, a genetic susceptibility to the disease seems to be required. A regimen of specific antibiotics known as multidrug therapy is used to treat the illness.
Mycobacterium leprae and Myelin
Mycobacterium leprae is a rod-shaped bacterium with rounded ends. It's a difficult organism to study because it's hard to grow to lab equipment and has little effect on lab animals. This means that scientists don't know as much about its biology as might be expected. The bacterium affects the skin and the peripheral nerves (those leaving the brain or spinal cord and travelling to the surface of the body). In severe cases of leprosy, it may also cause damage to some of the internal organs.
Researchers have known for some time that the bacterial infection causes the myelin sheath around neurons to disappear. Myelin is a fatty material that electrically insulates the axon of a neuron, allowing the nerve impulse to travel effectively. A nerve impulse is a type of electrical current, although it consists of a flow of ions instead of the flow of electrons that occurs in a wire.
The myelin around the neurons in peripheral nerves is made by Schwann cells. These cells spiral around the axon of a neuron, wrapping it in layers of cell membrane containing myelin. Some evidence suggests that the leprosy bacteria enter the Schwann cells and interfere with their production of myelin.
Mycobacterium lepromatosis also causes leprosy, although it appears to be a less common cause than M. leprae.
Facts About Leprosy
Genetic Reprogramming of Schwann Cells
In 2013, a group of researchers at the University of Edinburgh took Schwann cells from mice and added M. leprae to them. They found that the bacteria reprogrammed the cells by turning off genes used in mature Schwann cells and turning on ones used in immature ones. This reprogramming caused the cells to revert to an unspecialized form resembling that of a stem cell.
Stem cells are normally very useful because they can produce the specialized cells that we need when they are stimulated correctly. In the mouse experiment, however, the reprogrammed Schwann cells weren't useful because they were unable to make myelin.
The researchers placed the altered Schwann cells inside living mice. Some of the cells migrated to the muscles, carrying and distributing the bacteria as they travelled. This could be one way in which the bacteria spread through our body.
In 2017, a different team of researchers found evidence suggesting that leprosy bacteria may cause myelin destruction by altering the action of the patient's immune system.
Mycobacterium leprae and Macrophages
An international team of researchers has recently discovered that the bacteria that cause leprosy enter white blood cells known as macrophages and hijack their activity. The scientists say that this leads to the injury to the nerves. Macrophages are part of our immune system. This system protects us from disease by destroying microbes that can make us sick and by removing and destroying damaged material.
Macrophages are large cells that engulf and digest particles in a process called phagocytosis. The particles that are "eaten" include bacteria such as M. leprae as well as unwanted material. Normally, bacteria that enter the macrophages are destroyed, but this may not happen in the case of the leprosy bacterium.
The researchers inserted leprosy bacteria into zebrafish larvae, which were transparent. The scientists had previously genetically modified the fish so that their myelin glowed a fluorescent green colour. This enabled the scientists to more clearly see what was happening to the myelin. They then injected leprosy bacteria close to the myelin.
The researchers found that the bacteria appeared to settle on the nerve and that bubbles of myelin were released from the sheath. When the scientists examined their discovery in more detail, they found that the bacteria were located inside macrophages and that they were still intact.
The scientists say that it was actually the macrophages that damaged the myelin, not the bacteria. They confirmed this by destroying the macrophages in the zebrafish. The researchers found that the bacteria alone couldn't destroy the myelin. They also found that a molecule on the surface of the bacterium named PGL-1 altered the behaviour of the macrophages, causing them to make an excessive amount of nitric oxide. This chemical damaged the mitochondria of the nerve cells. Mitochondria produce energy for a cell. If a cell contains an insufficient number of mitochondria, it can't survive.
The researchers say that the altered macrophage damages neurons in two ways: it stops "patrolling" the neuron to protect it from damage and also damages nerve cells directly.
The Potential Importance of the Research
Both the 2013 and the 2017 reports about M. leprae are very interesting, but as far as I know each study has been performed by only one group of researchers. This doesn't mean that the results are incorrect, but results from another team could add evidence supporting the original study. One or both of the discoveries might be medically useful if they are correct.
A problem with the first study is that the bacterium's behaviour in mouse cells and living mice may not be the same as its behaviour inside our body. A problem with the second study is that discoveries in zebrafish larvae may not apply to humans. It's interesting to note that the fish have been useful in the study of an M. lepae relative called Mycobacterium tuberculosis, however. As its name suggests, this bacterium causes tuberculosis. In addition, the biology of zebrafish larvae has important similarities to that of mammals, including humans.
Both sets of researchers hope that that their discovery will help treat leprosy in some way. The 2013 researchers hope that leprosy can be diagnosed at an earlier stage. The 2017 researchers hope that nerve damage caused by the bacterium can be reversed. Both sets of researchers suspect that their research will lead to a better understanding and perhaps a better treatment for other demyelination disorders, including multiple sclerosis, or MS. In MS, the immune system is believed to destroy the myelin around nerves.
An Effort to Eliminate Leprosy
Leprosy is uncommon in the United States, but it does occur in the country.
Leprosy in the Present and the Future
The World Health Organization (WHO) reports that the incidence of leprosy is decreasing. Some health experts believe that certain countries are becoming complacent with respect to the disease and that far more cases exist than are being reported. This is very troubling because the illness can be treated and the worst of the permanent effects avoided. If people aren't identified as having leprosy, they won't be given the appropriate antibiotics and may develop life-altering symptoms that could have been prevented.
People with leprosy were treated badly in the past. Unfortunately, they still are in some countries. Education of the public is important. Better treatment for the effects of the illness would be wonderful. It's good that we can destroy the bacteria in patients. Depending on when the treatment is started, however, the bacterial infection may cause disabling and irreversible effects. I hope that the latest research eventually prevents this from happening.
- "Hansen's Disease (Leprosy)." Centers for Disease Control and Prevention. https://www.cdc.gov/leprosy/ (accessed August 24, 2017).
- "Leprosy Overview." WebMD. http://www.webmd.com/skin-problems-and-treatments/guide/leprosy-symptoms-treatments-history#1 (accessed August 24, 2017).
- "Leprosy." Merck Manual. http://www.merckmanuals.com/en-ca/home/infections/tuberculosis-and-leprosy/leprosy (accessed August 24, 2017).
- Telis, Gisela. "Leprosy Reprograms Body's Cells." American Association for the Advancement of Science. http://www.sciencemag.org/news/2013/01/leprosy-reprograms-bodys-cells (accessed August 25, 2017).
- "Leprosy turns the immune system against itself, study finds." Medical Xpress. https://medicalxpress.com/news/2017-08-leprosy-immune.html (accessed August 24, 2017).
- "Leprosy Elimination." World Health Organization. http://www.who.int/lep/disease/en/ ((accessed August 25, 2017).
- Lyons, Kate. "Shadow of leprosy falls again as experts claim millions of cases go undiagnosed." The Guardian. https://www.theguardian.com/global-development/2017/aug/03/leprosy-experts-claim-millions-of-cases-go-undiagnosed (accessed August 25, 2017).
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© 2017 Linda Crampton