In 1981, MacDonald joined the faculty at the University of Ottawa, where she founded the Division of Infectious Diseases. She led the Paediatric Infectious Diseases Service at the Children's Hospital of Eastern Ontario. In 1996 MacDonald founded the journal Paediatrics & Child Health, which was the first Canadian journal on paediatric medicine. Her research considered the microbiology of cystic fibrosis, sexually transmitted infections in adolescents and the development of vaccinations for infectious diseases. In 1999 MacDonald left Ottawa and moved to Halifax, Nova Scotia. At Dalhousie University she became the first woman in Canada to be elected Dean of a Faculty of Medicine, and held this position until 2004. That year she was a founding member of the World Health Organisation Global Advisory Committee on Vaccine Safety, and has held various positions on technical committees and in training development since then. She remains on their Strategic Advisory Committee on Immunisation, which considers the demand for vaccines, as well as serving as a consultant for vaccine safety. As part of her work with the WHO MacDonald is developing the 2021 – 2030 Global Vaccine Action Plan. In 2004, with support from the Canada Foundation for Innovation she founded the Canadian Center for Vaccinology. The CCfV was established to implement and evaluate vaccine technologies as well as training experts in infectious diseases and global health. She has spoken about the dangers of vaccine hesitancy and how the internet permits the dangerous messaging of anti-vaxxers. At Dalhousie University MacDonald teaches a course Addressing Evidence Denial in Public. MacDonald serves on the advisory board of the National Collaborating Centre for Infectious Diseases and on the Board of Directors of Academics Without Borders. MacDonald is interested in building the healthcare capacity of the developing world. She co-founded East Africa's MicroResearch, a program that looks to support local health providers. MicroResearch is modelled on principles from microfinance, developing solutions that are appropriate for the context and culture of African communities. From 2008 to 2019 MicroResearch had led more than forty two-week workshops across seven African countries, training in excess of 1000 healthcare professionals and community members. In particular MicroResearch looked to train women, improving their opportunities for leadership and tackling the gender gap in African research. The success of the programme resulted in a similar version being launched in Canada in 2016. She was invested into the Order of Nova Scotia in 2019. That year she was also awarded the Lifetime Achievement Award from the Canadian Society for International Health.
