Share this article on:


Chan, Linda M.D.


The Pediatric Infectious Disease Journal: June 1997 - Volume 16 - Issue 6 - p 631-632
Your Diagnosis, Please

Accepted for publication Feb. 12, 1997.

Division of Infectious Diseases; Children's Hospital; Oakland, CA

A previously healthy 2-month-old full term Hispanic boy with a 3-day history of cough and fever was admitted to a local hospital. A diagnosis of pneumonia was made based on the chest radiograph which showed a right lower lobe infiltrate. Additional laboratory tests included complete blood count, urinalysis and cerebrospinal fluid analysis, the results of which were all unremarkable. The patient was treated empirically with ampicillin and cefotaxime. Blood, urine and cerebrospinal fluid cultures were all negative and a repeat chest radiograph was normal after 5 days of hospitalization. The patient was discharged home.

Three weeks after discharge the infant again presented to the same hospital with 1 week of fevers and worsening cough. In the emergency room he was in severe respiratory distress with a blood oxygen saturation of 88% (breathing room air), heart rate 240 beats/min, respiratory rate 76 breaths/min and axillary temperature 38.1°C. The infant had intercostal retractions and was grunting. Chest radiograph showed a right middle lobe infiltrate. The infant was intubated because of deteriorating respiratory status, stabilized and transferred to Children's Hospital Oakland. On further questioning the patient's mother reported that she had had a cough for ∼1 month before onset of the child's illness.

Vital signs on admission revealed: temperature 38.4°C axillary; heart rate 200 beats/min; blood pressure 110/60 mm Hg; respiratory rate 35 breaths/min on the ventilator with FiO2 of 1.0; and weight 4.8 kg. Initial capillary blood gas revealed a pH of 7.41, partial pressure of carbon dioxide (pCO2) of 38 torr, partial pressure of oxygen (pO2) of 62 torr and bicarbonate of 23 meq/l. Physical examination showed a pharmacologically paralyzed and sedated infant. His pupils were equal and reactive to light and there was no conjunctival injection or discharge. Tympanic membranes were clear. There were diffuse coarse breath sounds with rales and rhonchi. The cardiac examination revealed sinus tachycardia. The abdomen was soft without organomegaly. Peripheral perfusion was good and no rashes were present.

Initial laboratory data included a white blood cell count of 118 000/mm3 with 42% neutrophils, 11% band forms, 41% lymphocytes and 4% monocytes. Hemoglobin was 11.1 g/dl, hematocrit 30.6% and platelet count 652 000/mm.3 Cerebrospinal fluid analysis showed: 1 white blood cell/mm3; 0 red blood cell/mm3; protein 126 mg/dl; and glucose 85 mg/dl. Serum electrolytes and liver transaminases were normal. Endotracheal aspirate was sent for routine culture, acid-fast bacilli smear and culture. Nasopharyngeal swabs for viral, Mycoplasma pneumoniae, Chlamydia, Ureaplasma and pertussis cultures were sent. Serology for M. pneumoniae, quantitative immunoglobulins and HIV antibody test were obtained. The patient was treated with with ampicillin, cefotaxime and erythromycin empirically.

On the third hospital day the infant developed generalized seizures and an electroencephalogram showed multifocal sharp wave discharges. Computed tomography of the head revealed global hypoxic-ischemic changes. His peripheral white blood cell count was 120 000/mm3, hemoglobin 8.8 g/dl and hematocrit 26.5%. On the fourth hospital day the patient had metabolic acidosis and developed increased ventilatory requirement and hypotension, and his chest radiograph showed worsening bilateral pneumonia. An echocardiogram showed evidence of increased pulmonary vascular resistance and severe pulmonary hypertension. The patient remained hypotensive in spite of receiving large amounts of fluid for volume expansion, dopamine and epinephrine infusions. He was then placed on venoarterial extracorporeal membrane oxygenation. The diagnosis was established after the results of the respiratory cultures and serologic studies became available.

Linda Chan, M.D.

Division of Infectious Diseases; Children's Hospital; Oakland, CA

For denouement see p. 634.

Back to Top | Article Outline

DENOUEMENT-Continued from p. 632

The nasopharyngeal swab from admission showed heavy growth of Bordetella pertussis 3 days after the culture was sent. The source of infection for this infant is unknown. It is possible that his mother, with a history of prolonged cough, was the source. Respiratory cultures for Chlamydia, Ureaplasma, Mycoplasma, mycobacteria and viruses were negative. Quantitative immunoglobulins were normal for age and an HIV antibody test was negative. The patient was treated with intravenous erythromycin for pertussis. In addition on the second hospital day, therapy was also started with ceftazidime, gentamicin and trimethoprim/sulfamethoxazole for presumed secondary bacterial pneumonia based on endotracheal aspirates which grew Acinetobacter baumannii and Stenotrophomonas maltophilia. The infant received extracorporeal membrane oxygenation for 23 days and was then decannulated from the circuit and placed on volume ventilation. The subsequent hospital course was complicated by development of chronic lung disease and persistent pulmonary atelectasis. The patient remained intubated for another 22 days and was finally extubated successfully. His respiratory status slowly improved and he was discharged home 4 months later without oxygen supplementation.

