Management Of Dengue Infection Research Articles

Possible effects of ancestry-related oxysterol-binding protein-like 10 genetic polymorphisms on dengue virus replication and anti-dengue immune response

PurposeOxysterol-binding protein-like 10 (OSBPL10) gene has been associated with reduced susceptibility to severe dengue in individuals of African descent. The aim of this study was to determine the possible effect of OSBPL10 on dengue virus (DENV) replication as well as the impact of African and European haplotypes of six OSBPL10 small nuclear polymorphisms (SNPs) on dengue multiplication and innate immune response. MethodsWe conducted gene knockdown experiments targeting OSBPL10 in THP-1 and Huh-7D12 cell lines, followed by a DENV-2 replication assay. Extracellular viral load was determined using qRT-PCR. To investigate the impact of SNPs haplotypes on viral replication and gene expression we cultured peripheral blood mononuclear cells (PBMC) from individuals with homozygous African and European haplotypes of OSBPL10 with DENV-2. Individual genotyping was performed using High Resolution Melt (HRM) analysis. The level of viral replication was assessed through plaque assay, while RT-PCR was employed to determine the expression levels of RXR-α, IFN-γ, IL-10 and IL-8 genes. ResultsIn vitro OSBPL10 knockdown significantly reduced DENV-2 replication. Individuals carrying European haplotypes showed higher DENV titers along with elevated levels of RXR-α and IL-8 mRNA compared to those carrying African haplotypes, who exhibited lower viral loads alongside increased IFN-γ and IL-10 expression. ConclusionsOur findings further explore the role of OSBPL10 in DENV multiplication, immune response to infection. The European haplotypes of OSBPL10 appear to increase DENV replication and promote RXR-α and IL-8 mRNA expression which correlates with the suppressive effect of these mediators on type I IFN, promoting viral replication and a deficient antiviral response. In contrast, the African haplotype showed a reduction in DENV replication and enhanced IFN-γ and IL-10 mRNA expression, which could be related to the better management of dengue infection and the low frequency of severe disease in this ethnic groupe.

Designing of a multiepitope-based chimeric vaccine against dengue virus serotype 3 (DENV-3) through next generation reverse vaccinology approaches

The dengue virus (DENV) causes dengue infection and has become a significant global public health concern. The successful application of immunotherapies in treating dengue infection has paved the way for developing various treatment strategies. Among these strategies, the multiepitope vaccine has emerged as a promising approach. We applied an in silico immune-informatics approach to develop a multiepitope vaccine including MHC-I, MHC-II, and B cell epitopes of the NS1, E, and M proteins. The vaccine was found to be a structurally stable protein (Z score = −4.71), indicating its effectiveness. High affinity was shown by molecular docking studies between the vaccine and human receptors (toll-like receptor 2 and toll-like receptor 4). Following codon optimization and in silico cloning, the vaccine was successfully expressed (CAI value of 0.9588) after being inserted into the pET-30a (+) plasmid of the E. coli K12 strain. However, the vaccine's potential to elicit immunological responses (such as B cell, T cell, antibody, and cytokine responses) against the dengue virus serotype 3 (DENV-3) has been established through immune simulation. The majority of existing dengue vaccines have shown little efficacy in the management of dengue infection. Furthermore, there is currently no licenced multiepitope vaccine for dengue virus serotype 3 (DENV-3) that encompasses all three significant proteins. Consequently, our proposed vaccine has the potential to be an effective weapon in combating dengue infection. Further studies should be conducted to evaluate the safety, effectiveness, and potential adverse effects of this multiepitope vaccine in human subjects to facilitate its further development.

Clinicopathological Profile of Dengue Infection in a Tertiary Care Centre in Nepal.

Dengue is a mosquito-borne viral disease with a wide spectrum of presentations ranging from subclinical disease to severe dengue. Dengue is endemic to the Terai of Nepal. Interestingly, an increasing incidence has been reported from hilly areas like Kathmandu valley. This study explored the clinicopathological profile of dengue infection. A total of 84 serologically confirmed dengue cases from September to November 2019 at KIST Medical College were recruited in a cross-sectional study after obtaining ethical approval. Dengue was categorized as dengue without warning signs, dengue with warning signs, and severe dengue. Clinicopathological information was recorded in the proforma by reviewing patients' records. A descriptive statistical tool and chi-square test were carried out. Out of 84 patients, 76% (64) were dengue without warning signs, 21.4% (18) were dengue with warning signs and 2.4% (2) were severe dengue. About 97.6% (82) presented with fever. During the course of illness, anemia was identified in 38.1% (32), thrombocytopenia in 65.5% (55), hemoconcentration in 6% (5), and leucopenia in 82.1% (69). Similarly, elevated aspartate transaminase and alanine transaminase (ALT) was observed in 67.7% (42) and 53.2% (33) respectively. The severity of dengue on presentation to hospital was significantly associated with thrombocytopenia, leucopenia, and elevated ALT. Similarly, the severity during course of illness in hospital was significantly associated with hemoconcentration, thrombocytopenia, leucopenia, and elevated ALT. Most common presentation of dengue infection was fever. The most common laboratory abnormalities were leucopenia, thrombocytopenia, hemoconcentration, anemia, and elevated liver enzymes. Awareness of these clinical and laboratory parameters is important for the prompt diagnosis, severity estimation, and overall management of dengue infection.

