BackgroundIdentification of dengue patients at risk for progressing to severe disease is difficult. Significant plasma leakage is a hallmark of severe dengue infection which can suddenly lead to hypovolemic shock around the time of defervescence. We hypothesized that the detection of subclinical plasma leakage may identify those at risk for severe dengue. The aim of the study was to determine the predictive diagnostic value of serial ultrasonography for severe dengue.Methodology/Principal FindingsDaily bedside ultrasounds were performed with a handheld ultrasound device in a prospective cohort of adult Indonesians with dengue. Timing, localization and relation to dengue severity of the ultrasonography findings were determined, as well as the relation with serial hematocrit and albumin values. The severity of dengue was retrospectively determined by WHO 2009 criteria. A total of 66 patients with proven dengue infection were included in the study of whom 11 developed severe dengue. Presence of subclinical plasma leakage at enrollment had a positive predictive value of 35% and a negative predictive value of 90% for severe dengue. At enrollment, 55% of severe dengue cases already had subclinical plasma leakage, which increased to 91% during the subsequent days. Gallbladder wall edema was more pronounced in severe than in non-severe dengue patients and often preceded ascites/pleural effusion. Serial hematocrit and albumin measurements failed to identify plasma leakage and patients at risk for severe dengue.Conclusions/SignificanceSerial ultrasonography, in contrast to existing markers such as hematocrit, may better identify patients at risk for development of severe dengue. Patients with evidence of subclinical plasma leakage and/or an edematous gallbladder wall by ultrasonography merit intensive monitoring for development of complications.

Severe dengue is characterised by thrombocytopenia, plasma leakage and bleeding. Platelets are important for preservation of endothelial integrity. We hypothesised that platelet activation with secondary platelet dysfunction contribute to plasma leakage. In adult Indonesian patients with acute dengue, we measured platelet activation status and the response to the platelet agonist TRAP using flow cytometer-based assays. Patients were monitored daily for plasma leakage by ultrasonography. Acute dengue was associated with platelet activation with an increased expression of the activated fibrinogen receptor (αIIbβ3), the lysosomal marker CD63 and the alpha-granule marker CD62P (P-selectin). Upon maximal platelet activation by TRAP, platelet function defects were observed with a significantly reduced maximal activated αIIbβ3 and CD63 expression and reduced platelet-monocyte and platelet-neutrophil complexes. Patients in the lowest tertile of activated αIIbβ3 and CD63 expression had an odds ratio for plasma leakage of 5.2 (95% confidence interval [CI] 1.3-22.7) and 3.9 (95% CI 1.1-13.7), respectively, compared to the highest tertile. Platelet-derived serotonin has previously been related to plasma leakage and we found increased intra-platelet serotonin concentrations in our patients. In conclusion, platelet activation with platelet function alterations can be found in patients with acute dengue and this may contribute to dengue-associated plasma leakage.

Introduction There is a high global incidence of typhoid fever, with an annual mortality rate of 200,000 deaths. Typhoid fever also affects younger children, particularly in resource-limited settings in endemic countries. Typhoid vaccination is an important prevention tool against typhoid fever. However, the available polysaccharide typhoid vaccines are not recommended for children under 2 years of age. A new typhoid conjugate Vi-diphtheria toxoid (Vi-DT) vaccine has been developed for infant immunization. We aimed to define the safety and immunogenicity of the Vi-DT vaccine among adults and children in Indonesia. Methods An observational, blinded, comparative, randomized, phase I safety study in two age de-escalating cohorts was conducted in East Jakarta, Indonesia, from April 2017 to February 2018. We enrolled 100 healthy subjects in 2 age groups: adults and children (18–40 and 2–5 years old). These groups were randomized into study groups (Vi-DT vaccine), and comparator groups (Vi-polysaccharide (Vi-PS) vaccine and another additional vaccine) which was administered in 4 weeks apart. Subjects were followed up to six months. Result One hundred healthy adults and children subjects completed the study. The Vi-DT and Vi-PS vaccines showed no difference in terms of intensity of any immediate local and systemic events within 30 minutes post-vaccination. Overall, pain was the most common local reaction, and muscle pain was the most common systemic reaction in the first 72 hours. No serious adverse events were deemed related to vaccine administration. The first and second doses of the Vi-DT vaccine induced seroconversion and higher geometric mean titers (GMT) in all subjects compared to that of baseline. However, in terms of GMT, the second dose of Vi-DT did not induce a booster response. Conclusion The Vi-DT vaccine is safe and immunogenic in adults and children older than two years. A single dose of the vaccine is able to produce seroconversion and high GMT in all individuals.

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The detection of AL, HFLC, IG, and IPF by Sysmex XE-5000 hematology analyzers can help to differentiate between common causes of febrile illnesses with thrombocytopenia in dengue endemic areas. We recommend further investigating the discriminatory value of these parameters in clinical practice.