Early-phase factors associated with pediatric severe dengue in the Thai-Myanmar cross-border region.

BACKGROUND: Dengue disease is caused by dengue virus, which is transmitted by Aedes mosquitoes in tropical and subtropical regions worldwide. Although most infected individuals have benign febrile illness or no apparent symptoms, a small percentage develop severe dengue, a potentially fatal condition that occurs after a febrile stage. Many studies have identified factors predicting dengue severity among different populations and time courses. To help find practical approaches applicable in remote settings, we focused on the investigation of early factors associated with severe dengue in Thai-Myanmar cross-border region. METHODS: This retrospective case-control study was performed to determine factors contributing to severe dengue in the pediatric population. We reviewed the hospital records of patients with dengue infection aged 0-19 years who were admitted to Maesot General Hospital, situated near the Thai-Myanmar cross-border region, between 2017 and 2022. Medical data during the first 5 days of illness and outcomes were collected and analyzed. RESULTS: This study included 144 patients with a serologically confirmed diagnosis of dengue infection, with 43 severe and 101 non-severe cases. Among biological factors, being an infant and belonging to an ethnic group in Myanmar showed a significant association with severe dengue in the univariable analysis. Multivariable logistic regression revealed that the presence of mucosal bleeding (adjusted OR 5.39, 95% CI 1.06-27.52, P = 0.043), a change in hematocrit ≥ 10% (adjusted OR 3.68, 95% CI 1.15-11.74, P = 0.028), and serum albumin < 35 g/L (adjusted OR 8.10, 95% CI 2.55-25.72, P < 0.001) during the first 5 days of illness were significantly associated with developing severe dengue. CONCLUSIONS: This study supports the use of certain WHO warning signs and hematocrit change during febrile phase to predict pediatric severe dengue in low-resource settings. Potential factors such as very young age and ethnic groups warrant further exploration to identify risks contributing to severe dengue infection.

Advanced Age and Increased Risk for Severe Outcomes of Dengue Infection, Taiwan, 2014-2015.

Dengue, a mosquitoborne flavivirus infection, is increasingly a disease of older adults who are more likely to have chronic diseases that confer risk for severe outcomes of dengue infection. In a population-based study in Taiwan, adjusted risks for dengue-related hospitalization, intensive care unit admission, and death increased progressively with age.

Impact of apoptotic biomarkers for prognosis of dengue disease severity among eastern Indian patients.

Dengue virus (DENV) induced severe manifestations is a precursor for fatality among infected patients. Previous autopsy examinations of severe dengue (SD) patients reported presence of apoptotic cells in liver, brain, intestinal and lung tissues. Thus, serum-level of major apoptotic proteins of dengue patients was evaluated in the current study, along with their biochemical parameters. Patients were categorized according to World Health Organization (WHO)-defined classification. DENV-infection was screened among 165 symptomatic patients by quantitative reverse transcription polymerase chain reaction, antidengue IgM, and IgG ELISA. Serum levels of apoptotic (Capase-3,7,8, Bcl-2 and FasL) and hepatic-markers, lipid profile, hematological parameters of 78 dengue-positive patients were determined by sandwich-ELISA/immunoturbidimetry/auto-analyzer. Significantly higher levels of caspase-3,7,8 and FasL was detected among SD patients compared to those without warning (WOW) signs. Amongst biochemical parameters, bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase serum concentrations significantly increased among severe patients. Principal component analysis followed by hierarchical clustering differentiated severe and with warning dengue patient groups from those WOW using caspase-3,7,8 and FasL biomarkers-thus clearly distinguishing severe-dengue group. Correlation analyses also established strong positive correlation between caspase-3,7,8 and FasL. Thus, serum level of caspase-3,7,8 and FasL during early stage of infection could be used as biomarkers for WHO-defined dengue disease severity.

Serotype-associated immune response and network immunoclusters in children and adults during acute Dengue virus infection.

