Pertussis

Whooping Cough

Clinical Description

Identification

An acute bacterial infection of the respiratory tract caused by Bordetella pertussis. The initial catarrhal stage has an insidious onset with an irritating cough that gradually becomes paroxysmal, usually within 1–2 weeks, and lasts for 1–2 months or longer. Paroxysms are characterized by repeated violent coughing; each series of paroxysms has many coughs without intervening inhalation and can be followed by a characteristic crowing or high-pitched inspiratory whoop. Paroxysms frequently end with the expulsion of clear, tenacious mucus, often followed by vomiting. Infants under 6 months, partially vaccinated children, adolescents and adults often do not have the typical whoop or cough paroxysm.

The number of fatalities in vaccinated populations is low. Most deaths occur in infants under 6 months, often in those too young to have completed primary immunization. In recent years, all deaths from pertussis in most industrialized countries occurred in infants under 6 months. In non-immunized populations, especially those with underlying malnutrition and multiple enteric and respiratory infections, pertussis is among the most lethal diseases of infants and young children. Complications include pneumonia, atelectasis, seizures, encephalopathy, weight loss, hernias and death. Pneumonia is the most common cause of death; fatal encephalopathy, probably hypoxic, and inanition from repeated vomiting occasionally occur. Case-fatality rates in unprotected children are less than 1 per thousand in industrialized countries; in developing countries they are estimated at 3.7% for children under 1 and 1% for children 1 to 4 years. In several industrialized countries with high rates of infant immunization for many years an increasing proportion of cases has been reported in adolescents and adults, whose symptoms vary from a mild, atypical respiratory illness to the full whooping syndrome. Many such cases occur in previously immunized persons and suggest waning immunity following immunization.

Parapertussis is a similar but occasional and milder disease due to Bordetella parapertussis.

Infectious Agents

B. pertussis, the bacillus of pertussis stricto sensu; B. parapertussis causes parapertussis. The Bordetella are Gram-negative aerobic bacteria; B. pertussis and B. parapertussis are similar species but the latter lacks the expression of the gene coding for pertussis toxin.


Diagnosis

Diagnosis is based on the recovery of the causal organism from nasopharyngeal specimens obtained during the catarrhal and early paroxysmal stages on Bordet-Gengou or Regan-Lowe culture media both supplemented with 15% defibrinated sheep or horse blood. WHO considers culture as the “gold standard” of laboratory confirmation; it is the most specific diagnosis, but it is not highly sensitive (60%). Polymerase chain reaction (PCR) is more sensitive, and can be performed on the same biological samples as cultures. It requires more technical skills to perform, however, and requires more expensive equipment. Direct fluorescent antibody staining of nasopharyngeal secretions is not recommended because of frequent false-positive and false-negative results. Indirect diagnosis by evaluating the immune response to the infection rather than directly detecting the organism (serology) consists of detecting specific IgG antibodies directed against the pertussis toxin in the serum of the infected individual, collected at the beginning of cough (acute serum); and in serum collected one month later (convalescent serum). Criteria for diagnosing pertussis using a single serum specimen have been proposed. The presence of antibodies in excess of population based threshold levels in the serum of a non-vaccinated individual indicates infection. Serology cannot be used for diagnosis during the year following vaccination, since it does not differentiate between antibodies due to the vaccine and those due to natural infection.

Differentiation between B. parapertussis and B. pertussis is based on culture and genetic, biochemical and immunological differences.


Epidemiology

Mode of Transmission

Direct contact with discharges from respiratory mucous membranes of infected persons by the airborne route, probably via large droplets. In vaccinated populations, bacteria are frequently brought home by an older sibling, and sometimes by a parent. Indirect spread through the air or contaminated objects occurs rarely if at all.

Incubation Period

Average 9–10 days (range 6–20 days).

Period of Communicability

Highly communicable in the early catarrhal stage and at the beginning of the paroxysmal cough stage (first 2 weeks). Thereafter, communicability gradually decreases and becomes negligible in about 3 weeks, despite persisting spasmodic cough with whoop. When treated with erythromycin, clarithromycin or azithromycin, patients are no longer contagious after 5 days of treatment.

Reservoir

Humans are believed to be the only host for pertussis. B. parapertussis can also be isolated from ovines.

Susceptibility

Susceptibility of non-immunized individuals is universal. The highest incidence of pertussis is in infants, and school-aged children are often the source of infection for younger siblings at home, but infection also occurs in adolescents and adults. Incidence, morbidity and mortality are higher in females than males. Secondary attack rates of up to 90% have been observed in non-immune household contacts. Although antibodies cross the placenta, transplacental immunity in infants has not been demonstrated.

