Effects of chloroquine or hydroxychloroquine treatment on non-SARS-CoV2 viral infections: A systematic review of clinical studies.

Chloroquine (CQ) and hydroxychloroquine (HCQ) have been used as antiviral agents for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. We performed a systematic review to examine whether prior clinical studies that compared the effects of CQ and HCQ to a control for the treatment of non-SARS-CoV2 infection supported the use of these agents in the present SARS-CoV2 outbreak. PubMed, EMBASE, Scopus and Web of Science (PROSPERO CRD42020183429) were searched from inception through 2 April 2020 without language restrictions. Of 1766 retrieved reports, 18 studies met our inclusion criteria, including 17 prospective controlled studies and one retrospective study. CQ or HCQ were compared to control for the treatment of infectious mononucleosis (EBV, n = 4), warts (human papillomavirus, n = 2), chronic HIV infection (n = 6), acute chikungunya infection (n = 1), acute dengue virus infection (n = 2), chronic HCV (n = 2), and as preventive measures for influenza infection (n = 1). Survival was not evaluated in any study. For HIV, the virus that was most investigated, while two early studies suggested HCQ reduced viral levels, four subsequent ones did not, and in two of these CQ or HCQ increased viral levels and reduced CD4 counts. Overall, three studies concluded CQ or HCQ were effective; four concluded further research was needed to assess the treatments' effectiveness; and 11 concluded that treatment was ineffective or potentially harmful. Prior controlled clinical trials with CQ and HCQ for non-SARS-CoV2 viral infections do not support these agents' use for the SARS-CoV2 outbreak.

Dengue Shock Syndrome: Its Similarity with Anaphylaxis and with the Homeopathic Medicine Apis mellifica (European Honeybee).

Dengue, with four viral serotypes, causes epidemics in tropical and sub-tropical regions. Allopathic antiviral therapies and a vaccine of general use are lacking. The homeopathic medicine Apis mellifica, advised in anaphylaxis from honeybee sting, is proposed to address the life-threatening dengue shock syndrome, which develops from dengue hemorrhagic fever and has features of anaphylaxis. In both dengue and anaphylaxis, immunoglobulin E activates, and released vasoactive mediators (importantly histamine, tryptase and platelet-activating factor) cause, a vascular permeability enabling shock. In dengue, another mechanism, namely antibody-dependent enhancement, due to secondary infection with a heterologous dengue serotype, is associated with release of vasoactive mediators. The homeopathic medicine Apis mellifica indicates plasma leak, shock, and the serous effusion that is noted in dengue patients, and is a suggested prophylactic and therapeutic medicine for dengue shock syndrome.

Use of intravenous N-acetylcysteine in acute severe hepatitis due to severe dengue infection: a case series.

BACKGROUND: Dengue fever is a common mosquito borne viral infection. Severe dengue fever associated severe hepatitis carries high mortality. Based on the beneficial effect of N-acetylcysteine (NAC) in paracetamol poisoning and non-acetaminophen induced liver failure, it is used in dengue fever associated hepatitis in clinical practice. We aim to study the reversal of liver enzymes with NAC in the setting of severe hepatitis due to severe dengue infection. METHODS: A retrospective analysis was conducted on hospitalized 30 adults with severe dengue fever with severe hepatitis. These 30 patients had aspartate transaminase (AST) and alanine transaminases (ALT) more than 500 U/L and/or PT INR (prothrombin time and international normalized ratio) more than 1.5. They were treated with NAC infusion of 100 mg/h for 3 to 5 days. RESULTS: The mean age of the group was 49.9 ± 11.46 years and 18 (60%) patients were males. Nineteen patients (63%) developed dengue shock. Of them 12 patients (40%) developed hepatic encephalopathy. Median AST on the day of administration of NAC was 1125 U/L interquartile range (IQR) 1653.25 while median ALT was 752 (IQR 459.25). There was a statistically significant reduction of both ALT (p = 0.034) and AST (p = 0.049) from day 1 to 4 after NAC infusion. Rise of platelet count between day 1 and day 4 also showed statistically significant difference (p = 0.011) but the reduction of prothrombin time and international normalized ratio (PT/INR) from 1 to day 4 did not show statistical significance difference. Mean duration of treatment with NAC was 3.61 ± 0.75 days while mean length of hospital stay was 6.2 ± 1.27 days. Only one patient died (3.3%). None of the patients reported adverse drug reaction due to NAC. CONCLUSION: Majority of patients demonstrated marked clinical and biochemical improvements and they recovered fully. We observed faster and significant recovery of liver enzymes following administration of NAC. Based on the above findings, this study provides preliminary evidence for the beneficial effect of NAC in severe hepatitis in dengue infection with greater survival benefits.