The present study was designed as an exploratory investigation to characterize the overall profile of chemokines, growth factors, and pro-inflammatory/regulatory cytokines during acute DENV infection according to DENV-1, DENV-2, DENV-4 serotypes and age: children: <1-10-year-old (yo); adolescents:11-20 yo; adults 21-40 yo; and older adults: 41-75 yo. The levels of soluble immunemediators were measured in serum by high-throughput microbeads array in 636 subjects including 317 DENV-infected and 319 age-matching non-infected control (NI). Overall, most soluble mediators were increased in DENV-infected patients as compared to NI group regardless of age and DENV serotype, with high magnitude order of increase for CCL2, CXCL10, IL-1ß, IFN-γ, IL1-Ra (fold change >3x), except PDGF in which no fold change was observed. Moreover, despite the age ranges, DENV-1 and DENV-4 presented increased levels of VEGF, IL-6, and TNF-α in serum but decreased levels of PDGF, while DENV-2 exhibited increased levels of CXCL8, CCL4, and IL-12. Noteworthy was that DENV-2 showed increased levels of IL-12, IL-15, IL-17, IL-4, IL-9, and IL-13, and maintained an unaltered levels of PDGF at younger ages (<1-10 yo and 11-20 yo), whereas in older ages (21-40 yo and 41-75 yo), the results showed increased levels of CCL2, IL-6, and TNF-α, but lower levels of PDGF. In general, DENV infection at younger age groups exhibited more complex network immunoclusters as compared to older age groups. Multivariate analysis revealed a clustering of DENV cases according to age for a set of soluble mediators especially in subjects infected with DENV-2 serotype. Altogether, our findings demonstrate that the profile of circulating soluble mediators differs substantially in acute DENV according to age and DENV serotypes suggesting the participation of serotype-associated immune response, which may represent a potential target for development of therapeutics and could be used to assist medical directive for precise clinical management of severe cases.

Abdominal and Chest Ultrasonography: A predictor for disease progression in nonsevere dengue.

Background: Dengue is one of the most rapidly spreading arboviral infections in the world. Ultrasound is well established in abdomino-thoracic evaluation of patients with dengue infection. The aim of this study was to explore the role of ultrasound in predicting occurrence of severe infection in dengue patients and in predicting deterioration in patients with nonsevere dengue. Methods: The serologically proven dengue patients who reported to hospital during the study period were divided into three categories based on the dengue infection severity score. Ultrasound findings of abdomen and chest in these patients were noted in the initial, as well as follow-up scans and inferences drawn. Results: 61% belonged to the category of Dengue Fever, 35% were in Dengue Hemorrhagic Fever category, and 4% had Dengue Shock Syndrome. Positive ultrasound findings were seen to be significantly higher in patients with severe dengue. Logistic regression analysis revealed the presence of pericholecystic fluid to be significantly associated with the severe disease, while the presence of gall bladder wall edema, ascites, and any ultrasound finding were significantly associated with the disease progression. The odds of a patient with severe dengue having gall bladder wall edema, ascites, or any ultrasound finding were 2.74, 2.04, and 2.619 times, respectively. Conclusion: Our study indicates that positive findings on ultrasound are significantly higher in severe dengue and also that ultrasound can be reliably used to identify the patients with nonsevere dengue who are likely to progress to severe dengue.

Clinical significance of differential serum-signatures for early prediction of severe dengue among Eastern Indian patients.

Dengue infection can result in simple dengue fever or life-threatening severe dengue. Early identification of severe patients is needed for proper disease management. Dengue infection was screened among 168 symptomatic patients by qRT-PCR, anti-dengue IgM, and IgG ELISA. Dengue patients were categorized according to WHO classification. Viral load and dengue serotypes were determined by qRT-PCR. Levels of acute-phase-proteins (SAP, SAA2; CRP and ApoA1), endothelial (Ang2, VEGF), coagulation (fibrinogen) markers were determined by sandwich ELISA/immunoturbidimetry/western-blotting. Hepatic (ALT, AST, ALP) and other blood biochemical parameters were studied by autoanalyzer and haematology cell counter. Statistical analysis and protein-protein-interaction network were performed by GraphPad-Prism and STRINGS database, respectively. Among 87 dengue patients, significantly higher levels of Ang2, VEGF, CRP, SAA2, ApoA1, AST, ALT, and AST/ALT ratio and low level of fibrinogen were detected in severe-dengue cases compared to dengue without warning-signs, with seven of them severely altered during febrile-phase. Higher fold-change of Ang2 and VEGF as well as decreased fibrinogen were observed among patients with haemorrhagic-manifestation, clinical-fluid accumulation and thrombocytopenia. Functional network analysis predicted Ang2, VEGF, and CRP to be functionally and physically connected and SAA2 and ApoA1 to be functioning together. Correlation analyses also validated this connectivity by a strong positive correlation between Ang2, VEGF, and CRP. PCA analysis followed by hierarchical clustering heatmap analysis segregated severe-dengue patients from the rest, with VEGF, Ang2, ApoA1, AST, and ALT clearly distinguishing the severe-dengue group. Thus, serum levels of VEGF, Ang2, ApoA1, AST, and ALT might act as potential biomarkers for predicting dengue severity during the early stage.

