Shigella sonnei infection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence.

Shigella flexneri is historically regarded as the primary agent of bacillary dysentery, yet the closely-related Shigella sonnei is replacing S. flexneri, especially in developing countries. The underlying reasons for this dramatic shift are mostly unknown. Using a zebrafish (Danio rerio) model of Shigella infection, we discover that S. sonnei is more virulent than S. flexneri in vivo. Whole animal dual-RNAseq and testing of bacterial mutants suggest that S. sonnei virulence depends on its O-antigen oligosaccharide (which is unique among Shigella species). We show in vivo using zebrafish and ex vivo using human neutrophils that S. sonnei O-antigen can mediate neutrophil tolerance. Consistent with this, we demonstrate that O-antigen enables S. sonnei to resist phagolysosome acidification and promotes neutrophil cell death. Chemical inhibition or promotion of phagolysosome maturation respectively decreases and increases neutrophil control of S. sonnei and zebrafish survival. Strikingly, larvae primed with a sublethal dose of S. sonnei are protected against a secondary lethal dose of S. sonnei in an O-antigen-dependent manner, indicating that exposure to O-antigen can train the innate immune system against S. sonnei. Collectively, these findings reveal O-antigen as an important therapeutic target against bacillary dysentery, and may explain the rapidly increasing S. sonnei burden in developing countries.

Pediatric Oncology Palliative Care Programs in Central America: Pathways to Success.

Palliative care offers children who have life-limiting and life-threatening oncologic illnesses and their families improved quality of life. In some instances, impeccable symptom control can lead to improved survival. Cultural and financial barriers to palliative care in oncology patients occur in all countries, and those located in Central America are no exception. In this article, we summarize how the programs participating in the Asociación de Hemato-Oncólogos Pediatras de Centro America (AHOPCA) have developed dedicated oncology palliative care programs. The experience in Guatemala, El Salvador, Costa Rica, Panama, Dominican Republic and Haiti is detailed, with a focus on history, the barriers that have impeded progress, and achievements. Future directions, which, of course, may be impacted by the COVID-19 pandemic, are described as well.

"Take Out This Thing": A Teen's Decision About Removal of a Gastrostomy Tube.

Medical decision-making in children is not a static process. In pediatrics, parents and health professionals actively participate in clinical decision-making. They always consider what is in the child's best interest and sometimes weigh that against other considerations. As children get older, the level of participation in this process may change according to their own cognitive development and maturity level. In this article, we present a case of an adolescent with a life-limiting condition at the end of life. He wants to participate in his health management and speak for himself. He does not always prefer interventions that his parents think are best. Health care practitioners must include mature minors in the decision-making process and be willing to listen to their voices.

Estimating the burden of congenital rubella syndrome in Costa Rica, 1996-2001.

BACKGROUND: The epidemiology of rubella in Costa Rica changed during recent decades, shifting the susceptible groups to the reproductive age. This study estimates the burden of congenital rubella syndrome (CRS) from 1996 to 2001 in this country. METHODS: Three methods to calculate CRS incidence were used. A retrospective search ("Observed cases") was conducted using hospital discharge records of children born from 1996 to 2001 with selected codes of ICD9 and ICD10 consistent with CRS and children <3 months of age with a positive serologic test for rubella IgM antibody at the National Children's Hospital (NCH). Cases were classified as either suspected, compatible or confirmed CRS and congenital rubella infection. "Expected" incidence of CRS was calculated using reported cases of rubella (women 15-45 years of age) and fertility rates, assuming CRS probability of 0.9 during the first trimester of pregnancy and 0.5 of asymptomatic rubella cases. "Estimated" CRS cases were calculated using incidence rates reported from modeling analysis during epidemic and endemic years. RESULTS: Of the 577 discharge charts reviewed and the 66 children reported as rubella IgM(+), 40 compatible CRS cases, 45 confirmed, and 4 with congenital rubella infection cases were identified. The range of annual incidence rate of CRS (per 1000 live births) was as follows: "Observed" = 0.00-0.33, "Expected" = 0.00-0.35 and "Estimated" = 0.5-1.5. Compared with the estimated number of CRS cases, only 27.2% of CRS cases were detected from the retrospective search and 10.1% would be expected when calculated using rubella reported cases. CONCLUSIONS: The under-detection of CRS cases using rubella reported cases in women of reproductive age and retrospective search of CRS reinforces the importance of suspecting CRS in the presence of a single compatible manifestation. Laboratory confirmation is indispensable to implement CRS elimination strategies and should be done in every suspected case.