Whoop, Whoop, Hooray

Cite this article as:
Andrew Tagg. Whoop, Whoop, Hooray, Don't Forget the Bubbles, 2016. Available at:
https://doi.org/10.31440/DFTB.8344

Henry Goldstein wrote an excellent article on pertussis a few years ago.  With some interesting new data coming to press with regard to risk factors for complications of the disease we thought it might be worthwhile doing some spaced repetition.

“My childhood was full of deep sorrow – colic, whooping cough, dread of ghosts, hell, Satan, and a deity in the sky who was angry when I ate too much plum cake” – George Eliot

Although cases have been described as far back as the Middle Ages it wasn’t until 1906 when the organism, Bordetella pertussis, was isolated by Bordet and Gengou. Up to 16 million cases develop worldwide every year with the majority of cases being in the developing world. Australia reported around 10,000 cases in 2009. Data from 2013 suggests it caused at least 61,000 death worldwide though this is likely to be a gross underestimate. Pertussis is one of the leading causes of vaccine preventable deaths worldwide.

Incubation

B. pertussis is highly infectious with the majority of exposed household contacts becoming infected to various degrees. The incubation period is usually quoted as 4-21 days with the average being 7-10 days.

Prodrome

Before the harsh coughing begins there is often a couple of weeks of symptoms that could easily be mistaken for a viral upper respiratory tract infection. Children may have a runny nose and a very mild tickly cough. This is the catarrhal phase. The classic ‘whoop’ might not be hard until week three or four of the illness.

Clinical course

The classical presentation is of a patient that has paroxysms of coughing that terminates in an audible inspiratory ‘whoop’. Like most classical presentations we learn about in medicine this presentation is rarer than we think. Children may also present with a protracted cough, or forceful post-tussive vomiting. Parents often seek advice as their children have had a couple of courses of antibiotics with no improvement in cough. It’s not know as the ‘one hundred day cough’ for nothing.

People with pertussis (adults and children alike) are infectious from the beginning of the catarrhal stage through to the third week after the onset of the paroxysmal stage of coughing. They cease being infectious five days after a course of antibiotics.

Diagnosis

Other than a suspicious clinical picture, formal diagnosis is best made by performing PCR for Bordetella on a nasopharyngeal swab. Once the initial three weeks have past though, it becomes increasing difficult to culture and it may be necessary to use rising IgA titres to make the diagnosis though this does not affect management.

Treatment

A number of treatments have been posited including vitamin C injections.

“In 66 [of 81] cases… [we saw] reduction of lip cyanosis in coughing attacks…[disappearance of] attacks with breathing difficulty, vomiting and recurrence … also the number of cough attacks diminished. Patients became lively, had good appetite and the convalescence progressed very satisfactorily.” – Concerning the Vitamin C Therapy of Pertussis [Whooping Cough]: Otani, Klinische Wochenschrift, December 1936

Coughs last, on average, 16 days. A Cochrane review found no specific benefit of steroids, bronchodilators or immunoglobulins for the treatment of the cough. Over the counter remedies are unlikely to help and may potentially cause harm.  To hear more listen to this great rant from Dr Anthony Crocco. The only thing that may help (a little) is honey.  Take a listen to Ken Milne’s podcast SGEM #26 – Honey, Honey for more on this subject.

What about antibiotics? Well (in adults) they are recommended in the initial catarrhal phase to help reduce duration of infectivity but they don’t seem to have much effect after the disease has been hanging around for three weeks. Because of this they are not recommended beyond this time period.

If they are needed then macrolides such as erythromycin, azithromycin or clarithromycin are recommended. Azithromycin should be used in children less than one month of age as erythromycin use has been linked to an increased incidence of hypertrophic pyloric stenosis.

Complications

Pertussis is far from benign in unvaccinated infants. According to the CDC, in children under 1 that are not fully vaccinated:-

  • 1 in 4 (23%) get pneumonia
  • 1 in 100 (1.1%) will have convulsions
  • 3 out of 5 (61%) will have apneoic episodes
  • 1 in 300 (0.3%) will develop encephalopathy
  • 1 in 100 (1%) will die

In Winter’s retrospective analysis of US pertussis deaths in infants under 120 days old mortality was linked with:

  • Significantly low birth weight
  • Younger gestational age
  • Younger age at onset
  • Higher WBC and higher lymphocyte count

In those less severely affected it may still cause sub-conjuctival haemorrhages, rib fractures and loss of bladder control.

