Dengue Fever Presenting As Acute Febrile Illness In Neonates: A Case Series From Pakistant.

Dengue fever is a mosquito-borne disease caused by flavivirus. It primarily infects people living in tropical and subtropical areas and can be transmitted vertically or horizontally to new-borns. We discuss the clinical spectrum, treatment, and outcomes of five neonates who presented with dengue fever at Aga Khan Hospital for Women in Karimabad, Karachi, Pakistan, during the 2021 post- monsoon season (October to December). Dengue infection was confirmed via positive NS1 antigen test. All new-borns had fever, flushing, and thrombocytopenia. Capillary leak syndrome and haemorrhagic complications occurred in one case. Two babies required oxygen support, with one mortality. Due to the severity of the disease in this population, we suggest that dengue fever should be evaluated as a differential diagnosis in neonates with sepsis and thrombocytopenia, especially in high-risk or endemic areas. Critical management strategies for neonatal dengue fever are the same as those for other paediatric patients and include judicious use of intravenous fluids and inotropes.

Association of different blood groups in patients with Dengue fever and their relationship with the severity of the illness.

Objective: To determine the association of different blood groups in patients with Dengue fever and their relationship with the severity of the illness. Methods: A hospital-based descriptive study was conducted in the Dengue Isolation Ward of Lady Reading Hospital Peshawar from March 2020 to September 2020. Patients with Dengue fever were included in the study. The severity of the illness was categorized as "Dengue fever (DF)", "Dengue hemorrhagic fever (DHF)", and "Dengue shock syndrome (DSS)". The patients' blood groups were determined as A, B, AB, and O groups. All the data were recorded and analyzed using SPSS® version 23. Chi-square (χ2) and student t-test were applied, and a p-value of ≤0.05 was considered significant. Results: Out of 160 patients, 119(74.4%) were males; the patient's mean age was 38.09±15.68 SD, IQR=25 years. Greater proportion (28%) of the young men (up to 40 years) was affected compared to 9% young women. Fever (99%) and body aches (96%) were the most common presentation of DF, complicated by bleeding in 30.6% and shock in 9.4% of the patients. The majority (63.1%) of the patients had DF; 27.5% had DHF, and 9.4% had DSS. Sixty three (39.4%) patients had blood Group-B and 5.6% had Group-AB (p=0.97). The proportion of patients with different blood groups and the type/severity of the DF were almost identical except the fact that none of the patient with group AB had DSS. There was significant gender difference of hemoglobin (p=0.008, 95%CI=0.439, 2.844), hematocrit (p=0.012, 95%CI=0.00974, 0.07946); and Alanine Aminotransferase levels (p=0.002, 95%CI=-332.032, -72.233). Conclusion: Patients with blood Group-B were more frequent and AB was least commonly affected by the Dengue-virus infections. However, no association was found between a particular blood group and disease severity. Greater proportions of the younger men had Dengue infections.

Clinicopathological alteration of symptoms with serotype among dengue infected pediatric patients.

Dengue fever is a self-limiting, acute febrile illness caused by an arbovirus. This infection may be asymptomatic or symptomatic with its potential life-threatening form as DHF/DSS. Severe dengue cases occur typically in children due to overproduction of proinflammatory and anti-inflammatory cytokines (called cytokines storm) as well as increased microvascular permeability in them. This study aimed to find circulating dengue serotype and their clinicopathological association among pediatric patients admitted to tertiary care hospitals in Kolkata, India. Overall, 210 patients were approached, among them, 170 dengue suspected children admitted to three tertiary care hospitals were included in this study. Dengue samples were screened for the presence of dengue NS1 antigen and IgM antibodies by enzyme-linked immunosorbent assay. Viral RNA was extracted from NS1 seropositive serum samples and subjected to molecular serotyping by semi-nested reverse-transcription polymerase chain reaction. All patients were followed up for clinical manifestations and biochemical parameters associated with dengue. Cocirculation of all four serotypes was observed and DENV2 was the major circulating strain. Physiological classification of associated clinical symptoms was done as per WHO guideline and represented as a percentage variable. A multivariate logistic regression approach was used for making a regression model including dengue-associated clinical symptoms with dengue positivity or negativity as dependent variables. Thrombocytopenia was observed in 69% of patients and the commonest bleeding manifestation was petechia. Liver function profiles of infected patients were observed during follow-up and represented using a box plot. A significant change in trends of dengue-associated clinical manifestations and differential expression of liver functional profile with different phases of transition of dengue fever was observed in this study population.