Assessing Aedes aegypti candidate genes during viral infection and Wolbachia-mediated pathogen blocking.

One approach to control dengue virus transmission is the symbiont Wolbachia, which limits viral infection in mosquitoes. Despite plans for its widespread use in Aedes aegypti, Wolbachia's mode of action remains poorly understood. Many studies suggest that the mechanism is likely multifaceted, involving aspects of immunity, cellular stress and nutritional competition. A previous study from our group used artificial selection to identify a new mosquito candidate gene related to viral blocking; alpha-mannosidase-2a (alpha-Mann-2a) with a predicted role in protein glycosylation. Protein glycosylation pathways tend to be involved in complex host-viral interactions; however, the function of alpha-mannosidases has not been described in mosquito-virus interactions. We examined alpha-Mann-2a expression in response to virus and Wolbachia infections and whether reduced gene expression, caused by RNA interference, affected viral loads. We show that dengue virus (DENV) infection affects the expression of alpha-Mann-2a in a tissue- and time-dependent manner, whereas Wolbachia infection had no effect. In the midgut, DENV prevalence increased following knockdown of alpha-Mann-2a expression in Wolbachia-free mosquitoes, suggesting that alpha-Mann-2a interferes with infection. Expression knockdown had the same effect on the togavirus chikungunya virus, indicating that alpha-Mann-2a may have broad antivirus effects in the midgut. Interestingly, we were unable to knockdown the expression in Wolbachia-infected mosquitoes. We also provide evidence that alpha-Mann-2a may affect the transcriptional level of another gene predicted to be involved in viral blocking and cell adhesion; cadherin87a. These data support the hypothesis that glycosylation and adhesion pathways may broadly be involved in viral infection in Ae. aegypti.

Identification of geographic clusters for temporal heterogeneity with application to dengue surveillance.

Identifying transmission of hot spots with temporal trends is important for reducing infectious disease propagation. Cluster analysis is a particularly useful tool to explore underlying stochastic processes between observations by grouping items into categories by their similarity. In a study of epidemic propagation, clustering geographic regions that have similar time series could help researchers track diffusion routes from a common source of an infectious disease. In this article, we propose a two-stage scan statistic to classify regions into various geographic clusters by their temporal heterogeneity. The proposed scan statistic is more flexible than traditional methods in that contiguous and nonproximate regions with similar temporal patterns can be identified simultaneously. A simulation study and data analysis for a dengue fever infection are also presented for illustration.

Maternal & perinatal outcome of fever in pregnancy in the context of dengue - A retrospective observational study.

Background & objectives: Pregnant women with dengue infection may be at increased risk of adverse maternal-foetal outcomes. This study was conducted to assess the maternal and perinatal outcomes in women who presented with fever and diagnosed to have dengue infection during pregnancy. Methods: A retrospective observational study was conducted on pregnant women admitted with fever, in a tertiary referral centre in South India, during January 2015 to December 2018. We compared outcomes of women diagnosed with dengue with that of women without dengue. The study outcomes included pre-term birth, stillbirth, low-birth weight (LBW), maternal mortality and thrombocytopenia. Results: During the study period, there were six maternal deaths following complications from dengue infection. Higher rates of thrombocytopenia (24.7% vs. 14.6%, P=0.02) were noted among those with recent dengue infection. The risk of still birth was 2.67 [95% confidence interval (CI) 1.09, 6.57], LBW [risk ratio (RR) 1.13, 95% CI 0.87, 1.45] and pre-term birth (RR 1.33, 95% CI 0.89, 1.97) among the cases. Interpretation & conclusions: Occurrence of adverse maternal and foetal outcomes was increased in pregnant women with fever diagnosed with dengue infection. Future studies are needed to formulate the optimum monitoring and treatment strategies in pregnant women, where dengue can have additive adverse effects to other obstetric complications.

Emergence of myasthenia gravis in dengue infection-first case report.

