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The Ph.D. thesis is based on three published papers and one unpublished survey article. The investigations have been performed at the Institute of Forensic Medicine at Aarhus University and at the School of Biological Sciences, University of Birmingham, UK.
The main issue has been to investigate the importance of infection and infectious mechanisms in sudden infant death syndrome (SIDS), with the focus on chlamydial infection and the role of cytokine release during infections, triggered by virus and/or bacterial toxins.
C. trachomatis is one of the most common causes of respiratory infections in childhood and furthermore the most common cause of sexually transmitted diseases in the Western world. Genital chlamydia infections are without any symptoms in about 70% of women, and pregnant women may transmit the agent to the infant during birth without knowing it.
In Denmark, pregnant women are not routinely screened for genital chlamydia infections. But from other countries it is known that about 7-12% of cervices are infected with C. trachomatis before delivery. Approximately two out of three infants who are exposed acquire the infection, and pneumonia will develop in about 10-20%. C. pneumonia and C. psittaci are both capable of producing respiratory infections.
In the present study, a possible connection between chlamydia and SIDS has been examined by determining the occurrence of chlamydia inclusions in the lungs of SIDS infants compared to a control group. Formalin-fixed lung sections from 166 SIDS and 30 control cases were retrospectively examined for chlamydia inclusions. Chlamydia inclusions could be demonstrated by a developed immunoflourescence assay in 32 of the 166 SIDS cases (19.4%) and one of the control cases (3.3%). Despite this significant difference, the lung sections of the 32 chlamydia positive SIDS cases did not show typical histological signs of pneumonia. Even though chlamydia inclusions were detected in the lungs of every fifth SIDS case examined, no direct causal relation between chlamydia infection and SIDS could be demonstrated. Therefore, it could be speculated whether SIDS victims are responding inadequately to infections. One of the many factors which have been associated with the cause of SIDS is infection of the respiratory tract, particularly viral infections. Different specific viruses have been isolated at postmortem; however, no direct correlation has been shown. Invasive bacterial infections have been found in about 10% of SIDS cases. These bacteria have mainly been toxin-producing. Furthermore, an increased occurrence of toxin-producing bacteria have been found in the nasopharyngeal flora of SIDS victims, suggesting a disordered flora.
SIDS has been considered as a biphasic phenomenon; “The infant victims might be preconditioned in a subtle way before birth, so that some of their critical physiologic functions are subtly deficient. Then at 2 to 4 months of age, when confronted by some challenge, they are unable to overcome or adapt to the stress and die seemingly without cause.” One of the critical physiological functions in infants is the development of the immune system. SIDS occurs during a period of the infant’s life, when it is rapidly losing maternal immunity to infectious agents and its own immune system is immature. The infant is protected in the early weeks of life by maternal immunoglobulins with decreasing effectivity as its own immunity is being fully established. In the same period, the infant normally becomes colonised with infectious agents in order to develop immunity. Infections could be the challenges SIDS victims are unable to overcome, especially viral infections subsequently followed by a toxin-producing bacterial superinfection.
Both viruses and bacterial toxins are capable of inducing inflammation through certain inflammatory mediators (interleukins or cytokines). In order to examine the involvement of cytokines in the inflammatory response, the production of IL-1, Il-6 and TNF in human leucocytes were examined. In an in vitro experiment, the leucocytes were stimulated with influenza virus and then subsequently with endotoxin. An enhanced production of inflammatory inducing cytokines was found when the leucocytes were stimulated with both virus and toxin. IL-1 and TNF are known to be somnogenic. Thus, these cytokines could trigger a depression of the respiratory center in the brainstem either directly or perhaps by inhibition of arousal from prolonged apnoea. The time schedule from stimulation of cytokines to the effect of these is short; thus coma and death without signs of inflammation or other obvious pathology is possible. The following may be hypothesised: Normally harmless infection/infections ? Overstimulation of the immune system ? Production/liberation of interleukines ? Down regulation of the respiratory center in the brainstem ? Coma and death.