Clinical Epidemiology Features and Risk Factors for Acute Diarrhea Caused by Rotavirus A in Vietnamese Children.

Introduction: Acute diarrhea caused by group A rotavirus (RVA) is a leading cause of morbidity and mortality globally in children less than 5 years old. Acute diarrhea caused by RVA is often manifested by loose/watery stool leading to different degrees of dehydration. The detection of risk factors, diagnosis, and prompt treatment of acute diarrhea caused by RVA is critical. We aimed to describe clinical epidemiological features of acute diarrhea caused by RVA and its associated risk factors. Subjects and Method. We conducted a cross-sectional study that included 321 children under 5 years old with acute diarrhea at Haiphong Children's Hospital, Vietnam, from 1 August 2019 to 31 July 2020. Results: Among the 321 children included in our analysis, 221 (68.8%) children were positive for RVA. Males represented 61.1% of cases, 41.2% of children were in the 12-<24-month age group, and the majority of cases were among children in suburban areas (71.5%). Clinical manifestations included loose and watery stool (100%), vomiting-fever-loose/watery stool (57.9%), vomiting-loose/watery stool (83.2%), fever-loose/watery stool (58.8%), dehydration (30%), hyponatremia (22.1%), hypernatremia (1.4%), and hypokalemia (15%). Risk factors for acute diarrhea caused by RVA included history of diarrhea, not exclusive breastfeeding in the first 6 months, living area, maternal education, and income. Conclusions: Acute diarrhea due to RVA was very prevalent in children under 5 years old. Clinical manifestations included a high prevalence of loose/watery stools/day and dehydration with electrolyte disorder. Mothers should exclusively breastfeed their children for the first 6 months to avoid the risk of acute diarrhea caused by RVA.

Treatment with the TLR7 agonist R848 induces regulatory T-cell-mediated suppression of established asthma symptoms.

The evolution of allergic asthma is tightly controlled by effector and regulatory cells, as well as cytokines such as IL-10 and/or TGF-ß, and it is widely acknowledged that environmental exposure to allergens and infectious agents can influence these processes. In this context, the recognition of pathogen-associated motifs, which trigger TLR activation pathways, plays a critical role with important consequences for disease progression and outcome. We addressed the question whether the TLR7 ligand resiquimod (R848), which has been shown to be protective in several experimental allergic asthma protocols, can also suppress typical asthma symptoms once the disease is established. To this end, we used an OVA-induced experimental model of murine allergic asthma in which R848 was injected after a series of challenges with aerosolized OVA. We found that the treatment attenuated allergic symptoms through a mechanism that required Tregs, as assessed by the expansion of this population in the lungs of mice having received R848, and the loss of R848-mediated suppression of allergic responses after in vivo Treg depletion. IL-10 provided only a minor contribution to this suppressive effect that was largely mediated through a TGF-ß-dependent pathway, a finding that opens new therapeutic opportunities for the pharmacological targeting of Tregs.

The TLR7 agonist R848 alleviates allergic inflammation by targeting invariant NKT cells to produce IFN-gamma.

It has been documented that TLR7 stimulation triggers not only antiviral responses, but also alleviates experimental asthma. Considering the implication of invariant NKT (iNKT) cells in both situations, we postulated that they might contribute to the anti-inflammatory effect of TLR7 ligands. We show in this study that spleen cells activated by the TLR7 agonist resiquimod (R848) attenuate allergic inflammation upon adoptive transfer when they are recovered from wild-type, but not from iNKT cell-deficient Jα18(-/-) mice, which proves the specific involvement of this regulatory population. Furthermore, we provide evidence that IFN-γ is critical for the protective effect, which is lost when transferred iNKT cells are sorted from IFN-γ-deficient mice. In support of a direct activation of iNKT cells through TLR7 signaling in vivo, we observed a prompt increase of serum IFN-γ levels, associated with upregulation of CD69 expression on iNKT cells. Moreover, we demonstrate that iNKT cells effectively express TLR7 and respond to R848 in vitro by producing high levels of IFN-γ in the presence of IL-12, consistent with the conclusion that their contribution to the alleviation of allergic inflammation upon treatment with TLR7 ligands is mediated through IFN-γ.

