Invasive Haemophilus influenzae Infection and Breastfeeding : Aspects of epidemiology and immunology

Abstract: Invasive Haemophilus influenzae (Hi) infection is still an important cause of morbidity and mortality in the world. Vaccination against Haemophilus influenzae type b (Hib) has been implemented in many industrial countries during the 1990s with a dramatic decrease in mortality and morbidity due to Hib. This is in sharp contrast to the situation in developing countries where Hib is still a threat.In a prospective study conducted in Örebro County, Sweden, between 1987 and 1992, before large scale Hib vaccination of children was introduced, the incidence of invasive Hi infection in children 0-4 years of age was 55/100 000 children/year. Hib caused 98% of the Hi cases in children.In a case control study it was found that duration of exclusive breastfeeding less than 13 weeks as well as a history of frequent infections were independent factors associated with an increased risk of invasive Hi infection with odds ratios, OR, of 3.79 (1.6-8.8) and 4.49 (1.0-21.0) respectively. For the age at onset of 12 months or older, the associations were stronger, OR 7.79 (2.4-26.6) and 5.86 (1,1-30.6), respectively. When breastfeeding duration in weeks was analysed as a continuous variable the OR was 0.95 (0.92-0.99), indicating a decreased risk for each additional week of breastfeeding.An ecologic study of the relation between incidence rates of Hi meningitis between 1956 and 1992 and breastfeeding rates in the population was performed. A strong negative correlation between breastfeeding and incidence of Hi meningitis was found with a maximum for a time Jag of 5-10 years. The correlation for contemporary data was intermediate. The result implies that a low breastfeeding rate was followed by an increased incidence rate of Hi meningitis up to 10 years later in time.In two laboratory assays the anti-Hib antibody response was investigated in children with invasive Hib infection as well as in healthy children in relation to age, duration of exclusive breastfeeding, history of frequent infections and exposure to passive smoking. Children 18 months or older with a duration of exclusive breastfeeding of 13 weeks or more had higher levels of anti-Hib antibodies of the IgG1, IgG2 and IgM isotypes during the Hib infection compared to those less breastfed. The differences between the breastfeeding groups (<13 weeks versus ≥ 13 weeks) were greatest for the IgG2 isotype. In control children a duration of exclusive breastfeeding of ≥ 13 weeks emerged as a protective factor against non-invasive and non-specific infections with an OR of 0.92 (0.86-0.99). The protective effect was stronger in children < 18 months of age with an OR of 0.87 (0.76-1,0). Duration of exclusive breastfeeding was not associated with anti-Hib antibody levels in children < 18 months of age. In children ≥ 18 months of age there was a weak association between duration of exclusive breastfeeding and anti-Hib antibody levels of the IgG2 isotype, strongest in those without frequent infections. Expression of idiotype I (Id-1) antibodies increased with age in contrast to idiotype 2 (Id-2) antibodies that were found only in children ≤ 24 months of age, but the levels of neither Id-1 nor ld-2 were related to duration of breastfeeding or exposure to passive smoking.In conclusion, exclusive breastfeeding seems to be protective against invasive Hi infections. Exclusive breastfeeding seems to be protective against Hi meningitis also at a population level. There are indications of a long lasting enhancing effect of breastfeeding on the antibody response to Hib in children, in particular on the IgG2 anti-Hib antibody production.