Diphtheria and Pertussis in adults: Are we witnessing a shift in their epidemiology?

Introduction

Since there is vaccination coverage against vaccinepreventable diseases that include pertussis and diphtheria in the childhood, the incidence of these diseases has decreased dramatically in the country. However, it has been observed that some countries including developed countries have witnessed reemergence of whooping cough and diphtheria due to waning immunity among adolescents and adults. The other added factors may be decreased immunization coverage amongst infants and children, and movement of people from one place to another thus losing an opportunity to immunize the children. India is also witnessing the changing epidemiology.

Recently, from 30th August 2019 to 4th September 2019, 38 cases were admitted to Gulbarga Institute of Medical Sciences’ Hospital, Kalaburagi on the grounds of clinical diagnosis and laboratory results. Of them 29 were female medicos staying in the Girls’ hostel of the institute. 13 (45%) cases were positive for culture of Corynebacterium diphtheriae. The number of diphtheria cases reported in Karnataka State during 2018 was 29 cases, and during the first 9 months of 2019 the number reported was 305. A high incidence of diphtheria has been reported from Kerala (519) also. Similarly, the reported incidence of pertussis in Karnataka was only 2 cases during 2018 which rose to 34 during the first 9 months of 2019.

Pertussis

Pertussis (Whooping cough) is a highly contagious disease caused by Bordetella pertussis. The bacteriologist, Jules Bordet identified the organism as the cause of whooping cough in 1906. The organism was isolated in pure culture.  Bordet is also known for the discovery of the principles of complement fixation test. It depends on the fact that foreign organic substances (bacteria) stimulate the formation in blood of compounds (antibodies) designed to fight and destroy the invading organism. Along with another bacteriologist, Octave Gengou, he devised tests for the detection of these antibodies in the blood serum.

Causative agent

Bordetella pertussis is a gram negative, aerobic, non-motile, cocco-bacillus. Humans are the only hosts and there is no zoonotic reservoir and the bacterium spreads by airborne droplets and its incubation period is seven to 21 days. Bacteria shed in discharges from the nose and throat and spread to others through droplets following coughing and sneezing. An infected person is contagious from the time of onset of symptoms to a period of 3 weeks. Treatment with appropriate antibiotic shortens the contagious period for about 5 days.

Clinical features

Natural history of whooping cough passes through three well-recognized stages referred to as catarrhal, paroxysmal and convalescent phases. During the initial catarrhal phase, there is runny nose, sneezing, mild fever and an irritating cough which gradually progress into a paroxysmal phase with repeated bouts of coughing followed by a high-pitched ‘whoop’ while inhaling air after cough. A ‘whoop’ is particularly evident in young children. There may be vomiting after coughing. The symptoms last for a month or two and cough begins to recede during convalescent phase.

Treatment

Antibiotics such as macrolides when given early in the course of the illness can decrease the infectious period. However, it may not have much effect either on duration or severity of disease. The patient becomes less infectious to others.

Pertussis in adults

In developed countries nearly half of all reported cases of pertussis occur among adults and adolescents. The condition in adults does not produce the classical symptoms and the cough is prolonged and lingering. Thus many adult pertussis cases are under-reported with many adult cases going unrecognized and frequently diagnosed as upper respiratory tract infection or bronchitis. The spasms of cough can last for weeks or months. As no boosters are given for pertussis beyond age of 6 years, virtually all adolescent and adults are susceptible to the infection.¹

There is a shift in the epidemiology of pertussis with more number of cases being reported in older age groups, which is due to waning immunity to Bordetella pertussis a number of years after immunization.² Surveillance studies from the developed world especially US have shown a gradual increase in adolescent and adult pertussis cases over the past decade. A real increase in pertussis cases is due to loss of vaccine-induced/ natural immunity further reduced by lack of natural boosting. There is no data on incidence of adolescent and adult pertussis in India but it is perceived to be significant especially in those states where childhood immunization coverage is good and reduced natural circulation of pertussis leading to infrequent adolescent boosting.

There is no report of laboratory confirmed pertussis from India. It has been observed that there are reports on a decrease in DPT vaccine compliance from different parts of India.³ A laboratory confirmed case study of pertussis in Delhi, has documented the circulation of pertussis in our country and there is poor vaccination compliance and avoidance of vaccination from fear of side effects.⁴

Prevention

Efforts to develop an inactivated whole cell pertussis vaccine began soon after growth organism in pure culture in 1906. A vaccine was developed from whole culture by Louis Sauer in 1920s in the US. Thorvald Madsen, a Danish Physician popularized whole cell pertussis vaccine by using it on a large population. In 1942, the US Scientist Pearl Kendrick combined the whole cell pertussis vaccine with diphtheria and tetanus toxoid to produce first DPT (diphtheria, pertussis, and tetanus) combined vaccine.

