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.