Published: July 1998


Hypotonic-Hyporesponsive Episodes to Immunisation

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Prescriber Update 16: 34–36
July 1998

Dr Osman Mansoor
Public Health Physician
Public Health Group, Ministry of Health

Dr David Coulter
Acting Medical Assessor
Centre for Adverse Reactions Monitoring (CARM), Dunedin

Hypotonic-hyporesponsive episodes (HHE) are recognised serious reactions to immunisation, especially pertussis-containing vaccine. Management involves checking the airway, breathing and circulation, then hospitalisation as a precaution. In reported cases, full recovery has occurred and there has been no long term sequelae. The paediatrician who assesses the child should also advise on the completion of the immunisation programme.

Since 1992, CARM has received 32 reports of children experiencing hypotonic-hyporesponsive episodes (HHE) following immunisation, all from pertussis-containing vaccines. The WHO database has over 600 reports of HHE, the majority following immunisation of pertussis-containing vaccines.

Serious effects but no long term sequelae reported

HHE is defined as an acute diminution in sensory awareness or loss of consciousness accompanied by pallor and muscle hypotonicity.1 Variously described as shock, collapse or HHE, onset is within 12 hours after immunisation. Most children are initially irritable and febrile, then become pale, limp and unresponsive or hyporesponsive. Respiration is shallow and cyanosis frequently occurs. The duration of an episode varies from a few minutes to 36 hours.

The initial response should be as in any case of shock (airway, breathing, circulation). Careful clinical observation and documentation of the event are vital for differential diagnosis. Urgent hospital referral is advised for paediatric assessment and to exclude other causes.

A return to normal after the reaction has been reported in all published cases.1 No long term sequelae have been identified in the small number of children who have had long term follow-up.2

HHE not a contraindication for further doses of pertussis vaccine

The Immunisation Handbook (pages 67 and 70) advises that HHE is no longer a contraindication to further doses of pertussis vaccine. The benefit/risk ratio should, however, be carefully considered for each child.

Paediatrician to advise on future immunisation options

The paediatrician who sees the child should also advise about future doses of pertussis and other vaccines. The options include:

  • continue with normal immunisations, but give the next dose under supervision (e.g. in a day hospital);.
  • omit pertussis in future (i.e. use DT plus Hib instead of DTPH). Note that although pertussis is most associated with this reaction, it has been reported with other vaccines including DT3 and DTaP4; or
  • use acellular pertussis vaccine (DTaP is available but not funded; DTaPH is not yet available in New Zealand) - limited data suggest a lower rate of HHE with acellular vaccine.5

A recently published Dutch study described 101 children who experienced HHE following immunisation, of whom 84 subsequently received further doses of pertussis vaccine.6 None experienced a recurrence or other adverse event. One of the 17 children who did not continue with normal immunisation experienced severe pertussis.

Wide variation in incidence

Different studies have found an incidence of HHE following immunisation with DTP or its pertussis component varying between 3.5 and 291 per 100,000 injections.1 This wide variation probably reflects the lack of an ideal case definition and difficult case recognition, as well as different vaccine formulations. The highest rate of 291 per 100,000 was found with plain DTP vaccine as opposed to a rate of 99 per 100,000 for adsorbed vaccines (the type used in New Zealand since 1971).1 The largest study found a rate of 57 per 100,000,7 and this is the rate quoted in the Immunisation Choices booklet and the Immunisation Handbook.

  1. Howson CP, Howe CJ, Fineberg HV, eds. Adverse effects of pertussis and rubella vaccines. Washington DC: Institute of Medicine, National Academy Press, 1991.
  2. Baraff LJ, Shields WD, Beckwith L, et al. Infants and children with convulsions and hypotonic-hyporesponsive episodes following Diphtheria-Tetanus-Pertussis immunization: follow-up evaluation. Pediatrics 1988;81:789-94.
  3. Pollock TM, Miller E, Mortimer JY, Smith G. Symptoms after primary immunisation with DTP and DT vaccine. Lancet 1984;2:146-9.
  4. Blumberg DA, Mink CM, Cherry JD, et al. Comparison of acellular and whole-cell pertussis component diphtheria-tetanus-pertussis vaccines in infants. J Pediatr 1991;119:194-204.
  5. Edwards KM, Decker MD. Acellular pertussis vaccines for infants. N Engl J Med 1996;334:391-2.
  6. Vermeer-de Bondt PE, Labadie J, Rümke HC. Rate of recurrent collapse after vaccination with whole cell pertussis vaccine: follow up study. BMJ 1998;316:902.
  7. Cody CL, Baraff LJ, Cherry J, et al. Nature and rates of adverse reactions associated with DTP and DT immunizations in infants and children. Pediatrics 1981;68:650-60.


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