Pertussis

Pertussis

Synonyms

Bordetella

Bordetella pertussis and Bordetella parapertussis are known to cause clinical symptoms in humans.

Related Conditions

Whooping cough, “100 days cough”, necrotizing pneumonia, respiratory tract infection with paroxysmal cough, respiratory failure, pulmonary hypertension

1. Description of the problem

What every clinician needs to know

Pertussis typically manifests as a cough illness with three distinct phases. There is a broad range of complications associated with B. pertussis infection. In children, these include conjunctival hemorrhage, inguinal hernia, pneumonia, respiratory distress syndrome, seizures, encephalopathy, and – mainly in young infants – apnea, pulmonary hypertension and sudden deaths.

Clinical features

Three phases of infection after the incubation period (6-10 days):

1- Catarrhal phase: 1-2 weeks, most contagious, indistinguishable from a mild upper respiratory tract infection (URI).

2- Paroxysmal phase: 3-6 weeks, with increase in cough frequency and severity with spells of coughing, characteristic whoop, vomiting, cyanosis and apnea.

3- Convalescent phase: up to several months with gradual decrease in symptoms.

Paroxysmal cough and apnea were the most frequent presentations. In one study only 31% of patients satisfied the definition of cough lasting longer than 2 weeks and one or more of paroxysmal cough, cough ending in vomiting or apnea and inspiratory whoop. Clinical manifestations of pertussis vary with age. Pertussis is most severe in young infants, with a case-fatality rate of approximately 1%.

2. Emergency Management

Supportive care is the primary goal in treatment for pertussis. Close attention to hydration status, nutritional support, treatment of hypoxia and respiratory distress.

1- Airway protection if there is any evidence of apnea or severe respiratory distress associated with paroxysmal coughs.

2- Respiratory support for respiratory failure secondary to pneumonia or superinfection with other organisms.

3- Cardiovascular support in severe cases associated with pulmonary hypertension and cardiovascular collapsed in systemic infection or sepsis.

3. Diagnosis

Diagnostic criteria and tests

Culture from the nasopharyngeal secretions is the gold standard to diagnosis B. pertussis infection. To increase the yield, specimens should be immediately plated onto selective Regan Lowe agar or Bordet Gengou medium. Generally 7-10 days are required for growth, isolation and identification. Highest yield is when specimens are obtained early in the course of illness, i.e., during the early catarrhal phase of the illness.

Polymerase chain reaction (PCR) is rapidly evolving as it provides a sensitive, rapid means for laboratory diagnosis in low yield culture circumstances. PCR sensitivity also decreases somewhat with the duration of cough and previously immunized individuals, it is nevertheless a significantly more robust tool for diagnosis for those in the later stages of the disease or for those who have already received antibiotics.

The greatest sensitivity and specificity for the serological diagnosis of B. pertussis infection is the ELISA measurement of IgG and IgA antibodies to pertussis toxin (PT) with two-fold increase in titer between acute and convalescent phases (24). Limitation in infants younger than 3 months, who do not develop measurable antibodies.

Establishing the diagnosis

Pertussis shares many similar features with other common viral infections such as RSV, influenza and parainfluenza infections, therefore it is important to pay close attention to the followings:

1- History of exposure to individuals with cough

2- PMH of not having received immunization for pertussis

3- Mild leukocytosis and moderate lymphocytosis

4- Lobar consolidation frequently involved many lobes on CXR

5- Clinical symptoms: paroxysmal coughing spells, whooping cough, post-tussive emesis, seizures, encephalopathy

6- Septic-like picture with cardiovascular collapse in conjunction with respiratory failure.

Differential diagnosis

Pertussis should be considered in the differential diagnosis for all patients who presented with aforementioned clinical symptoms.

Common and typical seasonal viral infections can share many similar clinical features:

• Respiratory syncitial virus (RSV); URI symptoms, fever, cough, post tussive emesis, apneas especially in infants, and superinfection with bacterial pneumonia

• Influenza and parainfluenza viruses: fever, URI symptoms, cough, encephalopathy, pneumonia.

4. Specific Treatment

Treatment of pertussis should be both symptomatic and directive at the causative organism.

1- Symptomatic treatment: fluid and nutrition support, avoiding cough, maintain normal oxygenation. Assisted ventilation in severe cases with apnea, pneumonia and respiratory failure.

Treatments of extreme leukocytosis (>100,000 WBC) and pulmonary hypertension are extremely challenging. Advanced technology to reduce leukocytosis has been used such as double volume exchange transfusion and plasmapheresis in these case. ECMO has been used in protracted respiratory and cardiovascular collapses associated with pneumonia and pulmonary hypertension.

2- Macrolides are the recommended treatments for pertussis

Antibiotics eradicate B. pertussis from the airway but limit the severity of disease only if start in the catarrhal phase. The standard treatment of pertussis has been a full dose of erythromycin for 14 days but evidence has suggested that a shorter 7-day course is equally effective.

Azithromycin has been shown to be effective in eradicating B. pertussis in 97% of cases after 2-3 days and 100% after 14-21 days. Benefits of Azithromycin are fewer GI symptoms, better tolerated and significant shorter length of therapy.

