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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.

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pertussis

PERTUSSIS

A Reemerging Infectious Disease

Dr Joe Gorvetzian

pertussis history
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 history3
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
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 bacteriology5
Pertussis (Bacteriology)
  • B pertussis growing on BG media plate
pertussis bacteriology6
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 bacteriology7
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 bacteriology8
Pertussis (Bacteriology)
  • Large lymphocytes seen in patient with pertussis, and small coccobacillary organisms seen on gram stain
pertussis bacteriology9
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 (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 epidemiology11
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 epidemiology13
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 epidemiology14
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 epidemiology15
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 epidemiology16
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 epidemiology17
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 epidemiology19
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 epidemiology20
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 epidemiology21
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
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 manifestations24
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 manifestations25
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 manifestations27
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 manifestations28
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 manifestations29
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
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 complications32
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 complications33
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
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 diagnosis35
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 diagnosis36
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 diagnosis37
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 diagnosis38
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 diagnosis40
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 diagnosis41
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
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 prevention43
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 prevention44
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 prevention46
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 prevention47
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 prevention48
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 prevention49
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 prevention50
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.
pertussis prevention51
Pertussis (Prevention)
  • FDA panel backs teen whooping cough vaccineDrug also 'safe and effective' for diphtheria and tetanus http://msnbc.msn.com/id/7189428/
pertussis prevention52
Pertussis (Prevention)
  • Difficulties in prevention strategies include:
  • Cost benefit analysis of adult/adolescent vaccination
  • Difficulties of vaccinating young healthy adult population (pregnant women)
  • ? Targeted vaccination to certain risk groups– parents of newborns, workers in pediatric units, day care personnel, teachers
pertussis prevention53
Pertussis (Prevention)
  • A recent study in Clinical Infectious Diseases from December 2004 looked at costs (medical and nonmedical) associated with pertussis.
  • Costs were significantly higher compared to other respiratory or childhood illnesses.
pertussis treatment
Pertussis (Treatment)
  • There have been relatively few advancements in therapy for this illness.
  • Infants with pertussis are at greatest risk for complications, and infants less than 1 year of age often require hospitalization for supportive care (oxygen, suctioning, iv hydration, etc.
pertussis treatment55
Pertussis (Treatment)
  • Erythromycin has been the mainstay of treatment, and gets good drug concentrations in the respiratory epithelium. It should be given for a full 14 day days, to avert relapse of disease.
  • Studies have shown that B. pertussis can no longer be isolated from the nasopharynx of most patients following 5 days of erythromycin therapy.
pertussis treatment56
Pertussis (Treatment)
  • There is still debate about how much erythromycin lessens symptoms of the disease, however.
  • The dose of erythromycin is 40-50 mg/kg/d for children and 1 -2 grams/day for adults ( ie 500 mg qid).
  • Doses used for treatment and prophylaxis are the same.
pertussis treatment57
Pertussis (Treatment)
  • Erythromycin may reduce symptoms (number of whoops, or duration of cough) if given in the early stages of disease (catarrhal stage or within 2 weeks of paroxysmal cough).
  • Side effects of erythromycin include GI symptoms, cramps, nausea, vomiting, diarrhea.
pertussis treatment59
Pertussis (Treatment)
  • TMP/SMX is an acceptable alternative and is effective in eradicating pertussis from the oropharynx, but there is less clinical experience with it.
  • Other antibiotics – penicillins, cephalosporins, fluoroquinolones, and tetracyclines are not effective for treating B pertussis.
