Recently, there was a very unfortunate case of a girl who passed away in Miri Hospital, Sarawak due to diphtheria at the age of two. This raised much concern over this archaic disease that, of late, is making a comeback. This is due to the drop in vaccination rates because parents are worried about various negative health impacts of vaccines, and the girl who passed away, was unvaccinated.
Diphtheria is caused by a bacterium called Corynebacterium diphtheriae (C. diphtheriae). This species of bacteria usually infects the upper respiratory tract (which includes the mouth, throat and down to the windpipe) or skin, and it produces toxins that may damage heart or nerve cells. Fortunately, not all strains of C. diphtheriae carry this toxin, hence the symptoms of diphtheria may range from a mild sore throat to deadly inflammations of the heart.
Signs and Symptoms
It is of interest to note that the word diphtheria actually came from the Greek word for leather. This refers to the hallmark of diphtheria infection, a tough membrane that is formed around the back of the throat (see picture below).
Symptoms of diphtheria typically start around 2 to 5 days after infection. Initial symptoms are mild, such as:
- sore throat
- swollen neck lymph nodes
- low-grade fever
As the disease progresses, the typical leathery-like membrane may be seen at the back of the throat. The appearance of this membrane is a sign that the infection is caused by the toxin-producing strain of diphtheria.
When the toxins enter the blood stream, it can wreak havoc in the organs of the body. Most notably it damages the heart (by causing it to be inflamed), the nervous systems and kidneys. In a study of 676 hospitalized patients with diphtheria, it was found that 30% had severe forms of the disease with 22% having myocarditis (inflammation of the heart). Another report from Finland showed that 28% of patients had disease involving the heart.
Apart from causing myocarditis, it can cause neuropathy (damage to nerve cells). This is usually presented as paralysis of the muscles within the mouth, and in more advanced stages, the face and wind pipe.
Finally, the toxins may also directly damage the kidneys, causing kidney impairment and also low blood pressure.
The skin is another possible site of infection besides the upper respiratory tract. This is called cutaneous diphtheria. It usually presents as a skin ulcer that is difficult to heal covered by a dirty gray membrane. The appearance of diphtheria ulcers is nonspecific and difficult to differentiate from other skin ulcers.
Due to the fact that this vaccine confers immunity only to the toxins of diphtheria, it does not make a person immune to the bacteria, C. diphtheriae, itself.
Pseudomembranous diphtheria and the toxin
The toxin producing strain of C. diphtheriae is called the tox+ strain and is the main cause of concern in this disease. The tough leathery membrane that is formed around the back of the throat described earlier is known as pseudomembranous diphtheria. It is within this membrane that the toxin is produced, therefore, with the appearance of the membrane, one can be sure that the strain that infects the patient is the tox+ strain.
The toxin produced by C. diphtheriae kills human cells by hindering protein synthesis in them. This renders the cells dysfunctional and ultimately perish.
It is from this toxin that Ramon from the Institut Pasteur discovered that by adding formalin to the toxin, if forms a nontoxic agent that can be used to induce immunity against it in 1926. This nontoxic agent, the diphtheria toxoid, when injected into the body elicits antibodies against the diphtheria toxins which prevent most manifestations of the disease. Due to the fact that this vaccine confers immunity only to the toxins of diphtheria, it does not make a person immune to the bacteria, C. diphtheriae, itself.
A vaccinated individual can still be infected by C. diphtheriae, but the disease would mostly take a milder course as the severe form of the disease, which is caused by the presence of diphtheria toxin is prevented.
How common is diphtheria?
Before the development of the vaccine, the annual incidence of diphtheria in the United States was as high as 191 cases per 100, 000 population in 1921. Since mass vaccination against diphtheria was introduced, the annual figure has fallen to below 5 cases per 100, 000 in the US.
In Malaysia, diphtheria cases are on the rise with 13 confirmed cases and 5 deaths in mid-2016 while in August 2017, there were 18 confirmed cases and 3 deaths. Just a few days ago, we have another victim of diphtheria in the Sarawak. This sudden surge may be attributed to the anti-vaccination trend.
In the 1930s to 1940s, diphtheria was almost completely eradicated in many developed countries after the introduction of mandatory childhood vaccination. With this, the tox+ strain lost its selective advantage against the nontoxic strains. As the general population becomes immune to the toxins of diphtheria, less cases of diphtheria are showing signs of the leathery membrane surfaces and hence there is less transmission to nonimmune individuals. Due to the way the vaccine works, by only making individuals immune to the toxins of diphtheria, there is no reduction in the prevalence of the carriers of non-toxigenic C. diphtheriae. Furthermore, vaccinated individuals, although immune to the toxins, can still be active carriers of C. diphtheriae. In areas where diphtheria is endemic, up to 5% of healthy individuals may carry C. diphtheriae unknowingly.
