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CASE 9
The patient was an 18-day-old female who at initial presentation was brought to the emergency department by her mother after a 3-day bout of coughing. Her mother also reported that her daughter had been “spitting up” more than usual and had episodes of tachypnea. During the initial exam, a rapid respiratory syncytial virus test was obtained with negative results. A review of systems was notable only for a nonproductive cough. Her pulse was 168 beats/min, her respiratory rate was 32 inspirations per minute, and oxygen saturation was 92 to 95% on room air. Her complete blood count was significant for a white blood cell count of 15,300 cells/μl with an absolute lymphocyte count of 10,900 cells/μl. The mother had a chronic cough of 4 weeks’ duration but had been afebrile. Six weeks before this patient’s admission, her 10-year-old brother also had a prolonged coughing illness that responded to breathing treatments and inhaled steroids.
After initial examination, the child was admitted to the hospital. Her initial hospital course was uneventful, and she was discharged after 2 days. However, she was readmitted the following day with worsening respiratory symptoms. Over the next several days she had increasing difficulty breathing, tachypnea up to 100 breaths per minute, and oxygen saturations in the low 80s during coughing episodes. She was admitted to the pediatric intensive care unit for respiratory support. She had an extremely complicated and prolonged intensive care unit course that included pulmonary hypertension, acute respiratory distress syndrome, and health care-associated pneumonia. After a 10-week hospital stay, she was eventually discharged to return home, where her recovery was uneventful.
1 1. Nucleic acid amplification testing (NAAT) was performed on a nasopharyngeal swab. The amplified DNA was screened for a particular agent with positive results, and the patient was begun on azithromycin. What was the etiologic agent infecting this patient? What findings in this case support this conclusion?
2 2. Why is a nasopharyngeal specimen superior to any other clinical specimen for diagnosing this infection? Why has NAAT replaced culture for the diagnosis of this pathogen?
3 3. Describe the clinical course of this disease. Why didn’t the patient respond to the antimicrobial she was given?
4 4. What about the pathogenesis of this disease puts this patient at increased risk for health care-associated pneumonia?
5 5. A vaccine exists to prevent infections such as the one in this patient. Explain why and how this patient was infected. What does this case tell you about the vaccine? Vaccine strategies for preventing infections with this organism have recently changed. What changes in the vaccine are making better prevention possible? In particular, what groups of individuals should receive this new vaccine?
6 6. What type of isolation precautions should have been used while this patient was in the hospital? What therapy (if any) should have been provided to health care workers in close contact with this patient prior to institution of appropriate precautions?
CASE 9 CASE DISCUSSION
1. The patient was infected with Bordetella pertussis, the causative agent of whooping cough. With classic whooping cough, children have paroxysmal coughing, which is a series of coughs during a single expiration. Paroxysms are often accompanied by a “whoop” sound in children due to rapid inspiration through a narrow trachea. (An audio file of a child with pertussis can be found at www.immunizationed.org.) Because of repetitive coughing and resulting disruption of breathing, children will have abnormal oxygen exchange and will often turn red and sometimes blue. The repetitive coughing may also result in vomiting or choking on respiratory secretions. Although the classic “whooping” sound was not described for this child, she did have bouts of coughing leading to increased respiration, decreased oxygenation, and posttussive vomiting. In infants <6 months old, apnea is more common than whooping inspirations. Further, the patient had a lymphocytosis, which is commonly seen in pertussis. Although the etiologic agent is a bacterium, the disease is toxin mediated, explaining the rise in lymphocyte count. Historically, the pertussis toxin (a key virulence factor of B. pertussis) has also been described as the “lymphocytosis-promoting factor.” Clinically, lymphocytosis, often as high as 70 to 80%, is routinely seen in patients with pertussis and is a distinguishing characteristic of this infection.
2. B. pertussis specifically binds to ciliated epithelial cells. This binding is mediated primarily by filamentous hemagglutinin, an important virulence factor of this organism. Since the nasopharynx is lined with ciliated epithelial cells, it is the most sensitive site for the detection of B. pertussis.
Culture has long been the gold standard for the laboratory diagnosis of pertussis owing to its superior specificity (~100%). However, there are many disadvantages to B. pertussis culture. First, the organism is very labile outside of the host. Second, it must be cultivated on specialized media such as Bordet-Gengou or Regan-Lowe agar. These attributes make the bacterium difficult to isolate. Third, it generally takes 7 to 10 days to isolate and identify B. pertussis from culture. In Fig. 9.1, we see an isolate of B. pertussis that grew after 7 days of incubation on a charcoal-containing medium, Regan-Lowe agar. In outbreak settings where B. pertussis can be rapidly spread from person to person, culture is too slow. Lastly, the clinical course of pertussis is complex (see answer 3), and the organism is generally only recovered during the first 2 weeks of illness. Sensitivity of culture during the first 2 weeks of pertussis is 30 to 60%, and it drops dramatically (1 to 3%) by the third week of illness. Sensitivity of culture is also negatively affected by antibiotic administration and prior vaccination. Nonetheless, the Centers for Disease Control and Prevention (CDC) recommends culturing of nasopharyngeal specimens during an outbreak so that specificity is preserved and isolates are obtained for susceptibility testing and epidemiologic studies.
Figure 9.1 Organism infecting this patient.
For many years, direct fluorescent-antibody assay (DFA) for B. pertussis was done. This assay takes ~2 hours, versus 7 to 10 days for culture, but it has a sensitivity of only 50 to 65%, and false-positive results may occur, especially when laboratorians are unaccustomed to reading these DFA smears. DFA is no longer in the CDC’s diagnostic algorithm for pertussis because of these limitations.
NAAT, and in particular PCR, has become the method of choice for diagnosing pertussis. Because PCR does not require