Diphtheria
Diphtheria
Disease History, Characteristics, and Transmission
Introduction
Diphtheria is an acute infectious illness affecting the throat and tonsils. In severe cases, suffocation may result and there may be complications involving the heart and nervous system. Diphtheria is caused by the bacterium Corynebacterium diphtheriae. In the past, diphtheria was a major killer, with children being especially susceptible. The introduction of mass immunization has made the disease rare in the industrialized world. However, immunity to diphtheria is lost over time. Those living in stable countries with high standards of public hygiene are unlikely to be at risk. The same cannot be said when health and political systems break down, or when childhood immunization is not universal. The re-emergence of diphtheria in the former Soviet Union in the 1990s resulted from a combination of these factors. The reintroduction of mass immunization eventually brought this epidemic under control. However, diphtheria remains a threat in countries where overcrowding, unsanitary conditions, and low levels of immunization are a fact of everyday life.
Disease History, Characteristics, and Transmission
C. diphtheriae is a Gram-positive bacillus. Bacilli are a group of bacteria characterized by their rodlike shape; Gram-positive refers to the way certain bacteria absorb stains applied for microscopic study of the organism. Most strains of C. diphtheriae produce a potent toxin that is responsible for the complications of diphtheria. There are two forms of the disease—respiratory diphtheria, which is the more common, and cutaneous diphtheria. The symptoms of respiratory diphtheria include painful tonsillitis and/or pharyngitis—inflammation of tonsils and/or throat. The voice may be hoarse and fever is often present. What distinguishes diphtheria from other throat infections is the presence of a pseudomembrane, a thick, bluish white or gray covering on the throat or tonsils that may develop greenish black patches. The pseudomembrane develops when the C. diphtheriae toxin kills cells within the mucous membrane lining the throat and tonsils. The membrane may spread downwards and can interfere with breathing, causing suffocation. At the same time, the neck tends to swell, giving the patient a characteristic “bull neck” appearance.
In 10 to 20% of cases, the toxin spreads to the heart and the peripheral nervous system. It can cause myocarditis, an inflammation of the heart muscle and heart valves, which may lead to heart failure in later life. In the nervous system, diphtheria toxin can cause paralysis, which could lead to respiratory failure. Even with prompt treatment, the death rate of respiratory diphtheria is 5 to 10%. Diphtheria tends to be more severe in children under five and in adults over 40.
Cutaneous diphtheria occurs when the bacterium infects bites or rashes and is more common in tropical regions. Again, a pseudomembrane forms at the site of the infection, and ulcers usually develop on the skin. However, the complications associated with respiratory diphtheria are far less common in the cutaneous form of the disease.
Diphtheria usually is transmitted by contact with droplets from the upper respiratory tract that are propelled into the air by the coughs and sneezes of infected individuals. It is highly infectious. People who are untreated remain infectious for two to three weeks. C. diphtheriae can also be spread by contaminated objects or food.
Scope and Distribution
Diphtheria was a major child killer in the eighteenth and nineteenth centuries. Now, thanks to mass immunization, it is rare in the United States and Western Europe. Before immunization there were 100 to 200 cases of diphtheria per 100,000 of the U.S. population; now there are only 0.001 cases per 100,000 of the population. In 1942, the year when immunization was introduced in the United Kingdom, there were 60,000 cases of diphtheria a year, of which around 4,000 proved fatal. Between 1937 and 1938 diphtheria was second only to pneumonia as a cause of death in childhood. With levels of immunization in the U.K. now reaching 94%, presently there are only very occasional cases. Several European countries have not seen a single case of diphtheria for many years.
Before the discovery of the vaccine, children were most at risk from diphtheria. Now all ages seem to be at risk and, although the risk is higher among those who have not been vaccinated, cases occur among those who have had the vaccine too, because immunity appears to decline over time. In the United States, Canada, and many countries in Western Europe, childhood vaccination beginning in the 1930s and 1940s led to a rapid reduction in cases. Where diphtheria does occur, it tends to be in an incompletely vaccinated, or unvaccinated person, of low socioeconomic status.