Post-exposure prophylaxis

So who should get antibiotics if exposed to a confirmed case of pertussis? Most guidelines recommend that the following groups of people receive antibiotic prophylaxis.  It’s not really to treat the illness but rather to halt the spread.

  • Pregnant mothers in the last month of gestation (WHY)
  • Members of a household that has an  infant that is not fully vaccinated
  • Healthcare workers and babies potentially exposed and in a newborn nursery environment

To be fully vaccinated the child must have three effective doses of pertussis vaccine given at least four weeks apart.

Prevention

Whilst childhood immunisation does prevent the majority of cases, individual immunity does appear to decrease with time so there has been an upswing in the number of older children and teenagers affected. Pertussis is a notifiable disease and over 70% of cases that are notified are in patients over the age of 15.

The current Australian immunisation schedule has pertussis vaccine being given as a part of the combined Diptheria, Tetanus, acellular Pertussis (DTaP) vaccine at two, four and six months of age. Other countries may have an alternative schedule. The child then receives a pre-school booster at 4 years old. Because of the waning immunity they should also receive a dose in their teenage years. An individual’s immunity to pertussis may well have disappeared by the time they reach adulthood so new parents, or grandparents living in a house with a newborn should be offered a booster.

 

HT to Tim Horeczko (@EMtogether) for the heads up regarding the latest data

 

References

Royal Children’s Hospital, Melbourne guidelines on Pertussis can be found here

Cherry JD. Historical review of pertussis and the classical vaccine. Journal of Infectious Diseases. 1996 Nov 1;174(Supplement 3):S259-63. full text here

Pertussis (Whooping cough) complications. (2015). Retrieved April 13, 2016, from https://www.cdc.gov/pertussis/about/complications.html

GBD 2013 Mortality and Causes of Death Collaborators. “Global, Regional, and National Age-Sex Specific All-Cause and Cause-Specific Mortality for 240 Causes of Death, 1990-2013: A Systematic Analysis for the Global Burden of Disease Study 2013.” Lancet 385.9963 (2015): 117–171. PMC. Web. 14 Apr. 2016.

Forsyth K, Plotkin S, Tan T, von König CH. Strategies to decrease pertussis transmission to infants. Pediatrics. 2015 Jun 1;135(6):e1475-82.

Hay AD, Wilson A, Fahey T, Peters TJ. The duration of acute cough in pre-school children presenting to primary care: a prospective cohort study. Family Practice. 2003 Dec 1;20(6):696-705

Winter K, Zipprich J, Harriman K, Murray EL, Gornbein J, Hammer SJ, Yeganeh N, Adachi K, Cherry JD. Risk factors associated with infant deaths from pertussis: a case-control study. Clinical Infectious Diseases. 2015 Oct 1;61(7):1099-106.

 

Pertussis

Cite this article as:
Henry Goldstein. Pertussis, Don't Forget the Bubbles, 2013. Available at:
https://doi.org/10.31440/DFTB.2722

Winston, a 4-month-old boy, presents to your emergency department after his mother noticed, during his last feed, that he appeared to stop breathing for around 15 seconds and turned blue.

He restarted breathing spontaneously. Further history reveals a two-day history of feeding difficulties, cough, irritability, and rhinorrhoea. He has also had a low-grade temperature (37.8 0C). There has been no diarrhoea and a few vomits, but only after coughing. He has no rashes. His oral intake has been reduced to about half normal, for the last 24 hours.

 

Bottom Line

  • Have a low threshold for suspicion in any child with a prolonged cough, especially those incompletely immunized
  • Pertussis has a non-typical presentation in infants
  • In clinically or laboratory diagnosed pertussis, antibiotics do not reduce the severity or frequency of coughing paroxysms.
  • Antibiotics do render the child noninfectious
  • Due to the high risk of morbidity and mortality in infants less than six months of age who are incompletely immunized, contact prophylaxis is recommended for families who have an infant less than six months of age

 

Further Assessment

Birth History

Winston was born at term weighing 3700g. Apgars were 91, 95 after an SVD without any risk factors for sepsis. His well neonate check and six week GP reviews were unremarkable. He is exclusively breastfed. He is up to date with his immunizations.