Awareness and Preventive Measure on Dengue Fever among Community People in Kathmandu

Introduction: More than one-third of the worldwide populations are affected by dengue fever. It is a public health problem. The objective of this study is to find out the awareness and preventive measure on dengue fever.
 Method: A Descriptive Cross-sectional research design was adopted to collect the data from 346 people by non-probability purposive sampling technique. A semi-structured questioner was developed based on intensive literature reviewed. The investigator herself after the approval of the IRC (Institutional review committee) TUIOM collected data. Before data collection, formal permission was obtained from the ward office of Chandragiri municipality-5. Written consent was obtained from each individual sampling unit before interview and observation. The findings were described in descriptive statistics.
 Result: All most all (95.4%) respondents were heard about dengue fever. All respondents answered dengue can be prevention, but 40.17% respondents were known it is viral infection, 29.19% belief it is communicable diseases transmitted by mosquito (48%), but the specific types of mosquito (Aedes aegypti), known only 36.7% of respondents. Majority of respondents (84.39%) known it is transmitted by mosquito to human being and below half (47.68%) of respondents known this type of mosquito is breeding in clean stagnation water and bite in day and dusk 67.63%. All most all respondents known about signs and symptoms of the dengue high fever (98.84%), headache (74.85), body ache (62.71%), retro orbital pain (36%), easily bleeding (32.26%) flushing (26.58%), sore throat (23.12 %), skin erythema (16.18%), and photophobia (15.89%), are early signs of dengue infection. Sixty-three percent respondents know the vomiting is late signs of dengue infection, lethargy (43.35 %), blood disorder (35.54%), weakness (30.92%), shock (22.54 %), and bleeding (21.38%), are late signs of dengue infection. Only 46.82% respondents know management of dengue infection, Below half (44.8%) respondents’ answered its prognosis is good, majority of respondents known about complication of dengue is bleeding and shock and 19% respondents known vaccine is not availed of dengue infection till date. In mosquito controls measures, highest number of respondents (66.5%) were aware on environment sanitation can control the mosquito; all most all respondents were aware on mosquito control is the only one solution of the dengue control.
 Conclusion: The awareness regarding dengue in the study participants are not sufficient and preventive practices are not satisfactory. Improvement of prevention practices for dengue transmission must be emphasized.

Refining Clinical Triage and Management of Dengue Infection in Children: A Timely Approach

Refining Clinical Triage and Management of Dengue Infection in Children: A Timely Approach

Dengue infection in international travellers visiting Bali, Indonesia.

BackgroundDengue, an acute febrile illness caused by infection with dengue virus (DENV), is endemic in Bali, Indonesia. As one of the world’s most popular tourist destinations, Bali is regularly visited by domestic and international travellers, who are prone to infection by endemic pathogens, including DENV. Currently, limited data are available on the characteristics of dengue in travellers visiting Bali. Information on the epidemiology and virological aspects of dengue in these tourists is important to gain a better understanding of the dengue disease in international travellers.MethodsWe performed a prospective cross-sectional dengue study involving foreign travellers visiting Bali, Indonesia in the period of 2015–17. Patients presenting at Kasih Ibu Hospital with fever and clinical symptoms of dengue were asked to participate in the study. Clinical and laboratory assessments were performed and sera were collected for molecular analysis, which included DENV serotyping, genome sequencing and phylogenetic analysis.ResultsAmong the 201 patients recruited, dengue was confirmed in 133 (66.2%) of them, based on detection of NS1 antigen and/or viral RNA. Of these, 115 (86.5%) manifested dengue fever (DF) and 18 (13.5%) dengue haemorrhagic fever (DHF). The temporal predominance of infecting DENV serotype was DENV-2 (48.7%), followed by DENV-3 (36.1%), DENV-1 (9.2%) and DENV-4 (3.4%). Phylogenetic analysis of DENV based on envelope gene sequences revealed that the source of DENVs was local endemic viruses.ConclusionOur study confirms that dengue is one of the causes of fever in travellers visiting Bali. Although it is a cause of significant morbidity, the majority of patients only experienced mild DF, with only a small proportion developing DHF. We revealed that DENVs isolated were autochthonous. Accurate diagnosis, preventive measures and continuous disease surveillance will be useful for better management of dengue infection in travellers.