Diphtheria is found in temperate climates. As with any highly infectious disease, diphtheria is more commonly found in areas with poor sanitation and over-crowding. The disease is endemic in the former Soviet Union, the Indian subcontinent, Southeast Asia, and Latin America. In temperate regions, diphtheria is more common in the colder months of the year. In 2000, the World Health Organization (WHO) reported 30,000 cases of diphtheria worldwide, of which 3,000 were fatal.
Treatment and Prevention
Since diphtheria is so rare in developed countries, it may be difficult for physicians to recognize when it does occur. However, the presence of the pseudomembrane, together with heart rhythm abnormalities linked to the toxin, should alert a physician to the possibility of diphtheria. Ideally, the presence of C. diphtheriae should be confirmed in the laboratory (it requires special methods for its identification), but this should not delay the start of treatment. Diphtheria is treated with antitoxin, which neutralizes the toxin before it can do too much damage, and antibiotics. The antitoxin, which was discovered in 1888, has saved the lives of many children, since it causes the pseudo membrane to recede dramatically. Diphtheria antitoxin is prepared from the serum of horses that have been immunized against the disease, and it needs to be given within four days of the onset of symptoms. Erythromycin and penicillin are the two most commonly prescribed antibiotics for diphtheria. Hospitalization and isolation are essential when dealing with diphtheria—the latter to prevent others from being exposed to the infection. If breathing is obstructed by the pseudomembrane, a tracheostomy may be needed. This procedure involves cutting an artificial opening in the trachea, or windpipe, and inserting a tube so that the patient can breathe.
Immunization has been shown to be the best way of preventing the spread of diphtheria. A toxoid is an inactivated version of a bacterial toxin. It has been found to give an excellent immune response in diseases where bacterial toxins play an important role, such as diphtheria and tetanus.
Most countries use diphtheria toxoid in combination with tetanus toxoid and pertussis (whooping cough) vaccine (DTP vaccine) to protect children. DTP is given by injection. WHO recommends children receive three separate doses of DTP. One vaccination schedule administers the three primary doses as the age of six, ten, and 14 weeks, with a booster between 18 months and six years of age. However, there is considerable variation between countries as to the vaccine and vaccination schedule used. For example, in the United States the Centers for Disease Control (CDC) recommends the use of DTaP, rather than DTP, as the safer version offering lessened side effects. Some countries have been using a combination vaccine that includes vaccines against diphtheria, tetanus, pertussis, hepatitis B, and pneumonia.
Parents often worry that a vaccine may harm their child, and this is one reason that vaccine coverage is never universal (some parents always opt out). DTP can cause fever shortly after the child receives an injection and some complain of pain, redness, and swelling at the injection site. More severe reactions, such as convulsions or shock, occur occasionally. However, for the vast majority of children, the benefits of DTP far outweigh the risk. DTP is not usually given after six years of age. Older children and adults are offered a tetanusdiphtheria toxoid vaccine (Td) and, in 2005, a combination tetanus, diphtheria, and pertussis vaccine (Tdap) was approved for adolescents and adults in the United States. Booster injections may be needed every ten years to maintain immunity, where this might be important (for instance, if traveling to an area where diphtheria is endemic). There is evidence that immunity to diphtheria tends to wane over time.
Impacts and Issues
Like cholera, diphtheria has a long history. The disease was first described by the Greek physician Hippocrates (ca. 460–357 BC), and it was also mentioned in ancient Syrian and Egyptian texts. In seventeenth century Spain, epidemic diphtheria was known as “El Garatillo” or “The Strangler.” There were also significant epidemics in England in the 1730s and in Western Europe in the second half of the nineteenth century. Diphtheria was known in America from the eighteenth century and reached epidemic proportions in 1735, often killing whole families. At the start of the twentieth century, diphtheria was still one of the leading causes of death among infants and children. When the first data on the disease were gathered, in the 1920s, there were around 150,000 cases and 13,000 deaths each year.
