Pertussis: The re-emerging disease

Pertussis: The re-emerging disease

Pertussis is also called a whooping cough because of characteristic whoop during its coughing. It is acute respiratory tract infection and can be life threatening at all ages with multiple complications. It has been described in medical literature since many centuries. It was a very common illness taking toll on young lives in the pre vaccination era. It is re-emerging in recent years because of many factors. So, it is again becoming a health concern in all parts of the world.

Etiology of Pertussis disease:

Pertussis is an infectious disease. Bordetella is small, fastidious and gram negative coco-bacilli. Bordetella pertussis is the cause of Pertussis disease in areas of the world where it is endemic. Even in areas where it is not endemic and occurs sporadically, Bordetella pertussis is the cause of infection. Some rare cases of Pertussis disease are because of Bordetella parapertussis. Bordetella holmesii can cause disease in immune-compromised hosts. Bordetella bronchiseptica infects mainly animals and can cause rare infection in humans who are immune-compromised and come in contact with animals. Bordetella pertussis and Bordetella parapertussis can infect only humans and some other primates. It can not infect other animals extensively. The coughing similar to Pertussis disease can be caused by Mycoplasma, adenovirus, RSV, influenza and parainfluenza virus.

Epidemiology of Pertussis disease:

Bordetella can colonize only ciliated columnar epithelium. Pertussis was the disease which was very common in the pre vaccination era. After widespread use of DPT vaccine the disease Pertussis and the deaths caused by that was largely reduced. Pertussis disease though decreased significantly it still remains a considerable health concern because of non coverage of vaccination and also because immunity after vaccinations may wane after some years. 

WHO estimates say there were 16 million cases of pertussis and 1.5 lakh childhood deaths because of Pertussis.In India after the launch of Universal Immunization Programme (UIP) the incidences of pertussis disease has decreased significantly. In 1970 India reported 200000 cases of Pertussis, the number reduced to 163000 in 1987 and to 37000 in 2011 and to 23000 in 2017. So we can see there is a steady decline of Pertussis cases in children in India. But still the number looks small as a small proportion of total cases actually get reported. Some cases caused by other viruses are also reported falsely in this figure. Additionally the data in adolescents and adults is lacking in the total figure.

How does Pertussis spread?

Bordetella pertussis is released in the air as aerosol droplets by the infected person. It stays in environment for very short span of time. The attack rate is almost 100 percent in susceptible contacts. Almost all who come in close contact of infected person and who are not immunized get the infection and Pertussis disease. Those who are immunized get subclinical infection 80 percent of times. Chronic carrier stage is not yet reported in humans. The source can be found in infected person by tracing the contacts.

Pathogenesis of Pertussis disease:

Bordetella spreads by aerosol droplets as discussed earlier. Bordetella can colonize only ciliated epithelium of the respiratory tract. When it comes in contact with ciliated epithelium it gets attached to this epithelium. Filamentous hemagglutinin, some agglutinogens non fimbrial surface protein called pertactin (Prn) are very important for the attachment to the ciliated epithelium. When it gets attached to the ciliated epithelium of the respiratory tract the host’s immunity tries to fight the infection. Tracheal cytotoxin, a dermonecrotic factor, adenylate cyclase helps the Bordetella to suppress the host immune mechanism which acts locally to prevent the attachment of Bordetella. All these toxins along with Pertussis Toxin (PT) help the Bordetella to damage the ciliated epithelium of the respiratory tract. Antibody to PT neutralizes the toxicity of the Bordetella and antibody to Prn provides protection by not allowing Bordetella to attach to respiratory epithelium.

What are clinical manifestations of the Pertussis disease?

Classically Pertussis disease presents in 3 stages. 

· Catarrhal stage: This stage occurs 3-12 days after the infection. The incubation period is about 3-12 days. This stage lasts for 10 to 14 days. In this stage as its name suggests patients show symptoms that are non specific to disease. There is nasal congestion and rhinorrhea, conjunctival congestion, mild grade fever, sneezing and lacrimation. 

· Paroxysmal stage: This stage usually comes after the catarrhal stage. In this paroxysmal stage the main symptom is coughing. It usually lasts for 2-6 weeks. Cough is initially dry cough that comes intermittently and appears irritant then develops into prolonged whoop which is characteristic of the disease pertussis. Child particularly a toddler appearing playful and comfortable with experiencing sudden aura holds the comforting parent tightly and starts taking deep breath followed by the cough of exhalation which is machine gun like an interrupted coughing. While coughing there is a wide opening of eyes with watering and redness and bending forward position with chin tightly holding comforting parents shoulder.  This Coughing is followed by a typical whoop sound and vomiting post-tussive followed by inhalation of air. Child is exhausted after the episode. The number and severity of these episodes increase over days and ,ay remain so for 1 month. Child may experience more than one episode per hour.

