Monday, February 6, 2017

What is Diphtheria,causes,signs and symptoms

Thanks to routine immunization, diphtheria is a disease of the past in most parts of the world. Since the 1980s only a handful of cases of the bacterial infection have been reported in the US, with just one case since 2004.

In countries where there is a lower uptake of booster vaccines, however, such as in India, there remain thousands of cases each year. In 2014, there were 6,094 cases of diphtheria reported in India, 1,079 in Nepal and 35 in Bangladesh.11

Fast facts on diphtheria
Here are some key points about diphtheria. More detail and supporting information is in the body of this article.
  • Diphtheria is now rare in the US because the disease, caused by bacteria, can be prevented by routine childhood vaccination.
  • Before the development of treatments and vaccines, diphtheria was widespread and mostly affected children under the age of 15.
  • Most cases are caused by Corynebacterium diphtheriae, and the infection is usually spread by contact with people breathing out droplets, but also by skin contact, and rarely via shared objects.
  • Certain strains of the bacterium produce a toxin that causes the serious complications of diphtheria.
  • Some of the symptoms of diphtheria are similar to those of the common cold, but the telltale sign, which the disease was named after, is the formation of a thick gray membrane over the back of the throat.
  • In the unusual cases where infection occurs in the skin, rather than the respiratory system, the disease is usually less serious and produces different symptoms.
  • In all infections that release the toxin, this can lead to complications of nerve damage, heart failureand, in around 5-10% of cases, death.
  • Diagnosis is suspected on the basis of symptoms and the patient's history, and confirmed with identification of the bacteria from swab specimens and laboratory testing of their toxicity.
  • Treatment, which is not always successful, is with antitoxin and antibiotics while the patient is isolated and monitored in intensive care. The best outcomes occur when diagnosis is swift and treatment prompt.
  • Immunization against diphtheria prevents the disease and is incorporated into vaccines for other infectious diseases, administered in children's early years.

What is diphtheria?

Diphtheria is now a rare bacterial infection in the US and most other countries thanks to the success of universal coverage with routine childhood vaccinations. Since the 1980s there have been no more than five cases of the infection in any one year in the US, and just one report of diphtheria in the last two decades.1,2
Diphtheria's historical timeline:3,4
  • 5th century BCE: Hippocrates is first to describe the disease. It can cause the formation of a new layer to mucous membranes - a 'pseudomembrane' - which is where the modern name for the disease, diphtheria, arises; diphthera is the Greek term for leather hide
  • 6th century: First observations of diphtheria epidemics
  • Late 19th century: Bacteria responsible for diphtheria are identified by the German scientists Edwin Klebs and Friedrich Löffler (Klebs observed it in the diphtheritic membranes created by the disease, while Löffler then cultivated the microbe)
  • 1892: Antitoxin treatment, derived from horses, first used in the US
  • 1920s: Development of the toxoid used in vaccines.
In countries that have a lower uptake of booster vaccines, there are still thousands of annual cases of the disease.1
India, for example, achieves around three-quarters coverage of the third and final childhood immunization dose, compared with full coverage in most countries.2 There have been between 3,000 and 8,000 reports of diphtheria in India every year since the decade starting in 2004.1
In people who are not vaccinated against the bacteria that cause diphtheria, infection can cause serious complications such as nerve problems, heart failure, and even death.4
Overall, between 5-10% of people who get infected with diphtheria will die, and this level has remained consistent for the past half century. Some people are more vulnerable than others, with a mortality rate of up to 20% in infected people under 5 or older than 40 years of age.4
The primary effect of the bacterium is to cause an infection of, in most cases, the nose and throat or the skin, although other parts of the body can also be affected.4,5
The following section explores in more depth how the bacteria cause the initial infection and the potentially serious complications of diphtheria.

What causes diphtheria?

Diphtheria is an infectious disease caused by bacterial microorganisms known as Corynebacterium diphtheriae.4 Other Corynebacterium species can be responsible, but this is rare.5
Some strains of this bacterium produce a toxin. Infection with these toxigenic diphtheria bacteria is what leads to the most serious complications of diphtheria. The bacteria are toxigenic because they themselves are infected by a certain type of virus.4,5
baby having vaccination
medicalnewstoday.com
Diphtheria is prevented by early-years vaccination.

