Health chiefs have urged the parents of more than 30,000 Birmingham children to receive a booster jab.
Officials say up to three-quarters of the city's 41,000 infants born between 2 April 1999 and 12 March 2003, do not appear to have received the recommended extra booster against the "Hib" infection.
The condition can lead to potentially fatal illnesses including meningitis, pneumonia or inflammation of the airways.
It is spread by coughing, sneezing or close contact with an infected person.
Young at risk
Letters are being sent to the parents of 30,800 children advising them to contact their doctor to get the extra jab.
Young children are most likely to be affected by the disease, with the risk of infection highest between the age of three-months and four years.
The extra dose of Hib - haemophilus influenzae type b - vaccine was recommended by the Department of Health earlier this year after a rise in cases across the country.
Dr Annette Wood, a consultant in communicable diseases in the Birmingham and Solihull Health Protection Unit, said: "Some of these children may well already have appointments with their GPs to receive the Hib booster, in which case their parents should just carry on and make sure they attend those.
"However, we do suspect that many well-meaning parents misunderstood the campaign and assumed that as their children have already received the standard course of three Hib vaccine doses they have no need for another jab."
Fourfold increase
Before 1992, when Hib vaccinations were introduced, there were around 600 cases of the disease a year in children aged under four, causing around 30 deaths and leaving about 80 children permanently brain damaged.
After vaccinations began the number of cases fell by 98% and over the last 10 years immunisation has prevented an estimated 7,300 cases and 270 deaths in children.
But from 1999 the number of cases occurring annually increased fourfold to 122 and the national Joint Committee on Vaccination and Immunisation advised added protection.
Dr Wood said: "In Birmingham we are aware of five confirmed cases of Hib infection since 1997.
"But there has been an increase in Hib around the country and we are concerned to make sure that children in this area are well-protected against this serious infection."