Neurological Complications of Dengue Fever.

PURPOSE OF REVIEW: To discuss the neurological complications of dengue virus (DENV) infection and their pathogenesis. RECENT FINDINGS: Include recognition of the four different serotypes of DENV and their epidemiology as well as recognition of the expanded dengue syndrome encompassing multisystem involvement in the severe form of the disease including involvement of the central nervous system (CNS). DENV is a neurotropic virus with the ability to infect the supporting cells of the CNS. Neural injury during the acute stage of the infection results from direct neuro-invasion and/or the phenomenon of antibody-dependent enhancement, resulting in plasma leakage and coagulopathy. Immune mechanisms have been implicated in the development of the delayed neurological sequelae through molecular mimicry. A myriad of neurological syndromes has been described as a result of the involvement of the CNS, the peripheral nervous system (PNS), or both. Neurological manifestations in DENV infection are increasingly being recognized, some of which are potentially fatal if not treated promptly. DENV encephalopathy and encephalitis should be considered in the differential diagnosis of other acute febrile encephalopathies, autoimmune encephalitides, and in cases of encephalopathy/encephalitis related to SARS-CoV2 infection, especially in dengue-endemic areas. Acute disseminated encephalomyelitis (ADEM) may be occasionally encountered. Clinicians should be knowledgeable of the expanded dengue syndrome characterized by the concurrent compromise of cardiac, neurological, gastrointestinal, renal, and hematopopoietic systems. Isolated cranial nerve palsies occur rather uncommonly and are often steroid responsive. These neuropathies may result from the direct involvement of cranial nerve nuclei or nerve involvement or may be immune-mediated. Even if the diagnosis of dengue is confirmed, it is absolutely imperative to exclude other well-known causes of isolated cranial nerve palsies. Ischemic and hemorrhagic strokes may occur following dengue fever. The pathogenesis may be beyond the commonly observed thrombocytopenia and include cerebral vasculitis. Involvement of ocular blood vessels may cause maculopathy or retinal hemorrhages. Posterior reversible encephalopathy syndrome (PRES) is uncommon and possibly related to dysregulated cytokine release phenomena. Lastly, any patient developing acute neuromuscular weakness during the course or within a fortnight of remission from dengue fever must be screened for acute inflammatory demyelinating polyneuropathy (AIDP), hypokalemic paralysis, or acute myositis. Rarely, a Miller-Fisher-like syndrome with negative anti-GQ1b antibody may develop.

Matrix metalloproteinases in the pathogenesis of dengue viral disease: Involvement of immune system and newer therapeutic strategies.

Globally, the burden due to dengue infection is increasing with a recent estimate of 96 million progressing to the disease every year. Dengue pathogenesis and the factors influencing it are not completely known. It is now widely speculated that there is an important role of matrix metalloproteinases (MMPs) in the initiation and progression of dengue pathogenesis; however, their exact roles are not fully understood. Overactivation of matrix metalloproteinases may contribute to the severity of dengue pathogenesis. Cytokines and various other mediators of inflammation interact with the vascular endothelium and matrix metalloproteinases may be one of the components among them. Extensive plasma leakage into tissue spaces may result in a shock. It is evident in the literature that MMP2 and MMP9 increase in dengue patients is correlated with the severity of the disease; however, the underlying mechanism is still unknown. Activation of innate cells and adaptive immune cells which include, B and T cells, macrophages or monocytes and dendritic cells also contribute to the dengue pathology. Newer therapeutic strategies include microRNAs, such as miR-134 (targets MMP3 and MMP1) and MicroRNA-320d, (targets MMP/TIMP proteolytic system). The use of antibodies-based therapeutics like (Andecaliximab; anti-matrix metalloproteinase-9 antibody) is also suggested against MMPs in dengue. In this review, we summarize some recent developments associated with the involvement of immune cells and their mediators associated with the matrix metalloproteinases mediated dengue pathogenesis. We highlight that, there is still very little knowledge about the MMPs in dengue pathogenesis which needs attention and extensive investigations.

