PERTUSSIS A Reemerging Infectious Disease Dr Joe Gorvetzian
Pertussis (History) • The earliest clear account of whooping cough was described in 1640 by Baillow, an epidemiologist • The name ‘pertussis’ means “violent cough”, and was first used to describe the disease in 1679. • In China, the disease is known as “the cough of 100 days”
Pertussis (History) There are 8 species of bordetella- but B pertussis and B parapertussis cause most human disease (most cause respiratory disease, otitis, sinusitis, but occasional species are associated with wound infections, sepsis, and septic arthritis. B. bronciseptia is an animal pathogen that causes kennel cough in dogs (and other species can cause disease in other animal hosts (rabbits, swine)
Pertussis (Bacteriology) • The Bordetella are minute coccobacillary gram negative organisms. • Bordetella grow slowly on culture media (often taking 3 or more days for pinpoint colonies to appear). • Bordetella makes a number of biologically active substances that are felt to play a role in disease--
Pertussis (Bacteriology) • B pertussis growing on BG media plate
Pertussis (Bacteriology) • Filamentous hemagglutinin (FHA), Pertussis toxin (PT), tracheal cytotoxin (TCT), tracheal colonization factor, BrkA (Bordetella resistant to killing factor) and others. • FHA causes agglutination of RBC’s and helps with bacterial attachment to epithelial cells • PT induces a lymphocytosis, and seems to affect the ability of phagocytes to clear the bacteria
Pertussis (Bacteriology) • PT is felt to be responsible for many of the systemic manifestations of disease, but how it does this is not clear. • Pertussis is not a single toxin disease (like tetanus, diphtheria, or others). • B pertussis can go through a variety of phase variations, in response to its environment, which may also affect its virulence in its host.
Pertussis (Bacteriology) • Large lymphocytes seen in patient with pertussis, and small coccobacillary organisms seen on gram stain
Pertussis (Bacteriology) • Pertussis toxin and filamentous hemagglutinin (FHA) allow binding of pertussis to repsiratory epithelial cells. • PT can then enter the bloodstream.
Pertussis (Epidemiology) • Pertussis is a disease of worldwide importance, with an estimated 285,000 deaths in 2001, with most occurring in Africa and SE Asia • According to the WHO, there are 20-40 million cases each year, with 90% occurring in developing countries. • In the US, an average of more than 160,000 cases and more than 5,000 deaths/year were reported in the 1920’s &1930’s.
Pertussis (Epidemiology) • In the 1950’s when whole cell vaccine became available, case reports of pertussis decreased by more than 99% by 1976, when the number of reported cases reached a record low of 1,010 cases. • In the US in 2002, there were 8,296 reported cases, the highest number in 40 years.
Pertussis (Epidemiology) • 2003
Pertussis (Epidemiology) • This increase is due in large part to disease diagnosed in adults and adolescents -- (more recognition of disease ?) • The disease is endemic, with epidemics occurring in 3 – 5 year cycles • B pertussis is very contagious, and attack rates among susceptible groups range from 50-100% depending on the nature of the exposure.
Pertussis (Epidemiology) • Transmission is felt to occur by aerosol droplet, and exposure to a coughing patient. • There are no known animal reservoirs for B pertussis, and the organism does not survive for prolonged periods in the environment. • No long-term carrier state had been identified, but asymptomatic culture positive persons can be detected during known exposures.
Pertussis (Epidemiology) • These asymptomatic people are not felt to be a source of infection since they are not coughing. • In the prevaccine era, pertussis was primarily a disease of young children, but less so infants ( because of passive immunity from the mother during the first year of life).
Pertussis (Epidemiology) • In a study from 1916, 60% of cases were in children ages 1 – 5, whereas only 19% were in children < 1 year old. • During those times, most adults had had pertussis, and were constantly reexposed, so they maintained a good antibody (immunity) level. • Whole cell pertussis vaccine has been respsonsible for a major reduction in disease incidence, but has caused a shift in the peak age of disease.
