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BackgroundDengue is the most common mosquito-borne viral disease in humans. Recently, there has been an epidemic shift of dengue from mainly affecting children to affecting more adults with increased severity. However, clinical factors associated with severe dengue in adults have varied widely between studies. We aimed to identify the clinical factors associated with the development of severe dengue according to the World Health Organization (WHO)’s 2009 definition.MethodsWe conducted a prospective study of adults with dengue admitted to the Hospital for Tropical Diseases in Bangkok, Thailand, from October 2012 to December 2014. Univariate and stepwise multivariate logistic regression analyses were performed.ResultsOf the 153 hospitalized patients with confirmed dengue viral infections, 132 (86.3 %) patients had non-severe dengue including dengue without warning signs (7 patients, 5.3 %) and dengue with warning signs (125, 94.7 %). The rest (21, 13.7 %) had severe dengue including severe plasma leakage (16, 76.2 %), severe organ involvement (16, 76.2 %), and severe clinical bleeding (8, 38.1 %). Using stepwise multivariate logistic regression, clinical factors identified as independently associated with the development of severe dengue were: (1) being >40 years old (odds ratio [OR]: 5.215, 95 % confidence interval [CI]: 1.538–17.689), (2) having persistent vomiting (OR: 4.817, CI: 1.375–16.873), (3) having >300 cells per μL of absolute atypical lymphocytes (OR: 3.163, CI: 1.017–9.834), and (4) having lactate levels ≥2.0 mmol/L (OR: 7.340, CI: 2.334–23.087). In addition, increases in lactate and absolute atypical lymphocyte levels corresponded with severe dengue (p < 0.05).ConclusionsOur study identified several clinical factors independently associated with the development of severe dengue among hospitalized adults with dengue. This can aid in the early recognition and prompt management of at-risk patients to reduce morbidity and mortality.

BackgroundThe mechanisms that differentiate rabies infections into furious and paralytic forms remain undetermined. There are no neuropathological features in human brains that distinguish furious and paralytic rabies. This could be due to methodology and/or examination of specimens late in the disease course.In this study, postmortem examination of brain (5 furious and 5 paralytic) and spinal cord (3 furious and 3 paralytic) specimens was performed in 10 rabies-infected dogs, sacrificed shortly after developing the illness. Rabies virus (RABV) antigen (percentage of positive neurons, average antigen area in positive neurons and average antigen area per neuron) and RNA were quantified at 15 different central nervous system (CNS) regions. The distribution and degree of inflammation were also studied.ResultsMore RABV antigen was detected in furious rabies than paralytic in many of the CNS regions studied. Caudal-rostral polarity of viral antigen distribution was found in both clinical forms in order from greatest to least: spinal cord, brainstem, cerebellum, midline structures (caudate, thalamus), hippocampus, and cerebrum. In contrast, RABV RNA was most abundant in the cerebral midline structures. Viral RNA was found at significantly higher levels in the cerebral cortex, thalamus, midbrain and medulla of dogs with the furious subtype. The RNA levels in the spinal cord were comparable in both clinical forms. A striking inflammatory response was found in paralytic rabies in the brainstem.ConclusionsThese observations provide preliminary evidence that RABV antigen and RNA levels are higher in the cerebrum in furious rabies compared to the paralytic form. In addition, brainstem inflammation, more pronounced in paralytic rabies, may impede viral propagation towards the cerebral hemispheres.