What is Corynebacterium Diphtheriae (Diptheria)?
“Diphtheria” is a word that comes from the Greek term meaning “hide or leather”. This name is due to the leathery covering, known as a “pseudomembrane”, that the disease-causing germs create at the site of infection. Diphtheria is a dangerous disease that primarily affects the upper respiratory tract and can be prevented with a vaccine. The disease can manifest in several ways, including: as an asymptomatic carrier (where people carry the disease without showing symptoms), as a skin infection, or as a throat infection with symptoms like sore throat, fever, feeling unwell, and swollen neck glands. A distinctive sign of the disease is the formation of the pseudomembrane at the infection site, which usually occurs on the pillars of the tonsils and the back wall of the throat.
Before we had a universal vaccine in the 1940s and 1950s, diphtheria was a leading cause of illness and death in children and young adults. The introduction of widespread vaccination reduced the occurrence of the disease dramatically, to about 5000 cases globally each year. Nonetheless, diphtheria outbreaks still happen, often associated with conditions like poverty, insufficient income, lack of public health access, war and displacement, and poor monitoring of vaccination schedules. This discussion aims to offer a refresher on the diphtheria-causing bacteria, Corynebacterium diphtheria.
What Causes Corynebacterium Diphtheriae (Diptheria)?
Corynebacterium diphtheria is a type of bacteria that can live with or without oxygen, and is marked by its distinct stick-like shape. It is a specific kind that does not move, make spores, or have a protective shell known as a capsule, but it does produce toxins which can cause disease. There are four versions of this bacteria: gravis, mitis, intermedius, and belfanti. Each type causes a different severity of the disease, with C. mitis causing a milder form, C. intermedius causing a middle form, and C. gravis causing a more severe form.
Bad living conditions, lower socioeconomic status, a weakened immune system, and not having complete immunization can all contribute to a higher risk of getting and spreading the infection caused by this bacteria.
Risk Factors and Frequency for Corynebacterium Diphtheriae (Diptheria)
Universal immunization programs have greatly reduced diphtheria cases, with a 70% decrease noted by 1980. However, there have still been various outbreaks around the world. Notably, some states in the former Soviet Union experienced over 157,000 cases and around 5,000 deaths. Additionally, from 2000-2009, Latvia reported the highest incidence of diphtheria in the European region, around 23.8 cases per million people every year. Interestingly, about 74% of the patients, including 93% of infants who died, had not been vaccinated, underscoring the importance of universal vaccination.
Other countries also reported diphtheria outbreaks, including Nigeria in 2011 and India from 2010 to 2016. From 2015 to 2018, Haiti, Venezuela, and Yemen experienced outbreaks due to low income, limited access to healthcare, and ineffective vaccination and surveillance. Outbreaks occurred in 2017 under similar conditions in refugee resettlement centers in Bangladesh and Indonesia. The World Health Organization recorded 16,611 reported cases in 2018. However, the actual disease burden is likely much higher due to the large number of unreported cases, especially in Asia, Africa, and Eastern Mediterranean countries.
Active vaccination against the toxic strain of C. diphtheria successfully controlled the disease to some extent. But the non-toxic strain of C. diphtheria remains a problem and is becoming more common in developed countries. By the late 1990s, severe infections from non-toxic strains were reported in several European countries and Canada and Brazil. The most significant increase in cases was in England and Wales, where the number of non-toxic strain cases rose from 1 to 294 in the 2000s and continues to rise.
Signs and Symptoms of Corynebacterium Diphtheriae (Diptheria)
Diphtheria is an infection that manifests itself in a variety of ways, both locally (at the site of infection) and systemically (impacting the entire body). Here are some of the common symptoms and complications:
- Producing gray or white-colored necrotic (dead tissue) membranes at the infection site. These are usually found in the tonsils or the back of the throat. The amount of these membranes can give us an idea of how serious the condition is, as extensive membrane production can lead to breathing problems and, in extreme cases, death. If these materials are inhaled into the lungs, it can lead to pneumonia,
- A sore throat and swollen neck lymph nodes, creating a “bull’s neck” appearance,
- Whole-body symptoms such as fever, general feeling of being unwell, shortness of breath, and cough, along with potential heart and nerve complications due to the toxins released by the bacteria into the bloodstream,
- Heart issues such as inflammation of the heart muscle (myocarditis), heart blockages, and severe heart failure,
- Nerve damage causing weakness to full paralysis, similar to Guillain-Barre syndrome,
- Non-healing ulcers on the skin, typically the hands, legs, and feet, often coexisting with Staphylococcus and Streptococcal infections,
- Some non-toxin producing strains of the bacteria can still cause infections such as throat inflammation, blood poisoning (sepsis), heart valve diseases (endocarditis), and bone infections (osteomyelitis).
