January 2007

Dr. Brien’s note: This column was written by the late Dr. Juan Guido Tatá Cumana of Venezuela.

A 5-month-old boy was admitted to the hospital with severe cough. His symptoms began about two weeks earlier with the onset of upper respiratory tract congestion and a milder cough. He was seen in a walk-in clinic by a primary provider who did no tests and prescribed symptomatic treatment. The cough worsened to the point of causing some posttussive emesis and brief loss of breath with cyanosis. He was an otherwise healthy infant with no past history of illness or surgery. He had no allergies, received no medicines except the over-the-counter decongestant given during his first visit, and had no immunizations. His only sick contact was his 18-year-old mother, who has had a coughing illness for several weeks. The rest of his history, including birth and postnatal history, was unremarkable. Specifically, there had been no history of conjunctivitis.

Examination revealed a normal-appearing baby in no acute distress with marked upper airway congestion. Breath sounds revealed moist, bilateral rhonchi with minimal wheezing. During the exam, he began coughing (figure 1), which persisted for more than 30 seconds (figure 2), resulting in some brief dusky cyanosis. After the coughing spell he appeared exhausted, crying weakly. The rest of the exam is unremarkable. A complete blood count showed a WBC count of 34,000 with 85% lymphocytes. A chest radiograph revealed a non-specific, diffuse bilateral perihilar pattern (figure 3).

What’s Your Diagnosis?

1. Bordetella pertussis
2. Chlamydia trachomatis
3. Adenovirus
4. Bordetella parapertussis

Answer

There are plenty of hints that strongly suggest choice A, Bordetella pertussis. The clinical course combined with the marked lymphocytosis and positive close exposure to his adolescent mother, who had a chronic cough, is fairly compelling. Laboratory confirmation can be by culture on appropriate, selective media (Regan-Lowe or Bordet-Gengou) or by polymerase chain reaction (PCR), of a properly obtained specimen.

The specimen should be obtained as soon as the diagnosis is suspected, as recovery markedly diminishes after the paroxysmal stage begins. It should be obtained from the nasopharyngeal mucous, preferably with a deep nasopharyngeal swab or by aspiration. The specimen should then quickly be transported to the lab for processing. If it cannot get to the lab in a short time, placement into a transport system with Regan-Lowe media can be used (figure 4).

The same specimen can be used for rapid identification by the direct fluorescent antibody (DFA) technique or by PCR. Both techniques have limitations. The DFA is highly dependent on the skill of the technician, as there may be much debris that will fluoresce, making identification of the organism difficult. Also, the animal antisera may contain antibodies against normal nasopharyngeal flora resulting in a false positive. For these reasons, DFA is no longer recommended. And, of course, PCR is a technically demanding test, requiring a special room that limits any possibility of airborne contamination, resulting in false positives.

In a classic case like the one presented, confirmation should not be required for the patient to receive treatment. However, one should not expect treatment to have a significant effect on the clinical course of the patient once the disease has progressed to the paroxysmal stage. On the other hand, treatment will decrease the contagiousness of the disease, therefore limiting nosocomial spread. Droplet precautions are recommended for three weeks after the onset of the paroxysmal stage or five days after the onset of appropriate therapy.

The treatment of choice is erythromycin estolate for 14 days; however, other macrolides can be used with fewer adverse effects, and probably for shorter periods. According to the Red Book, azithromycin can be used at a dose of 10 mg/kg/day to 12 mg/kg/day for five days or clarithromycin at 15 mg/kg/day to 20 mg/kg/day for seven days can be used. The recommended dose of azithromycin for treating pertussis is higher than that recommended for otitis media. If erythromycin is to be used in a young infant, one should be aware and warn the parents of the increased risk of pyloric stenosis.