A novel anti-NS2BNS3pro antibody-based indirect ELISA test for the diagnosis of dengue virus infections.

Dengue virus reportedly circulates as four genetically distinct serotypes for which there is no widely accepted vaccine or drug at present. Morbidity and mortality caused by this virus are alarming for the possible increased threat to human health. A suitable diagnostic test is the prerequisite for designing and developing control measures. But, the tests being employed at present possess one or the other drawback for this disease diagnosis. During the dengue virus infections, NS2B is essential for the stability and catalytic activity of the NS3 protease. N-terminal 185 amino acids of NS3 protease domain along with hydrophilic portion of NS2B (NS2BNS3pro) is being used to screen dengue inhibitors but not for diagnosis until now. In the present study, we have used purified NS2BNS3pro as an antigen to trap anti-NS2BNS3pro antibodies of the clinical samples. Antibodies were detected successfully in both Western blot analysis and enzyme-linked immunosorbent assay (ELISA) tests. In ELISA, antibodies were detected in both primary and secondary infections of all serotypes. Interestingly, 17 samples declared as other febrile infections by NS1 and IgM/IgG tests were found to be positive in present test, which were further confirmed by reverse-transcription polymerase chain reaction. In silico studies suggested the absence of conserved epitopes between NS2BNS3pro and the counterpart in JEV, Zika, and CHIKV, indicating less possibility of crossreaction, which was in turn confirmed by using synthetic peptides representing the above epitopes. Statistical analysis with 76% specificity, 87% sensitivity, and 95% concordance also supported the present test as a suitable test for large scale diagnosis of dengue virus infections.

Comparison of clinical manifestation of dengue fever in Bangladesh: an observation over a decade.

BACKGROUND: The clinical presentation of dengue fever had been observed to change with time since its first outbreak in 2000 in Bangladesh. This report showed the clinical presentation of the 2019 outbreak in Bangladesh along with its comparison to previous outbreaks witnessed in this region. METHODS: This hospital-based cross-sectional study was conducted in one of the largest tertiary care hospitals in Dhaka city. A total of 553 laboratory-confirmed and 194 probable dengue cases were interviewed. The clinical manifestation of the confirmed cases of the current outbreak was compared with three of the outbreak reports retrieved from the databases. R version 3.6.3 was used for data analysis. RESULTS: Among the confirmed cases, two-thirds were male (63.2%) and the average age was 27(± 11) years. Positive tests for NS1 and IgM were present in 99.6% (n = 525/527) and 82.6% (n = 38/46) of the cases, respectively. Thrombocytopenia was present in 66.1% of cases. Fever (100%) was common for all. Gastrointestinal (GIT) features, including abdominal pain (86.5%), anorexia and/or vomiting (69.6%), and Diarrhea (> 3 motions/day) (26.2%) were more frequent than typical rash and other pain symptoms. Hypotension was present in approximately a quarter of patients (25%). GIT features (anorexia, nausea, and/or vomiting) and hypotension were more common among adult participants while bleeding manifestation (melena and vaginal bleeding, p = 0.009 & 0.032) was more frequent in pediatric patients. Compared to outbreaks of 2008, 2016, and 2018, increasing trends in GIT symptoms e.g. anorexia, abdominal pain, and diarrhea were observed. While a negative trend in hemorrhagic manifestations (skin rash, melena, and conjunctival hemorrhage/hemorrhagic sclera) and arthralgia/joint pain were found. CONCLUSION: The present outbreak was noticeably characterized by GIT symptoms and hypotension in addition to the typical clinical features like rash and pain symptoms. An increasing trend in GIT features and decreasing trend in hemorrhagic manifestations was noted over the last decade of dengue outbreaks.

Modeling the Relationship Between Antibody-Dependent Enhancement and Disease Severity in Secondary Dengue Infection.