Experimental in vitro and in vivo systems for studying the innate immune response during dengue virus infections.

Dengue is the most prevalent arboviral disease in humans and leads to significant morbidity and socioeconomic burden in tropical and subtropical areas. Dengue is caused by infection with any of the four closely related serotypes of dengue virus (DENV1-4) and usually manifests as a mild febrile illness, but may develop into fatal dengue hemorrhagic fever and shock syndrome. There are no specific antiviral therapies against dengue because understanding of DENV biology is limited. A tetravalent chimeric dengue vaccine, Dengvaxia, has finally been licensed for use, but its efficacy was significantly lower against DENV-2 infections and in dengue-naïve individuals. The identification of mechanisms underlying the interactions between DENV and immune responses will help to determine efficient therapeutic and preventive options. It has been well established how the innate immune system responds to DENV infection and how DENV overcomes innate antiviral defenses, however further progress in this field remains hampered by the absence of appropriate experimental dengue models. Herein, we review the available in vitro and in vivo approaches to study the innate immune responses to DENV.

Frequency of worsening liver function in severe dengue hepatitis patients receiving paracetamol: A retrospective analysis of hospital data.

OBJECTIVE: To determine the frequency of worsening liver function among hospital in-patients with severe dengue hepatitis receiving paracetamol. METHODS: This retrospective study was conducted at the Department of Medicine, Aga Khan University Hospital, Karachi, and comprised records of dengue patients with severe hepatitis who received paracetamol for control of fever between June 2007 and December 2014. Alanine aminotransferase at baseline and following paracetamol administration was noted, as well as dosage and duration of paracetamol, along with participants' demographic details. Frequency of patients who developed worsening or improvement of alanine aminotransferase was also noted. SPSS 19 was used for data analysis. RESULTS: Of the 113 subjects, 73(64.6%) were male and 40(35.4%) were female. Overall improvement was observed in subsequent alanine aminotransferase levels (491 units per litre, IQR 356.5 TO 775 vs 151 units per litre, IQR 49.5 to 299.5). Most commonly prescribed dose of paracetamol was 2g (IQR 1 to 5 grams), which was taken for a median duration of 1 day (IQR 1 to 3 days). Moreover, 100(88.5 %) patients showed improvement in alanine aminotransferase. Only 13(11.5 %) patients developed worsening of alanine aminotransferase. Of those with worsening liver function, 8(61.5 %) were discharged home with no clinical deterioration and 5(38.5 %) deaths were observed. However, causes of deaths were unrelated to liver dysfunction. CONCLUSIONS: The frequency of worsening liver function following paracetamol administration in patients with severe dengue hepatitis was relatively low.

Diagnostic laboratory for bleeding disorders ensures efficient management of haemorrhagic disorders.

Haemorrhagic disorders like Postpartum haemorrhage and Dengue haemorrhagic fever are life threatening and requires an active and efficient transfusion service that could provide the most appropriate blood product which could be effective in managing them. This would essentially require prompt identification of the coagulopathy so that the best available product can be given to the bleeding patient to correct the identified haemostatic defect which will help control the bleeding. This would only be possible if the transfusion service has a laboratory to correctly detect the haemostatic defect and that too with an accuracy and precision which is ensured by a good laboratory quality assurance practices. These same processes are necessary for the transfusion services to ensure the quality of the blood products manufactured by them and that it contains adequate amounts of haemostasis factors which will be good to be effective in the management of haemorrhagic disorders. These issues are discussed in detail individually in the management of postpartum haemorrhage and Dengue haemorrhagic fever including when these can help in the use of rFVIIa in Dengue haemorrhagic fever. The requirements to ensure good-quality blood products are made available for the management of these disorders and the same have also been described.

