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Severe pertussis disease in early infancy remains a significant problem, both in developed countries with long-standing pertussis immunization programs and in poor countries. We review current understanding of the disease burden and potential prevention strategies.Even with intensive care support, infants with pertussis pneumonia still die, so prevention is the key. The source of pertussis in infants under 3 months of age is often not clear, but in countries with high childhood immunization coverage, the sources are usually adults. Strategies to protect these infants may be indirect (timely primary immunization and boosters for older children and adults) and direct (mother during pregnancy or infant soon after birth). ‘Cocooning’ by immunizing all potential adult contacts is probably the most effective indirect strategy but needs funding and programmatic support for successful implementation. Maternal immunization is attractive but unproven and has significant practical hurdles. The evidence on immunization at birth is conflicting and impact, including interference with response to other infant vaccines, is unclear.Adult booster immunization, either universal or targeted (mothers during pregnancy or ‘cocoon’), would probably be effective but is challenging to implement. If shown to be safe and effective, immunization at birth has significant practical advantages. Different strategies (alone or combined) may be needed in different settings.