It is important to identify and treat diphtheria effectively to prevent these complications.
Testing for Corynebacterium Diphtheriae (Diptheria)
If you have symptoms like fever, sore throat, fatigue, swollen glands in your neck, or notice a grayish/whitish/blackish colored layer on the back part of your throat, your doctor may suspect that you have diphtheria. This requires a quick start of treatment, which includes immediate administration of an antidote. The diagnosis of diphtheria is confirmed by culturing a bacteria of the Corynebacterium species and by running toxicity tests.
In some cases, when bacterial cultures don’t show positive results, perhaps due to recent antibiotic therapy, having a known exposure to diphtheria, evidence of low antibody levels in blood tests, and a positive PCR test can still support the diagnosis. The cultured bacteria, when grown in Loffler’s medium and stained with Albert stain, presents a specific color pattern. When grown on a different medium known as tellurite medium, the bacteria appear dark grey or black because it reduces tellurite to tellurium.
An Elek test, which is a technique that identifies toxin-producing Corynebacterium species, can also confirm the diagnosis. The process involves placing bacteria and a paper strip coated in antibodies into an agar medium. After 24 to 48 hours, a clear line appearing where the toxins meet the antibodies confirms the diagnosis. If the disease is suspected, more recent methods such as matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF) can identify specific bacteria in about 30 minutes.
Other diagnostic tests include echocardiography (an ultrasound of the heart), electrocardiography (ECG, which records the electrical activity of the heart), and CT scans, which can identify complications in the heart or an increase in the thickness of the pericardium (the sac that surrounds the heart). X-rays can also show non-specific findings that can be related to diphtheria, such as changes in the lungs or heart size.
In the context of diphtheria, increases in certain biomarkers like total white blood cell count and levels of serum glutamic oxalo-acetic transaminase (SGOT) represent a more severe case of the disease. Similarly, increased levels of CPK MB and cardiac troponin can reflect the activity level of the disease.
Treatment Options for Corynebacterium Diphtheriae (Diptheria)
When treating diphtheria, the main strategies include promptly giving an antitoxin and starting antibiotics. Studies show that this approach is highly effective, being successful in nearly all cases. It’s also very important to isolate the patient to prevent the disease from spreading to other people.
The diphtheria antitoxin is usually derived from horses that have been immunized against the diphtheria toxin. This antitoxin can neutralize the toxin that is still circulating in the body but it’s not effective against toxin already bound to cells. That’s why it’s crucial to give the antitoxin as soon as diphtheria is suspected, even before laboratory tests confirm the diagnosis.
The role of antibiotics is to eliminate the bacteria causing the disease. The most common ones used are penicillin and erythromycin. Normally, they are taken for at least two weeks. After the antibiotic treatment is completed, tests are taken to make sure the bacteria are gone. If they are still present, another 10-day course of antibiotics is given. However, there are concerns about diphtheria bacteria becoming resistant to antibiotics, but this has so far been rare.
Vaccination is a key prevention measure against diphtheria. The vaccination series starts in infancy and is usually completed by the time the child is around a year old. But because the vaccine’s protection decreases over time, adults should receive a booster dose every ten years. Anyone traveling to a region where diphtheria is common should also get a toxoid treatment as an extra layer of protection.
What else can Corynebacterium Diphtheriae (Diptheria) be?