Hemophagocytic lymphohistiocytosis following dengue hemorrhagic fever in Hb H/Hb Constant Spring patient.

Infection-associated hemophagocytic syndrome (IAHS), a secondary form of hemophagocytic lymphohistiocytosis (HLH), has been found following several types of infections and can be fatal. We report herein a case of IAHS following dengue infection in a 14-year-old patient with underlying α-thalassemia syndrome (non-deletional Hb H/Hb Constant Spring disease). He developed prolonged fever, thrombocytopenia, and progressive splenomegaly. Further investigations indicated hyperferritinemia, and increased reactive histiocytes with hemophagocytic activity in the bone marrow. He responded promptly to dexamethasone and i.v. immune globulin. Physicians should be aware of this condition, especially in countries where both dengue hemorrhagic fever and thalassemia are prevalent. The fatal outcome of IAHS can be prevented with prompt appropriate treatment.

Corticosteroids for dengue infection.

BACKGROUND: Dengue is a common and important mosquito-borne viral infection. In many low- and middle-income countries it is endemic and is an important public health problem. Severe dengue is an important cause of death in children. There is no specific treatment for dengue, but observational studies suggest corticosteroids may have a benefit in dengue-related shock, and some people believe corticosteroids may prevent the progression to severe illness if given early in the course of the illness. OBJECTIVES: To compare treatment of dengue with and without use of corticosteroids or placebo in relation to preventing shock-related death and disease progression in children and adults. SEARCH METHODS: We searched the Cochrane Infectious Disease Group Centralized Register; CENTRAL; MEDLINE; EMBASE; and LILACS, up to 6 January 2014. We screened reference lists and contacted the relevant study authors for additional information where required. SELECTION CRITERIA: Randomized controlled trials or quasi-randomized controlled trials comparing corticosteroids with placebo or no corticosteroids in patients diagnosed with dengue-related shock, or patients in an early symptomatic state of dengue with positive serology. DATA COLLECTION AND ANALYSIS: Two researchers independently screened eligibility of records, extracted data and assessed quality of the studies. We presented findings in meta-analysis and summary of findings tables and evaluated the quality of evidence using GRADE. MAIN RESULTS: We included eight studies enrolling 948 participants in this review. Paitents with dengue-related shock Four studies enrolled children younger than 15 years with dengue-related shock at hospitals in Southeast Asia and evaluated intravenous corticosteroids. The trials did not detect an effect on death (four trials, 284 participants, very low quality evidence), the need for blood transfusion (two trials, 89 participants, very low quality evidence), pulmonary haemorrhage (one trial, 63 participants, very low quality evidence), convulsions (one trial, 63 participants, very low quality evidence), or duration of hospitalization (one trial, 63 participants, very low quality evidence). The body of evidence is too small to confidently prove or exclude clinically important effects. Furthermore, the trials are more than 20 years old with several methodological limitations. Patients with dengue at an early stage Four studies enrolled 664 children and adults with dengue at an early stage of infection (without shock) in Columbia, India, Sri Lanka and Vietnam. In these participants there were no evidence of effects of oral or intravenous corticosteroids on mortality (four trials, 664 participants, low quality evidence), or on the development of complications of severe dengue such as shock (two trials, 286 participants, very low quality evidence), severe bleeding (two trials, 425 participants, very low quality evidence), severe thrombocytopaenia (one trial, 225 participants, very low quality evidence), ascites (one trial, 178 participants, very low quality evidence) and intensive care unit (ICU) admissions (two trials, 286 participants, very low quality evidence). AUTHORS' CONCLUSIONS: The evidence from trials using corticosteroids in dengue is inconclusive and the quality of evidence is low to very low. This applies to both the use of corticosteroids in dengue-related shock and for dengue at an early stage. There is insufficient evidence to evaluate the effects of corticosteroids in the treatment of early stage dengue fever and dengue-related shock outside of the context of a randomized controlled trial.

Grape Seed Proanthocyanidins Inhibit Replication of the Dengue Virus by Targeting NF-kB and MAPK-Mediated Cyclooxygenase-2 Expression.