Trimethoprim-sulfamethoxazole can be used in those unable to take macrolides. Adjunctive therapy with oxygen should be considered, even though the baby may not be hypoxic between paroxysms. The use of bronchodilators should be individualized, and reserved for those with demonstrable bronchospasm. There is no proven role for steroids or immune globulin at this time. Prophylaxis with a macrolide should be offered to all household and close contacts regardless of immunization status. For more details about pertussis, I would consult the 2006 Red Book, which has an extensive section on the disease. Remember, it is now recommended that adolescents receive one of the new Tdap vaccine, which should go a long way toward preventing disease in infants.

Choice D, Bordetella parapertussis may cause a pertussis-like illness, but is generally less severe and lacks the lymphocytosis that is typical of pertussis. Diagnosis can be confirmed using the same techniques as for pertussis, and treatment is also the same.

Chlamydia trachomatis bronchopneumonia may cause a coughing illness in young infants that resembles pertussis but is not nearly as severe, with a “staccato” cough and similar chest radiograph. Also, the patient presented is at the upper limit of the age range normally seen. These patients may also have a history of conjunctivitis in the newborn period, indicating perinatal colonization. Diagnosis is usually with a PCR, DNA probe, DFA or enzyme immunoassay (EIA). Treatment is the same as for pertussis.

Adenovirus is capable of causing severe conjunctivitis (figure 5) and respiratory infections that may mimic pertussis. I would be more suspicious if the baby had conjunctivitis, especially if it’s hemorrhagic, at the same time as a severe coughing illness. Diagnosis is with viral culture. Some labs may have PCR capability. There will likely be sick contacts with conjunctivitis and/or pneumonia. From a practical standpoint, the diagnosis will initially be based on clinical suspicion. If hospitalized, patients with adenovirus should be in both contact and droplet precautions and discharged as soon as it is safe to do so. Treatment is supportive.

Commentary

I first met Dr. Cumana (far left in figure 6) at one of the National Pediatric Infectious Disease Seminars (NPIDS), which he attended on a regular basis with his wife and friends from Venezuela, Argentina and Mexico. At the end of the 25th NPIDS, we exchanged CDs that were loaded with cases we had collected over the years, and this case of pertussis was among those he passed on to me. Sadly, a few months later, Dr. Cumana died unexpectedly, and I remain grateful for his humanity and generosity.

As in the United States, pertussis in Venezuela is not uncommon, probably occurring much more often than documented. However, as I mentioned above, the newly recommended Tdap vaccine for adolescents and adults, should go a long way in protecting these young infants from exposure (like to their adolescent mothers), and therefore preventing infection with this organism. Although I am sure my immunity to pertussis is fairly high due to the anamnestic response of recurrent exposure over the years, I plan to take the vaccine as soon as it is available at our institution, while I’m still young enough to take it. Sanofi Pasteur’s Adacel is approved for patients up to 64 years, and my time is running out.

By the way, the organism, B. pertussis, was named after the Nobel Prize-winning Belgian bacteriologist Jules Jean Baptiste Vincent Bordet (1870-1961), who described the bacillus, and, with his brother-in-law, Octave Gengou, developed the long-used selective media to grow the organism. The word “pertussis” is from the Latin words for intensive cough. However, for some young infants, it could have been called tussis mortalis, Latin for “cough leading to death,” as mortality in infants prior to pediatric intensive care and the use of pertussis vaccine, was common.

Lastly, I have been concerned in recent years that the war(s), and their associated casualties, had fallen off the front pages, being relegated to the second or third sections, if mentioned at all. However, it appears that to those who count (the voters), it is still front and center. In all previous conflicts, the Medical Corps of the various services have always brought back improvements in the management of trauma and treatment of certain diseases. It would be nice to review the “lessons learned” from these conflicts (Iraq and Afghanistan), which may be of help in peacetime. If you have knowledge of new innovations or therapies that have come out of these areas, please let me know and I’ll collect the information and report back in a future column, or better yet, let one of you be a guest columnist to do the same. Please keep in touch at jhbrien@aol.com.