Pertussis or whooping cough is an ancient disease, currently preventable through vaccination, but presenting an important resurgence in the past several years, especially in children. This could perhaps be due to the shift from the use of whole cell vaccine to acellular vaccine especially in developed countries.1 Adults also do occasionally develop the disease, but since it is seldom suspected, the diagnosis often remains elusive. Young children, older children with waning immunity and sometimes even adults are sources of transmission. The disease remains grossly underdiagnosed because of decreased awareness amongst clinicians and lack of accessibility to diagnostic tests for confirmation of the disease.

Case report

A 42 year old nonsmoking man from South India, banker by profession, presented with history of cough for the past three weeks. He described his symptoms as paroxysms of cough followed by a short noisy inspiratory sound. He also reported that these episodes were followed by vomiting. There was minimal mucous expectoration. There was no history of associated rhinitis, sore throat or myalgia. He reported having low grade fever for a couple of days at the beginning of the illness. He denied having history of dyspepsia or abdominal pain. There was no history of dyspnea on exertion, wheezing, chest pain or hemoptysis. He gave history of allergic rhinitis in the past but the current episode had not been preceded by rhinitis. There was no recent history of exposure to dust, fumes, or pets. He initially presented to a physician in his home area who did the basic blood investigations, which revealed a total white cell count of 8800/cmm, with 66% polymorphs and 34% lymphocytes. A diagnosis of cough variant asthma was made and he was started on oral cephalosporins, oral steroids, bronchodilators and cough suppressants. But his symptoms were relentlessly persisting despite being on these medications for nearly two weeks.

At this moment, he was referred to our respiratory clinic. On examination he appeared anxious, but he was not in distress. There was no pallor, cyanosis, clubbing, pedal edema or generalized lymphadenopathy. His blood pressure was 130/80 mmHg, his heart rate 80/min, regular, respiratory rate 18/min and he was saturating 97% in room air. Examination of his respiratory system was unremarkable. His blood investigations revealed leukocytosis – total white cell count of 12,300/cmm with 81% polymorphs and 13% lymphocytes and a C reactive protein value of 33.7 mg/L. Other routine blood investigations were unremarkable. His chest X-ray in posteroanterior view was also normal. A spirometry was performed and it was normal.

On detailed interrogation, he revealed that his ten year old son also had dry cough associated with post-tussive vomiting and that his symptoms also started nearly at the same time. In this clinical background and with the available investigations we considered an infectious cause for his cough. His sputum Gram stain did not demonstrate any organisms and the culture yielded normal flora only. His throat swab for respiratory viral PCR (influenza and metapneumovirus) was negative.

The typical description of paroxysms of cough associated with post-tussive vomiting, along with a possible history of contact, prompted us to consider pertussis as a possible diagnosis. He was empirically started on a course of azithromycin for five days and supportive measures. Since the patient presented to us three weeks after onset of symptoms, it was decided to send the serological test for pertussis, namely, IgG antibody against Bordetella pertussis. He had received only childhood vaccination and denied receiving recent vaccination against pertussis. Notably, his child had missed taking the pertussis vaccine at school entry. The IgG – pertussis antibody level was 117 U/mL, by ELISA (reference range: negative <16, indeterminate 16-24, positive > 24 U/mL) thereby favoring a diagnosis of pertussis. As the patient had presented after the third week, Bordetella culture and PCR were not done as the diagnostic yield would be low beyond the third week of illness.

His household contacts were also given a course of azithromycin for five days as post-exposure prophylaxis and advised to undergo Tdap (tetanus, diphtheria, pertussis) vaccination.² His son was also advised to consult his pediatrician in the backdrop of diagnosis of pertussis, for appropriate testing and further management.

Once better, the patient was discharged and he was totally relieved of his cough when he came for further follow up after one month. He was also advised to take a booster dose of Tdap vaccine.^3,4

Final clinical diagnosis (Centers for Disease Control and Prevention – CDC criteria)⁵: Pertussis

Case classification (as per CDC criteria)⁵: Probable pertussis infection

Pertussis is a disease primarily caused by Bordetella pertussis but other species such as Bordetella parapertussis and Bordetella bronchiseptica, can also be involved. In 2012, the World Health Organization reported a bit over 200,000 cases of pertussis.⁶ A recent change in the epidemiology of pertussis infection has been documented and various explanations can be proposed. It has been hypothesized that genetic changes contribute to vaccine failures.⁷ Most of the cases have been reported from developing countries. A study from Brazil has reported an incidence of 8% in adults more than 21 years of age.⁸

According to the CDC, the clinical case definition for pertussis is "a cough illness lasting for at least 2 weeks with one of the following: paroxysms of coughing, inspiratory whoop, or post-tussive vomiting, without any other apparent cause”.⁹ In infants paroxysms of cough followed by apnea instead whoop may be the presentation. Pertussis displays three stages: catarrhal, paroxysmal and convalescent. One or two weeks of generalized malaise, rhinorrhea and mild cough are the features of the catarrhal stage. History of prolonged cough in other family members increases the odds of pertussis. This was true in our case as well. Paroxysms of cough mark the paroxysmal stage, which generally commences during the second week of illness. Paroxysms are more frequent at night and may be precipitated by cold air, causes of stress or loud noises. Patients are most infectious during the catarrhal stage but they can remain infective for up to six weeks. The classic paroxysms of cough are rare or sometimes even absent in adolescents or adults who have previously received vaccination.¹⁰ They present primarily with persistent cough, which can be complicated by pneumonia, syncope, rib fracture, incontinence, encephalopathy and seizures.¹¹ About one third of adolescents and adults having a coughing illness lasting longer than 6 days display positive pertussis serology.¹²

Since the cough in pertussis infection runs a subacute to chronic course, the prime differential diagnosis one has to consider are upper airway cough syndrome (UACS, or postnasal drip), gastroesophageal reflux disease which sometimes manifests as irritable laryngeal syndrome or laryngopharyngeal reflux and cough variant asthma. Of these, laryngopharyngeal reflux disease very closely mimics the signs and symptoms of pertussis. A detailed history of sequence of events and an assessment with a nasal endoscopy or esophagogastroduodenoscopy will help in the diagnosis of reflux related disease, although in some cases, esophageal pH monitoring may be needed to confirm the diagnosis.

