Pertussis overview

# Overview
Pertussis, also known as whooping cough, is a highly contagious infectious disease caused by the bacterium Bordetella pertussis, a Gram-negative, aerobic, non-motile coccobacillus. The incidence of pertussis is approximately 1.5 to 3.0 per 100,000 individuals, with approximately 5,000 to 7,000 cases reported annually. Pertussis is primarily a toxin-mediated disease. It is highly contagious and is usually transmitted to the human host by direct contact with aerolized mucus of infected individuals. Risk factors in the development of pertussis include no or incomplete vaccination against pertussis, exposure to infected individuals, infants or children < 5 years of age, and immunocompromised status. The clinical course of the illness is divided into three stages: catarrhal, paroxysmal, and convalescent.  If left untreated, the majority of patients develop low-grade fever and coryza (runny nose, occasional cough) for 1-2 weeks, followed by paroxysmal fits of whooping cough that may last 1-6 weeks, before finally recovering from the disease. Compared with children, adolescents and adults usually experience a milder course of the disease, and the characteristic whooping cough may be absent. Unvaccinated or incompletely vaccinated infants younger than 12 months of age have the highest risk for developing severe infection and life-threatening complications and death. Prognosis is generally excellent, but unvaccinated or incompletely vaccinated infants younger than 12 months of age have the highest risk for severe and life-threatening complications and death. Complications of pertussis may include apnea, pneumonia, otitis media, pneumothorax, refractory pulmonary hypertension, and seizure. Pertussis is usually suspected based on clinical findings and confirmed by either nasopharyngeal culture, polymerase chain reaction (PCR), or serology. The mainstay of treatment of pertussis is antibiotic therapy with either a macrolide or trimethoprim-sulfamethoxasole. Post-exposure prophylaxis may be recommended among high-risk individuals. The primary prevention method for pertussis is vaccination with multiple doses of the DTaP vaccine during childhood and adolescence/adulthood. Patients who had been infected with pertussis or who have received vaccination against pertussis in the past may be re-infected in the future, but typically experience a milder course of the disease.

# Historical Perspective
The first description of Pertussis dates back to the 12th century. The earliest outbreaks of pertussis were recognized by Bahaodwole Razi in 1502 in Persia and by Guillaume de Baillou in 1578 in France. Bordetella pertussis was first isolated by Jules Bordet and Octave Gengou in 1906. Bordet and Gengou developed the first vaccine and serological test for Pertussis. In the 1940s, Grace Elderling, Loney Gordon, and Pearl Kendrick combined diphtheria and tetanus with the pertussis and develop the first combination DTP vaccine. In response to adverse side effects of DTP, a safer acellular DTaP vaccine was created in Japan in 1981.

# Pathophysiology
Pertussis is primarily a toxin-mediated disease. Bordetella pertussis is highly contagious and is usually transmitted to the human host by direct contact with aerolized mucus of infected individuals. B. pertussis attaches to the cilia of the respiratory epithelial cells, proliferates and produces virulence factors that paralyze the cilia, and causes inflammation of the respiratory tract, which interferes with the clearing of pulmonary secretions. B. pertussis  utilizes virulence factors - including pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbriae (FIM), adenylate cyclase toxin (ACT), tracheal cytotoxin (TCT), lipooligosaccharide (LOS), and dermonecrotic toxin (DNT) - to attach, proliferate, and and evade the host immune system.

# Causes
Bordetella pertussis is a Gram-negative, aerobic, non-motile, non-spore-forming coccobacillus. It is the pathogen responsible for pertussis (whooping cough). Unlike B. bronchiseptica, B. pertussis is not motile. Humans are the only known reservoir for B. pertussis. The lipopolysaccharide-containing outer membrane of B. pertussis is unique and contains a different phosphate composition from other bacterial outer membranes.

# Differential Diagnosis
Pertussis must be differentiated from other causes of cough, dyspnea, and coryza, such as asthma, pneumonia, bronchiolitis, croup, common cold, cystic fibrosis, foreign body aspiration, gastroesophageal reflux disease, and sinusitis.

# Epidemiology and Demographics
In the United States, the incidence of pertussis is approximately 1.5 to 3.0 per 100,000 individuals, with approximately 5,000 to 7,000 cases reported annually. The incidence of pertussis is thought to be on the rise due to the decline in vaccination rate and diminished herd immunity. Infants and young children < 5 years of age are more commonly infected with pertussis than adults. There is no gender predilection for the development of pertussis. Pertussis-related deaths are rare, but are more common in developing countries, among infants < 6 months of age, and among adult patients with significant co-morbidities.

# Risk Factors
Risk factors in the development of pertussis include no or incomplete vaccination against pertussis, exposure to infected individuals, infants or children < 5 years of age, and immunocompromised status.

# Natural History, Complications and Prognosis
The clinical course of the illness is divided into three stages: catarrhal, paroxysmal and convalescent.  If left untreated, the majority of patients develop low-grade fever and coryza (runny nose, occasional cough) for 1-2 weeks, followed by paroxysmal fits of whooping cough that may last 1-6 weeks, before finally recovering from the disease. Compared with children, adolescents and adults usually experience a milder course of the disease, and the characteristic whooping cough may be absent. Unvaccinated or incompletely vaccinated infants younger than 12 months of age have the highest risk for developing severe infection and life-threatening complications and death.  Complications of pertussis include apnea, pneumonia, seizure, and death. Prognosis is generally excellent, but unvaccinated or incompletely vaccinated infants younger than 12 months of age have the highest risk for severe and life-threatening complications and death.

# Diagnosis

## History and Symptoms
Initially, symptoms of pertussis include cough, sneezing, and runny nose. After one to two weeks, the cough changes character, and patients typically experience whooping cough, which are paroxysms of violent coughing followed by an inspiratory "whooping" sound.

## Physical Examination
The physical examination of a patient with pertussis is usually unremarkable. Low grade fever, cyanosis, and conjunctival hemorrhages may be observed. Involvement of the lower respiratory tract indicates another underlying or concomitant process.

## Laboratory Findings
Several laboratory tests may be used to diagnose pertussis. Culture, obtained by nasopharyngeal swab, is considered the gold standard for diagnosis. Other tests that can be performed include polymerase chain reaction (PCR) and serology.

## Chest X-Ray
Chest radiography is usually unremarkable among patients with pertussis. Possible findings include atelectasis and lymphadenopathy.

## Other Diagnostic Studies
Pertussis can also be diagnosed using direct flourescent antibody (DFA) and pulsed-field gel eletrophoresis tests.

# Treatment

## Medical Therapy
The mainstay of treatment of pertussis is antibiotic therapy. Early treatment is essential: individuals aged >1 year should be treated within 3 weeks of cough onset, infants aged <1 year and pregnant women (especially near term) should be treated within 6 weeks of cough onset. The recommended antimicrobial agents for treatment of pertussis are macrolides. Trimethoprim-sulfamethoxasole is an alternative in those who do not tolerate macrolide antibiotics.

## Primary Prevention
The primary prevention method for pertussis is vaccination using the DTaP vaccine. Five doses are recommended in children, with a booster dose recommended during adolescence/adulthood using a similar vaccine with smaller concentrations of diphtheria and pertussis toxoids known as Tdap.

## Secondary Prevention
Patients who had been infected with pertussis or have received vacccination against pertussis in the past may be re-infected (milder symptoms upon re-infection). Effective measures of secondary prevention include post-exposure antibiotic prophylaxis for individuals who are considered high-risk for developing the disease or having serious complications. Antibiotic prophylaxis regimens are similar to those used for treatment, and vary with the individual's age.