Pertussis (Epidemiology) • Immunity from the vaccine is of limited duration (~10- 12 years), so fully immunized children were protected, but adults had little or no immunity. (hence no passive transfer to newborns either). • Therefore young infants who had not been completely vaccinated were at greatest risk for morbidity and mortality, and were the least protected.
Pertussis (Epidemiology) • In 1982-1983, 53% of cases occurred in children < 1 year old. • Since no boosters are currently given beyond childhood (4-6 yo), virtually all adolescents and adults are susceptible. • Among the 29,134 cases reported to the CDC from 1997-2000, about half occurred in those over 10 years old, and this group is a major source of transmission.
Pertussis (Epidemiology) • A study from JAMA in 2003, showed that the incidence of reported cases increased 49% from the 1980’s to the 1990’s, the increases were primarily noted in infants less than 5 months old. • A number of studies have addressed the incidence of pertussis in the older age groups (often focusing on individuals presenting with a prolonged cough).
Pertussis (Epidemiology) • Using serologies and other tests for detection of recent exposure, it appears that as many as 20-30% of patients with a prolonged cough may have pertussis. • A study done at Vanderbilt Univ Hospital in 1995 showed that ~25% of patients who presented to the ER with a chronic cough (>2 weeks), had evidence of pertussis infection (+DFA, or serology, 0 positive cx)
Pertussis (Clinical Manifestations) • After an incubation period of 1-3 weeks, signs and symptoms of the catarrhal phase begin • Symptoms include rhinorrhea, lacrimation, conjunctival injection, malaise, low grade fever, and are indistinguishable from those of many other URI’s. • After a few days and up to a week of these symptoms, a dry nonproductive cough develops, and this evolves into a characteristic paroxysmal phase.
Pertussis (Clinical Manifestations) • Patients are most contagious during the catarrhal phase and during the first two weeks after the onset of coughing. • Prodromal symptoms during this phase can include complaints of pharyngeal discomfort. • During this phase, patients can develop a marked leukocytosis, with WBC counts greater than 50,000, with a relative lymphocytosis (less common in adults).
Pertussis (Clinical Manifestations) • The cough paroxysm consists of a short series of expiratory bursts, followed by an inspiratory gasp, which results in the typical “whoop”. • The paroxysmal phase usually lasts 1-6 weeks, but can last up to 10 weeks • Not all children with pertussis exhibit the characteristic whoop, and it is fairly uncommon in infants, who may have apneic episodes.
Pertussis (Clinical Manifestations) • In adults, whooping is variable, ranging from 20-40% in various studies. The disease is generally milder, but the paroxysmal cough may be just as prolonged. • Paroxysms can number more than 30 per 24 hours, and are more frequent at night, and can be stimulated by external stimuli, such as noises or cold air.
Pertussis (Clinical Manifestations) • Classically they may end with a vomiting episode. They can be associated with sweating, flushing and syncope. Patients may cough up thick yellow plugs. • Pertussis is generally more severe in infants, but presentation can be more atypical in infants, as well as partially immunized children and previously immunized adolescents and adults. • In these groups the catarrhal phase can be shortened, and the true whooping phase may be absent.
Pertussis (Clinical Manifestations) • The convalescent phase begins with a decrease in the intensity of the cough and paroxysms, but can still last for weeks. • It is not clear if pertussis can cause long term impairment of pulmonary function.
Pertussis (Complications) • The principal complications of pertussis are secondary infections- otitis media or pneumonia (either secondary to pertussis or other organisms) • Aspiration can occur secondary to the whooping and associated gasping
Pertussis (Complications) • Patients can develop subconjunctival hemorrhages, facial and truncal petechiae, pneumothoraces, SQ emphysema, hernias, and rectal prolapse from the severe coughing. Rib fractures and herniated discs can also occur • CNS abnormalities can occur particularly in children 6 months and younger.
Pertussis (Complications) • These include convulsions in 1.4 %, and encephalopathy in 0.2%. Possible etiologies include hypoxia, hypoglycemia, or direct effects of pertussis toxin.