The association of dengue infection (DI) with atypical neurological manifestations was first reported in 1976. DENV-2 and DENV-3 serotypes are mostly related to neurological problems. DI has shown an overall risk of 21 autoimmune diseases, and 4% may develop neuromuscular complications. The pathogenetic mechanisms behind myasthenia gravis (MG) occurring during DI is thought to be linked to the neurotrophic effect of the infection. We report a unique case of DENV-1 infection presenting with bilateral ptosis and dysphagia in a previously healthy adult.

Cardiac evaluation in adults with dengue virus infection by serial echocardiography.

BACKGROUND: Dengue virus infection (DVI) is a major health problem in many parts of the world. Its manifestations range from asymptomatic infections to severe disease. Although cardiac involvement has been reported in DVI, its incidence has not yet been well established. METHODS: From July 2016 to January 2018, patients hospitalized at the Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Thailand, with dengue virus infection confirmed by positive NS1 or positive dengue immunoglobulin M findings, participated in the study. We characterized the incidence and change in cardiac function by serial echocardiography and levels of troponin-T and creatine kinase-myocardial band (CK-MB) on the day of admission, the day of defervescence, the first day of hypotension (if any), and at 2 week follow-up. RESULTS: Of the 81 patients evaluated, 6 (7.41%) exhibited elevated biomarker levels. There was no difference in clinical presentation amongst dengue fever, dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), except for the amount of bleeding. Cardiac involvement was found in 22.2% of patients: 3 (3.70%) had left ventricular systolic dysfunction, 3 (3.70%) had transient diastolic dysfunction, 6 (7.41%) had increased levels of at least one cardiac biomarker (troponin-T or CK-MB), and 6 (7.41%) had small pericardial effusion. Myocarditis was suspected in only two patients (with DHF); thus, myocarditis was uncommon in patients with dengue virus infection. Three patients developed DSS during admission and were transferred to the intensive care unit. CONCLUSION: Cardiac involvement in adults with dengue infection was common, ranging from elevated cardiac biomarker to myocarditis. Abnormalities in cardiac function had resolved spontaneously by the day of follow-up, without specific treatment. We found that DHF was a significant risk factor for cardiac involvement. Echocardiography is the investigation of choice for evaluating the haemodynamic status of patients with DVI, especially in severe dengue.

Hydrocephalus secondary to dengue encephalitis in an infant: case report.

BACKGROUND: Dengue is the leading cause of mosquito-borne viral infection. It is responsible for high morbidity and mortality in children living in endemic areas. Nowadays, neurological complications are progressively referred to and include a broad spectrum of symptoms. It can be secondary to metabolic alterations, direct invasion by the virus, and enhanced autoimmune response. CASE PRESENTATION: Here, we report a rare case of hydrocephalus secondary to dengue encephalitis. A 13-day-old boy was diagnosed with dengue. He evolved with seizures and impaired consciousness being diagnosed with encephalitis. After clinical treatment, he was discharged fully recovered. Three months later, he presented with signs and symptoms of intracranial hypertension. Brain MRI revealed hydrocephalus secondary to acquired aqueduct stenosis. The patient underwent an endoscopic third ventriculocisternostomy. CONCLUSION: Dengue infection is a differential diagnosis for acute febrile neurological impairment in children from endemic areas. Follow-up should be offered after dengue encephalitis to detect possible late-onset complications, as hydrocephalus.

Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion Associated with Dengue Infection in a Child.

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a clinico-radiological syndrome in children secondary to viral or bacterial infections. The causes include viral (influenza, human herpes virus-6, adenovirus, rota) as well as bacterial infections. However, AESD with dengue infection has not been reported earlier. Here, we present an infant with dengue infection and AESD which recovered completely following treatment with intravenous human immunoglobulin therapy. A 9-month-old girl presented with seizures following fever and loose stools. Seizures recurred after 2 days of seizure-free interval. Cerebrospinal fluid analysis was not contributory. Dengue infection was confirmed by lab tests. Magnetic resonance imaging brain after the second seizure revealed diffusion restriction involving the bilateral frontal and parietal white matter, both hemispheres with a typical central perisylvian sparing lesion suggestive of AESD. This case report expands the reported spectrum of neurological manifestations of dengue infection.

Correlation of C-reactive protein levels, gene polymorphism and platelets count in Dengue infection.