Clinical suspicion is paramount in the diagnosis of pertussis. Culture is the gold standard for diagnosis,¹³ but its sensitivity decreases after two weeks. PCR is the most sensitive method if done during the first three weeks of illness, but it is not recommended after 5 days of appropriate antibiotic use.¹⁴ Serologic tests are useful for adults and adolescents who present late (beyond 3 weeks), with paroxysms of cough leading to a clinical suspicion of pertussis.

Paired sera demonstrating a twofold rise is diagnostic, but a positive serology from a single sample can be enough in clinical practice to establish a probable diagnosis of pertussis.¹⁵A common practical issue with serologic testing is the timing of obtaining the acute phase specimen. If there is a delay in collection of the acute phase specimen, antibody titers may have already peaked and a further rise in the convalescent specimen may not be observed. Alternatively, a single sample titer above a designated threshold (typically IgG anti-PT ≥100 to 125EU/mL)can be considered to be diagnostic of pertussis. Single specimen titers are useful in adolescents and adults but not in children, since recent immunization can affect the results.Pertussis vaccination in the previous year will affect serology interpretation even in adolescents and adults.¹⁵

Current case definitions for pertussis are not uniform and different countries follow different criteria. Newer case definitions are more specific and sensitive, age-based and can be used in resource limited countries as well. In Europe, high IgG against pertussis in a patient without recent vaccination is considered laboratory confirmed and is recorded as
"confirmed pertussis".¹⁶

Most individuals appear to clear the infection without antibiotic treatment within six weeks.¹⁷ During the early (catarrhal) phase of pertussis, antibiotic treatment may decrease the duration and severity of cough, but the diagnosis is rarely established during this phase among adolescents and adults. Antibiotic treatment administered later in the course of disease will not affect the course of symptoms but might be helpful to reduce the spread of the infection.

The drugs of choice for treatment of pertussis are the macrolides. The CDC recommends the following treatment schedule:azithromycin five days (500 mg day one, 250 mg on days two through five) orclarithromycin(500 mg twice daily for seven days).²For adults who cannot tolerate a macrolide antibiotic,trimethoprim-sulfamethoxazole(one double-strength tablet twice daily for 14 days) is an acceptable alternative treatment.

All close family members, relatives, and exposed healthcare personnel should also be given post-exposure prophylaxis within 21 days to prevent symptomatic infection as well as transmission of the disease.¹⁸Although our patient came three weeks after development of cough, all his household contacts were given post-exposure prophylaxis, in view of the fact that there were two symptomatic cases in the family. The antibiotic regimens for post-exposure prophylaxis are identical to those used for the treatment of pertussis.²

The patient was advised to take a booster dose of Tdap vaccine since neither natural infection nor vaccination confers lifetime immunity. Vaccination offers protection for two years and then the immunity gradually wanes off.³ Similarly, the immunity offered by natural infection wanes after 4 to 20 years.⁴

Even with appropriate treatment with antibiotics, the cough may persist for weeks before it subsides. The cough is attributed to destruction of respiratory ciliated cells due to pertussis toxins, leading to trickle of secretions from the nasopharynx into the larynx. For resolution of the cough, regrowth of these cells is essential.¹⁹ There is no proven effective therapy for symptomatic treatment of severe cough, but cough suppressants are commonly prescribed in an attempt to alleviate the cough.

Another point worth emphasizing is the role of vaccination in prevention of pertussis. Initially the whole cell pertussis vaccine combined with diphtheria and pertussis (DTwP) was part of childhood immunization. Although it was very effective, there were significant local as well as systemic adverse effects. Hence in 1996 it was replaced with the acellular pertussis vaccine (DTaP), which has been shown to have a lesser protective effect as compared to the whole cell vaccine. Also the protective effect of the acellular vaccine has been shown to wane after a few years.^3,4 Instead of the current practice of giving tetanus toxoid as per the Indian guidelines, a booster dose of Tdap is indicated for all adolescents and adults followed by Td every 10 years.¹²The CDC’s adolescents immunization schedule has included a booster dose of Tdap. In view of the spurts of outbreaks of pertussis infection after the introduction of the acellular vaccine, there is an ongoing debate regarding the revival of the whole cell vaccine,²⁰ however, safety concerns should be taken into consideration. The introduction of vaccination of pregnant women is a very important progress in the prevention of mortality due to this disease in not yet vaccinated children.²¹ These infants are the most vulnerable group, with the highest mortality, and they often acquire the infection from older children and adults.

Pertussis in adults is not uncommon and can still occur, despite the advancements that have been achieved with vaccination. The classical history of paroxysms of cough, followed by a whoop and very often associated with post-tussive vomiting, should alert the clinician to the possibility of pertussis infection. We would like to highlight the knowledge of appropriate diagnostic testing based on timing of presentation, the recommended antibiotic regimen for treatment, importance of vaccination, with particular emphasis on the need for an adolescent and adult booster dose, indications for post exposure prophylaxis for close family contacts and healthcare personnel.

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