Dengue virus (DENV) infection is a serious global health issue as it causes severe dengue hemorrhagic fever and dengue shock syndrome. Since no approved therapies are available to treat DENV infection, it is necessary to develop new agents or supplements that can do this. In this study, grape seed proanthocyanidins extract (GSPE), which is widely consumed as a dietary supplement, dose-dependently suppressed the replication of four DENV serotypes. The inhibitory mechanism demonstrated that GSPE downregulated DENV-induced aberrant cyclooxygenase-2 (COX-2) expression, revealing that the inhibitory effect of the GSPE on DENV replication involved targeting DENV-induced COX-2 expression. Mechanistic studies on signaling regulation have demonstrated that GSPE significantly reduced COX-2 expression by inactivating NF-κB and ERK/P38 MAPK signaling activities. Administrating GSPE to DENV-infected suckling mice reduced virus replication, mortality, and monocyte infiltration of the brain. In addition, GSPE substantially reduced the expression of DENV-induced inflammatory cytokines associated with severe dengue disease, including tumor necrosis factor-α, nitric oxide synthase, interleukin (IL)-1, IL-6, and IL-8, suggesting that GSPE has potential as a dietary supplement to attenuate DENV infection and severe dengue.

Dengue hemorrhagic fever as a rare cause of bleeding following percutaneous nephrolithotomy.

Post percutaneous nephrolithotomy (PNL) bleeding is an uncommon yet serious complication and is almost always related to a surgical cause. Nevertheless, medical cause of bleeding is rarely encountered as a cause of this dangerous complication. Dengue has been rarely reported as a cause of post operative bleeding. Bleeding diathesis in dengue occurs not only due to thrombocytopenia but also due to dysfunctional surviving platelets and increased fibrinolysis. We report a patient who developed bleeding after an uneventful PNL due to dengue hemorrhagic fever. Medical causes of bleeding such as locally endemic viral hemorrhagic fevers should also be kept in mind and evaluated especially when a surgical cause of the bleed is not found or suspected in bleeding after any surgery.

Should colloid boluses be prioritized over crystalloid boluses for the management of dengue shock syndrome in the presence of ascites and pleural effusions?

BACKGROUND: Although the WHO guideline for the management of dengue fever considers the presence of ascites or pleural effusions in the diagnosis of DSS, it does not emphasize the importance of their presence when selecting fluids for resuscitation. CASE PRESENTATION: We highlight three patients with DSS who received boluses of crystalloids on priority basis as recommended by WHO guidelines during resuscitation. All three patients had varying degrees of third space fluid loss (ascites and pleural effusions) at the time of development of DSS. Ascites and pleural effusions were detected in all 3 patients at the time of shock irrespective of whether iv fluids were given or not. All three patients had documented liver involvement at the time of shock evidenced by elevation of AST (4800 iu/L, 5000 iu/L and 1960 iu/L). One patient who had profound shock died 6 hours after admission with evidence of acute pulmonary oedema in the convalescence phase. All of them needed CPAP ventilator support and potent diuretics. CONCLUSIONS: We therefore feel that resuscitation of patients with DSS who already have third space fluid accumulation with crystalloid boluses on priority basis may contribute to recovery phase pulmonary oedema.

Modulation of cytokine and cytokine receptor/antagonist by treatment with doxycycline and tetracycline in patients with dengue fever.

Dengue virus infection can lead to dengue fever (DF) or dengue hemorrhagic fever (DHF). Disease severity has been linked to an increase in various cytokine levels. In this study, we evaluated the effectiveness of doxycycline and tetracycline to modulate serum levels of IL-6, IL-1B, and TNF and cytokine receptor/receptor antagonist TNF-R1 and IL-1RA in patients with DF or DHF. Hospitalized patients were randomized to receive standard supportive care or supportive care combined with doxycycline or tetracycline therapy. Serum cytokine and cytokine receptor/antagonist levels were determined at the onset of therapy and after 3 and 7 days. Cytokine and cytokine receptor/antagonist levels were substantially elevated at day 0. IL-6, IL-1ß, and TNF remained at or above day 0 levels throughout the study period in untreated patients. Treatment with tetracycline or doxycycline resulted in a significant decline in cytokine levels. Similarly, IL-1RA and TNF-R1 serum concentrations were elevated at baseline and showed a moderate increase among untreated patients. Both drugs resulted in a significant rise in IL-1Ra levels by day 3 in patients. In contrast, treatment did not affect a similar result for TNF-R1. When compared to the control group, however, a significant rise post-treatment was seen upon intragroup analysis. Further analysis demonstrated that doxycycline was significantly more effective at modulating cytokine and cytokine receptor/antagonist levels than tetracycline.