OBJECTIVE: To determine the correlation of polymorphism in C-reactive protein gene with variation in serum levels in dengue patients. METHODS: The cross-sectional study was conducted at Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi, Pakistan, from October 2017 to October 2018, and comprised blood samples from dengue patients which were used to measure the serum levels of C-reactive protein. Deoxyribonucleic acid extraction followed by tetra amplification-refractory mutation system polymerase chain reaction was used to analyse the genotype variation T>G for single nucleotide polymorphism rs199953854 using allele-specific primers. Correlation of serum C-reactive protein levels with the C-reactive protein polymorphism in dengue patients was explored. Data was analysed using SPSS 21. RESULTS: Of the 200 patients, 108(54%) had very high C-reactive protein levels, 48(24%) had levels slightly higher than the upper limit, 14(7%) had low and 30(15%) had normal levels. Also, 162(81%) patients had low platelets count. Amplification of only T alleles was noted. CONCLUSIONS: C-reactive protein levels were found to be increased with suppressed platelets count in dengue patients. Single nucleotide polymorphism rs199953854 appeared to have no polymorphism.

Dengue Infection Complicated by Hemophagocytic Lymphohistiocytosis: Experiences From 180 Patients With Severe Dengue.

BACKGROUND: Globally, ~500 000 people with severe dengue (SD) require hospitalization yearly; ~12 500 (2.5%) die. Secondary hemophagocytic lymphohistiocytosis (sHLH) is a potentially fatal hyperinflammatory condition for which HLH-directed therapy (as etoposide and dexamethasone) can be life-saving. Prompted by the high mortality in SD and the increasing awareness that patients with SD may develop sHLH, our objectives were to (1) determine the frequency of dengue-HLH in SD, (2) describe clinical features of dengue-HLH, (3) assess mortality rate in SD and dengue-HLH, and (4) identify mortality-associated risk factors in SD. METHODS: A 5-year retrospective single-center study in all adult patients with SD admitted to a tertiary intensive care unit in Malaysia. RESULTS: Thirty-nine of 180 (22%) patients with SD died. Twenty-one of 180 (12%) had HLH defined as an HLH probability ≥70% according to histo score (HScore); 9 (43%) died. Similarly, 12 of 31 (39%) fulfilling ≥4 and 7 of 9 (78%) fulfilling ≥5 HLH-2004 diagnostic criteria died. Peak values of aspartate aminotransferase (AST), alanine aminotransferase, lactate dehydrogenase, and creatinine correlated to fatality (odds ratios [ORs], 2.9, 3.4, 5.8, and 31.9; all P < .0001), as did peak ferritin (OR, 2.5; P = .0028), nadir platelets (OR, 1.9; P = .00068), hepatomegaly (OR, 2.9; P = .012), and increasing age (OR, 1.2; P = .0043). Multivariable logistic regression revealed peak AST (OR, 2.8; P = .0019), peak creatinine (OR, 7.3; P = .0065), and SOFA (Sequential Organ Failure Assessment) score (OR, 1.4; P = .0051) as independent risk factors of death. CONCLUSIONS: Be observant of dengue-HLH due to its high mortality. A prospective study is suggested on prompt HLH-directed therapy in SD patients with hyperinflammation and evolving multiorgan failure at risk of developing dengue-HLH.

The effect of KIR and HLA polymorphisms on dengue infection and disease severity in northeastern Thais.

Killer cell immunoglobulin-like receptors (KIRs) are cell surface receptors on natural killer (NK) cells and subsets of T cells. The interaction between KIRs and their cognate ligands (Human leukocyte antigen class I molecules, HLA class I) modulates the immune response of NK cells, in particular through clearance of virus-infected cells. Here, we investigated the effect of KIRs and HLA ligands on dengue infections and disease severity. The KIRs and HLA ligands were identified in 235 healthy controls (HC) and 253 dengue patients (DEN) using polymerase chain reaction with sequence specific primer (PCR-SSP); moreover, DEN was classified to 100 dengue fever (DF) and 153 dengue haemorrhagic fever (DHF). Risks were expressed as odds ratios (ORs) and 95% confidence intervals (CIs) with significance set at a two-tailed P value of < 0.05. The Bonferroni correction was applied for multiple comparisons. Twelve significant associations were observed in dengue infections and disease severity; however, two outcomes survived after the Bonferroni correction. Of these, HLA-A11 was associated with an increased risk to develop dengue disease (OR 2.41, 95% CI 1.62-3.60, Pc = 0.004), while KIR3DS1+ Bw4 was a protective genotype to developing DHF (OR 0.28, 95% CI 0.16-0.48, Pc < 0.001). This study revealed an important role of KIR and HLA ligands in innate immune responses to dengue viral infections and, in particular, their effect on clinical outcomes and disease severity.