Incidence is highest in children aged less than 5 years, except where infant vaccination programs have been very effective, and a shift has occurred toward adolescents. Milder and missed atypical cases occur in all age groups. One attack usually confers prolonged immunity, although subsequent attacks (some of which may be attributable to B. parapertussis) can occur. Cases in previously immunized adolescents and adults in countries with long-standing and successful immunization programs occur because of waning immunity, and are a source of infection for non-immunized young children.

Occurrence

An endemic disease common to children (especially young children) everywhere, regardless of ethnicity, climate or geographic location. Outbreaks occur typically every 3 to 4 years. A marked decline has occurred in incidence and mortality rates over the past 40 years, chiefly in communities with active immunization programs and where good nutrition and medical care are available. In 2003, despite an estimated global vaccination coverage of around 75% with 3 doses of pertussis-containing vaccines, there were still an estimated 17.6 million pertussis cases, with an estimated 279 000 deaths. A substantial proportion of those deaths are occurring in Africa, where vaccine coverage is lowest. Altogether, in 2006 an estimated 26.3 million children had not received full immunization with three doses of DTP. Incidence rates have increased in countries where pertussis immunization rates fell in the past (e.g. Japan in the early 1980s, Sweden and the United Kingdom), and dropped again when immunization programs were reestablished. In countries with high vaccination coverage, the incidence rate in children under 15 is less than 1 per 100 000.


Prevention and Control

1)    Preventive measures:

a)    Educate the public, particularly parents of infants, about the dangers of whooping cough and the advantages of initiating immunization on time (between 6 weeks and 3 months depending on the country), and of adhering to the immunization schedule. This continues to be important because of the wide negative publicity given to adverse immunization reactions.

b)    Immunization is the most rational approach to pertussis control: whole-cell vaccine against pertussis (wP) has been effective in preventing pertussis for more than 40 years. Active primary immunization against B. pertussis infection is done by administering 3 doses of a vaccine consisting of either a suspension of killed bacteria (wP) or acellular preparations (aP) that contain 1–5 different components of B. pertussis. These are usually given in combination with diphtheria and tetanus toxoids adsorbed on aluminum salts (Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed, DTwP or DTaP). In terms of severe adverse effects aP and wP vaccines appear to have the same high level of safety; local and transient systemic reactions are less commonly associated with aP vaccines. Similar high efficacy levels (more than 80%) occur with the best aP and wP vaccines, although the level of efficacy may vary within each group. Protection is greater against severe disease, and begins to wane after about 5 years. Acellular pertussis vaccines do not protect against infection by B. parapertussis.

Although the use of aP vaccines is less commonly associated with local and systemic reactions such as fever, price considerations affect their use, and wP vaccines are the vaccines of choice for most developing countries. Japan, USA and many other industrialized countries have completely replaced wP vaccines with aP vaccines. Schedules vary: North America vaccinates at 2, 4, 6 months; France and the United Kingdom at 2, 3, 4 months; and Sweden at 3, 5, 12 months. Many developing countries vaccinate at 6, 10 and 14 weeks of age, according to the initially proposed schedule of the expended program on immunization. In all countries and particularly where pertussis is still endemic and poses a serious health problem, the priority should be to reach at least 90% coverage with a primary series of 3 doses of DTP in infants in all areas. In countries where immunization programs have considerably reduced pertussis incidence, a booster dose approximately one to six years after the primary series is recommended. The optimal timing of the booster dose of DTP—as well as the possible need and timing for additional booster doses—depends on the epidemiological situation, and should be assessed by national programs. Some other countries recommend booster doses at 15–18 months of age and at school entry. As of 2006, 67 of 193 WHO member states had a recommended schedule including one booster dose in addition to the initial series, and 57 countries recommended 2 or more booster doses. Vaccines containing wP are not recommended after the seventh birthday, since local reactions may be increased in older children and adults. Formulations of acellular pertussis vaccine for use in adolescents and adults have been licensed and are available in several countries. As of 2006, 10 countries were reporting the introduction of adolescent or adult booster doses in the routine immunization scheme.

DTaP/DTwP can be given simultaneously with oral poliovirus vaccine (OPV), inactivated poliovirus vaccine (IPV), Hemophilus influenzae type b (Hib), hepatitis B (HepB) vaccine, pneumococcal and meningococcal conjugate vaccines and measles, mumps and rubella vaccine (MMR) at different sites. Combination vaccines with Hib, IPV and HepB are available and are widely used in Europe and North America.

