Expires: October 1, 2024
Robin Patel, M.D., is the Division Chair of Clinical Microbiology in the Department of Laboratory Medicine and Pathology in Rochester, Minnesota. She holds the academic rank of Professor of Medicine and Microbiology.
Contact us: MMLHotTopics@mayo.edu.
Hi, I’m Ross Reichard, Vice Chair of Quality, for the Department of Laboratory Medicine and Pathology at Mayo Clinic. Did you know that pertussis is highly contagious and spreads rapidly through families, schools, and hospitals? While adults and children may have relatively mild symptoms, the disease can be deadly for infants and neonates. In today’s “Hot Topic,” my colleague, Dr. Robin Patel, will discuss how early diagnosis and treatment can improve these outcomes by using nucleic acid amplification, which have become the recommended tests for detection of Bordetella pertussis and Bordetella parapertussis infection. I hope you enjoy this month’s Hot Topic, and I want to personally thank you for allowing Mayo Clinic the opportunity to be a partner in your patient’s health care.
Thank you, Dr. Reichard.
Here is a list of my disclosures.
Bordetella pertussis and Bordetella parapertussis are aerobic, small nonmotile, Gram-negative coccobacilli that cause a disease called pertussis.
Pertussis is a respiratory illness that begins with a catarrhal stage with cold-like symptoms, progresses to severe paroxysms of cough, and evolves into a convalescent stage. Symptoms typically develop within 5 to 10 days after being exposed and begin with a runny nose, low-grade fever, and mild cough. After 1 to 2 weeks, severe paroxysmal coughing begins. Violent coughing fits, associated with the characteristic inspiratory “whoop,” may continue for weeks. In China, pertussis is referred to as the “100-day cough.” Coughing can be so severe that it can result in vomiting, exhaustion, rib fractures, and/or loss of bladder control. Symptoms may be less severe in immunized or partially immunized individuals, in whom the characteristic “whoop” may be absent; such individuals may simply have a prolonged cough illness.
Although infection may be associated with mild symptoms in adults and older children, neonatal infections can be deadly. In infants, cough may be minimal or absent. However, the illness may be severe, with up to half of infants, especially younger infants, requiring hospitalization. Apnea, pneumonia, seizures, and encephalopathy may occur with pertussis in infants.
Pertussis is highly contagious; transmission occurs by direct contact with or inhalation of airborne droplets generated when an infected individual coughs. Susceptible contacts are highly likely to become infected with the potential for rapid spread in families, schools, or hospitals. Because in its early stages pertussis may appear to be nothing more than a common cold, it is often not suspected or diagnosed until more severe symptoms appear. Pertussis is, however, contagious from the beginning of the catarrhal stage through the third week of the onset of paroxysms of cough or until five days after administration of an effective antimicrobial treatment.
Rates of Bordetella pertussis infection vary by season, with yearly peaks during the months of July and August. The chart shows our data from the past decade, with the percent of Bordetella pertussis PCR tests positive shown in purple and the number of tests performed shown in blue.
Bordetella pertussis is found exclusively in humans, with adolescents and adults serving as a source of infection of younger children and infants.
The pathogenesis of Bordetella pertussis infection relates to the production of a number of virulence factors, including endotoxin, pertussis toxin, filamentous hemagglutinin, adenylate cyclase, pertactin, and tracheal cytotoxin.
Following the introduction of the pertussis vaccination, the incidence of pertussis declined, reaching a nadir (low point) in 1976. The yearly incidence has, however, increased in recent years. Whole-cell pertussis vaccines, made of thermally or chemically inactivated Bordetella pertussis cells, were introduced in the 1940s and later combined with diphtheria and tetanus toxoids to form “DTP” or the diphtheria and tetanus toxoids and pertussis vaccine. Though efficacious and immunogenic, tolerability was limited by vaccine reactions, including local reactions, fever, and febrile seizures. Acellular pertussis vaccines, denoted by a small “a” preceding the “p/P” of pertussis, are composed of proteins purified from bacterial cell lysates. Acellular pertussis vaccines have fewer adverse effects than whole-cell vaccines. Acellular pertussis vaccines were introduced in the 1990s, gradually replacing whole-cell pertussis vaccines. Several acellular pertussis vaccines have been used, all of which have contained pertussis toxin, with or without pertactin, filamentous hemagglutinin, and/or fimbrial proteins.
Several factors have likely contributed to the recent increase in pertussis cases, including decreased efficacy of the current vaccines resulting in less long-term immunity, increased awareness and improved recognition of pertussis, improved laboratory diagnostics, increased surveillance and reporting of pertussis, and microbial evolution resulting in vaccine evasion.
We reported that a 2012 pertussis outbreak in Southeastern Minnesota included multiple strains of Bordetella pertussis, all putatively lacking pertactin, which would be predicted to lower the efficacy of acellular vaccines.
Note that pertussis vaccination does not prevent Bordetella parapertussis infection, which generally causes disease in a younger age group than Bordetella pertussis. In our study of the 2012 outbreak in Southeastern Minnesota, the mean age of patients with Bordetella parapertussis was 3.8 years, whereas the mean age of those with Bordetella pertussis was 15.6 years. Outbreaks of Bordetella parapertussis occur; we have reported an outbreak that occurred in Southeastern Minnesota and the United States in 2014.
Diagnosis of pertussis is based on having a high clinical index of suspicion for the infection, along with confirmation by laboratory testing. Laboratory testing methods include nucleic acid amplification tests such as PCR, serology, culture, and direct fluorescent antibody testing. Culture and direct fluorescent antibody testing are limited by low sensitivity, rendering nucleic acid amplification tests and serology the tests of choice. The Centers for Disease Control and Prevention recommends PCR testing of nasopharyngeal swabs or aspirates for patients suspected of having acute pertussis. Bordetella pertussis PCR detects roughly twice as many cases as culture. Bordetella pertussis DNA can be detected for up to 4 weeks or longer, up to 8 weeks in our experience, after symptom onset. However, over time, the amount of Bordetella pertussis and Bordetella parapertussis DNA will diminish, rendering the assay less sensitive. A serologic response to Bordetella pertussis is typically mounted by two weeks following infection, and therefore, detection of IgG-class antibodies to pertussis toxin, which are produced in response to Bordetella pertussis but not Bordetella parapertussis, may be used as an adjunct for diagnosis at later stages of pertussis at a time when the amount of organism may be below the limit of detection of the PCR assay. Because pertussis vaccination will result in a Bordetella pertussis IgG response, serology should not be used in neonates or young infants, or in children between the ages of 4 to 7 years, as the routine childhood vaccine schedule may interfere with result interpretation and should also not be used in those who have not received a pertussis vaccine in the prior six months.
Early treatment of pertussis is helpful, especially for infants. If patients are diagnosed late, antibiotics will not alter the course of the illness, and even without antibiotics, patients should no longer be infectious. Recommended treatment of pertussis includes azithromycin, clarithromycin, erythromycin, and trimethoprim-sulfamethoxazole, with the treatment choice guided by potential adverse effects and drug interactions, tolerability, ease of medication adherence, and cost.