Pertussis continues to be an important pathogen causing respiratory illness and morbidity in young children. Since the availability of the whole cell vaccine in the late 1940s, the incidence of pertussis has declined in this country from a high in 1934 of 260 000 cases to a low of 1010 cases in 1976. However, the incidence has increased since 1981. It is unclear whether this represents a true increase in incidence of pertussis or is a function of improved reporting. There has also been a shift in the infected age groups to involve not only the very young infants but also children 10 years of age or older.1 This again may reflect improved reporting of cases among individuals older than 10 years of age. According to the Centers for Disease Control and Prevention, from 1992 to 1994, 41% of pertussis cases were seen in infants ≤1 year of age, 20% from 1 to 4 years old, 11% from 5 to 9 years old and 28% ≥10 years old. Rates of hospitalization and complications are highest in children <6 months of age and decline with increasing age. Complications such as pneumonia, encephalitis and seizures are all more common in infants <2 months old.

Complications of the disease include apnea, bradycardia, cyanosis, seizures, encephalopathy, severe respiratory distress, secondary bacterial pneumonia and death.2 There have been a few case reports of pulmonary hypertension with a course similar to our patient's, leading to shock and death from pertussis infection.3 The exact mechanism whereby B. pertussis causes pulmonary hypertension is unclear. However, it has been shown that pulmonary hypertension can lead to an increased right ventricular end diastolic volume and leftward shift of the septum. Consequently decreased left ventricular compliance occurs and left ventricular end diastolic pressure is increased, thus impeding left ventricular filling and cardiac output.3,4 Hyperventilation and alkalinization represent the conventional means by which to manage pulmonary hypertension. Other more recent and aggressive modalities include nitric oxide and extracorporeal membrane oxygenation for the critically ill infants not responding to conventional therapies.

Pertussis is not easy to diagnose because growth of the B. pertussis from NP culture is difficult. NP swab obtained by calcium alginate-tipped swabs must be plated promptly onto appropriate media. Seven days of incubation are often required for the growth of the organism. The highest rate of recovery is achieved if the culture is obtained during the initial 3 to 4 weeks of illness in the catarrhal stage when the disease is least suspected. Isolation rates are reduced by immunization, antibiotic use and advanced disease. Other diagnostic methods include a direct fluorescent antibody test used to detect the organism in smears from NP swabs. This test, although rapid, has both false positive and false negative results. Another laboratory finding typically seen is leukocytosis with marked lymphocytosis.2,5,6 Gan and Murphy2 in their series reported total leukocyte counts ranging from 4.4 to 82.4 × 109/l (mean, 21.4 × 109/l). Leukemoid reactions (total leukocyte count, >50 × 109/l) were seen in 4% of patients.2

Antibiotics for the treatment of pertussis are effective when given early in the catarrhal stage. Erythromycin (50 mg/kg/day) for 14 days is the drug of choice because it penetrates well into the nasopharyngeal secretions and has good activity against B. pertussis. Ampicillin, trimethoprim/sulfamethoxazole, tetracycline and rifampin all have in vitro activity against B. pertussis, but their rates of bacteriologic eradication are inferior to that of erythromycin.

Killed whole cell pertussis vaccines have been widely used since the 1940s as the mainstay of prevention. The vaccine was licensed in 1945 and has been used successfully in combination with diphtheria and tetanus toxoids. It is 60 to 70% effective in preventing disease after two doses and 80 to 90% after three doses.1,2 Natural infection confers permanent and complete immunity. Encephalopathy within 7 days of injection and immediate anaphylaxis constitute the only absolute contraindications for the use of this vaccine.

In 1991 the first acellular pertussis vaccine combined with diphtheria and tetanus toxoids, ACEL-IMUNE®, became available in the United States. ACEL-IMUNE® is produced by Lederle-Praxis Biologicals and contains four antigens, pertussis toxin, filamentous hemagglutinin, pertactin and agglutinogen. The diphtheria and tetanus toxoids is equally immunogenic and has less frequent and less severe adverse reactions compared to the whole cell products. A second acellular vaccine, Tripedia®, produced by Connaught Laboratories, was approved by the Food and Drug Administration in July, 1996, to be used for the primary series of immunization in infants 2 months of age and older. This vaccine contains pertussis toxin and filamentous hemagglutinin only.

Vaccine-induced immunity wanes over time. Protection is reduced starting 3 years after vaccination and continues to diminish thereafter with time.7,8 Subsequent disease in previously immunized individuals is mild; however, these individuals can transmit the organism to infants and young children. In the future booster immunization with the acellular vaccine to adolescents and adults in addition to early childhood vaccination may be necessary to protect children from this serious disease.

1. Centers for Disease Control. Pertussis surveillance: United States, January 1992-June 1995. MMWR 1995;44:525-9.
2. Gan VN, Murphy TV. Pertussis in hospitalized children. Am J Dis Child 1990;144:1130-4.
3. Goulin GD, Kaya KM, Bradley TS. Severe pulmonary hypertension associated with shock and death in infants infected with Bordetella pertussis. Crit Care Med 1993;21:1791-4.
4. Perkin RM, Anas NG. Pulmonary hypertension in pediatric patients. J Pediatr 1984;105:511-22.
5. Heininger U, Stehr K, Cherry JD. Serious pertussis overlooked in infants. Eur J Pediatr 1992;151:342-3.
6. Waler JA. Index of suspicion: Case 3 presentation. Pediatr Rev 1996;17:181-3.
7. Committee on Infectious Diseases, Report of the Committee on Infectious Disease, Elk Grove Village, IL: American Academy of Pediatrics, 1994:355-67.
8. Feigin RD, Cherry JD. Pertussis. In: Feigin RD, Cherry JD, eds. Textbook of pediatric infectious disease. ed 3. Philadelphia: Saunders, 1992:1208-18.

Pertussis; pulmonary hypertension; extracorporeal membrane oxygenation; leukemoid reaction

© Williams & Wilkins 1997. All Rights Reserved.