Clarithromycin and trimethoprim-sulfamethoxazole (TMP-SXM) can also be used as alternative treatments for B. pertussis.

3- Antihistamines, diphenhydramine, corticosteroids and salbutamol have been used to treat cough, however benefits remain uncertain.

AAP recommends chemoprophylaxis to all household contacts and other close contact regardless of age and immunization status. Therapy for prophylaxis is similar to treatment of pertussis.

Refractory cases

Co-infection with other viruses (RSV, influenza, parainfluenza) or other bacteria (nasopharyngeal flora, staph) should be considered. Broader spectrum of antibiotic and anti-viral coverage should be added until further cultures available.

Leukodepletion via double volume exchange transfusion of plasmapheresis has shown to be beneficial in patients with severe leukocytosis (WBC >60,000). Advanced assisted ventilation and ECMO are used for retracted respiratory failure due to infection and pulmonary hypertension.

Pulmonary hypertension is a known and common complication of severe pertussis infections especially in infants. Treatment for pulmonary hypertension such as nitric oxide, milrinone, 100% oxygen, bicarb infusion and fluid bolus should be instituted if patient continue to have evidence of pulmonary vascular vasoconstriction with acute and severe episodic hypoxemia.

5. Disease monitoring, follow-up and disposition

Expected response to treatment

Treatment is aimed to eradicate the organism. Antibiotic therapy has some effects on the severity of the disease only if treatment is started in the early phase. Eradication of the organism is 100% 7 days after completion of treatment in both erythromycin and azithromycin. However symptoms of pertussis may persist long after clearance of the infecting organisms.

Follow-up

Nutritional support with close attention to hydration is important in the immediate post infection. Neurodevelopment evaluation is essential for infants with severe infection especially those who were hospitalized in ICU.

Pathophysiology

Aerosolized droplets are the transmitting vehicles for B. pertussis. Several virulent factors facilitate the invasion and damage of the epithelium of the airway and the alveoli by interfering with ciliary movements. These factors are namely fimbriae, pertactin, pertussis toxin, filamentous hemagglutinin, adenylate cyclase, tracheal cytotoxin, dermonecrotic toxin, lipopolysaccharide, tracheal colonization factor, serum resistance factor and type III secretion.

The combined actions of the toxins have direct effects on the lung parenchymal while some affect the immune regulation.

Immunoparalysis with failure to overcome primary or associated secondary infections. Adenylate cyclase impairs the bactericidal function of immune effector cells and inhibits neutrophil recruitment to lungs. Lymphocytosis promoting factor of B. pertussis appears to act directly on lymphoid cells, causing immunodepletion in the thymus, made patient more vulnerable to co-infection.

Pertussis infections of the lung parenchyma show evidence of necrotizing bronchitis, bronchiolitis and alveolitis (“necrotizing pneumonia”) but not a primary thrombosis of pulmonary vessels. A consequence of toxins mediated process or an aggressive infection affecting the bronchial and alveolar epithelium may lead to problems with secondary pulmonary vascular resistance and pulmonary hypertension.

Vascular occlusion without evidence of thrombosis is considered a contributing factor to pulmonary hypertension. Stasis of lymphocytes and neutrophils was noted in the small and medium sized arteries and veins.

Hypoxemia is the result of extensive damage to the alveolar and bronchiolar epithelium. The debris of necrotic tissues contribute to the hallmark of thick tenacious secretion of this disease. The combination of hypoxia, abundant and tenacious secretion and the damage of the alveoli epithelium exacerbates the vaso-reactivity of the pulmonary vasculature further accentuates pulmonary hypertension.

Epidemiology

Whole-cell pertussis vaccine was introduced in 1940s with the steady decrease in reported cases from 200,000 annually to the nadir of 1,010 in 1976 in the US population. However, since that time, there has been a substantial increase in the number of cases reported reaching 8.9 per 100,000 in 2004 with nearly 19,000 provisional reported cases.

It is also widely noted that in recent years there is a general shift in the age distribution of pertussis, with adults and adolescents an under-recognized but significant source of infection for neonates and infants.

Pertussis is not a “childhood disease”. Waning of both vaccine-induced immunity and infection-acquired immunity is widely cited as an important reason for recent epidemiologic trends. Furthermore, disease manifestations are frequently atypical when re-contract pertussis. As such, their illness is often under diagnosed and poses a potentially serious public-health concern.

Prognosis

Pneumonia is the most frequent complication. Others are sinusitis, otitis media, both bacterial and viral superinfection, nutritional deficiency and neurological complications which are due mostly to hypoxia during coughing spells and apnea.

Infants and adults carry higher risk of complication. Neonatal pertussis disease is more virulent and associated with highest morbidity and mortality. 10% of survivors sustained neurodevelopmental problems. <10% of survivors had subsequent respiratory disease.

Associated risk factors to develop respiratory or neurodevelopmental problems are: extreme age (<2mo), no previous immunization. Additional risk factors after adjustment for age and immunization are the present of co-morbidity, lymphocytosis, ICU admission for seizure or encephalopathy or shock.

Death from pertussis is inversely related to age with 90% of reported deaths occurring in unvaccinated infants less than 1 year old.

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