Today, most physicians in the United States will never see a case of diphtheria. Though diphtheria, like tuberculosis, is highly infectious, it is likely to be endemic in less developed countries where there is poverty, overcrowding, malnutrition, and poor sanitation. Mass immunization is known to be an essential tool in the prevention of diphtheria. However, less developed countries tend not to have the access to vaccine supplies or the health infrastructure to achieve WHO's goal of a 95% immunization rate.
Moreover, diphtheria still has the ability to spread and cause significant illness and death, even in a modern society where it had previously been all but eradicated. This was demonstrated clearly by the outbreaks and epidemics of the disease that occurred in the former Soviet Union in the 1990s. During the first half of the twentieth century, diphtheria rates were high in the Soviet Union; inthe1950stherewerearound750,000casesinRussia alone, but, after this time, the Communist regime of the former Soviet Union developed an excellent record on immunization. By 1976, rates of the disease were practically zero and eradication was thought to be within reach. However, in 1977, the disease began to make a comeback, with rates increasing in all age groups rather than just among children. Rates peaked in 1984 and then began to decline thereafter, although they never returned to the low of 1976. Researchers for the Centers for Disease Control and Prevention (CDC) argue that the military may have contributed to the spread of diphtheria in the 1980s. Military service was universal and led to the housing of recruits, many of whom had not been immunized, in overcrowded conditions. Adult immunity, among those immunized many years earlier, appeared to be declining, accounting for adult cases of diphtheria. The immunization schedule among children was also less intense than previously, in part due to a campaign against immunization that found favor in a population increasingly distrustful of its government.
WORDS TO KNOW
ANTIBODY: Antibodies, or Y-shaped immunoglobulins, are proteins found in the blood that help to fight against foreign substances called antigens. Antigens, which are usually proteins or polysaccharides, stimulate the immune system to produce antibodies. The antibodies inactivate the antigen and help to remove it from the body. While antigens can be the source of infections from pathogenic bacteria and viruses, organic molecules detrimental to the body from internal or environmental sources also act as antigens. Genetic engineering and the use of various mutational mechanisms allow the construction of a vast array of anti-bodies (each with a unique genetic sequence).
ANTITOXIN: An antidote to a toxin that neutralizes its poisonous effects.
CUTANEOUS: Pertaining to the skin.
RE-EMERGENCE: Reemergence is when something that has been absent appears again.
The breakup of the Soviet Union in the late 1980s and early 1990s was the final event that set the stage for a new wave of diphtheria in the former Soviet Union. In 1990, diphtheria returned to Russia in force. There were over 1,000 cases reported from St Petersburg, Kaliningrad, Orlovskaya, and Moscow. The epidemic grew over the next few years and deaths occurred because of failures in a health care system facing economic crisis. Epidemic diphtheria became established in urban Russia, Ukraine, and Belarus. In 1993, 19,462 cases were reported of which 15,211 were in Russia, an increase of nearly 300% from the previous year. Many of these cases were, again, among adults. This was the first largescale diphtheria epidemic in a developed country for over three decades. At the peak of the epidemic, in 1995, there were over 50,000 cases reported in the region, compared to only 24 cases in the rest of Europe.
In 1994 and 1995, WHO, the United Nations Children's Fund, other agencies, and governments in the affected countries undertook massive efforts to vaccinate both children and adults. These efforts soon began to bring the epidemic under control, resulting in a 60% drop in cases by 1996. According to WHO data, gathered in 2000, incidence rates of diphtheria in Armenia, Estonia, Lithuania, and Uzbekistan were 0.5 to 1 per 100,000 of the population. In Russia and Tajikistan, rates were as high as 27 to 32 per 100,000 of the population. Fatality rates were 2 to 3% in Russia and Ukraine and 6 to 10 %in Armenia, Kazakhstan, Moldova, and Latvia. In Azerbaijan, Georgia, and Turkmenistan the death rate from diphtheria was 17 to 23%. By 2004, the number of cases reported to the WHO European region, which includes the former Soviet Union, was down to 176.
