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Invasive infections from Haemophilus influenzae serotype a (Hia) have been reported with increasing frequency, especially among indigenous populations. However, there are limited population-based studies of clinical severity. We studied invasive Hia infections in Alaska to determine clinical characteristics, mortality and sequelae.We defined an invasive Hia infection as the first detection of Hia from a usually sterile site in a child <10 years of age from Alaska. We identified cases using the Alaska Invasive Bacterial Diseases Surveillance System and reviewed medical charts up to 2 years after reported illness.We identified invasive Hia infections in 36 children, 28 (78%) <1 year old, 34 (94%) living in an Alaskan village and 25 (69%) without documented underlying illness. Overlapping clinical presentations included meningitis in 15 children (42%); bacteremia and pneumonia in 10 children (28%); and bone, joint or soft tissue infections in 10 children (22%). In 4 other children, no source of invasive infection was identified. Intensive care was provided for 11 children (31%); 12 children (33%) required surgical intervention. One year after infection, 4 children (11%) had died from Hia, and 5 children (14%) had ongoing neurologic sequelae.Invasive Hia infections in Alaska occurred predominantly in Alaska Native infants in rural communities. Although one-third of children had preexisting conditions, most cases occurred without known comorbidity. Clinical syndromes were frequently severe. One year after infection, 1 in 4 children had either died or had neurologic sequelae. An effective vaccine would prevent significant morbidity and mortality in affected populations.