Diagnosis of viral gastroenteritis in children: interpretation of real-time PCR results and relation to clinical symptoms.

Molecular methods such as real-time polymerase chain reaction (PCR) are rapidly replacing traditional tests to detect fecal viral pathogens in childhood diarrhea. This technique has now increased the analytical sensitivity so drastically that positive results are found in asymptomatic children, leading to complex interpretation of real-time PCR results and difficult distinction between asymptomatic shedding and etiological cause of disease. We performed a review of the literature including pediatric studies using real-time PCR and a minimal inclusion period of one year to exclude bias by seasonality. We searched for studies on rotavirus, norovirus, adenovirus, astrovirus, and sapovirus, known to be the most common viruses to cause gastroenteritis in the pediatric population. For these viruses, we summarized the detection rates in hospitalized and community-based children with clinical symptoms of gastroenteritis, as well as subjects with asymptomatic viral shedding. Moreover, insight is given into the different viral sero- and genotypes causing pediatric gastroenteritis. We also discuss the scoring systems for severity of disease and their clinical value. A few published proposals have been made to improve the clinical interpretation of real-time PCR results, which we recapitulate and discuss in this review. We propose using the semi-quantitative measure of real-time PCR, as a surrogate for viral load, in relation to the severity score to distinguish asymptomatic viral shedding from clinically relevant disease. Overall, this review provides a better understanding of the scope of childhood gastroenteritis, discusses a method to enhance the interpretation of real-time PCR results, and proposes conditions for future research to enhance clinical implementation.

Genetic variation of innate immune response genes in invasive pneumococcal and meningococcal disease applied to the pathogenesis of meningitis.

The susceptibility, severity and prognosis of infectious diseases depend on the ability of the host immune system to respond to pathogens. Genetic variation of immune response genes is associated with susceptibility to and severity of infectious diseases. Bacterial meningitis (BM) is a serious and life-threatening infectious disease of the central nervous system (CNS). Despite adequate antibiotic treatment and immunization strategies, mortality remains high, especially in developing countries. Streptococcus pneumoniae and Neisseria meningitidis are the two most common causative microorganisms of BM worldwide. The pathogenesis of BM starts with mucosal bacterial colonization, followed by invasion and survival of bacteria in the bloodstream, crossing of the blood-brain barrier, finally causing infection in the CNS, where host defense is less adequate. Host defense to BM starts with a complex cascade of pathogen recognition and subsequent intracellular signaling causing transcription of genes leading to the production of inflammatory mediators. Although this immune reaction is essential for killing microbes, it is also associated with damage to healthy cells and thus adverse disease outcome. This review provides an overview of the pathogenesis of invasive pneumococcal disease and invasive meningococcal disease related to the influence of genetic variation in genes involved in innate immunity, focusing on BM.

Rituximab administration in third trimester of pregnancy suppresses neonatal B-cell development.

We describe the effect on the neonate of administration of rituximab to a woman with idiopathic thrombocytopenic purpura (ITP). Rituximab, an anti-CD20 antibody, was given weekly for 4 weeks to a woman with ITP in her third trimester of pregnancy. One month after the last rituximab administration a healthy girl was born. She had normal growth and development during the first six months. At birth, B-lymphocytes were not detectable. Rituximab levels in mother and neonate were 24000 and 6700 ng/mL, respectively. Only 7 cases of rituximab administration during pregnancy were described. No adverse events are described for fetus and neonate. We demonstrate that rituximab passes the placenta and inhibits neonatal B-lymphocyte development. However, after 6 months B-lymphocyte levels normalized and vaccination titres after 10 months were adequate. No infection-related complications occurred. Rituximab administration during pregnancy appears to be safe for the child but further studies are warranted.

[A boy with cholera from India]. / Een jongen met cholera uit India.

A 7-year-old Indian boy travelling from India to the United Kingdom was brought to the Emergency Clinic of Airport Medical Services at Schiphol airport in Amsterdam, the Netherlands. He had had watery diarrhoea in the aircraft and had lost consciousness. In view of the strong indications for cholera and the rice water-like diarrhoea, he was admitted to the paediatric ward of the VU Medical Centre where intravenous rehydration was carried out. He recovered within three days. A large number of comma-shaped, motile, Gram-negative rods were found in the faeces. After two days, the faeces culture revealed Vibrio cholerae O1 El Tor, serotype Inaba. On the day of the flight, the patient had drunk a litre of water from a bottle that later turned out to have been from the New Delhi water supply. Cholera is rare as an import disease in the Netherlands. Due to the severe dehydration, the infection can run a serious course and even be fatal. The infection is not transmitted from person to person. Therefore, no special measures are needed when a patient with cholera is admitted to hospital.

Dummy use, thumb sucking, mouth breathing and cot death.