Association of serum C-reactive protein level and polymorphisms with susceptibility to dengue infection and severe clinical outcome among eastern Indian patients.

Dengue virus (DENV) infection is a major public health concern in India ranging from simple febrile illness to severe outcome. This study aimed to investigate association of serum CRP level and CRP gene polymorphisms towards development of dengue disease susceptibility and severity among eastern Indian patients. Blood was collected from 348 symptomatic patients. Sera was subjected to serological diagnosis for the presence of anti-dengue IgM, anti-dengue IgG antibodies and dengue NS1 antigen by ELISA. Viral RNA was extracted and the presence of DENV genome, viral load, serotypes was determined by qRT-PCR. CRP level and polymorphisms were determined by immunoturbidimetry and polymerase chain reaction-restriction fragment length polymorphism, respectively. Statistical analysis was performed by GraphPad-Prism. Among 206 dengue patients, CRP level increased significantly among patients within acute phase, and patients with qRT-PCR/NS1 antigen positivity, high viral load (HVL), secondary infection, and DENV4 and DENV2 infections. rs3091244, TT genotype positively associated with dengue susceptibility (p = 0.03). CT genotype of rs3093059 and TT genotype of rs3091244 were found to correlate with elevated CRP level and development of WHO-defined warning signs. TT genotype of rs3091244 was more prevalent among HVL patients. Thus, these CRP polymorphic variants and CRP concentration might act as potential prognostic biomarkers for predicting disease severity among acute-stage dengue patients.

Dengue Infection: A Hidden Cause of Acute Insult in a Case of Acute on Chronic Liver Failure in Endemic Area.

Acute on chronic liver failure (ACLF) can be precipitated by several factors such as bacterial infection, alcohol intake, viral hepatitis, surgery, etc. Identification of precipitating factor is an important part of management of ACLF. A middle aged gentleman was presented with features of acute liver failure and after through history and investigations, he was diagnosed as acute on chronic liver failure. Chronic liver disease was first diagnosed after this event of acute insult. Precipitating factor of ACLF was dengue fever in this case report. Therefore, in endemic area of dengue infection, dengue serology tests which are not routinely done should be advised to identify dengue infection as an acute insult in ACLF.

Differences in activation and tissue homing markers of natural killer cell subsets during acute dengue infection.

Dengue virus (DENV) infection is considered one of the most important mosquito-borne diseases. It causes a spectrum of illness that could be due to qualitative and/or quantitative difference(s) of the natural killer (NK) cell responses during acute DENV infection. This view prompted us to perform a detailed phenotypic comparative characterization of NK cell subsets from DENV-infected patients with dengue fever (DF), patients with dengue haemorrhagic fever (DHF) and healthy controls. The activation/differentiation molecules, CD69 and CD57 and a variety of tissue homing molecules were analysed on the CD56hi CD16- and CD56lo CD16+ NK cells. Although there was no increase in the frequency of the total NK cells during DENV infection compared with the healthy individuals, there was a significant increase in the frequency of the CD56hi CD16- subset and the frequency of CD69 expression by both NK cell subsets during the febrile phase of infection. We also found an increase in the frequencies of cells expressing CD69 and CD57 in the CD56lo CD16+ subset compared with those in the CD56hi CD16- subset. Moreover, although the CD56lo CD16+ subset contained a high frequency of cells expressing skin-homing markers, the CD56hi CD16- subset contained a high frequency of cells expressing bone marrow and lymph node trafficking markers. Interestingly, no differences of these NK cell subsets were noted in samples from patients with DF versus those with DHF. These findings suggest that activation and differentiation and the patterns of tissue homing molecules of the two major NK cell subsets are different and that these might play a critical role in the immune response against acute DENV infection.

Successful treatment of thrombotic microangiopathy associated with dengue infection: A case report and literature review.

Dengue infection has been associated with multiple renal complications, including glomerulonephritis, acute tubular necrosis, tubulointerstitial nephritis, and thrombotic microangiopathy (TMA), this last one being a rare complication of dengue, with only a few reported cases. TMA associated with dengue can be explained by an alteration in the activity of the enzyme ADAMTS13, leading to thrombotic thrombocytopenic purpura; or it can be secondary to direct or indirect endothelial injury by the virus, which leads to hemolytic uremic syndrome. Here, we present a case of severe TMA, not related to ADAMTS13, which was clearly associated with dengue infection.