Corynebacterium diphtheriae, the bacterial cause of diphtheria, can present with symptoms that closely resemble other diseases. Here are a few of the medical conditions that it can be mistaken for:
- A viral throat infection
- A bacterial throat infection caused by Streptococcus bacteria
- Acute epiglottitis, which is a swelling of the flap at the base of the tongue
- Mononucleosis, commonly known as ‘mono’ or ‘kissing disease’
- Oral yeast infection, also known as oral thrush
- A heart infection, known as infective endocarditis
- Angioedema, which is a type of swelling beneath the skin
- Epiglottitis, another type of inflammation of the epiglottis
- Retropharyngeal abscess, an accumulation of pus at the back of the pharynx
These conditions all share similar symptoms with diphtheria and it’s vital for medical professionals to make the right diagnosis for effective treatment.
What to expect with Corynebacterium Diphtheriae (Diptheria)
The death rate from diphtheria has not changed much over the past 100 years, staying steady around 10%. The main reason why patients with diphtheria die is due to heart-related problems, which 10-30% of diphtheria patients develop. Unfortunately, for those affected by these heart complications, the likelihood of death is around 50%.
There are a number of factors that can affect the outcome of the disease. For example, whether the patient has been vaccinated, how long they’ve had symptoms, and when they were diagnosed can all influence how severe the disease becomes. Another thing that doctors look at is how much of a certain type of dangerous tissue buildup, known as a pseudomembrane, has formed. Severe swelling of soft tissue, which can cause a condition known as “bull neck”, is typically a sign of a worse outcome.
Laboratory tests, such as a rising SGOT and a high white blood cell count, are also associated with worse outcomes. One study from 2004, which looked at 154 Vietnamese children with diphtheria, found that an extensive pseudomembrane and bull neck appearance are both strong signs that the child may develop serious heart problems due to diphtheria and therefore have a worse prognosis. The study also found that evidence of heart inflammation on admission to the hospital, combined with an extensive pseudomembrane, were the best predictors of a fatal outcome. An increased level of AST, a type of enzyme, was the best predictor for developing heart problems due to diphtheria.
Possible Complications When Diagnosed with Corynebacterium Diphtheriae (Diptheria)
If diphtheria, a serious bacterial infection, is not promptly identified and treated, it can spread and produce a harmful toxin. This diphtheria toxin can enter the bloodstream and reach the heart, brain, kidneys and other organs, leading to a range of complications.
If the toxin reaches the heart, it can cause problems like inflammation of the heart muscle, covering of the heart, or inner lining of the heart. It can also disrupt the heart’s electrical system causing a complete heart block, and in severe cases can even lead to heart failure.
The spread of diphtheria can also cause neurological complications due to damage to the protective covering of the nerves, a condition known as demyelination. This could lead to mild weakness or even total paralysis. There’s even a chance the infection could cause symptoms that resemble Guillain-Barre syndrome – a disorder where the body’s immune system attacks the nerves.
Diphtheria toxin can also interfere with the production of certain essential proteins leading to a condition known as diphtheritic polyneuropathy. This condition starts with weakness in the upper part of the throat but can gradually advance to other parts of the body ultimately causing breathing difficulties and, in severe cases, death. This condition distinguishes itself from Guillain-Barre syndrome through symptoms like bulbar palsy, involvement of other organs such as the heart, and a slower onset of neuropathy, or damage to the nerves, taking more than four weeks. The toxin can also cause other specific organ complications like inflammation of the kidneys.
Preventing Corynebacterium Diphtheriae (Diptheria)
Factors such as societal and economic conditions, low-income status, joblessness, cultural and religious beliefs, misconceptions about vaccines, the level of education of mothers, preterm birth and parental inattentiveness can influence whether an individual gets immunized. This could, in turn, increase their likelihood of becoming infected with a harmful strain of the diphtheria bacteria. Certain health concerns, like tooth decay, heart conditions, and diabetes, can enhance the risk of being infected with a less harmful strain of the bacteria. Additionally, IV drug or alcohol misuse and being homeless are key risk factors for getting the disease.
Boosting public health actions to ensure that toddlers, adults, and travelers to regions where the disease is common are properly immunized is a crucial step in controlling disease outbreaks. It’s key to have a robust strategy for spotting outbreaks among vulnerable populations. It’s also essential to educate patients about vaccinations through counselling, mass media, and other methods, to change misconceptions and enhance compliance.