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  • Hypotonic-hyporesponsive episode (HHE) is characterized by:sudden onset of reduced muscle tone; hyporesponsiveness (to verbal or other stimuli)\' changed skin color (pallor, cyanosis). HHE has occurred after immunization with the following vaccines: diphtheria; tetanus; Haemophilus influenzae type b; hepatitis B vaccines. Most reports followed administration of pertussis component vaccines. More often associated with: whole-cell vaccines than acellular types; during primary immunization, generally following the first dose. Unclear if observed phenomena are related to: characteristics of the vaccine; immunologic phenomenon; toxic component(s) in the vaccine; combination of factors. In US vaccine surveillance system (VAERS), slightly more females (53%) than males experienced HHE, however, more reports of HHE in males have been noted in the Netherlands vaccine surveillance system. Time to onset of signs after immunization is generally three to four hours but can range from immediately to up to 48 hours post-immunization. Episode typically lasts six to thirty minutes. Up to one-third of cases also describe a fever. The Brighton Collaboration (BC) HHE Working Group - in developing a case definition for HHE - described diagnostic algorithms with three levels of certainty based on clinical observations at the time of the episode:
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