Family History

Of note, Winston’s 11-year-old brother has had two weeks of rhinorrhoea and cough but is clinically well.

Examination

You see a slightly tachypnoeic, thriving 4/12 male. Chest clear. Mildly dehydrated. Irritable. Normotensive fontanelle. No rashes. No focal findings on the chest. Unremarkable cardiovascular and abdominal examinations. ENT; TMs are mild erythematous bilateral without effusion, tonsils are also mildly erythematous, not overly enlarged.

 

What is the most concerning feature of this history?

Apnoea – apnea is a particularly concerning feature in infants.

 

What are your differentials and most likely diagnosis – why?

Whooping cough, caused by Bordetella pertussis, a gram-negative coccobacillus whose only reservoir is humans. It’s transmitted by respiratory secretions, particularly in the first few weeks after exposure.

Clinically, pertussis classically progresses in three stages.

  • Firstly, the catharrhal phase which consists of one to two weeks of nonspecific symptoms.
  • This is followed by the paroxysmal phase, in which the characteristic ‘whoop’ sound at the end of a coughing paroxysm may be heard (infants and older children are less likely to have typical whooping cough).
  • Finally comes the convalescent phase in which the coughing paroxysms become less frequent and less severe.

Notably, infants may manifest pertussis infection only as feeding difficulties, cough or apnoeas. Also, immunized children may manifest a more attenuated illness that doesn’t demonstrate the classic three phases of illness.

 

How is it diagnosed?

Laboratory diagnosis is by nasal swab or nasopharyngeal aspirate showing PCR positive for Bordetella pertussis.

Additionally, when considering which children to swab, there was a distinct paucity of evidence. There were several comparisons of PCR vs culture, but no firm criteria about who should score an NPA or flocked swab in the first place.

The US CDC recommends: “Early diagnosis and treatment might limit disease spread. When pertussis is strongly suspected, attempts to identify and provide prophylaxis to close contacts should proceed without waiting for laboratory confirmation. When suspicion of pertussis is low, the investigation can be delayed until there is laboratory confirmation of the diagnosis. However, prophylaxis of infants and their household contacts should not be delayed because pertussis can be severe and life-threatening to young infants.”

Ditte & colleagues’ excellent (but quite technical) 2004 article investigated a sample size of 3096 patients, swabbed for suspected pertussis.

PCR was superior for detection in patients aged 6 months – 3 years and was highly sensitive for the diagnosis of pertussis.

Also of note, pertussis serology may be of use to confirm diagnosis around the time a patient enters the catarrhal phase, but will unlikely change management as discussed above.

 

Who is at most risk?

Infants under six months have the highest mortality from pertussis; the mortality rate is estimated at around 1%, with 80% of these deaths occurring in infants under 2 months. Comorbid apnoea, pneumonia, and seizures may complicate pertussis infection. Less commonly, a leukocytosis >50,000×109/L or encephalopathy potentially caused by pertussis toxin may occur and is associated with a poor prognosis.

 

Treatment

Let’s have a look at the evidence around antibiotic management of whooping cough as well as the indications for prophylaxis. This Cochrane review (assessed as up to date in Jan 2011) is the basis for a number of current guidelines.

Altunaiji SM, Kukuruzovic RH, Curtis NC, Massie J. Antibiotics for whooping cough (pertussis). Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD004404. DOI: 10.1002/14651858.CD004404.pub3.

The review looks at 13 RCTs regarding the efficacy of antibiotics for treatment & prophylaxis of pertussis. Eleven trials looked at treatment and had the following objectives:

 

Do antibiotics achieve microbiological eradication of B. pertussis?

  • Multiple studies showed a number of agents successfully eradicating b. pertussis, including erythromycin, oxytetracycline.
  • Azithromycin and clarithromycin as macrolides equivalent to erythromycin has been shown effective at eradicating B. Pertussis.
  • A number of head to head studies showed no superior agent. However, a 1997 study showed roxithromycin was two to four-fold less effective at B. pertussis eradication vs erythromycin.

Do antibiotics improve the clinical illness of whooping cough?

  • No difference in mortality.
  • With regard to clinical cure/ remission; erythromycin ethyl succinate (EES) vs erythromycin estolate. Patients judged they were equivocal re: frequency of cough, and that erythromycin estolate was slightly superior to EES, regarding clinical cure / remission.
  • Erythromycin & azithromycin had no relapses after proven negative culture post-treatment.