Sequential infections with different dengue serotypes (DENV-1, 4) significantly increase the risk of a severe disease outcome (fever, shock, and hemorrhagic disorders). Two hypotheses have been proposed to explain the severity of the disease: (1) antibody-dependent enhancement (ADE) and (2) original T cell antigenic sin. In this work, we explored the first hypothesis through mathematical modeling. The proposed model reproduces the dynamic of susceptible and infected target cells and dengue virus in scenarios of infection-neutralizing and infection-enhancing antibody competition induced by two distinct serotypes of the dengue virus during secondary infection. The enhancement and neutralization functions are derived from basic concepts of chemical reactions and used to mimic binding to the virus by two distinct populations of antibodies. The analytic study of the model showed the existence of two equilibriums: a disease-free equilibrium and an endemic one. Using the concept of the basic reproduction number [Formula: see text], we performed the asymptotic stability analysis for the two equilibriums. To measure the severity of the disease, we considered the maximum value of infected cells as well as the time when this maximum is reached. We observed that it corresponds to the time when the maximum enhancing activity for the infection occurs. This critical time was calculated from the model to be a few days after the occurrence of the infection, which corresponds to what is observed in the literature. Finally, using as output [Formula: see text], we were able to rank the contribution of each parameter of the model. In particular, we highlighted that the cross-reactive antibody responses may be responsible for the disease enhancement during secondary heterologous dengue infection.

Role of C- reactive proteins and liver function tests in assessing the severity of dengue fever.

OBJECTIVE: To determine whether C-reactive protein and liver function tests can serve as severity markers for dengue fever. METHODS: The cross-sectional study was conducted in 2015-16 in Karachi and comprised patients with dengue fever visiting a tertiary care hospital. World Health Organisation classifications 1997 and 2009 were used to categorise patients according to clinical signs and symptoms. Receiver Operating Characteristics curve was used to determine discriminative ability and optimum cut-off value of biochemical markers. Comparisons were done through one-way analysis of variance using SPSS 17. RESULTS: Of the 218 patients, 133(61%) were males and 85(39%) were females. The overall mean age was 35.07±15.96 years. Levels of C-reactive protein and total bilirubin were significantly higher for dengue haemorrhagic fever compared to dengue fever; dengue shock syndrome compared to dengue fever; dengue shock syndrome compared to dengue haemorrhagic fever; and dengue shock syndrome compared to dengue fever / dengue haemorrhagic fever (p<0.05 each). Levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were significantly higher for dengue shock syndrome compared to dengue fever; dengue shock syndrome compared to dengue haemorrhagic fever; and dengue shock syndrome compared to dengue fever / dengue haemorrhagic fever (p<0.05 each). Levels of C-reactive protein, total bilirubin, alanine aminotransferase and alkaline phosphatise in patients with severe dengue were significantly higher compared to non-severe dengue. CONCLUSIONS: C-reactive protein and liver function tests were found to be effective biochemical markers in assessing dengue fever severity.

An unusual case of dengue shock syndrome complicated by ilio-femoral deep vein thrombosis; a case report.

BACKGROUND: Dengue fever is a hemorrhagic fever caused by flaviviruses. Hemorrhagic manifestations are well known to be associated with dengue fever, though the thrombotic events are only seldom reported. Underlying pathophysiology of thrombotic events is multifactorial and the management is challenging due to associated thrombocytopenia and bleeding tendency. We report a case of dengue shock syndrome with severe thrombocytopenia complicated by ilio-femoral deep vein thrombosis. CASE PRESENTATION: A 16 year old boy presented with dengue fever. He had dengue shock syndrome after entering the critical phase on the fifth day of the illness. With the recovery from the critical phase he developed deep vein thrombosis involving right external iliac, common femoral and superficial femoral veins. There were no provocative factors other than dengue fever itself. His platelet count was 12,000/µl at the time of diagnosis with deep vein thrombosis. Anticoagulation was started with intravenous unfractionated heparin 500 IU/hour while closely being observed for bleeding complications. 1000 IU/hour dose was commenced with the recovery of the platelet count above 50,000/µl. Thrombophilia screening was negative and he was discharged on warfarin. Venous duplex done after 6 weeks showed normal lower limb venous flow and warfarin was omitted after three months. CONCLUSIONS: With dengue fever, complications like deep vein thrombosis can be easily missed given its rarity and that the major concern is on hemorrhagic complications. Management is challenging due to associated thrombocytopenia and hemorrhagic complications.