· Convalescent stage: Over time the number and severity of paroxysms decrease and that is the beginning of the convalescent stage. Convalescent stage may last up to 2 weeks.

Though these distinct stages are described they may not be distinguished in young infants especially those less than 3 months of age. The young infant may not experience the catarrhal stage or the catarrhal stage in such young infants may go unnoticed. After some days infants start to startle to light, sound, air which may initially appear normal but keeps on increasing in severity finally leading to a point where infants appear anxious, red faced, gasping or gagging or choking with extremities becoming flail and cold. Infants do not have enough muscular power to show the whoop and cough may not appear. Apnea and cyanosis may be followed after the attack. Apnea with cyanosis is more common with Pertussis disease in infants. Other viruses which produce similar symptoms like RSV may not show cyanosis so commonly. In infants the convalescent stage shows whoop paradoxically increasing the severity in convalescent stage. The paroxysmal and convalescent stages are longer in infants and may last for months. Subsequent respiratory illnesses may exacerbate the attack. 

Adolescents who were immunized previously may get asymptomatic infection or may get symptomatic infection. If they get symptomatic infection all the stages are shortened in duration. Adults may not experience the distinct stages but may feel sudden strangulation followed by machine gun-like uninterrupted coughing. They may feel suffocation, decrease consciousness, headache and then gasping for air. The gap between cough episodes may be in hours. Post tussive vomiting may occur. Sometimes in adults cough may be non-specific and mimic other illnesses only differentiating feature is it may last for more than 21 days.

Findings on physical examination are non-specific and are not diagnostic. The lower respiratory tract findings are lacking unless other infections occur together. Conjunctival hemorrhage and petechiae are common in the upper body.

How Pertussis disease is diagnosed?

The diagnosis of Pertussis should be considered in patients in whom cough is predominant complain but there is lack of malaise, myalgia, wheeze or rales. Generally there is lack of hoarseness of voice, sore throat or tachypnea. In areas where disease is not endemic and occurs only sporadically, cough lasting for more than 14 days with one symptom of whoop, post tussive vomiting has sensitivity of 81 percent and specificity 58 percent. In infants in whom gaging, gasping, choking and cyanosis occurs the diagnosis of Pertussis should be considered. In older children whose cough increases 7-10 days but comes intermittently with post tussive vomiting the diagnosis of Pertussis should be considered.

Adenovirus usually causes fever, sore throat and conjunctivitis along with cough. Mycoplasma may show similar cough but it is more frequent and also associated with headache and body ache and on lower respiratory tract wheeze can be heard. Purulent conjunctivitis, tachypnea and wheezes can be associated with coughing in Chlamydia trachomatis infection. In RSV typically lower respiratory tract findings are more prominent with cough. In Pertussis cough does not come after each breath it comes after interval. Cough after each breath occurs in other infections.

On hemogram, Leukocytosis with absolute lymphocytosis is seen. Lymphocytes are small lymphocytes not like immature large lymphocytes like in other viral infections. Lymphocytosis is by both B and T lymphocytes. Absolute count of neutrophils if increased it is generally due to overlapping bacterial infection. Rapid rise in leukocytes and thrombocytes is associated with increased mortality. Chest radiograph may be normal in even severe cases but consolidation indicates the other bacterial infection. Sometimes pneumothorax or subcutaneous emphysema may be seen.

Current tests which are available for diagnosis have very limited sensitivity and specificity and it is difficult to collect the sample correctly. Culture samples are obtained from deep nasopharyngeal swabs. It should be remembered that the swab dipped in calcium alginate is better to collect the sample. While collecting the swab it should be held for 15-20 sec in deep nasopharynx till the cough comes. Special care is needed while collecting, carrying and isolating the swab.

1 percent casamino acid can be used to hold the swab for 2 hours while transporting the sample. Stainer-scholte broth is used if the swab is to be held for a longer period up to 4 days. Regan-Lowe charcoal agar is used for culturing the sample with 10 percent horse blood and cephalexin. 35-37 degree Celsius is optimal temperature for the culture. The culture is to be examined daily for slow growing and glistening growth. Direct fluorescent antibody testing if used enhances the results increasing the sensitivity. Culture and PCR tests on swab have similar sensitivity. They are likely to come positive during catarrhal stage and early paroxysmal stage in unimmunized individuals. In remotely immunized individuals only 20 percent patients give positive results with both tests. Serological detection by antibodies in blood is useful for epidemiological diagnosis.

What is treatment of Pertussis disease?