Management of severe refractory thrombocytopenia in dengue hemorrhagic fever with intravenous anti-D immune globulin.

Dengue hemorrhagic fever (DHF) is a potentially lethal complication of dengue fever due to shock and/or bleeding. Bleeding in DHF is due to thrombocytopenia and/or coagulopathy. The authors present their experience of usage of intravenous anti-D in 5 children with DHF and severe refractory thrombocytopenia (<10,000/mm(3)). It was administered in a dose of 50 to 75 µg/kg. Mean platelet count was 6800/mm(3) before and 33,600, 44,600, and 79,000/mm(3) after intravenous anti-D administration at 24, 48, and 72 hours, respectively. Average drop in hemoglobin after administration of anti-D was 2.28 g/dL. Intravenous anti-D can possibly be a treatment option for refractory thrombocytopenia in DHF.

Adjunctive corticosteroid therapy in 149 grade II (non-shock) adult DHF patients: an analysis during January 2008-February 2010.

BACKGROUND: It is well known that immunopathogenesis play an important role in the development of severe complications in DHF. Since 2006, the authors have experience in giving immunomodulators to save life of many severe complicated adult DHF patients. This experience stimulates our interest on the benefit of adjunctive corticosteroid therapy in adult grade II DHF patients. OBJECTIVE: To find out whether there are some benefits of giving adjunctive corticosteroid therapy in adult grade II DHF patients. DESIGN OF THE STUDY: Retrospective analysis during January 2008-February 2010. MATERIAL AND METHOD: One hundred and forty nine adult grade II DHF patients were admitted at Vichaiyut Hospital. They were divided into 3 groups according to the different therapy designed by the responsible clinicians. Group 1 consisted of 59 cases who received full dose-short course of intravenous dexamethasone (4 milligram every 6 hours for 2-3 days). Group 2 consisted of 61 cases who received intermittent 4 milligrams intravenous dexamethasone only at febrile episode and group 3-29 cases did not received corticosteroid. All the patients were investigated similarly. Age, sex, symptoms and signs including daily hematologic studies (Hct, Wbc, differential count, platelet count) were recorded. Serum SGOT SGPT bilirubin, alkaline phosphatase and albumin BUN, creatinine were performed on admission and repeated as indicated. The parameter to measure the benefit of adjunctive corticosteroid included 1) severity of thrombocytopenia, 2) liver impairment, 3) the days of illness as determined by fever and 4) the length of the hospital days. RESULTS: The clinical severity of all the three groups were quite similar. There was no benefit of using adjunctive corticosteroid therapy in term of changing the severity of thrombocytopenia and liver impairment. However, the days of illness and the length of hospital days were shorter at 4.6 days and 3.7 days respectively in the group who received full dose, continuous-short course of dexamethasone intravenously. This is statistically significant when compared to the other two groups who had the longer total days of fever at 5.8 days and 6.03 days and the longer length of hospital days at 5.19 days and 4.5 days respectively (p < 0.05). CONCLUSION: Adjunctive corticosteroid by given full dose, continuous short course in grade II adult DHF reduced the course of illness (days of fever) and the length of hospital days. These findings indicated the benefit of using adjunctive corticosteroid therapy in grade II adult DHF patients.

Multi-Tissue Transcriptomic-Informed In Silico Investigation of Drugs for the Treatment of Dengue Fever Disease.

