A hypotonic-hyporesponsive episode (HHE) is defined as the sudden onset of hypotonia (muscle limpness), reduced responsiveness or unresponsiveness and pallor or cyanosis occurring after vaccination in early childhood (< 2 years of age).

Most children are initially irritable and febrile prior to the event and respiration may be shallow during the event. HHE’s can be immediate or delayed. The immediate HHE’s are often preceded by crying, breath holding and are like an immediate vasovagal phenomenon. Close inspection is required to ensure there are no features suggestive of an allergic reaction. The delayed reactions usually occur 1 to 48 hours after vaccination and resolve spontaneously; the median episode duration is 6-30 minutes. Diagnosis of HHE is made clinically and often no investigations are required.

This occurs where no other cause is evident, such as seizure or anaphylaxis. This is distinguished from a vasovagal-syncope (fainting episode), which presents with similar signs and symptoms but occurs soon after vaccination (< 5mins) and usually occurs in an older age group (≥ 2 years of age).

The pathogenesis of HHE is unknown but is likely to be multifactorial. HHE is rare and results in transient signs, and hence, there are limitations to investigation.

Associations and incidence

HHE has been documented to occur after immunisation with all vaccines, but historically had been most associated with whole-cell pertussis vaccines in early infancy. There has been a decreased incidence following the change from whole-cell pertussis to acellular pertussis vaccines.

HHE has been observed mainly after the first doses of vaccines at 6 to 8 weeks of age.

In Australia during 2012, 2.2 cases of HHE were reported per 100,000 doses of pertussis-containing vaccine given to children <1 year of age.


These episodes self-resolve and often don’t need any treatment. However, the initial management should be for shock and include assessment of airway, breathing and circulation. Careful clinical observation and documentation of the event are vital for differential diagnosis. Urgent medical review is advised for paediatric assessment and to exclude other causes.

Implications and considerations for future vaccines

HHE is not a contraindication to further doses of vaccines, including pertussis containing vaccines.

The recurrence rate for a further HHE is 3.5% [refer to Resources]. No long term sequelae have been identified in the small number of children who have had long term follow-up.

The next scheduled immunisations may need to be given under medical supervision, this can be arranged by contacting the vaccine safety service in your state.

Any adverse event following immunisation (AEFI) in Victoria should be reported to SAEFVIC.


Authors: Daniela Say (MVEC Immunisation Fellow) and Teresa Lazzaro (Paediatrician, Immunisation Service, Royal Children’s Hospital Melbourne)

Reviewed by: Rachael McGuire (MVEC Education Nurse)

Date: November 29, 2022

Materials in this section are updated as new information and vaccines become available. The Melbourne Vaccine Education Centre (MVEC) staff regularly reviews materials for accuracy.

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