Adherence to Clinical Practice Guidelines (CPG) management of dengue infection in adults (revised 2nd edition).

The Malaysian Dengue Clinical Practice Guidelines (CPG) have been developed to provide evidence-based guidance in the management of dengue infections. The use of these guidelines is essential to ensure its recommendations are being practiced. However, the adherence to the guidelines for management of dengue (revised 2nd edition) by healthcare providers still remains unknown. Therefore, the aim of this study was to evaluate the proportion among healthcare providers that adhere to this Dengue CPG. A retrospective cohort study of dengue cases registered from 1 January 2014 to 1 June 2015 was conducted in public hospitals and health clinics in Selangor, Putrajaya and Kuala Lumpur. Adherence to the CPG recommendations were recorded by reviewing patients’ case notes. Overall proportion of adherence in clinical components of the recommendation were (7.1 to 100.0% versus 7.7 to 73.8%) in history taking, (6.7 to 100.0% versus 12.3 to 60.0%) in physical examinations, (18.4 to 100.0% versus 23.1 to 83.2%) in assessment of warning signs, (0.6 to 100.0% versus 12.3 to 87.7%) in assessment of haemodynamic status, (60.0 to 100.0% versus 27.7 to 40.0%) in diagnosis, (46.6 to 80.0% versus 52.3%) in case notifications, (73.2 to 100.0% versus 89.2 to 96.9%) in performing specific laboratory investigations and (7.9 to 100.0% versus 21.5%) in monitoring, for outpatient versus inpatient, respectively. Adherence trends were demonstrated to be higher in hospital settings compared to outpatient settings. Adherence to this Dengue CPG varies widely with overall good clinical outcomes observed.

A rare case of dengue encephalopathy complicating a term pregnancy

BackgroundDengue fever has an expanded clinical spectrum ranging from an asymptomatic infection to life threatening dengue hemorrhagic fever and refractory shock. Dengue infection in pregnancy can be a diagnostic dilemma, particularly considering the physiological changes in pregnancy and the obstetric complications encountered in clinical practice. Hence the knowledge of its diagnosis and management in its atypical presentations is of paramount importance. Here we report an unusual case of uncomplicated dengue encephalopathy in a term mother, probably the first to be reported from the Indian subcontinent.Case PresentationA 28 year old woman, 37 weeks of pregnancy presented with fever of four days duration. She eventually developed irritability, altered sensorium, somnolence, and unresponsiveness to commands by the 5th day of febrile illness without any circulatory compromise. Physical examination and investigations including serology confirmed dengue fever. After excluding all other possible causes, the transient neurological deterioration was finally attributed to dengue encephalopathy which is an uncommon manifestation of the disease, particularly in pregnancy. Her deteriorated neurological status which had lasted for 6 days improved spontaneously with the convalescence of dengue infection. Cautious fluid management was carried out in correlation to clinical and hematological parameters. The pregnancy was continued uncomplicated till the platelet count had risen to more than 50,000 cells/cumm. She delivered vaginally a healthy male baby.ConclusionsDengue fever in pregnancy is increasingly being encountered due to its rising disease burden. Dengue encephalitis/encephalopathy must be suspected in the differential diagnosis of fever and altered sensorium, even in pregnancy, in the tropical countries where the infection is rampant. Management of dengue infection in term pregnancy is a challenge for both the clinician and obstetrician. Further discussion and research are mandatory to decide on optimal management of these patients, with regard to monitoring, fluid management, and the precise timing and mode of delivery in order to prevent fatal morbidity and mortality to both mother and fetus.