pertussis treatment60
Pertussis (Treatment)
  • The newer macrolides (azithromycin and clarithromycin) have good in vitro acitivty against B pertussis, and Clarithromycin (500 mg bid) used for 10 – 14 days and Azithromycin (500 mg/d) used for 5 – 7 days have been used with good results.
  • There have not been any relapses noted in a few small studies done with these drugs, and they are reasonable alternatives for those who cannot tolerate erythromycin.
pertussis treatment61
Pertussis (Treatment)
  • Steroids may reduce the number and severity of cough paroxysms, but are generally only recommended for infants with serious disease.
  • Aerosolized steroids may be beneficial (in anecdotal reports), but there have not been any controlled trials looking at this.
pertussis control prevention64
Pertussis (Control & Prevention)
  • Antibiotics can be used for 2 purposes in the control and prevention of pertussis:
  • 1) Treatment to modify clinical symptoms of pertussis by administering to symptomatic patients
pertussis control prevention65
Pertussis (Control & Prevention)
  • 2) Prevention of secondary spread of pertussis by administering to:
  • a) Symptomatic patients (treatment) and interrupting infectiousness and transmission by eliminating the organism from the respiratory system.
  • b) Asymptomatic contacts (prophylaxis) and interrupting transmission by eliminating any organisms that may have been contracted.
pertussis control prevention66
Pertussis (Control & Prevention)
  • Overall data from studies suggest that treatment of patients and prophylaxis of contacts are most effective when erythromycin is given in the early stages of disease or within 3 weeks of exposure (limited benefit in giving treatment or prophylaxis after 3 weeks, as it does not lessen symptoms, and many will have cleared spontaneously, anyway.)
pertussis control prevention67
Pertussis (Control & Prevention)
  • Data from microbiologic studies has shown that 80-90% of untreated patients will clear B pertussis from the respiratory tract within 3-4 weeks of cough onset; untreated and unvaccinated infants may remain culture positive for more than 6 weeks.
  • The effectiveness of erythro is short term, (during an outbreak repeated exposure may require repeat course of prophylaxis)
pertussis control and prevention
Pertussis (Control and Prevention)
  • Hospital/nosocomial outbreaks of pertussis have occurred, but generally involve small numbers of cases, and are not associated with fatalities, but they can cause significant morbidity, and cause disruptive furloughs of employees, with direct associated costs.
pertussis control and prevention70
Pertussis (Control and Prevention)
  • Pertussis can be introduced by HCW’s, visitors, or by patients or residents (eg in nursing homes) exposed from other sources.
  • HCW’s should be considered exposed and regarded as close contacts if exposed to a confirmed case.
pertussis control and prevention71
Pertussis (Control and Prevention)
  • Close contact includes such activities such as performing a PE, suctioning, intubation, feeding, bathing and other procedures requiring prolonged or close interaction.
pertussis control and prevention72
Pertussis (Control and Prevention)
  • All healthcare workers should wear a mask when examining a patient with suspected or confirmed pertussis.
pertussis control and prevention73
Pertussis (Control and Prevention)
  • Most individuals who were in waiting rooms or other care areas at the same time as a pertussis case should not be considered close contacts, however IC recs should be individualized.
  • Patients and caretakers who had direct contact with respiratory secretions from a case, or had intense close contact (extended playing time), may be considered close contacts.
pertussis control and prevention74
Pertussis (Control and Prevention)
  • Patients who were in direct contact with a symptomatic HCW with pertussis or who received direct patient care of an extended nature (ie, a complete PE), should be considered close contacts.
  • All symptomatic HCW should be tested for pertussis as soon as possible.
  • HCW who are close contacts of a pertussis case while wearing a mask should also be considered for prophylaxis.
pertussis control and prevention75
Pertussis (Control and Prevention)
  • Due to the closed nature of most institutions (ie nursing homes), and potential for frequent or repeated exposures, entire wards or institutions may require prophylaxis.
  • Symptomatic patients should be placed in isolation and droplet precautions for the first 5 days of a full course of treatment.
pertussis control and prevention76
Pertussis (Control and Prevention)
  • If they cannot or won’t take antibiotics, the person should be placed in isolation for 21 days from the onset of the cough.
pertussis control and prevention77
Pertussis (Control and Prevention)
  • HCW with symptoms of pertussis should be excluded from work for at least the first 5 days of antibiotics. Asymptomatic HCW who have had close contact with a case should be put under close surveillance with employee health and given prophylaxis.
  • HCW who cannot or refuse to take antibiotics should be excluded from work for 21 days.
pertussis78
Pertussis
  • There have been 12 cases in 2005 so far .
pertussis summary
Pertussis (Summary)
  • Bacteriology of Pertussis
  • Symptomatology
  • Diagnosis- newer techniques (PCR)
  • Treatment
  • Epidemiology- changing patterns of disease
  • Control and Prevention- new paradigms re vaccination
  • Infection Control