Pertussis is a vaccine preventable disease. The immunization schedule as per the recommendations of Indian Academy of Pediatrics (IAP) is as follows (5):

Older versions of the vaccine involved inactivated cells. Newer versions are acellular and are less likely to provoke adverse effects. There used to be local reactions in the form of redness, soreness, and swelling at the site of injection, and fever and irritability as systemic adverse reactions. To minimize the frequent side effects of pertussis component of vaccine, the Japanese Scientist Yuji Sato developed an acellular pertussis vaccine containing purified haemagglutinins⁶ and an acellular pertussis vaccine was introduced in 1981 The local and systemic adverse reactions are much less common with acellular DTaP vaccine.⁷

IAP endorses the continued use of whole cell pertussis (w) vaccine because of its proven efficacy and safety. Acellular pertussis (a) vaccine may undoubtedly have fewer side effects, but this minimal advantage does not justify the inordinate cost involved in the routine use of this vaccine.

Infection with pertussis induces temporary natural immunity. Immunization against pertussis does not confer life-long immunity. While adults rarely die if they contact pertussis after the effects of their childhood vaccine get worn off, they may transmit the disease to people at much higher risk of death from pertussis.  The duration of protection against pertussis following vaccination may last for 3 to 6 years.

Outbreaks of pertussis have been noted following waning immunity in older children and adolescents. A booster dose of adult formulation of pertussis vaccine combined with diphtheria and tetanus toxoid is recommended to all adults planning pregnancy, for both parents as soon as possible after delivery of an infant and for grand parents and other individuals taking care of young children, and infants less than 12 months of age.

Any person who has not had pertussis or who has not received the pertussis vaccine can get the disease. Immunity following disease or vaccine is not life-long. Older children, adolescents and adults can become susceptible to pertussis for five to 10 years after their last dose of pertussis vaccine. Older children and adults can carry the organism and spread it manifesting only mild symptoms for which treatment might not be received.

Booster vaccine was introduced in 2005 and it offers protection against whooping cough. The vaccine contains small amount of tetanus and diphtheria toxoids with acellular pertussis vaccine (Tdap). The small letters indicate that the vaccines contain small amount of diphtheria and pertussis vaccines. These vaccines have been produced by chemically treating the diphtheria, pertussis and tetanus toxoids to render them nontoxic yet capable of eliciting an immune response in vaccinated individuals. Thus the vaccine is considered an ‘inactivated’ vaccine. It is inactivated vaccine because it does not contain live bacteria and cannot replicate. That is the reason for giving multiple doses of vaccine to produce immunity.

Tdap is given as a one-time vaccine and it contains small amounts of diphtheria toxoid and acellular pertussis vaccine. Thus there is a need for administration of the sixth injection of pertussis vaccine during adolescence at 15-17 years of age. The vaccine consists of adult formulation, which has lower concentrations of pertussis antigens (ap) than childhood vaccine (aP). This will prevent the individuals to become victims of whooping cough and be a source of infection to infants.⁸

To reduce morbidity and spread of disease Canada, France, the US, Germany and Australia have approved booster dose administration. Thus the recommended course of pertussis vaccination involves sixth injection to help protection from disease and to maintain immunity. This will help in prevention of disease outbreak. The vaccine is administered in the deltoid region. The only contraindication to pertussis vaccine is anaphylaxis following a previous dose of an acellular pertussis vaccine or anaphylaxis following any vaccine component.⁹ IAP has recommended use of Tdap at the age of 10 years.⁵

Most pregnant women who were not previously vaccinated with Tdap are to get one dose of Tdap postpartum before leaving the hospital or berthing centre. Getting vaccinated with Tdap is especially important for families with and care-givers of infants. The CDC recommends that adults 19 to 64 years of age (and adolescents 11 to 18 years of age) receive a booster dose of Tdap.

Diphtheria

Diphtheria is a localized infection of mucus membranes of the throat caused by facultative anaerobic, Gram-positive bacteria called Corynebacterium diphtheriae.The organism was discovered by Fredrich Loeffler in 1884. In 1880s German Physician Emil von Behring developed an antitoxin that had the capability of neutralizing the toxin. He received the first Noble Prize in Medicine in 1901. Behring developed the first successful vaccine for diphtheria in 1913. The first inactivated toxin or toxoid against diphtheria was developed in 1921 and it became widely available in the subsequent decade.