The treatment of Pertussis disease depends upon age and severity of the disease. The infants who are less than 3 months old should be admitted in hospital if Pertussis is suspected in them. At age 3-6 months and above if the paroxysms are severe should be admitted to hospital for the treatment. Prematurely born infants have increased chances of mortality in infants. Those with muscular, neurological, cardiac and pulmonary disease have increased chances of complications as well as death. During the admission supportive care is provided and also the patient is assessed for the progression of the disease and risk of mortality by life threatening events. Optimal nutrition is maximally given. If any complications are found those are treated. Parents are educated about the natural course of the disease. 

The characteristics of the paroxysms are to noted by the health care workers. Continuous monitoring of heart rate, pulse oximetry and respiratory rate is monitored so that paroxysm is detected early. The characteristics of paroxysms determine the life threatening even. Those paroxysms that are lasting for less than 45 seconds and red color during paroxysm, no cyanosis during paroxysm, tachycardia, bradycardia not less than 60 beats/min, spontaneous recovery in oxygen desaturation, whooping after the attack, strength of rescue breaths after attacks, exhaustion but not unresponsiveness after attack, self expectorated mucus plug indicate that current paroxysms not likely to cause life threatening event but need observation. The person who is expert in providing stimulation, suctioning and oxygenation should be present to monitor the situation. Feeding Pertussis infant is challenging. 

Nasogastric tube feeding is not of any benefit over nipple feeding. Large volumes are avoided during feeding. Thickening of food does not seem to provide any additional benefit.

Patients are observed for 48 to 72 hours before analyzing the situation. The record of characteristics of paroxysms gives idea whether disease is worsening or improving or is continuing to be the same. Large number of Pertussis patients, when given treatment with antibiotics early in the course of disease, are improved during this period. If the disease is improving with decreased frequency and severity of paroxysms that did not need intervention during this observation period and parents are sufficiently trained about feeding, the patient can be discharged. Apnea and seizures occur if disease is worsening.

For severe paroxysms that repeatedly lead to life threatening events need intubation and ventilation. These patients also need pharmacologically induced paralysis.

Antibiotics macrolides are useful for the treatment. In neonates erythromycin is avoided for the fear of hypertrophic pyloric stenosis. Azithromycin can be used in neonates. Patients with prolonged QT intervals need observation. In neonates if azithromycin is used they are observed for hypertrophic pyloric stenosis. 

Symptomatic treatment with salbutamol was not found to be effective. Corticosteroids and intravenous immunoglobulin were not found to be effective in recent trials.

The patient of Pertussis is needed to be kept in isolation with respiratory droplet precaution. Healthcare workers should use masks while treating. And the patient is isolated till the 5 days of macrolide treatment is completed. If a child in a child care facility gets Pertussis disease the children and staff are excluded from the work till 5 days of macrolide course is completed.

What if someone comes in contact with a Pertussis patient?

All contacts regardless of history of immunization and age should be started post exposure prophylaxis macrolides in recommended dosages for 5 days at least. Those family members should be excluded from work. Children less than 7 years old who received fewer than 3 doses of DPT vaccine should be given the dose or asked to complete the series. Those who have received 3rd dose more than 6 months back should get 4th dose and those who received 4thdose more than 3 years back should be given a dose of DTaP. Adults and adolescents need Tdap dose if not taken. Healthcare workers not using masks should be assessed and adequate prophylaxis needed to be given. Contacts are to be excluded from work till the 5 days course of macrolide antibiotics is completed.

What are complications of Pertussis disease?

Pertussis mortality is highest in infants particularly those who are below 4 months of age. Those who are born preterm and those who are born to adolescent or young mothers have high mortality. Pneumonia, seizures and encephalopathy are highest in neonates causing death in them. Neonates with Pertussis suffer substantially high mortality and complications. They suffer more days of hospitalization and more need of supplemental oxygenation and ventilation. Following are some complications of the Pertussis disease:

· Apnea leading to respiratory failure needing ventilation.

· Secondary bacterial infection, pneumonia and otitis media.

· Physical sequelae of forceful coughing.

· Scleral or conjunctival hemorrhage.

· Retinal hemorrhage.

· Petechiae on upper body, ecchymosis, emphysema.

· Hemorrhage in the central nervous system.

· Pneumothorax and emphysema.

· Umbilical and inguinal hernias.

· Progressive pulmonary hypertension and cardiogenic shock are usually the cause of death in young infants. More increased the lymphocyte in platelet counts more are chances of death.

· Hypoxia during or after paroxysm leads to central nervous system complications leading to seizures.

· Inappropriate secretion of antidiuretic hormone occurs during pneumonia or central nervous system injury leading to hyponatremia.

· Children who had Pertussis disease before 2 years of age may have abnormal pulmonary function tests during adulthood also.

How to prevent Pertussis?

Pertussis is a vaccine preventable illness. Multiple doses are needed to develop the immunity to Pertussis. The vaccination starting from infancy should continue till adulthood. Pertussis vaccine is even helpful in contact




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