Dengue Fever in the Darfur Area, Western Sudan.

We report an outbreak of dengue in Darfur, western Sudan, during September 2014-April 2015. Dengue virus-specific PCR testing of 50 samples from nonmalaria febrile illness case-patients confirmed 35 dengue cases. We detected 7 cases of dengue shock syndrome and 24 cases of dengue hemorrhagic fever.

Serum fatty acids and progression from dengue fever to dengue haemorrhagic fever/dengue shock syndrome.

PUFA might modulate inflammatory responses involved in the development of severe dengue. We aimed to examine whether serum PUFA concentrations in patients diagnosed with dengue fever (DF) were related to the risk of progression to dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). A secondary aim was to assess correlations between fatty acids (FA) and inflammatory biomarkers in patients with DF. We conducted a prospective case-control study nested within a cohort of patients who were diagnosed with DF and followed during the acute episode. We compared the distribution of individual FA (% of total FA) at onset of fever between 109 cases who progressed to DHF/DSS and 235 DF non-progressing controls using unconditional logistic regression. We estimated correlations between baseline FA and cytokine concentrations and compared FA concentrations between the acute episode and >1 year post-convalescence in a subgroup. DHA was positively related to progression to DHF/DSS (multivariable adjusted OR (AOR) for DHA in quintile 5 v. 1=5·34, 95 % CI 2·03, 14·1; P trend=0·007). Dihomo-γ-linolenic acid (DGLA) was inversely associated with progression (AOR for quintile 5 v. 1=0·30, 95 % CI 0·13, 0·69; P trend=0·007). Pentadecanoic acid concentrations were inversely related to DHF/DSS. Correlations of PUFA with cytokines at baseline were low. PUFA were lower during the acute episode than in a disease-free period. In conclusion, serum DHA in patients with DF predicts higher odds of progression to DHF/DSS whereas DGLA and pentadecanoic acid predict lower odds.

Series of 10 dengue fever cases with unusual presentations and complications in Sri Lanka: a single centre experience in 2016.

BACKGROUND: Dengue has global importance as a dreaded arboviral infection. It has 4 serotypes of epidemiological imporatnce. The classification denotes two clinical spectrums- dengue fever (DF) and dengue haemorragic fever (DHF). Most cases are stereotype and amenable to fluid resuscitation. However, unusual manifestations cause fatalities and often overlooked. This study describes 10 such dengue cases to fill the knowledge gaps. CASE PRESENTATION: All 10 patients presented to the Teaching Hospital, Peradeniya, Sri Lanka during mid-year epidemic of dengue in 2016. The mean age is 27 years (range 12-51 years) comprising 6 females and 4 males. The group had 7 DHF, 3 DF and 2 primary dengue infections who predominantly had severe bleeding into gut. Other potentially life threatening problems were acute severe hepatitis, severe septic shock, myocarditis, erratic rapid plasma leak, intracranial bleeding, diarrhoea and decompenstaed dengue shock due to 3rd space fluid leak. Blood transfusions and other empirical therapeutic methods were used apart from meticulous fluid management to suit issues of each patient. Bedside ultrasound scanning helped early detection of critical phase. All recovered fully. CONCLUSIONS: Dengue is an extremely challenging infection to treat in the globe today. Above unusual presentation and complications could be fatal, if not detected early where therapeutic window period is very short. Clinicians need awareness of these problems which are not uncommon, but underreported and often overlooked. The clinical management of each patient was described for the purpose sharing the experiences.

Acute Renal Failure Adversely Affects Survival in Pediatric Dengue Infection.

AIMS: Dengue is currently one of the most important mosquito-borne viral infections. Acute renal failure (ARF) is a serious complication among children suffering from dengue infection. SUBJECTS AND METHODS: A retrospective cohort review of baseline characteristics, disease outcomes, and risk factors of dengue-infected patients, with and without renal failure (RF), were compared. RESULTS: Among 97 children with dengue, 13.4% had RF (estimated glomerular filtration rate <60 ml/min/1.73 m2) at presentation. In comparison to all children (100%) of RF cohort, only 32% children of non-RF cohort (P < 0.0001) were suffering either from dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). The 7-day survival rate was 61.5% (8/13) among RF group as compared to 96.4% (81/84) in non-RF group (P < 0.001). When a fraction of patients who needed vasopressor support were significantly higher in RF cohort (70% vs. 14% for RF and non-RF, respectively, P < 0.001), requirement of mechanical ventilation (15% vs. 11%, P = 0.67) was comparable in both cohorts. CONCLUSIONS: DHF/DSS is an independent risk factor for the development of ARF in patients with dengue infection. Mortality rate is high once RF develops in these children.