The pro-Th2 cytokine IL-33 directly interacts with invariant NKT and NK cells to induce IFN-gamma production.

IL-33 has recently been identified as a cytokine endowed with pro-Th2 functions, raising the question of its effect on invariant natural killer T cell (iNKT), which are potent IL-4 producers. Here, we report a two-fold increase of iNKT-cell counts in spleen and liver after a 7-day treatment of mice with IL-33, which results from a direct effect, given that purified iNKT cells express the T1/ST2 receptor constitutively and respond to IL-33 by in vitro expansion and functional activation. Conversely to the expected pro-Th2 effect, IL-33 induced a preferential increase in IFN-gamma rather than IL-4 production upon TCR engagement that depended on endogenous IL-12. Moreover, in combination with the pro-inflammatory cytokine IL-12, IL-33 enhanced IFN-gamma production by both iNKT and NK cells. Taken together these data support the conclusion that IL-33 can contribute as a co-stimulatory factor to innate cellular immune responses.

Invariant NKT cells inhibit development of the Th17 lineage.

T cells differentiate into functionally distinct effector subsets in response to pathogen encounter. Cells of the innate immune system direct this process; CD1d-restricted invariant natural killer T (iNKT) cells, for example, can either promote or inhibit Th(1) and Th(2) responses. Recently, a new subset of CD4(+) T helper cells, called Th(17), was identified that is implicated in mucosal immunity and autoimmune disorders. To investigate the influence of iNKT cells on the differentiation of naïve T cells we used an adoptive transfer model of traceable antigen-specific CD4(+) T cells. Transferred naïve CD25(-)CD62L(+) CD4(+) T cells were primed by antigen immunization of the recipient mice, permitting their expansion and Th(17) differentiation. This study establishes that in vivo activation of iNKT cells during T-cell priming impedes the commitment of naïve T cells to the Th(17) lineage. In vivo cytokine neutralization experiments revealed a role for IL-4, IL-10, and IFN-gamma in the iNKT-cell-mediated regulation of T-cell lineage development. Moreover, by comparing IL-17 production by antigen-experienced T cells from unmanipulated wild-type mice and iNKT-cell-deficient mice, we demonstrate an enhanced Th(17) response in mice lacking iNKT cells. This invigorated Th(17) response reverts to physiological levels when iNKT cells are introduced into Jalpha18(-/-) mice by adoptive transfer, indicating that iNKT cells control the Th(17) compartment at steady state. We conclude that iNKT cells play an important role in limiting development of the Th(17) lineage and suggest that iNKT cells provide a natural barrier against Th(17) responses.

Epidemiology of amebiasis in a region of high incidence of amebic liver abscess in central Vietnam.

The recent identification of Entamoeba dispar as a separate species, which is nonpathogenic for humans but morphologically indistinguishable from Entamoeba histolytica, has prompted the World Health Organization to recommend reinforced efforts for reassessment of the epidemiology of amebiasis and, in particular, of E. histolytica. In this regard, the distribution of amebic liver abscess (ALA) cases were analyzed in the province of Thua Thien Hué (TT Hué) in central Vietnam, a region known for its high incidence of invasive amebiasis. In addition, in a particular area of Hué City, a parasitologic and seroepidemiologic survey was performed to identify possible risk factors for transmission of E. histolytica. Based on the analysis of hospital charts from April 1990 to April 1998, 2,031 cases of ALA were identified, indicating an ALA incidence of at least 21 per 100,000 inhabitants per year. Incidence varied substantially between the various districts of TT Hué and directly correlated with population density. The risk for ALA was significantly higher in summer and was age and sex dependent because 95% of the cases were adults, of which more than 80% were males. There was no clustering of cases within households and recurrent cases of ALA occured more frequently than predicted in the study population. Despite the higher incidence of ALA in males, the parasitologic and seroepidemiologic survey revealed a significant higher infection rate for intestinal protozoon parasites, including E. histolytica in females. Besides level of education and access to a toilet or tapwater, use of river water was identified as an important risk factor for E. histolytica infection.