Spread of infection

Diphtheria is potentially fatal. The infection causes its lethal effects through its toxin. It spreads by droplets during coughing and sneezing by infected persons. It can also spread by direct contact with wounds or fomites. Infected person can spread disease up to 4 weeks from the time of onset of symptoms, and the carriers can spread the disease longer than 4 weeks. Any person who has not been immunized against diphtheria when exposed to a person infected with diphtheria becomes susceptible to diphtheria. It takes 2 to 5 days to develop symptoms after exposure to the infection.

Clinical features

The clinical features develop insidiously as mild fever, sore throat, difficulty in swallowing, painful swallowing, malaise, hoarseness, cough, rapid breathing, and anorexia. A firm, fleshy grey adherent membrane (pseudomembrane) develops in the throat, which bleeds if attempts are made to remove it. There will be cervical lymphadenopathy. The haematogenously distributed toxin will have effect on the heart, nervous system and kidney causing myocarditis, peripheral and cervical neuropathy and renal failure respectively.^10,11

Treatment

Diphtheria is treated with antitoxin to neutralize the circulating toxin. Penicillin and erythromycin are recommended against infection. The patients are treated in isolation until they are no longer capable of infecting others usually about 48 hours after antibiotic treatment has begun.

Diphtheria in adult

Immunisation has led to a marked decrease in the incidence of the disease and also has reduced the size of the reservoir of toxigenic Corynebacterium diphtheriae organisms. But a high proportion of adult cases of diphtheria have been reported from former Soviet Union.

Before vaccination became widespread, exposure to toxigenic strains of diphtheria organisms was common and it provided natural boosts for development and maintenance of immunity against diphtheria. Children were susceptible and most adults remained immune to the disease. As immunization has become widespread, diphtheria has become rare, and concomitantly exposure to the organism (natural boosts of immunity) has become uncommon. With neither natural exposure to the bacteria nor booster dose of the vaccine, vaccine-induced immunity wanes and adults become susceptible to the disease.¹² This has necessitated the need for maintenance of immunity in adults.

Since diphtheria infection can occur among previously vaccinated persons, the immunity gap observed among adults should be closed by regular diphtheria booster. A single booster vaccine is sufficient to provide long-term protection for those in the risk group.¹³

Prevention

Diphtheria is a vaccine preventable disease. Diphtheria vaccine offers protection against the disease. The vaccine is recommended as part of routine immunization to the infants in their first year of life. It is administered thrice as a combined vaccine with tetanus toxoid and pertussis vaccines (DPT) at intervals of 4 weeks commencing from 6 weeks of age in infants. Diphtheria vaccine contains a toxoid (a modified vaccine of the diphtheria toxin) and it is not given as a single injection. DPT vaccine is recommended at the age of 18-24 months and at 5 years of age as booster.

Immunity against diphtheria is achieved after vaccination. Diphtheria antitoxin acts against the toxin produced by the organisms. The immunogen is prepared by treating a cell-free preparation of toxin with formaldehyde, thereby converting it into an innocuous diphtheria toxoid. The absolute contraindications      to diphtheria vaccine are anaphylaxis following a previous dose of vaccine or anaphylaxis following any component of vaccine.

Another booster dose of diphtheria vaccine is recommended at the age of 15-17 year. Booster vaccine against diphtheria is recommended to all adults if they have not received booster dose of diphtheria vaccine in preceding 10 years. Booster vaccine is useful to the adults since the benefits of the vaccine decrease with age without constant re-exposure. All diphtheria immunization for children is given in the forum of an injection combined with tetanus toxoid and pertussis vaccine.

Adults and adolescents receive diphtheria toxoid combined with tetanus toxoid, and pertussis acellular vaccine as a booster. Such vaccine contains a small amount of diphtheria and tetanus toxoid, which are modified to make them harmless and small amounts of purified components of pertussis acellular vaccine and aluminium salt (Tdap). After the vaccine has been given, it generally takes about 2 weeks to build immunity in the body.

The adult/ adolescent Tdap vaccine is recommended as a one-time vaccine to those who have previously completed a schedule of the immunization. Such a booster vaccination is recommended to adults before planning pregnancy or for both parents as soon as possible at birth and to adults working with or caring young children. After vaccination it generally takes about two weeks to build protection in the body. The vaccine is safe and well tolerated. Occasionally there can be side effects such as mild fever, tenderness and soreness at the site of injection. These side effects can be reduced by drinking extra amount of fluids, by applying a cold wet cloth to the sore injection site and by taking paracetamol to reduce any discomfort and fever. A high vaccination rate in the country protects the population from resurgence of diphtheria.

Conclusion

As there is a shift in the epidemiology of pertussis and diphtheria, immunisation against diphtheria and pertussis is necessary to protect adolescents and adults. All adults younger than age 65 years should receive a one time dose of Tdap as soon as feasible in adolescence.