Vitamin D serostatus and dengue fever progression to dengue hemorrhagic fever/dengue shock syndrome.

Vitamin D could modulate pathways leading to dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). We examined the associations of serum total 25-hydroxy vitamin D [25(OH)D] and vitamin D binding protein (VDBP) concentrations in patients with uncomplicated dengue fever (DF) with risk of progression to DHF/DSS. In a case-control study nested in a cohort of DF patients who were followed during the acute episode in Bucaramanga, Colombia, we compared 25(OH)D and VDBP at onset of fever between 110 cases who progressed to DHF/DSS and 235 DF controls who did not progress. 25(OH)D concentrations were also compared between the acute sample and a sample collected >1 year post-convalescence in a subgroup. Compared with 25(OH)D ⩾75 nmol/l, adjusted odds ratios (95% CI) for progression were 0·44 (0·22-0·88) and 0·13 (0·02-1·05) for 50 to 75 nmol/l (vitamin D insufficiency) and <50 nmol/l (vitamin D deficiency), respectively (P, trend = 0·003). Mean 25(OH)D concentrations were much lower post-convalescence compared with the acute episode, regardless of case status. Compared with controls, mean VDBP was non-significantly lower in cases. We conclude that low serum 25(OH)D concentrations in DF patients predict decreased odds of progression to DHF/DSS.

Complete genome characterization and evolutionary analysis of serotype-4 associated with severe dengue.

Dengue virus circulates as four independent serotypes posing a major public health threat around the globe. In the recent years, frequent dengue outbreaks are being reported in many parts of the world including India. Among four serotypes, Den-4 is the least sampled and studied serotype until recent times, but the reported cases with Den-4 infections were mostly known to associate with severe dengue. In the past three decades, only one complete genome sequence of Den-4 has been published from India. Hence there is a deficit in information with reference to this serotype which would be required in deciphering its association with severe dengue. In this study, we have carried out the complete genome characterization of Den-4 virus, isolated from a dengue shock syndrome patient during the 2015 outbreak from Hyderabad, South India. Phylogenetic analysis revealed the circulation of genotype I (lineage C) which showed close relatedness to the reported virulent strains. The data also indicated few unique amino acid substitutions which are known to be important in virus replication and epitope presentation. This is the first report of complete genome characterization of Den-4 from South India, which may assist in shaping the genetic diversity of circulating strains in India.

Co-circulation and co-infections of all dengue virus serotypes in Hyderabad, India 2014.

The burden of dengue virus infections increased globally during recent years. Though India is considered as dengue hyper-endemic country, limited data are available on disease epidemiology. The present study includes molecular characterization of dengue virus strains occurred in Hyderabad, India, during the year 2014. A total of 120 febrile cases were recruited for this study, which includes only children and 41 were serologically confirmed for dengue positive infections using non-structural (NS1) and/or IgG/IgM ELISA tests. RT-PCR, nucleotide sequencing and evolutionary analyses were carried out to identify the circulating serotypes/genotypes. The data indicated a high percent of severe dengue (63%) in primary infections. Simultaneous circulation of all four serotypes and co-infections were observed for the first time in Hyderabad, India. In total, 15 patients were co-infected with more than one dengue serotype and 12 (80%) of them had severe dengue. One of the striking findings of the present study is the identification of serotype Den-1 as the first report from this region and this strain showed close relatedness to the Thailand 1980 strains but not to any of the strains reported from India until now. Phylogenetically, all four strains of the present study showed close relatedness to the strains, which are reported to be high virulent.

Changing pattern of dengue virus serotypes circulating during 2008-2012 and reappearance of dengue serotype 3 may cause outbreak in Kolkata, India.