The transmission of diphtheria
Diphtheria is spread through close contact with materials containing the pathogen such as mucus secretions from the respiratory system or secretions from skin ulcers. It is believed that humans are the only known reservoir for C. diphtheriae and is more common in the colder months.
Diagnosis and treatment
Doctors diagnose diphtheria based on signs of the disease in the patient as described above. Once diagnosed through the signs of the disease, they may take a sample (through a cotton swab) of the membrane or secretions and send it for laboratory analysis to further confirm the diagnosis. However, once the diagnosis is made (though the signs of the disease), they may administer diphtheria antitoxin and antibiotics without waiting for the laboratory analysis results.
Read our follow-up article on the Diphtheria, Tetanus and Pertussis Vaccination Myths and Truths.
- Abzug, M., Deterding, R., Hay, W. and Levin, M. (2016). Current diagnosis & treatment pediatrics. New York, N.Y.: McGraw-Hill Education LLC.
- Barroso, L. and Pegram, S. (2018). Clinical manifestations, diagnosis, and treatment of diphtheria. [online] Uptodate.com. Available at: https://www.uptodate.com/contents/clinical-manifestations-diagnosis-and-treatment-of-diphtheria [Accessed 19 Mar. 2018].
- Barroso, L. and Pegram, S. (2018). Epidemiology and pathophysiology of diphtheria. [online] Uptodate.com. Available at: https://www.uptodate.com/contents/epidemiology-and-pathophysiology-of-diphtheria [Accessed 19 Mar. 2018].
- gov. (2018). Childhood Vaccines and Febrile Seizures Concerns | Vaccine Safety | CDC. [online] Available at: https://www.cdc.gov/vaccinesafety/concerns/febrile-seizures.html [Accessed 19 Mar. 2018].
- gov. (2018). Multiple Vaccines and the Immune System | Concerns | Vaccine Safety | CDC. [online] Available at: https://www.cdc.gov/vaccinesafety/concerns/multiple-vaccines-immunity.html [Accessed 19 Mar. 2018].
- Dosing Health. (2018). [Infographic] Immunisation Schedule for National Immunisation Program, Ministry of Health Malaysia. [online] Available at: https://dosinghealth.com/2017/10/07/infographic-immunisation-schedule-for-national-immunisation-program-moh-malaysia/ [Accessed 19 Mar. 2018].
- Kasper, D., Fauci, A., Hauser, S., Longo, D., Jameson, J., Loscalzo, J. and Harrison, T. (2015). Harrison’s principles of internal medicine. New York: McGraw Hill Education.
- Lau, H. (2018). How safe are vaccines and their contents?. [online] Dosing Health. Available at: https://dosinghealth.com/2017/11/13/safe-vaccines-contents/ [Accessed 19 Mar. 2018].
- Tiong, J. (2018). Why do you care if I don’t vaccinate my child? Stop being nosy!. [online] Dosing Health. Available at: https://dosinghealth.com/2017/10/27/care-dont-vaccinate-child-stop-nosy/ [Accessed 19 Mar. 2018].
- Tiong, J. (2018). Will vaccines make my child autistic?. [online] Dosing Health. Available at: https://dosinghealth.com/2017/08/04/will-vaccines-make-my-child-autistic/ [Accessed 19 Mar. 2018].
- com. (2018). Patient education: Febrile seizures (The Basics). [online] Available at: https://www.uptodate.com/contents/febrile-seizures-the-basics [Accessed 19 Mar. 2018].
- com. (2018). Patient education: Tdap vaccine (The Basics). [online] Available at: https://www.uptodate.com/contents/tdap-vaccine-the-basics [Accessed 19 Mar. 2018].
- NST Online. (2018). Five diphtheria deaths in Malaysia so far. [online] Available at: https://www.nst.com.my/news/2016/06/155591/five-diphtheria-deaths-malaysia-so-far [Accessed 19 Mar. 2018].
- NST Online. (2018). 18 cases of Diphtheria, three deaths so far in Malaysia this year. [online] Available at: https://www.nst.com.my/news/nation/2017/08/265448/18-cases-diphtheria-three-deaths-so-far-malaysia-year [Accessed 19 Mar. 2018].
- com.my. (2018). Toddler dies of diphtheria after parents refused to vaccinate her against disease – Nation | The Star Online. [online] Available at: https://www.thestar.com.my/news/nation/2018/03/17/fear-and-superstition-prove-deadly-toddler-dies-of-diphtheria-after-parents-refused-to-vaccinate-her/ [Accessed 19 Mar. 2018].
- Image credit: https://www.historyofvaccines.org/content/cutaneous-diphtheria