What is the appropriate dose and duration of therapy?

  • There was no benefit for a prolonged course of antibiotics vs a standard course.

What are the side effects profile of antibiotics used to treat whooping cough?

  • Regarding side effects, azithromycin 3/7 was superior to erythromycin ethyl succinate 14/7 and clarithromycin 7/7 was superior to erythromycin estolate 14/7
  • Compliance was best for azithromycin vs erythromycin estolate and clarithromycin vs EES

Additionally, Honien et al (1999) describe seven cases of infantile hypertrophic pyloric stenosis in a cohort of 200 neonates treated with erythromycin; a significantly increased risk or IHPS in this population.

 

Prophylaxis

Two trials (401 patients in total) reviewed prophylaxis:

Do antibiotics achieve microbiological eradication of B. pertussis?

As for treatment, above.

Do antibiotics prevent the clinical illness of whooping cough?

  • slightly less” but not statistically significant frequency of whooping cough, paroxysms in household contacts of the prophylaxis arm.
  • slightly lower” but not statistically significantly lowered attack rate in prophylaxis groups.

The appropriate dose and duration of therapy?

As for treatment, above.

The side effects profile of antibiotics used for prophylaxis of whooping cough?

  • Placebo was better than erythromycin estolate for compliance and side effect profile.

Of note, erythromycin estolate is not available in Australia.

The reviewers commented on the marked heterogeneity of studies with regard to the outcome measures and definitions. They note that treatment renders patients noninfectious but does not alter the clinical course. Consequently, they make the following recommendations.

The best regimens for microbiological clearance, with fewer side effects, are:

  • three days of azithromycin (10 mg/kg as a single dose);
  • five days of azithromycin (10 mg/kg on the first day of treatment and 5 mg/kg once daily on the second day to fifth days of treatment); or
  • seven days of clarithromycin (7.5 mg/kg/dose twice daily).

Seven days of trimethoprim/sulphamethoxazole (20 mg trimethoprim with 100 mg sulphamethoxazole per dose, twice daily, for children under six months of age; double this dose for older children) appears to be effective in eradicating B. pertussis from the nasopharynx and may serve as an alternative antibiotic treatment for patients who can not tolerate a macrolide.

Additionally, in Australia, a pertussis booster vaccine is recommended for close household contacts of newborns; this advice is part of a neonatal discharge check within the hospital.

 

Antibiotics for prophylaxis against whooping cough – summary

There is insufficient evidence to determine the benefit of prophylactic treatment of pertussis contacts. Prophylaxis with antibiotics was significantly associated with side effects and did not significantly improve clinical symptoms, whoop, paroxysmal cough, number of cases who develop culture-positive B. pertussis or paroxysmal cough for more than two weeks in contacts older than six months of age. Due to the high risk of morbidity and mortality in infants less than six months of age who are incompletely immunized, contact prophylaxis is recommended for families who have an infant less than six months of age. The recommended antibiotics and dosages for contact prophylaxis are the same as those recommended in the treatment of whooping cough.

Additionally, the American CDC guidelines written in 2006 were reviewed more recently and not rewritten. They were published prior to the 2007 Cochrane Review.

 

References

Altunaiji SM, Kukuruzovic RH, Curtis NC, Massie J. Antibiotics for whooping cough (pertussis). Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD004404. DOI: 10.1002/14651858.CD004404.pub3.

Chan MH et al. The California Pertussis Epidemic 2010: A Review of 986 Pediatric Case Reports From San Diego County J Ped Infect Dis (2012) 1 (1): 47-54 doi:10.1093/jpids/pis007 Accessed 24/06/2013.

Ditte MD, Dohn B, Madsen J, Jensen JS, Comparison of culture and PCR for detection of Bordetella pertussis and Bordetella parapertussis under routine laboratory conditions. J Med Microbiol August 2004 vol. 53 no. 8 749-754.

Faulkner A, Skoff T, Martin S, Cassiday P, Lucia Tondella M, Liang J, Ejigiri OG, Surveillance Manual, 5th Edition, 2011 Pertussis: Chapter 10-1. 8 July 2011. Accessed 09/07/2013.

Snyder, J & Fisher, Pertussis in Childhood. Pediatrics in Review Vol. 33 No. 9 September 1, 2012 pp. 412 -421 (doi: 10.1542/pir.33-9-412).