Dengue virus infection is a major cause of morbidity within the endemic tropical and subtropical regions of the world. Dengue virus has four distinct serotypes with specific clinical manifestations. In this study, we observed the changing pattern of dengue serotypes, age-wise dengue infection and useful sero-detection methods needed in a dengue endemic region. We identified dengue serotypes during a period of 5 years among patients with dengue symptoms visiting one of the largest tertiary care infectious disease hospitals of eastern India in Kolkata. A total of 433 dengue RNA positive samples were isolated from 712 acute dengue suspected cases. Age wise distribution highlighted the susceptible age group being >21 years (24.02%) followed by 11-15 years (21.71%) and 5-10 years (21.02%) of the total infected population. Higher numbers of infected cases were found within females as they are involved in more indoor works. The period of study experienced two dengue outbreaks one in 2008 and another in 2012. For early dengue detection, NS1 was found to be more confirmatory than IgM ELISA regarding sensitivity and specificity. DENV-1, 2, and 4 serotypes were the common circulating strains from 2008 until 2010, after which DENV-3 serotype infections rise and led to a massive dengue outbreak in Kolkata with increased numbers of DHF and DSS cases in 2012. The finding within our study emphasizes the public health importance of such prospective surveillance programs with respect to the changing dengue viral etiology and serotypes. J. Med. Virol. 88:1697-1702, 2016. © 2016 Wiley Periodicals, Inc.

Outcome of Severe Dengue Viral Infection-caused Acute Liver Failure in Thai Children.

To determine clinical course and outcomes of liver functions in children with dengue viral infection-caused acute liver failure (ALF), the records of patients aged <15 years attending our institution during 1989-2011 were reviewed. Of the 41 ALF patients, 2, 6 and 33 patients had dengue hemorrhagic fever grade II, III and IV, respectively. Multiorgan failure including respiratory failure, massive bleeding and acute kidney injury occurred in 80.0%, 96.0% and 84.0% of the ALF cases, respectively, with an overall fatality rate of 68.3%. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were highest on the day that the patient developed ALF. Lactate dehydrogenase levels had positive correlations with AST (r = 0.95) and ALT (r = 0.87) (all p < 0.01). The median (interquartile range) days before the AST and ALT levels returned to lower than 200 U/L after the ALF were 10.5 (8.8, 12.8) and 10.5 (7.8, 14.0) days, respectively.

Factors associated with death from dengue in the state of Minas Gerais, Brazil: historical cohort study.

OBJECTIVES: To analyse the clinical and epidemiological profiles of dengue haemorrhagic fever (DHF), dengue shock syndrome (DSS) and complicated dengue cases and deaths from 2008 to 2010 that occurred in the state of Minas Gerais, south-eastern Brazil, and to identify factors associated with death from dengue. METHODS: Historical cohort study using data from the Brazilian Information System for Notifiable Diseases. A descriptive analysis of the DHF, DSS and complicated dengue cases and deaths was performed; the incidence, mortality and case-fatality rates were estimated. Logistic regression analysis was used to identify factors associated with death from dengue. Comorbidities were not included in the analysis because the information system does not contain such data. RESULTS: During the study period, 2214 DHF, DSS and complicated dengue cases were reported, including 156 deaths. The annual case-fatality rates for DHF/DSS and complicated dengue cases in the period of 2008-2010 were 7.3%, 4.8% and 7.9%, respectively. The factors associated with death from dengue included residence in a municipality with a population of fewer than 100,000 inhabitants [odds ratio (OR) 2.46; 95% confidence interval (CI) 1.71-3.55], age over 65 years (OR 3.05; 95% CI 1.99-4.68) and plasma leakage (OR 1.69; 95% CI 1.16-2.46). CONCLUSIONS: The results support the importance of plasma leakage as a warning sign associated with death from dengue as well as the signs and symptoms that allow the diagnosis of DHF. Moreover, our findings suggest that increased attention is necessary for individuals over 65 years of age and in municipalities with populations under 100,000 inhabitants to ensure a better quality of care during the management of severe patients of dengue in these locations. Differences in the interpretation of the DHF definition have hindered the comparison of data from different countries; it can improve from the WHO 2009 dengue classification.