UNLABELLED: In the Netherlands a case control study into cot death was undertaken as part of the European Concerted Action on sudden infant death syndrome. Children between 1 week and 2 years of age who died suddenly and unexpectedly were reported. Non cot death cases were excluded after a consensus by three pathologists. The study comprised 73 cot death cases and two controls per case, matched for date of birth. Compared to national data, the coverage was 91%. We investigated whether in the Netherlands new risk or preventive factors might have emerged. The present report focuses on the relative risks of dummy use, thumb sucking, breast versus bottle feeding, and sleeping with the mouth open. CONCLUSION: Dummy use seems to be an important preventive factor for cot death in the Netherlands, independent of other risk factors such as prone sleeping and bedding. We recommend dummy use at least for bottle-fed infants. We found no indication that dummies influence the frequency or duration of breast feeding but more data are needed. Mouth breathing appears to be associated with an increased risk for cot death, but again further research is needed.

Risk and preventive factors for cot death in The Netherlands, a low-incidence country.

UNLABELLED: In the Netherlands an 18 months case control study into cot death was undertaken as part of the European Concerted Action (ECAS) on sudden infant death syndrome to determine the relative risk of prone sleeping and other sleep practices. Physicians in the Netherlands were asked to report to the study centre all sudden and unexpected deaths of children between 1 week and 2 years of age. Non cot death cases were deleted from further analysis after a consensus was reached by three pathologists, not primarily involved in the post mortem diagnosis. A positive response of families was achieved in 91% of cases registered in the Central Bureau of Statistics. The study comprised 73 cot deaths and 146 controls, two for each case and matched for date of birth. All families were visited at home for completion of a questionnaire. The cot death rate has dropped considerably over the past 10 years after the recommendations on supine sleeping to a low of 0.26 per 1000 live born infants. In addition to the ECAS objective, we wanted to establish whether previously found risk factors are still valid in the present situation or that new factors might have emerged, some of them possibly protective. CONCLUSION: Placing an infant prone or on side on last occasion, secondary prone position (not placed prone but turned to prone), inexperienced prone sleeping and use of a duvet, leading to head and body being covered, were shown to be risk factors. Preventive factors were using a cotton sleeping-sack and a dummy. Even in a low incidence country, such as the Netherlands, there are indications that further prevention is possible.

Sudden unexpected death in infancy: epidemiologically determined risk factors related to pathological classification.

Infants that died suddenly and unexpectedly were studied as part of the European Concerted Action on sudden infant death syndrome (SIDS). Three paediatric pathologists, first independently of each other and later in a consensus meeting, classified 63 cases into 3 groups: SIDS (19 cases), borderline SIDS (30 cases) and non-SIDS (14 cases). The interobserver agreement among the pathologists before the consensus meeting was moderate (Kappa = 0.41) and jointly it was higher (Kappa = 0.83). The distribution of epidemiologically determined risk factors was studied over these three groups. Maternal smoking after birth, low socioeconomic status and thumb sucking were found more often in SIDS than in the other cases. Inexperienced prone sleeping was a determinant for SIDS, but not for non-SIDS. Previous hospital admission, low birthweight and/or short gestation were associated with borderline SIDS. Non-SIDS cases received more breastfeeding, the parents hardly smoked during pregnancy and after birth, a firm mattress had been used, and more often signs of illness had been reported by the parents, compared with the SIDS and borderline SIDS cases. Bedding factors and both primary and secondary prone sleeping were equally distributed over the three groups which supports the hypothesis that, in SIDS and borderline SIDS, as well as in non-SIDS cases, some similar external and preventable factors might influence the events leading to death. Research should therefore focus on all sudden unexpected deaths, after which subgroups such as SIDS cases can be separately analysed. The postmortem is an essential part of the whole work-up of each case and the results should be interpreted with all other available data to arrive at a sound evaluation of cases and thus form the basis for the prevention of all sudden unexpected infant death.

Case-control study of current validity of previously described risk factors for SIDS in The Netherlands.

This study aimed to assess whether previously established risk factors for sudden infant death syndrome (SIDS) are still valid now that the incidence in the Netherlands has dropped to 0.26 per 1000 liveborn infants. A distinction was made between immutable and mutable risk factors. This case-control study (part of the European Concerted Action on SIDS) comprised 73 SIDS cases and 146 controls and lasted from March 1995 to September 1996. Adjustments were made for sleeping position and bedding factors by treating them as covariables. Apart from these factors, well known risk factors that remain of importance in the Netherlands are: male sex, young maternal age, twins, and low socioeconomic status. These factors are largely immutable. Other well known risk factors which might reflect attitudes to child care and could possibly be mutable are: smoking, alcohol consumption by the mother, bottle feeding, and change of babycare routine. Intervention strategies should focus on early signalling, thereby assisting parents in changing these unfavourable parenting attitudes. Information on optimal child care and extra support by public health nurses specifically aimed at families at risk could help to decrease further the incidence of SIDS in the Netherlands.