Pertussis (Diagnosis) • Obviously the diagnosis must be considered! • A variety of methods have been developed to detect B Pertussis, its products, or the immune response to them, however they all have limitations.
Pertussis (Diagnosis) • Isolation of B pertussis by culture is highly specific, but is limited in its sensitivity. Special media is required (BG medium or Regan-Lowe media), (which is supplemented with cephalexin to impair growth of normal flora), but plating of the specimen must be done at the bedside.
Pertussis (Diagnosis) • A nasopharyngeal swab or NP aspirate must be done to obtain the specimen. • Calcium alginate swabs must be used. (Cotton inhibits growth of the organism). • Cultures should be held for 7 days .
Pertussis (Diagnosis) • Direct fluorescent antibody tests (DFA) are often used as well, but they can be less sensitive and less specific, and may lead to overdiagnosis and overtreatment (higher false positives from cross reaction with normal naso-pharyngeal flora). • With new PCR technology becoming available, the ability to diagnose Bordetella infection has been greatly enhanced.
Pertussis (Diagnosis) • Live organisms aren’t necessary to get a positive test result ( so can get + tests in people already on treatment). • Serologic tests for detection of antibodies are useful epidemiologically, but less so in acute illness. Antibody tests against the PT (pertussin toxin) are the most commonly used.
Pertussis (Diagnosis) • A clinical case is defined as a cough illness lasting at least 2 weeks without other apparent cause accompanied by one of the following • Paroxysms of coughing • Inspiratory ‘whoop’ • Posttussive vomiting
Pertussis (Diagnosis) • In an outbreak setting or following household exposure, a clinical diagnosis can be made in a patient without typical features if the cough lasts 2 weeks or longer. • The sensitivity of this case definition in outbreak investigations is about 80%, and the specificity is about 60% (ie, there are many other reasons for a cough, especially in adults).
Pertussis (Prevention) • With the recognition of pertussis as a contagious illness, but before the availability of prophylaxis, isolation was the only reasonable prophylactic measure available. • However, the non-specific nauture of the symptoms, especially early on, made this a not too effective strategy.
Pertussis (Prevention) • Whole cell vaccines became available in the 1950’s, and the DTP vaccine is still in use in much of the world, but is no longer available in the US. • The efficacy of whole cell vaccine has ranged from 60-90% depending on the specific vaccine typed used, as well as other factors.
Pertussis (Prevention) • Whole cell vaccine is associated with a variety of side effects and systemic effects, including fever, pain, fretfulness, vomiting, and possibly more severe symptoms including encephalopathy and permanent neurologic sequale, although this is uncertain.
Pertussis (Prevention) • Acellular pertussis vaccines have been developed, primarily because of the concern of reactogenicity of whole cell vaccines. • These contain purified proteins of PT or FHA (filamentous hemagglutinin). • It is not clear exactly how the acellular vaccines provide protection, or exactly which antibodies produced provide a protective effect.
Pertussis (Prevention) • Cell mediated immunity is also felt to play a role in providing protection and elimination of the organism from the host. • Acellular vaccines are preferred because of similar efficacy to whole cell vaccine, with less incidence of adverse events. • Symptoms generally occur about 1/10 to ½ as frequently with the acellular vaccine
Pertussis (Prevention) • Erythema (30% vs 70%), fever (5% vs 15%), and other side effects occur with similarly less frequency. • There are a variety of acellular pertussis vaccines currently available (DaPT), including some in combination with hepatitis B and polio virus (Pediarix), or hemophilus vaccine, in addition to DT.
Pertussis (Prevention) • There is no product currently available for general use as an adult booster. • There has been discussion of giving boosters of acellular pertussis vaccine to adults, as it is felt that adults may play an important role in transmission of the disease.
Pertussis (Prevention) • Vaccinating women of childbearing age may induce passive immunity should they become pregnant, which would help protect infants in the first few months of life. • Acellular pertussis vaccine trials are underway to test the efficacy and safety of aP vaccine in adults.