Histopatología ilustrada de casos fatales de dengue en Colombia
Dengue is the most important arboviral disease in humans in tropical and subtropical countries and considered endemic by the World Health Organization. It has been estimatedthat 390 million cases occur annually, 96 of them clinically diagnosed as symptomatic dengue fever (1). Although most infections are asymptomatic, the more severe forms of dengue (formerly called hemorrhagic or shock syndrome) could result in organ failure or death (2), with around a half million cases reported each year, an estimated average of 10,000 fatal cases per year (between 1990 and 2013) and a peak in 2010 (11,302 fatal cases) (2). Dengue incidence has seen a 30-fold increase in the last 50 years (3), making it a major public health concern currently.
In Colombia, dengue virus infection has an endemic and epidemic behavior with a steady increment in the last 20 years. The Colombian national surveillance system reported the highest historicpeak of dengue cases in 2010 (157,000 cases) and 9.777 severe dengue cases, with a worrying 217 fatalities (2.28% lethality rate) (4). During 2011, there was a decreasein dengue cases, but the lethality rate increased to 3.75% (5). The burden of the 2010 dengue epidemic was 14-fold higher than those of the years 2011 or 2012 (57.017 vs. 3.989 disability-adjusted life years were lost, respectively). Additionally, the estimation of the 2010 epidemic costs rose to US$ 65.5 million, almost 4-fold higher expenses compared to a regular endemic or epidemic year. Approximately 30% of these costs corresponded to those involving the loss of income due to fatalities.
Dengue is caused by a virus that belongs to the Flaviviridaefamily of the genus Flavivirusand presents four antigenically different serotypes (DENV-1 to 4). Each serotype is capable of producing an asymptomatic infection or an infection with clinical signs and symptoms ranging from a mild febrile disease to a severe infection characterized by an imbalanceof endothelial function leading to massive plasma leakage, severe hemorrhage and multi-organ failure (6). The infection could be fatal, involving different organs such as the liver, brain, spleen, lungs, and kidney (7).
Different cell types can be infectedby dengue virus andpathological manifestations can be variable (8, 9). Most severe cases show damage in the vascular endothelium which resultsin plasma extravasation and coagulation imbalance, liver function impairment with high transaminase levels and histologic alterations (10-12).
Histopathological analyses of fatal cases indicate that the liver and spleen are the organs most affected during dengue virus infection. In the liver, it is common to find small necrotic foci, microvesicular steatosis, hyperplasia and apoptosis of Kupffer cells, lymphocyte infiltration in the portal tract and Councilman bodies (necrotic foci, acidophilic bodies and pyknotic nuclei) (13)(14-16), although occasionally intranuclear glycogen can be found (17).
Regarding the spleen, histopathologicalanalysis shows interstitial edema, white pulp vascular and cellular congestion with reactive hyperplasia (13, 18). Atypical alterations have also been reportedin the kidneys, lungs, heart, and brain in which hemorrhage, edema andleukocyte infiltrate are observed, with no specific morphological findings for each tissue (8, 19-22).
On the other hand, immunohistochemistry for DENV antigens showed different patterns, from one organ location to widerorgan presence. This work aims to describe, illustrate and compare different histological alterations found in 95 fatal confirmed dengue cases using 87, 42, 32, 37, 22, and 16 samples of liver, spleen, kidney, lung, heart, and brain, respectively. The main alterations found in the liver were necrosis (78.2%) and hyperplasia of Kupffer cells (82.7%), while in the spleen, reactive plasmacytosis (69%) and vascular congestion (92.9%) were the most observed findings. Edema was the most frequent alteration found in the lungs (83.8%) and brain (68.8%). Interestingly, most heart (77.3%) and kidney (65.3%) tissues had a normal histopathological aspect (see figures 1-12). Figure 13, illustrates in more detail the frequencies of the alterations found in each tissue.
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