The CDC says that the outbreak of diphtheria in the former Soviet Union shows that adults can become vulnerable to childhood diseases again when immunization does not confer lifelong immunity. This condition applies in any other country where there is mass immunization against diphtheria. However, there have been no similar epidemics anywhere else in the Western world. It was probably the combination of factors in the Soviet Union at the time that set the scene for the epidemic. Added to the decline in both childhood and adult immunity was the political breakup of the Soviet Union and the formation of several new states. Economic pressures led to mass migrations of people from rural areas into the cities in Russia; many failed to find work and ended up sleeping in primitive or crowded conditions. Many diphtheria cases occurred in this group. Refugees fleeing from fighting in Georgia, Armenia, Azerbaijan, and Tajikistan were also at risk. People were on the move in the region on a scale never seen before. This powerful factor—not seen in neighboring nations—probably encouraged the spread of the disease. The success of mass vaccination in controlling the epidemic in the former Soviet Union reconfirms the importance of this primary tool for fighting diphtheria.
A WHO report of a diphtheria outbreak in Afghanistan illustrates the factors that increase the risk of the disease. Between June and August 2003, there were 50 cases of diphtheria, including three deaths, in a resettlement camp for internally displaced people in Kandahar. About 75% of the patients were ages five to 14. A mass immunization campaign for the 40,000 residents of the camp was launched in August 2003. The Ministry of Health was assisted by WHO and several other organizations, such as Médecins sans Frontières-Holland and the Red Cross, in provision of drugs, antitoxin, and vaccine supplies to help bring the outbreak under control.
Lessons learned from Russia and Afghanistan can be applied to other diseases and other countries. Improving living conditions, mass immunization, and establishing a health infrastructure within a stable political system are the ways in which highly infectious diseases can best be controlled.
Primary Source Connection
Advances in the treatment of diphtheria and many other infectious diseases (along with advances in the treatment of illnesses such as diabetes) have significantly changed the expectations of parents and communities in countries with advanced health care and public health capacity.
Russell Baker is a Pulitzer Prize-winning writer. The excerpt below is republished from his autobiography and allows readers some insights into the resignation and thinking of a time, less than a century ago in America, when disease “mostly with prayer, and early death was commonplace.”
IN CONTEXT: REAL-WORLD RISKS
The Coordinating Center for Infectious Diseases/Division of Bacterial and Mycotic Diseases states that diphtheria “circulation appears to continue in some settings even in populations with 80% childhood immunization rates. An asymptomatic carrier state exists even among immune individuals.”
Because immunity lessens over time “decennial booster doses are required to maintain protective antibody levels. Large populations of adults are susceptible to diphtheria in developed countries—[and] appear to be increasing in developing countries as well.”
SOURCE: Coordinating Center for Infectious Diseases/Division of Bacterial and Mycotic Diseases, Centers for Disease Control and Prevention (CDC)
See AlsoCholera; Médecins Sans Frontières (Doctors Without Borders).
BIBLIOGRAPHY
Books
Garrett, Laurie. The Coming Plague: Newly Emerging Diseases in a World out of Balance. London: Virago Press, 1995.
Wilson, Walter R., and Merle A. Sande. Current Diagnosis & Treatment in Infectious Diseases. New York: McGraw Hill, 2001.
Periodicals
Vitek, C.R., and M. Wharton. “Diphtheria in the Former Soviet Union: Reemergence of a Pandemic Disease.” Emerging Infectious Diseases 4 (October-December 1998). This article is available online <http://www.cdc.gov/ncidod/eid/vol4no4/vitek.htm>
Web Sites
Health Protection Agency. “Diphtheria.” February 2, 2006. <http://www.hpa.org.uk/infections/topics_az/diphtheria/gen_info.htm> (accessed February 16, 2007).
Todar's Online Textbook of Bacteriology. “Diphtheria.” <http://textbookofbacteriology.net/diphtheria.html> (accessed February 16, 2007).
World Health Organization. “Diphtheria.” <http://www.who.int/topics/diphtheria/en/> (accessed February 16, 2007).
Susan Aldridge