Fatal Dengue Hemorrhagic Fever Research Articles

DENV-1 Infection of Macrophages Induces Pyroptosis and Causes Changes in MicroRNA Expression Profiles.

Dengue virus (DENV) is the most widespread mosquito-borne virus, which can cause dengue fever with mild symptoms, or progress to fatal dengue hemorrhagic fever and dengue shock syndrome. As the main target cells of DENV, macrophages are responsible for the innate immune response against the virus. In this study, we investigated the role of pyroptosis in the pathogenic mechanism of dengue fever by examining the level of pyroptosis in DENV-1-infected macrophages and further screened differentially expressed microRNAs by high-throughput sequencing to predict microRNAs that could affect the pyroptosis of the macrophage. Macrophages infected with DENV-1 were induced with decreased cell viability, decreased release of lactate dehydrogenase and IL-1β, activation of NLRP3 inflammasome and caspase-1, cleavage of GSDMD to produce an N-terminal fragment bound to cell membrane, and finally induced macrophage pyroptosis. MicroRNA expression profiles were obtained by sequencing macrophages from all periods of DENV-1 infection and comparing with the negative control. Sixty-three microRNAs differentially expressed in both the early and later stages of infection were also identified. In particular, miR-223-3p, miR-148a-3p, miR-125a-5p, miR-146a-5p and miR-34a-5p were recognized as small molecules that may be involved in the regulation of inflammation. In summary, this study aimed to understand the pathogenic mechanism of DENV through relevant molecular mechanisms and provide new targets for dengue-specific therapy.

Kinetics of dengue viremia and its association with disease severity: an ambispective study

BackgroundDengue virus (DENV) infection is an important public health problem and causes significant morbidity and mortality. DENV typically causes a febrile illness that ranges from mild asymptomatic infection to fatal dengue hemorrhagic fever (DHF) and/or dengue shock syndrome (DSS). Early prediction of severe dengue disease is of utmost importance for providing prompt monitoring and treatment. The search for an ideal biomarker (host or viral factors) for early prediction of severe dengue remains elusive.AimTo standardize a real time qRT-PCR for quantifying dengue viremia in serum samples and evaluate the kinetics of dengue viremia and its significance in disease severity.ResultsIn this ambispective study of 126 laboratory confirmed dengue patients, 72 were primary infections and 54 were secondary infections. The most common serotype was serotype 1 (n = 37) followed by serotype 2 (n = 34). According to WHO 1997 dengue case classification, 111 patients were cases of dengue fever (DF), 13 from DHF and 02 from DSS. Day 3 viremia levels were significantly elevated in severe dengue patients (DHF/DSS) as compared to that of DF (p < 0.05). However, no such association was found between viremia levels and serotype or immune status.ConclusionDengue viremia has a significant association with disease severity and day 3 viremia levels may be used as a predictor for dengue disease severity.

Innovations in dengue virus detection: An overview of conventional and electrochemical biosensor approaches.

Globally, people are in great threat due to the highly spreading of viral infectious diseases. Every year like 100-300 million cases of infections are found, and among them, above 80% are not recognized and irrelevant. Dengue virus (DENV) is an arbovirus infection that currently infects people most frequently. DENV encompasses four viral serotypes, and they each express comparable sign. From a mild febrile sickness to a potentially fatal dengue hemorrhagic fever, dengue can induce a variety of symptoms. Presently, the globe is being challenged by the untimely identification of dengue infection. Therefore, this review summarizes advances in the detection of dengue from conventional methods (nucleic acid-based, polymerase chain reaction-based, and serological approaches) to novel biosensors. This work illustrates an extensive study of the current designs and fabrication approaches involved in the formation of electrochemical biosensors for untimely identifications of dengue. Additionally, in electrochemical sensing of DENV, we skimmed through significances of biorecognition molecules like lectins, nucleic acid, and antibodies. The introduction of emerging techniques such as the CRISPR/Cas' system and their integration with biosensing platforms has also been summarized. Furthermore, the review revealed the importance of electrochemical approach compared with traditional diagnostic methods.

In-silico screening and identification of potential drug-like compounds for dengue-associated thrombocytopenia from Carica papaya leaf extracts

Dengue virus is a mosquito-borne pathogen that causes a variety of illnesses ranging from mild fever to severe and fatal dengue haemorrhagic fever or dengue shock syndrome. One of the major clinical manifestations of severe dengue infection is thrombocytopenia. The dengue non-structural protein 1 (NS1) is the primary protein that stimulates immune cells via toll-like receptor 4 (TLR4), induces platelets, and promotes aggregation, which could result in thrombocytopenia. The leaf extracts of Carica papaya seem to have therapeutic benefits in managing thrombocytopenia associated with dengue. The present study focuses on understanding the underlying mechanism of the use of papaya leaf extracts in treating thrombocytopenia. We have identified 124 phytocompounds that are present in the papaya leaf extract. The pharmacokinetics, molecular docking, binding free energy calculations, and molecular dynamic simulations were performed to investigate the drug-like properties, binding affinities, and interaction of phytocompounds with NS1 protein as well as the interactions of NS1 with TLR4. Three phytocompounds were found to bind with the ASN130, a crucial amino acid residue in the active site of the NS1 protein. Thus, we conclude that Rutin, Myricetin 3-rhamnoside, or Kaempferol 3-(2''-rhamnosylrutinoside) may serve as promising molecules by ameliorating thrombocytopenia in dengue-infected patients by interfering the interaction of NS1 with TLR4. These molecules can serve as drugs in the management of dengue-associated thrombocytopenia after verifying their effectiveness and assessing the drug potency, through additional in-vitro assays. Communicated by Ramaswamy H. Sarma