The accuracy of newly proposed warning signs in the third edition of Malaysian guideline on the management of dengue infection in adult

The accuracy of newly proposed warning signs in the third edition of Malaysian guideline on the management of dengue infection in adult

Role of clinical laboratory parameters in management of dengue infection, beyond infancy: a tertiary care experience

Role of clinical laboratory parameters in management of dengue infection, beyond infancy: a tertiary care experience

Disease severity & its Importance in selecting cost effective measures for Dengue management

Background: In recent years Dengue has been referred to as “multimillion disease” because of the high cost in diagnosis and treatment including prolonged hospitalization. India has the world’s highest population suffering from dengue infection with varying degrees of severity resulting in deaths. The high mortality rate in our community has forced doctors to treat dengue injudiciously at times resulting in increase in the cost of treatment and diagnosis. Millions of dollars are spent annually for purchasing diagnostic kits and medicines. The estimation of degree of severity of dengue among the local population may play an important role in selecting the cost effective measure in dengue diagnosis and treatment. Aims and Objective: In the present study, all the dengue positive cases were examined for degree of severity of dengue infection among the local population and asses the role of platelet transfusion in treatment. Materials and Methods: The serum samples were tested for dengue IgM antibodies by ELISA method and the platelet count was estimated by using the autoanalyzer. Results: A total of 82(22.96%) patients were reported positive for dengue-specific IgM antibodies. The analysis of disease risk showed that majority of patients (85.36%) had either low or no risk of developing complications associated with dengue, where as 6% & 8.5% had high and moderate risk to develop dengue complications. Conclusion: Although dengue infection has been reported with high seropositivity, it is present in milder form which not require hospitalization. In such cases monitoring of platelet count and supportive therapy with analgesic and complete bed rest will be help in management of dengue infection with minimal cost. Keywords: Dengue severity, management cost and IgM-ELISA

Dengue Preceding Diabetic Ketoacidosis

Diabetic ketoacidosis (DKA) is an important hyperglycemic complication of diabetes mellitus. Infection is confirmed as an important underlying etiology of DKA. Here, the author presents an interesting case of dengue preceding DKA. The case is a 61-year-old female presenting to the physician with the complaint of high fever without relief by self-prescription of acetaminophen. She had an underlying disease, diabetes mellitus (DM). Her body temperature was 39.4 degrees Celsius and her complete blood count showed an important finding: thrombocytopenia (platelet count = 85.000). The serological test was done and the diagnosis of dengue hemorrhagic fever was finally confirmed. This case was treated by standard fluid replacement therapy (normal saline regimen). On day 3, the patient developed new symptoms, frequent urination (more than 3 times in an hour, abdominal pain, nausea, vomiting and rapid breathing). Complete blood count was done but platelet count was within normal limit at this time. However, the urinalysis showed many positive findings, sugar 4+ and ketone 3+. Her additional blood chemistry results showed a blood glucose level of 454 mg/dL and positive serum ketone. The patient was finally diagnosed to have DKA and endocrinologists were consulted for the management. Of interest, this is a simple case of DKA but the interesting issue is the underlying condition leading to DKA in this patient. Although there are many reports confirming that infection can induce DKA, this is the first reported case of dengue preceding DKA. Indeed, there is a previous report from Thailand on a female patient presented to the physician with concurrent DKA and dengue infection (1). However, DM had not previously been diagnosed in the present case. The dengue infection is common in the tropical world and DM is also the important emerging health problem in this area. Some reports note that DM can be an aggravating factor in the development of dengue shock (2,3). There is an interesting report stating that patients suffering from dengue fever should be cautioned for development of diabetes in future (4)”. However, dengue has rarely been mentioned as a risk factor in the development of DKA. Based on the present situation that DM is a very common problem, testing blood glucose during the management of dengue infection is useful (4). The concern on the diabetic complications such as DKA should also be kept in mind in the treatment of patients suffering from dengue. Moreover, it should be noted that not only bacterial but also viral infections (such as dengue, herpes, etc.) can induce DKA (1,5). The good example is a previous report on herpes simplex virus infection inducing DKA (5).

Proceedings of the Dengue Symposium at the 9th International Congress of Tropical Pediatrics

