Abstract. The mechanisms underlying the bleeding manifestations and coagulopathy associated with dengue remain unclear, in part because of the focus of much previous work on severe disease without an appropriate comparison group. We describe detailed clinical and laboratory profiles for a large group of children with dengue of all severities, and a group with similar non-dengue febrile illnesses, all followed prospectively from early presentation through to recovery. Among the dengue-infected patients but not the controls, thrombocytopenia, increased partial thromboplastin times and reduced fibrinogen concentrations were apparent from an early stage, and these abnormalities correlated strongly with the severity and timing of vascular leakage but not bleeding. There was little evidence of procoagulant activation. The findings do not support a primary diagnosis of disseminated intravascular coagulation to explain the intrinsic coagulopathy. An alternative biologically plausible hypothesis is discussed.

BackgroundDengue is the most important mosquito-borne viral infection to affect humans. Although it usually manifests as a self-limited febrile illness, complications may occur as the fever subsides. A systemic vascular leak syndrome that sometimes progresses to life-threatening hypovolaemic shock is the most serious complication seen in children, typically accompanied by haemoconcentration and thrombocytopenia. Robust evidence on risk factors, especially features present early in the illness course, for progression to dengue shock syndrome (DSS) is lacking. Moreover, the potential value of incorporating serial haematocrit and platelet measurements in prediction models has never been assessed.Methodology/Principal findingsWe analyzed data from a prospective observational study of Vietnamese children aged 5–15 years admitted with clinically suspected dengue to the Hospital for Tropical Diseases in Ho Chi Minh City between 2001 and 2009. The analysis population comprised all children with laboratory-confirmed dengue enrolled between days 1–4 of illness. Logistic regression was the main statistical model for all univariate and multivariable analyses. The prognostic value of daily haematocrit levels and platelet counts were assessed using graphs and separate regression models fitted on each day of illness. Among the 2301 children included in the analysis, 143 (6%) progressed to DSS. Significant baseline risk factors for DSS included a history of vomiting, higher temperature, a palpable liver, and a lower platelet count. Prediction models that included serial daily platelet counts demonstrated better ability to discriminate patients who developed DSS from others, than models based on enrolment information only. However inclusion of daily haematocrit values did not improve prediction of DSS.Conclusions/SignificanceDaily monitoring of platelet counts is important to help identify patients at high risk of DSS. Development of dynamic prediction models that incorporate signs, symptoms, and daily laboratory measurements, could improve DSS prediction and thereby reduce the burden on health services in endemic areas.

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HighlightsThe diarrhoeal disease burden in a large, prospective infant cohort in Vietnam is defined.Minimum incidence of clinic-based diarrhoea in infants: 271/1000 infant-years.Rotavirus was most commonly identified, followed by norovirus and bacterial pathogens.Frequent repeat infections with the same pathogen within 1 year.Inclusion of rotavirus in the immunization schedule for Vietnam is warranted.

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A Higgs sextet is introduced in order to generate Dirac and Majorana neutrino masses in the 331 model with right-handed neutrinos. As will be seen, the present sextet introduction leads to a rich neutrino mass structure. The smallness of neutrino masses can be achieved via, for example, a seesaw limit. The fact that the masses of the charged leptons are not effected by their new Yukawa couplings to the sextet is convenient for generating small neutrino masses.Comment: RevTeX4, 5 pages, no figure. To appear in Phys. Rev. D. Misprints removed (v.2

It is shown that an effective (nonrenormalizable) coupling of lepton multiplets to scalar triplets in the 331 model with sterile/exotic neutrinos, can be a good way for generating neutrino masses of different types. The method is simple and avoids radiative/loop calculations which, sometimes, are long and complicated. Basing on some astrophysical arguments it is also stated that the scale of SU3 L symmetry breaking is at TeV scale, in agreement with earlier investigations. Or equivalently, starting from this symmetry breaking scale we could have sterile/exotic neutrinos with mass of a few keV's which could be used to explain several astrophysical and cosmological puzzles, such as the dark matter, the fast motion of the observed pulsars, the re-ionization of the Universe, etc.

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