Minor adverse reactions such as local redness and swelling, fever and agitation often occur after immunization with wP vaccine (1 in 2–10). Prolonged crying and febrile seizures are less common (<1 in 100); hypotonic-hyporesponsive episodes are rare (<1 in 2 000). Although febrile seizures and hypotonic-hyporesponsive episodes may follow DTwP and are disturbing to parents and physicians alike, there is no scientific evidence that these reactions have any permanent consequences. Recent detailed reviews of all available studies conclude that there is no demonstrable causal relationship between DTwP and chronic nervous system dysfunction in children. The only true contraindication to immunization with aP or wP is an anaphylactic reaction to a previous dose or to any constituent of the vaccine. In young infants with suspected evolving and progressive neurological disease, immunization may be delayed for some months to permit diagnosis, in order to avoid possible confusion about the cause of symptoms.

c)    When an outbreak occurs, consider protection of health workers who have been exposed to pertussis cases, using a 7-day course of erythromycin. Clarithromycin and azithromycin are expensive but better-tolerated alternatives. Use of aP can be considered for health workers where ongoing transmission is a concern.


2)    Control of patient, contacts and the immediate environment:

a)    Report to local health authority: Case report of suspected and confirmed cases obligatory in most countries, Class 2; early reporting permits better outbreak control. The WHO-recommended clinical case definition is “a case diagnosed as pertussis by a physician or a person with a cough lasting at least 2 weeks and at least one of the following symptoms: paroxysms (fits) of coughing, inspiratory ‘whooping,’ post-tussive vomiting (vomiting immediately after coughing) without other apparent cause.”

b)    Isolation: Respiratory isolation for known cases. Suspected cases should be removed from the presence of young children and infants, especially non-immunized infants, until the patients have received at least 5 days of antibiotics. Suspected cases who do not receive antibiotics should be isolated for 3 weeks after onset of paroxysmal cough or until the end of cough, whichever comes first.

c)    Concurrent disinfection: Disinfection measures are of little impact.

d)    Quarantine: Inadequately immunized household contacts under 7 may be excluded from schools, day care centers and public gatherings for 21 days after last exposure or until the cases and contacts have received 5 days of appropriate antibiotics.

e)    Protection of contacts: All contacts must have their immunization status verified and brought up-to-date. Passive immunization has not been demonstrated to be effective, and there is no such product currently commercially available. The initiation of active immunization following recent exposure is not effective against infection but should be undertaken to protect the child against further exposure in case he or she has not been infected. Close contacts under 7 who have not received 4 DTP doses or have not received a DTP dose within 3 years should be given a dose as soon after exposure as possible. A 7-day course of erythromycin or clarithromycin, or a 5-day course of azithromycin, for household and other close contacts—regardless of immunization status and age—is recommended for households where there is a child under 1. Prophylactic antibiotic therapy in the early incubation period may prevent disease, but difficulties of early diagnosis, the costs involved and concerns related to the occurrence of drug resistance all limit prophylactic treatment to the following selected individual conditions:

i)    Children under 1 year and pregnant women in the last 3 weeks of pregnancy (because of the risk of transmission to the newborn)

ii)    Stopping infection among household members, particularly if the household contains children aged less than 1 and pregnant women in the last 3 weeks of pregnancy.

f)    Investigation of contacts and source of infection: A search for early, missed and atypical cases is indicated where a non-immune infant or young child is or might be at risk.

g)    Specific treatment: Erythromycin, clarithromycin and azithromycin shorten the period of communicability, but do not reduce symptoms except when given during the incubation period, in the catarrhal stage or early in the paroxysmal stage.

3)    Epidemic measures:

A search for unrecognized and unreported cases may be indicated to protect preschool children from exposure and to ensure adequate preventive measures for exposed children under 7. Accelerated immunization, with the first dose at 4–6 weeks of age and the second and third doses at 4-week intervals, may be indicated; more important is to make sure that immunization is completed for those whose schedule is incomplete, and that the vaccines are given on time according to the national schedule.

4)    Disaster implications:

Pertussis is a potential problem if introduced into crowded refugee camps containing many non-immunized children.

5)    International measures:

Ensure completion of primary immunization of infants and young children before they travel to other countries; review need for a booster dose.

Source: Heymann (Ed.). (2008). Control of Communicable Diseases Manual, 19th edition. Washington, DC: American Public Health Association.
 


Available Vaccines

WHO-Prequalified pertussis vaccines

 

Common Disease Taxonomy: