The second episode features Dr. Margaret Hessen covering pertussis, including the following:
- Clinical presentation of patients
- Confirmation of diagnosis
- Benefits of antibiotics
- Vaccines and indications
Dr. Margaret Hessen
Editor-in-chief of Elsevier’s Point of Care content
Dr. Margaret Hessen is board certified in internal medicine and infectious disease, and was in clinical practice for 17 years. She has also worked with a number of professional organizations on a variety of public health initiatives relating to infectious diseases and disaster preparedness.
1. Why are we hearing so much about pertussis in recent years, and why is it a concern?
After a long period of declining incidence following the introduction of whole cell pertussis vaccine in the 1940s, the first decade of the 21st century has seen an increase in cases. The reason for the increase is not entirely clear.
What is known is that neither vaccination nor naturally acquired disease provides lifelong immunity, so there is always a susceptible population that serves as a reservoir for the disease.
Pertussis is of concern because of its potentially fatal complications and the fact that manifestations are due to the production of bacterial toxins which, once produced, remain active and unaffected by antibiotic treatment. While antibiotics are given to eradicate the organism, they have little impact on the disease manifestations.
2. How does pertussis present, and when should a clinician suspect it?
Pertussis presents classically in three stages. The first is the catarrhal stage, indistinguishable from the common cold, with low-grade or no fever, coryza, sneezing and a mild cough which becomes progressively more severe 7-10 days into the course. The persistent, severe and prolonged cough characterizes the second, or paroxysmal stage. Long-lasting bursts of coughing result in the inspiratory “whoop” that gives the disease its vernacular name, whooping cough. The violence and duration of the paroxysm can result in rib fractures, pneumothorax, cerebral bleeding, seizures, and hernias. Inability to clear secretions despite vigorous coughing is a result of toxin mediated paralysis of the endobronchial ciliary, and contributes to pneumonia, the most common complication and the most frequent cause of death due to pertussis. Most patients present a week or 10 days into the paroxysmal phase, which may last 6 weeks or more before gradually waning in the convalescent period. Physicians should suspect the disease based on the characteristic features of prolonged paroxysms of coughing followed by an inspiratory whoop and even vomiting. Infants may lack the inspiratory force to produce a whoop, but may become cyanotic during the paroxysm. Patients often appear dramatically ill and distressed during and immediately following the paroxysm, but relatively well between spells.
3. How is the diagnosis of pertussis confirmed?
The gold standard is culture. That having been said, culture requires a nasopharyngeal specimen (not a throat swab) and special growth media. The organisms are very fastidious and viability is easily lost under suboptimal transport or storage prior to processing. Cultures may take over a week to grow, and recovery of organisms usually occurs only before the first week or two of the paroxysmal phase. Other laboratory studies may be of more immediate practical value. Direct fluorescent antibody testing, particularly with a monoclonal antibody, can be used on nasopharyngeal secretions. DFA tests are widely available and very specific, meaning that a positive result is likely a true positive. However, these tests lack sensitivity, and a negative does not rule out disease. Many labs are turning to polymerase chain reaction, which is highly sensitive but associated with high rates of false positives. Serology is usually not helpful unless the patient presents fairly late in the course of the illness, and even then, a single positive test does not distinguish between acute disease versus previous infection or immunization. Non-microbiological laboratory support of the diagnosis may be seen in a high white blood cell count with a relative lymphocytosis. The bottom line is that practitioners should rely on their clinical judgment to identify the characteristic constellation of features, and may need to consider more than one modality to confirm the diagnosis. Laboratory directors and public health authorities may provide invaluable guidance.If the disease manifestations are due to a toxin that doesn’t respond to antibiotics, is there any value to prescribing them, and if so, what is the antibiotic of choice?
If the diagnosis is made early in the course of disease and antibiotics are administered promptly, they may be of some benefit to the patient by forestalling further production of toxin. The primary benefit, however, is in preventing transmission of this highly contagious infection to contacts. This is of paramount importance in contacts of infants who may not be fully immunized. Erythromycin, azithromycin or trimethoprim/sulfamethoxazole should be prescribed to the patient and also to household contacts. In addition to medication, household contacts who are less than 7 years old who have not completed the initial 4-dose course of vaccine should complete the series with the shortest recommended interval, and children between 4 and 6 years who have not received the 5th dose should have it.
Over the past few years, a number of new pertussis vaccines and indications have been approved. Could you review these developments? Whole cell pertussis vaccine was the standard formulation for many years. However, while effective, it was associated with moderate local reactions, fever, prolonged crying in infants, and possibly implicated in more severe reactions. Acellular pertussis vaccine was developed as an alternative, and became available in pediatric formulations in the 1990s. More recently, the FDA has approved formulations for adolescents and adults. Acellular pertussis vaccine is available only in combination with diphtheria and tetanus toxoids.
The proportions of the three components differ between pediatric and adolescent/adult preparations, and the differences are designated as DTaP for pediatrics and TDaP for adolescent and adult use. The age range for which the adolescent/adult vaccine is approved varies slightly from one manufacturer to another, so consult the package insert. Some combination vaccines also include other components such as hepatitis B and polio vaccines. Appropriate dosing schedules for these combinations are fairly complex, and again, it is best to check the package insert or ACIP guidelines carefully. These references also address issues of interchangeability. All children should receive acellular pertussis vaccine in some form at 2, 4, 6, and 15-18 months of age, for a total of 4 doses, followed by a booster at 4-6 years of age, preferably before starting school. During outbreaks or if a return visit is deemed unlikely, the 4th dose may be given at 12 months if it has been 6 months since the 3rd dose.The availability of TDaP for adolescents and adults introduced the possibility of boosting waning immunity in that population, thus potentially reducing the reservoir of pertussis. The majority of recent cases have been reported in adolescents and adults. The majority of fatal cases occurs in infants less than 3 months of age, and most of these cases are acquired from adolescents or adults. Reducing susceptibility in adults through immunization therefore may protect infants who are too young to be fully immunized. While a single dose of TDaP is recommended for all adolescents and adults, particular attention should be paid to those known to have close contact with an infant less than 12 months of age, a strategy known as “cocooning.” Pregnant women who have not had a dose of TDap should receive it during the last 20 weeks of pregnancy or as soon postpartum as possible.
The acellular vaccine was developed to address safety issues, but is it as effective as the older vaccine, or are we seeing more pertussis because the acellular vaccine is less effective?
There are probably a number of factors leading to the increase. The rise in pertussis cases actually began in the 1980s, before the acellular vaccine was in use. Improvements in diagnostic testing are thought to account for some of the increase. With regard to the vaccine, there are conflicting data. Early comparative studies actually showed acellular preparations to be more effective than whole cell vaccine in pediatric subjects, but some recent studies find the acellular vaccine less effective. Genetic changes in the pathogen have also been postulated to contribute to the rise in cases and to less effective vaccine protection. That having been said, it is important to remember that we see far less pertussis now than in the pre-vaccine era. The current prevalence is about 4% of that seen before immunization was available.
So what do you see happening with the incidence of pertussis, and what is the take home message? Predictions are difficult, because we don’t really know the reasons for the rising incidence of pertussis over the last few decades. But I’m hopeful that the availability of the adolescent/adult preparation will make significant inroads in the reservoir of infection. The take home message is that prevention is much more effective than treatment of this disease, and clinicians need to be aware that the adolescent/adult formulation is available and that a one-time adolescent or adult dose is recommended for everyone. It should be strenuously encouraged for anyone who has contact with an infant, whose life might depend on it.