Dengue is the most important mosquito-borne viral disease. With four different serotypes, it is a burden throughout tropical and subtropical regions and a potential threat to almost half of the world’s population. Recent studies estimate that 50–100 million people are infected each year, of whom about 500,000 develop dengue haemorrhagic fever – a severe form of the disease – and 22,000 of whom die. Dengue haemorrhagic fever is also a leading cause of hospitalisation, placing tremendous pressure on strained medical resources, with an associated major economic and societal impact. Many factors have contributed to the recent dramatic rise in the number of cases of dengue fever, including increased urbanisation and travel. The heavy burden of dengue can only be lifted by strong cooperation between international institutions and agencies to create a new strategy targeting prevention of deaths, reducing morbidity and lessening the associated social and economic losses. In addition, a dengue vaccine is seen as the best way to control dengue effectively. Proper management of dengue infection, mosquito control measures as well as a candidate dengue vaccine, requires a comprehensive update of knowledge in all relevant aspects. This parallel symposium was organised by the Thailand Chapter of the International Society of Tropical Pediatrics on 20 October 2011, in collaboration with the 9th International Congress of Tropical Pediatrics, which was held on 18–20 October 2011 in Bangkok, Thailand. The objective of the symposium was to provide the participants with a unique opportunity to share their experiences and discuss various issues relating to the pathophysiology, epidemiology, management and control of dengue. Through this symposium, participants gained knowledge and experience from invited speakers from various parts of highly endemic areas. In this context, the symposium also illustrated the importance of sharing best practice and knowledge across all regions and specialities involved in the struggle against dengue. These proceedings summarise the Parallel Symposium on Dengue held at the Queen Sirikit National Convention Center, Bangkok, Thailand, on 20 October 2011. The supplement begins with an interesting commentary from Scott Halstead as he seeks to analyse and resolve six key controversies in dengue fever research, including the utility of the 1997 World Health Organization (WHO) case definition of dengue haemorrhagic fever and an examination of several theories of dengue infection pathogenesis. Following this, Roberto Tapia-Conyer and colleagues consider the more practical aspects of dengue fever management: community participation, structured by an integrated management strategy. It has the overall aim of improving the efficacy, cost-effectiveness, environmental impact and sustainability of vector control strategies. Tapia-Conyer and his co-authors then discuss in detail the problem of dengue fever infection in Latin America overall. They suggest various ways in which the disease could be combated, including using a vaccine or involving the community, but conclude that politics, finance and co-operation are all areas that need to be managed. A contrasting case study is then presented by Fred Were, focusing on dengue in Africa and the possible differences in the spread of the disease compared with the remainder of the dengue-endemic population. However, Were points out that it is difficult to characterise the disease in Africa owing to the poor surveillance infrastructure and under-recognition of the disease, as there is often a greater focus on malaria. Terapong Tantawichien follows this with a discussion of the increasing prevalence of dengue infection in adolescents and adults, with an in-depth analysis of its clinical manifestations and specific treatment in this age group. On a similar theme, Annelies Wilder-Smith focuses on a particular subset of the adult population threatened by dengue infection – travellers. Travellers are not only at risk themselves but they contribute to the spread of dengue; furthermore, they may serve to alert the international community to current epidemics. Sri Rezeki Hadinegoro considers the diagnoses of dengue fever, dengue haemorrhagic fever and dengue shock syndrome in relation to the WHO classification systems of 1997 and 2009. There has been much debate surrounding these classification criteria and Hadinegoro suggests that the evolution of dengue over past years has contributed to the limited applicability of the older case definitions. Following the DENCO study, the newer classification system was formed, but the effectiveness of this is still being debated. Finally, Nguyen Thanh Hung describes the types of intravenous solutions for treatment of children with dengue; he concludes that isotonic crystalloid solutions can be used for the majority of children, and colloids can be considered a second option. We should like to express our sincere thanks to all of the distinguished invited speakers and resource persons for their contribution. We hope that these proceedings will prove of great interest, and help the global dengue community to improve the prevention, diagnosis and management of dengue infection.

Impact of Renal Failure on the Outcome of Dengue Viral Infection

In the 2002 dengue outbreak in Taiwan, some fatal cases had the underlying disease of renal failure (RF). Physicians faced difficulty in diagnosis and treatment of these patients; however, the impacts of RF on the clinical presentations and outcomes of dengue infection have not been reported previously. A retrospective review was conducted of medical records, clinical presentations, laboratory findings, and underlying diseases for all cases of dengue infection in a medical center. Characteristics and outcomes of dengue-infected patients with and without RF were compared. From January 2002 through January 2003, 519 dengue-infected patients were enrolled, including 412 patients with classical dengue fever (DF) and 107 patients with dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). Twelve patients died in this outbreak, and all had DHF/DSS. Twenty-one (4.0%) patients were defined as being in the RF group. The RF group had a higher mortality rate than non-RF group (28.6 versus 1.2%; P < 0.001). The severity of GFR impairment was associated with higher percentages of DHF/DSS (P = 0.029) and mortality (P < 0.001). Differences in symptoms/signs and laboratory abnormalities between DF and DHF/DSS were significant in the non-RF group but not apparent in the RF group. The diagnosis and management of dengue infection among patients with RF must be cautious, because complicated clinical courses with a higher mortality rate were well observed.