Transcriptomics, proteomics and pathogen-host interactomics data are being explored for the in silico-informed selection of drugs, prior to their functional evaluation. The effectiveness of this kind of strategy has been put to the test in the current COVID-19 pandemic, and it has been paying off, leading to a few drugs being rapidly repurposed as treatment against SARS-CoV-2 infection. Several neglected tropical diseases, for which treatment remains unavailable, would benefit from informed in silico investigations of drugs, as performed in this work for Dengue fever disease. We analyzed transcriptomic data in the key tissues of liver, spleen and blood profiles and verified that despite transcriptomic differences due to tissue specialization, the common mechanisms of action, "Adrenergic receptor antagonist", "ATPase inhibitor", "NF-kB pathway inhibitor" and "Serotonin receptor antagonist", were identified as druggable (e.g., oxprenolol, digoxin, auranofin and palonosetron, respectively) to oppose the effects of severe Dengue infection in these tissues. These are good candidates for future functional evaluation and clinical trials.

An open pilot study of the efficacy and safety of Polygeline in adult subjects with dengue haemorrhagic fever.

AIM: To observe the efficacy and safety of Polygeline colloid (Haemaccel) in adults with stage I - II of dengue haemorrhagic fever (DHF). METHODS: An open, non-comparative clinical trial. The subjects were male or female between 17 - 55 years old, who fulfilled the criteria of stage I or II of DHF according to WHO and selected with consecutive sampling. Fluid treatments were given following this protocol: polygeline i.v. infusion: 500 ml over first 6 hours and continued with 500 ml for the next 18 hours, and maintained to 1000 mL/24 hours from day-2 until maximum day-5. Ringer's lactate infusion: 1000 mL/18 hours from the first day to maximum day-5, as maintenance. Efficacy and safety of polygeline colloid were evaluated using initial stabilization of haematocrite level, measured as percentage of clinical trial subject who has stabilization of haemodynamic status based on serial haematocrite levels examinations, total parenteral fluid required and length of hospitalization. Statisticial analysis was done using ANOVA test and post hoc analysis using Turkey test. RESULTS: There were 43 subjects who completely participated in this study and included in analysis. From baseline levels, haematocrite decreased in first 6 hours during fluid treatment. This decrement persisted in 48 hours of observation. Statistical analysis with ANOVA test showed the significant differences of haematocrite level during observation (Sum of square between groups 495 and within group 4845, p= 0.000). Post hoc analysis with Turkey test showed significant differences of haematocrite level from baseline level to 48, 72 and 96 hours during observation periods. CONCLUSION: This pilot study showed that polygeline colloid was a safe initial fluid treatment and can be used for maintaining fluid adequacy in adults with stage I-II of DHF.

Drug repositioning for dengue haemorrhagic fever by integrating multiple omics analyses.

To detect drug candidates for dengue haemorrhagic fever (DHF), we employed a computational drug repositioning method to perform an integrated multiple omics analysis based on transcriptomic, proteomic, and interactomic data. We identified 3,892 significant genes, 389 proteins, and 221 human proteins by transcriptomic analysis, proteomic analysis, and human-dengue virus protein-protein interactions, respectively. The drug candidates were selected using gene expression profiles for inverse drug-disease relationships compared with DHF patients and healthy controls as well as interactomic relationships between the signature proteins and chemical compounds. Integrating the results of the multiple omics analysis, we identified eight candidates for drug repositioning to treat DHF that targeted five proteins (ACTG1, CALR, ERC1, HSPA5, SYNE2) involved in human-dengue virus protein-protein interactions, and the signature proteins in the proteomic analysis mapped to significant pathways. Interestingly, five of these drug candidates, valparoic acid, sirolimus, resveratrol, vorinostat, and Y-27632, have been reported previously as effective treatments for flavivirus-induced diseases. The computational approach using multiple omics data for drug repositioning described in this study can be used effectively to identify novel drug candidates.

Synthesis and evaluation of N-substituted acridones as antiviral agents against haemorrhagic fever viruses.