Inhibits the production of proteins by cells
The toxin that is released:4
  • Destroys the tissue at the site of the infection
  • Leads to membrane formation - which leads to the telltale sign at the back of the throat
  • Gets taken up into the bloodstream and distributed around the body's tissues
  • Causes myocarditis (inflammation of the heart) and neuritis (nerve damage)
  • Can cause low platelet counts (thrombocytopenia) and produce protein in the urine (proteinuria).
Diphtheria is an infection spread only among humans - people are the only known reservoir for it. It is contagious via direct physical contact with:4-6
  • Droplets breathed out into the air (as an aerosol, in the same way as the spread of flu)
  • Secretions from the nose and throat (again, similar to other upper respiratory infections)
  • Infected skin lesions
  • Intermediary objects such as bedding or clothes (rarely).
The spread from an infected patient to a susceptible new person can be to any mucous membrane, but the toxic infection typically attacks the nasopharynx (the lining of the nose and throat).4,5

Signs and symptoms of diphtheria

Specific signs and symptoms of diphtheria depend on the particular strain of bacteria involved, and the site of the body affected.
One type of diphtheria, more common in the tropics, causes skin ulcers rather than respiratory infection. These atypical cases are usually less serious than the classic cases, first described by Hippocrates, that lead to severe illness and sometimes death.
The classic case of diphtheria is an upper respiratory infection caused by toxin-producing bacteria that leads to the creation of a gray pseudomembrane over the lining of the nose/throat, around the area of the tonsils. This pseudomembrane may also be greenish or blueish, and even black if there has been bleeding. 4,5,7,8
Early features of the infection, occurring prior to the appearance of the nasopharyngeal pseudomembrane, include:4,5,7,8
  • Fever (though not usually a very high temperature), malaise and weakness
  • Enlarged lymph nodes at the front of the neck (popularly referred to 'swollen glands')
  • Swelling of soft tissue in the neck (giving a 'bull neck' appearance)
  • High heart rate (tachycardia, disproportionately high for the level of fever).
Children with a pharyngeal diphtheria infection are more likely to have the following early features:5
  • Nausea and vomiting
  • Chills, headache and fever.
After a person is first infected with the bacteria there is an average incubation period of 5 days before early signs and symptoms appear.
This 'prodromal period' lasts between 12 and 24 hours and, if the bacteria colonizing the nasopharynx are toxic, a pseudomembrane forms over the following 2-3 days, leading to:4-8
  • Sore throat
  • Difficulty swallowing (dysphagia)
  • Possible obstruction that causes difficulty breathing (shortness of breath - dyspnea).
If the membrane extends to the larynx, the symptoms of hoarseness and a barking cough are more likely, as is the danger of complete obstruction of the airway. The membrane may also extend further down the respiratory system towards the lungs.4

Complications of diphtheria

Further illness, and the most severe and potentially life-threatening stage of the disease, results from the absorption of the toxin into the bloodstream, which then goes on to damage other vital tissues, as follows.4,5

Myocarditis - heart damage

Myocarditis is a heart condition, involving inflammation of the heart muscle, in this case caused by the diphtheria toxin. This condition can lead to heart failure, and the greater the degree of bacterial infection, the higher the toxicity to the heart, producing effects that range from abnormalities that are only apparent on a heart monitor, to sudden death.5
The heart problems usually appear 10-14 days after the start of the infection, although problems can take weeks to appear and vary in severity. Heart problems associated with diphtheria include:5
  • Changes visible on an electrocardiograph (ECG) monitor
  • Atrioventricular dissociation (where the chambers of the heart lose their synchronicity, beating independently)
  • Complete heart block (where no electrical pulses travel between the atria and the ventricles)
  • Ventricular arrhythmias (where the beating of the lower chambers, the ventricles, is abnormal)
  • Heart failure (where the heart is unable to maintain sufficient blood pressure and circulation).
The abnormal heart rhythms and heart failure caused by diphtheria are accompanied by a high chance of death.5

Neuritis - nerve damage

Neuritis is a less common effect of diphtheria and is inflammation of nerve tissue that results in damage to cranial and peripheral nerves. This complication of diphtheria occurs in about 5% of patients, usually after a severe respiratory infection with diphtheria. Typically, the condition develops as follows:5
  • In the 3rd week of illness, there can be paralysis of the soft palate
  • After the 5th week, paralysis of eye muscles, limbs, and diaphragm can occur
  • Pneumonia and respiratory failure may occur secondarily to paralysis of the diaphragm.

Less severe disease from infection at other locations

If the bacterial infection is atypical and affects tissues other than the throat and respiratory system, the illness is generally milder. This is because the body absorbs lower amounts of the toxin, especially if the infection affects the skin only.5 Mild diphtheria can also be caused by strains of the bacteria that do not produce the toxin.4
If the skin is the site of the infection, any lesions that occur are usually at the extremities and these lesions normally vary in appearance. The infection can coexist with other infections and skin conditions, and may look no different from eczemapsoriasis, or impetigo. However, diphtheria in the skin can produce ulcers in which there is no skin at the centre and which have clear edges, and sometimes grayish membranes.4,5
Other mucous membranes can become infected by diphtheria - including the conjunctiva at the eyes, women's vulvovaginal tissue, and the external ear canal.4

Three general levels of bacterial toxicity and disease severity

The location of the infection is not the only factor in determining disease severity and effects. There are three key toxigenic bacterial strains responsible for diphtheria, each with a different degree of virulence and toxicity, resulting in one of three levels of disease severity.6
All three bacterial strains produce the same toxin, and disease severity relates to the rate and amount of toxin production. The three strains of Corynebacterium diphtheriae are:6
  • Gravis. This strain grows quickly, creating the most severe disease by growing quickly - it has a 'generation time' in a laboratory dish of 60 minutes
  • Intermedius. This strain takes longer to colonize the throat, with an in vitro generation time of 100 minutes
  • Mitis. This one takes the longest, 180 minutes, and leads to the least severe disease.

