Both experimental and observational studies provide evidence indicating that infection and inflammation might play a role in sudden infant death syndrome (SIDS). Indeed, as early as 1889, Paltauf demonstrated mild inflammatory changes in the walls of the bronchioles in SIDS cases (1). In the 1950s the notion of minimal inflammation of the airways in SIDS was again noted, and since then several studies have reported that a large proportion of SIDS victims have signs of infection prior to death (2-5). Several of the factors associated with susceptibility to infection and inflammation have also proven to be risks for SIDS. A mild upper respiratory infection has been reported in about half of SIDS cases in the last days prior to death (6).

Signs of slight infection are often found by microscopic investigations, just as markers of infections and inflammation are often found at autopsy in SIDS. There are several studies indicating that the mucosal immune system is activated in SIDS (7-9). A higher number of IgM immunocytes in the tracheal wall, as well as a higher number of IgA immunocytes in the duodenal mucosa, have been reported in SIDS cases compared to controls (7). It has also been shown that SIDS victims have higher IgG and IgA immunocyte density in the palatine tonsillar compartments than controls (8). Furthermore, a higher number of CD45⁺ stromal leucocytes, as well as intensified epithelial expression of human leukocyte antigen—antigen D related (HLA-DR) and secretory component, and an increased expression of HLA class I and II have been reported in the salivary glands in SIDS (9). These observations confirm that the immune system is activated in SIDS, probably with release of certain cytokines that are known to up-regulate epithelia expression of HLA-DR and secretory component.

There are a vast number of studies reporting findings of bacteria in SIDS (4, 5, 10-14). It has been reported that there is a higher prevalence of S. aureus in nasopharyngeal flora from SIDS, and samples from the intestinal tract in SIDS have shown that S. aureus and staphylococcal endotoxins were more prevalent in SIDS compared to samples of feces from healthy controls (10-12). It is suggested that the toxins from S. aureus might contribute to SIDS via synergistic interactions with other colonizing species, in particular E. coli (4). E. coli colonizes the bowel of infants in the first days of life, and both a higher detection rate and a higher variety of serotypes have been reported in SIDS compared to controls (13, 14). Also, detection of H. pylori antigen in feces is associated both with SIDS and deaths due to infections (15). This study suggests that H. pylori infection in infancy may be involved as the triggering pathogen for sudden death during the first five months after birth. Taken together, it is plausible that common bacterial toxins, together with a viral infection, can cause SIDS in a vulnerable infant (16).

There are also several studies indicating that virus infections may play a role in SIDS, and higher rates of viruses have been isolated in samples from SIDS compared to controls (17-19). The involvement of viruses may be direct, by induction of a cytokine storm upon viral infection, or indirect, through synergistic interactions with bacterial virulence factors and/or immunregulatory polymorphisms. However, so far, no single respiratory virus has been exclusively found in a high proportion of SIDS cases: rather, a range of viruses are found at a higher frequency in SIDS compared to controls.