Individual case reports indicate an association between hypotonic-hyporesponsive episode (HHE) and vaccination of young children in connection with basic immunisation. HHE is considered to be a benign, self-limiting adverse effect after vaccination and is not a contraindication for further vaccination.
Hypotonic-hyporesponsive episode and basic immunisation in infants
Incident data |
Description |
|---|---|
Case: 2021 Age: 2 months Sex: female Medicinal product:
Active substances:
Indication: Basic immunisation according to the Swiss vaccination plan ADR: hypotonic-hyporesponsive episode Outcome: recovered |
A few hours after basic immunisation, the 2-month-old child had an apathetic episode lasting approx. 30 minutes. During this time, she was very pale and unresponsive. In the emergency department, the child again had a brief episode of reduced responsiveness to stimuli with discreet monitoring. A physical examination was normal. The child was admitted to hospital for monitoring for 48 hours. The monitoring revealed nothing abnormal. The comprehensive diagnostic tests performed were also normal (see below). Investigations: Laboratory tests: no signs of inflammation, normal; Urine, blood cultures: normal; Cardiac ultrasound: ASD type 2, not haemodynamically relevant; ECG: normal; Cranial ultrasound: normal; EEG: normal; Nasopharyngeal swab showed no presence of viruses. Medical history: normal. |
Case: 2022 Age: 3 months Sex: female Medicinal product:
Active substances:
Indication: Basic immunisation ADR: hypotonic-hyporesponsive episode Outcome: recovered |
Three hours after basic immunisation, the child suddenly began screaming and breathing abnormally. She was unresponsive for a few seconds and seemed tired and listless to the parents. The same episode was repeated an hour later, but the child also had a pale grey to cyanotic skin colouring. On arrival at the emergency department, she was in a good, alert general condition. The clinical examination, blood and urine tests and electrocardiogram were normal. In conjunction with the findings, a tentative diagnosis of two hypotonic-hyporesponsive episodes following vaccination was made. No further episodes occurred overnight, and in the morning the child was in a sub-febrile, good general condition and could be discharged. |
Summary and recommendation
During a hypotonic-hyporesponsive episode (HEE), there is reduced muscle tone and reduced responsiveness accompanied by pale skin colouring. This occurs within 48 hours of a childhood vaccination in children under 2 years. Children always recover completely and relatively quickly, usually after a few minutes or hours.
The pathological mechanism is unknown. No risk factors were found. No long-term consequences or damage following HHE are known. However, other causes should be ruled out.
An increased reporting rate of hypotonic-hyporesponsive episodes has been observed for combined vaccinations with concomitant administration of Infanrix hexa and Prevenar 13. Hypotonic-hyporesponsive episodes are listed in the Information for healthcare professionals as very rare (Infanrix hexa) and rare (Prevenar 13) adverse drug reactions. The risk of recurrence is low (< 4%) and an HHE does not contraindicate further vaccinations.
See also
Further references
Buettcher M, Heininger U, Braun M, Bonhoeffer J, Halperin S, Heijbel H, de Menezes Martins R, Vermeer-de Bondt P; Brighton Collaboration HHE Working Group. Hypotonic-hyporesponsive episode (HHE) as an adverse event following immunization in early childhood: case definition and guidelines for data collection, analysis, and presentation. Vaccine. 2007 Aug 1;25(31):5875-81. doi: 10.1016/j.vaccine.2007.04.061. Epub 2007 May 8. PMID: 17537554.
Tracy S. DuVernoy, M. Miles Braun, the VAERS Working Group; Hypotonic–Hyporesponsive Episodes Reported to the Vaccine Adverse Event Reporting System (VAERS), 1996–1998. Pediatrics October 2000; 106 (4): e52. 10.1542/peds.106.4.e52
Vigo A, Costagliola G, Ferrero E, Noce S. Hypotonic-hyporesponsive episodes after administration of hexavalent DTP-based combination vaccine: a description of 12 cases. Hum Vaccin Immunother. 2017;13(6):1375–78. PMID: 28301267. doi:10.1080/21645515.2017.1287642
Medicinal product information
Electronic reports via the ElVis portal