Diagnosis and tests for diphtheria

There are definitive tests for diagnosing a case of diphtheria, so if symptoms and history cause a suspicion of the infection, it is relatively straightforward to confirm the diagnosis.
man with painful throat
Classic cases of diphtheria cause sore throat and swollen lymph nodes in the neck, and the formation of a characteristic 'pseudomembrane' over the back of the throat.

Doctors should be suspicious when they see the characteristic membrane, or patients have unexplained pharyngitis, swollen lymph nodes in the neck, and low-grade fever. Hoarseness, paralysis of the palate, or stridor (high-pitched breathing sound) are also clues.
Tissue samples taken from a patient with suspected diphtheria can be used to isolate the bacteria, which are then cultured for identification and tested for toxicity:9
  • Clinical specimens are taken from the nose or nasopharynx, and throat
  • All suspected cases and their close contacts are tested
  • If possible, swabs are also taken from under the pseudomembrane, or removed from the membrane itself.
Once the diphtheria bacterium has been isolated, it is 'biotyped' to elucidate the particular strain, which will point to its toxicity, as outlined above.
Toxigenicity is further tested using the Elek test, which determines whether the organisms produce the diphtheria toxin; if positive, it triggers the diagnosis of diphtheria.
The tests may not be readily available, and so doctors may need to rely on a specialist laboratory.

Treatment of diphtheria

Treatment is most effective when instituted early, which makes a prompt diagnosis important.3,10 The antitoxin that is deployed does not work against the diphtheria toxin once it has bound with the tissues and caused the damage.3
Treatment aimed at countering the bacterial effects has two components:4,5,10
  • Antitoxin - also known as anti-diphtheritic serum - to neutralize the toxin released by the bacteria
  • Antibiotics - erythromycin or penicillin to eradicate the bacteria and halt their spread.
Patients with respiratory diphtheria and symptoms would be treated in an intensive care unit in the hospital, and monitored for respiratory and cardiac complications. Health care staff would take isolation precautions to prevent the spread of the infection via respiratory droplets or physical contact.5
Such treatment conditions are maintained until tests for bacteria repeatedly return negative results in the days following the completion of the course of antibiotics (or until the death of the patient).5

Prevention of diphtheria through vaccination

Vaccines are routinely used to prevent diphtheria infection in almost all countries. The vaccines are derived from purified toxin that has been removed from a strain of the bacterium. The cell-free C. diphtheriae toxin is treated with formaldehyde before being absorbed onto an aluminium salt to help trigger an immune system response that leads to the creation of antibodies to the toxin.4,7
Two strengths of diphtheria toxoid are used in routine diphtheria vaccines:7
  • 'D' - a higher-dosed primary vaccine (containing at least 30IU of toxoid) for children under 10 years of age. This is usually given in three doses - at two, three and four months of age
  • 'd' - a lower-dosed version (with about 2IU of toxoid) for use as a primary vaccine in children over 10 years, and as a booster for reinforcing the usual immunization in babies, about three years after the primary vaccine, normally between 3.5 and 5 years of age.
In the 1940s in the US, diphtheria toxoid was routinely incorporated in the tetanus toxoid and pertussis vaccine.4
Modern vaccination schedules continuing to this day include diphtheria toxoid in the childhood immunization known as DTaP (diphtheria and tetanus toxoids and acellular pertussis vaccine).4
This vaccine is the option of choice recommended by the US Centers for Disease Control and Prevention (and more information is provided by the CDC, including why some children should not get the DTaP vaccine or should wait). The doses are given as follows:4
  1. Age 2 months
  2. Age 4 months and after an interval of 4 weeks
  3. Age 6 months; interval 4 weeks
  4. Age 15-18 months; interval 6 months
  5. If the fourth dose is given before the fourth birthday, this fifth, booster, dose is recommended at 4 through 6 years of age (but is not needed if the fourth primary dose was given on or after the fourth birthday).
Booster doses of the adult form of the vaccine, tetanus-diphtheria toxoids vaccine (Td), may be needed every ten years to maintain immunity.

credit/source:
http://www.medicalnewstoday.com/articles/159534.php
All photos are credit to the original writer's references and sources.

Additional article and for more information click the link:

https://www.cdc.gov/diphtheria/about/