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Editor,—We read with interest the article by Kerret al. While the proportion of samples positive for H pylori DNA were significantly higher in the SIDS group compared with the control group, the findings need to be interpreted with caution.
PCR is a useful tool for detection of DNA. It is, however, evidence that the DNA of the organism is present, not evidence that the organisms were alive or caused disease. Culture, microscopy, serological evidence or histological evidence of inflammatory or immune responses are needed to support the hypothesis that the bacteria were involved with pathological processes, not just transient contamination of the infant with DNA from non-viable bacteria.
There are several points that detract from the paper:
In relation to the findings reported:
- Only the PCR assays provided positive evidence. In contrast to other studies reported as abstracts, microscopic examination of the stained sections did not find any evidence of H pylori. This discrepancy needs to be explained. There were no serological data to support the PCR findings and no data from histological examinations to provide evidence that the bacteria were causing infection or that inflammatory responses had been elicited.
- The proportion of PCR positive samples among SIDS infants (88%) was significantly larger than that among controls (12.5%). The possibility of contamination was not addressed for SIDS or the positive control case. There was no demonstration by molecular methods that the DNA detected was from different strains. H pylori strains show great genetic variability and previous studies demonstrated that most individuals carry unique strains. Isolates from different individuals that appear to be genetically identical are those obtained only from close contacts, usually within a family.
The interpretation of the epidemiological data forH pylori and socioeconomic factors was not assessed in relation to incidence of SIDS among different ethnic groups. In Britain, white families in lower socioeconomic groups have more evidence of H pylori infections and more SIDS. If the data for incidence of infections withH pylori is assessed for ethnic groups and SIDS, this parallel breaks down. The incidence of seropositivity forH pylori among Bangladeshi women in the UK ranges from 66% among women born abroad to 81% among women born in the UK1; however, the incidence of SIDS in Bangladeshi families was the lowest in Britain (0.3%).2 A similar trend was observed in the United States; seropositivity forH pylori is 61% among Hispanics and 26.2% among non-Hispanic whites.3 In the paper quoted in the manuscript, the incidence of seropositivity was similar for Hispanic and black groups and both were significantly higher than that of non-Hispanic whites.4 The SIDS rates per 100 000 for US populations were 5.1 for blacks, 1.3 for Hispanics, and 1.2 for non-Hispanic whites.5 This evidence questions the assumptions made by the authors.
While there is increasing evidence for other hypotheses that SIDS might be triggered by inflammatory responses to infection,6-8there is no physiological or histological evidence to support the hypothesis that urease in the lung of the infants is causing increased levels of ammonia in the blood (see detailed assessment of pathology of SIDS in relation to this hypothesis below). Animal models9 10 do not reflect the combination of genetic, environmental, and developmental factors associated with SIDS, and results from animal studies must be interpreted with extreme caution when extrapolated to the human infant. H pylori infection does not fit the common bacterial hypothesis, a mathematical model which accurately predicted the age range for SIDS.11 According to the model, 50% of infants should acquire the bacteria during the first 50 days of life. While 19% of Gambian children were positive for the C13 urea breath test by 3 months of age,12 in industrialised countries the evidence is thatH pylori infection in infants under 1 year of age is much lower. Among 67 Belgian children born to seropositive mothers, only 1 (1.5%) had a positive breath test by the age of 12–15 months.13 Among Finnish children 10.6% had IgG toH pylori at birth, but the antibodies disappeared in all but one child before the age of 7 months and there were no seroconversions in these children. The Finnish study concluded that maternal seropositivity is not a straight forward risk factor for acquiring H pylori infection.14
The oral/oral route of transmission is suggested to be the route by which infants acquire H pylori, mainly by vomit.15 H pylori has been cultured from one of four vomit samples from children and detected by PCR in two of four culture negative samples. There is much stronger direct (culture) evidence for transmission from mother to child of other bacterial species implicated in SIDS.16
The pathogenic mechanism proposed for the role of ammonia cannot be substantiated by the available evidence:
- There are no acute changes in the upper respiratory tree or lungs consistent with inflammatory responses to H pylori.
- The presence of ammonia in the lower respiratory tree would initiate a bronchospasm which should produce clinical features such as wheezing which has not been reported by parents of SIDS infants. This type of reaction should be demonstrable histologically by muscular, glandular and secretory changes identified by microscopy.
- If ammonia is present in excess in the blood as a proximate cause of death, this should be demonstrable in blood samples and vitreous fluid, and there is no evidence for this.
- The liver in SIDS cases shows no abnormality and had it been acutely affected by an influx of ammonia, there should be changes.
- Ammonia in excess leads to cerebral changes of an acute type and none have been demonstrated.
- If the ammonia is postulated as a cause of petechiae in the lungs due to local damage, this does not account for the presence of petechiae in the thymus and pericardium.
There is evidence to explain how risk factors could contribute to susceptibility of infants to infectious agents to triggering the series of events leading to SIDS17; however, that presented for H pylori needs to be substantiated by more than one method and testable hypotheses proposed to explain how these bacteria might contribute to the series of events that lead to SIDS.
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