BACKGROUND: In the present study, a series of N-substituted acridone derivatives was synthesized and evaluated against two haemorrhagic fever viruses (HFV). METHODS: Compounds were tested against Junin virus (JUNV), an arenavirus agent of Argentine haemorrhagic fever, and dengue virus (DENV), a flavivirus agent of the most prevalent arthropod-borne viral disease in humans. RESULTS: Among tested compounds, two N-allyl acridones (derivatives 3c and 3f) elicited a potent and selective antiviral activity against JUNV (strain 1V4454) and DENV-2 (strain NGC) with 50% effective concentration values between 2.5 and 5.5 microM, as determined by virus yield inhibition. No cytotoxicity was detected at concentrations up to 1,000 microM, resulting in selectivity indices >181.8-400.0. Both acridones were effective against a wide spectrum of arenaviruses and the four serotypes of DENV. Furthermore, 3c and 3f failed to inactivate virus before cell infection as well as to induce a refractory state by cell pretreatment, indicating that the inhibitory effect was exerted through a blockade in virus multiplication during the infectious process. CONCLUSION: These data are the first demonstration that acridone derivatives have a potent antiviral activity that block in vitro multiplication of HFV belonging to Arenaviridae and Flaviviridae, such as JUNV and DENV.

Choice of colloidal solutions in dengue hemorrhagic fever patients.

BACKGROUND: DHF is characterized by plasma leakage and abnormal hemostasis. About 20% of DHF patients do require colloidal solution in addition to conventional crystalloid solution for the treatment. There is only one colloidal solution, 10% Dextran-40 in NSS that proved to be effective for this group of DHF patients. OBJECTIVE: To compare 10% dextran-40 in NSS with 10% Haes-steril in NSS in the management of DHF cases with severe plasma leakage for their effectiveness and impact on renal function, hemostasis, disease severity, and complications. MATERIAL AND METHOD: DHF patients admitted to Dengue Unit, QSNICH, who do not respond to conventional crystalloid solution, are randomly assigned to receive either dextran or haes-steril. Clinical and laboratory comparison are recorded and analyzed using SPSS for Window version 14.0. RESULTS: There are 104 DHF patients enrolled in the study; 57 are assigned in dextran and 47 in haes-steril group. The mean ages are 8.6 +/- 3.9 years. About half of the patients in both groups require one dose of colloidal solution and 25% require 2 and 3 doses (p = 0.138). The average amount of IV fluid infused in dextran and haes-steril group are 119.4 and 129.3 ml (p = 0.227). The average drop in Hct after the bolus dose of both colloid are 7.9 and 8.5% (p = 0.381). About 80% of the patients in each group have shock (p = 0.843). The mean elevation of AST are 598 and 822 U (p = 0.548) while ALT elevation are 182 and 306 U (p = 0.265) in dextran and haes-steril group, respectively. BUN and creatinine are within normal limits and are decreased after the use of colloidal solutions. The amount of urine on day 1, 2 and 3 after the use of both colloidal solutions are not different. Coagulogram studies (PT, PTT and TT) in both groups are not different. Patients with significant bleeding and who require blood transfusions are 15.8 and 19.2% in dextran and haes-steril group (p = 0.423).The incidence of fluid overload in dextran and haes-steril group are 35.1 and 40.4% (p = 0.360). Other complications are not different between dextran and haes-steril group as follows: hypocalcaemia, hyponatremia, hypokalemia and acidosis. The overall severity and complications in both groups of patients are much higher than in DHF patients who respond to conventional crystalloid solution. No allergic reaction was found after the use of both colloidal solutions. CONCLUSION: 10% Haes-steril is as effective as 10% dextran-40 in the treatment of DHF patients who have severe plasma leakage. There are no differences in DHF disease severity and complications in both groups but the disease severity and complications, especially fluid overload are observed to be more comparative with admitted DHF patients. Both colloidal solutions are safe in DHF patients with no allergic reaction observed and no interference in renal functions and hemostasis.

Intravenous immunoglobulin for severe thrombocytopenia in secondary dengue.

A 30-year-old woman with severe dengue presented on the sixth day of her illness with life-threatening thrombocytopenia, refractory to multiple platelet transfusions. Dengue IgM antibody and the non-structural-1 antigen tests as of day 3 were negative. The IgG antibody against the same was positive, suggesting a past episode of dengue. Since she had a history of menorrhagia prior to the current illness, a working diagnosis of idiopathic thrombocytopenic purpura was made, for which intravenous immunoglobulin (IVIg) was administered that led to a rapid rise in the platelet count with no adverse events. Subsequently, dengue IgM antibody repeated on day 6 came back positive, confirming dengue. This case report re-emphasises the potential use of IVIg in patients with severe thrombocytopenia in dengue.