Death due to Dengue Encephalitis: Section A Rare Case Report

Dengue is a global public health concern, affecting around 50 million individuals and causing mortality in 20,000 patients per year. It is an arboviral disease caused by a single-stranded Ribonucleic Acid (RNA) virus belonging to the Flavivirus group and is transmitted by mosquitoes, specifically Aedes aegypti or albopictus. It comprises four serotypes, DENV1 to DENV4, and infection from one serotype only provides lifelong immunity for that subtype. Due to antibody-dependent enhancement, past infection with one serotype increases the prevalence of dengue haemorrhagic fever. The disease spectrum can range from asymptomatic infection to fever, fatal dengue haemorrhagic fever, or dengue shock syndrome. Due to improved disease knowledge, its involvement in the neurological system has been explored. Neurological abnormalities in dengue infection are rare and can be misdiagnosed due to other causes. Present case is of a young 23-year-old male with a history of fever 3-4 days prior, which later manifested with seizures and drowsiness. Despite emergency treatment, encephalitis and viral myocarditis developed, eventually leading to brain death within 24 hours of admission.

Flavivirus proteases: The viral Achilles heel to prevent future pandemics

Flaviviruses are important human pathogens and include dengue (DENV), West Nile (WNV), Yellow fever virus (YFV), Japanese encephalitis (JEV) and Zika virus (ZIKV). DENV, transmitted by mosquitoes, causes diseases ranging in severity from mild dengue fever with non-specific flu-like symptoms to fatal dengue hemorrhagic fever and dengue shock syndrome. DENV infections are caused by four serotypes, DENV1-4, which interact differently with antibodies in blood serum. The incidence of DENV infection has increased dramatically in recent decades and the CDC estimates 400 million dengue infections occur each year, resulting in ∼25,000 deaths mostly among children and elderly people. Similarly, ZIKV infections are caused by infected mosquito bites to humans, can be transmitted sexually and through blood transfusions. If a pregnant woman is infected, the virus can cross the placental barrier and can spread to her fetus, causing severe brain malformations in the child including microcephaly and other birth defects. It is noteworthy that the neurological manifestations of ZIKV were also observed in DENV endemic regions, suggesting that pre-existing antibody response to DENV could augment ZIKV infection. WNV, previously unknown in the US (and known to cause only mild disease in Middle East), first arrived in New York city in 1999 (NY99) and spread throughout the US and Canada by Culex mosquitoes and birds. WNV is now endemic in North America. Thus, emerging and re-emerging flaviviruses are significant threat to human health. However, vaccines are available for only a limited number of flaviviruses, and antiviral therapies are not available for any flavivirus. Hence, there is an urgent need to develop therapeutics that interfere with essential enzymatic steps, such as protease in the flavivirus lifecycle as these viruses possess significant threat to future pandemics. In this review, we focus on our E. coli expression of NS2B hydrophilic domain (NS2BH) covalently linked to NS3 protease domain (NS3Pro) in their natural context which is processed by the combined action of both subunits of the NS2B-NS3Pro precursor. Biochemical activities of the viral protease such as solubility and autoproteolysis of NS2BH-NS3Pro linkage depended on the C-terminal portion of NS2BH linked to the NS3Pro domain. Since 2008, we also focus on the use of the recombinant protease in high throughput screens and characterization of small molecular compounds identified in these screens.

A Computational Alanine Scanning of Heptapeptide RRRSAGM Targeting Dengue NS2B/NS3 Protease

The pathogenic dengue virus (DV) transmitted mainly by the Aedes aegypti mosquito has been the most rapidly spreading mosquito-borne viral disease and became a serious threat to global health issue in tropical and sub-tropical countries. The clinical symptoms ranging from mild to a fatal dengue hemorrhagic fever and dengue shock syndrome, characterized by failure of the circulation system that may lead to death. There are still no drugs or vaccines available in the market to prevent or treat dengue infections. Hence, the development of successful drugs that are safe and offer a long-lasting protection against dengue viruses is needed. Recently, the discovery of peptides with high specificity, selectivity, and efficacy; and relatively safer than small-molecule drugs have become a promising agent for a new drug. Previously, a molecular dynamic simulation reported that peptide NRRRRSAGMI from the capsid’s cleavage region had the most hydrogen bonds with NS2B/NS3 protease, thus it leads into a starting linear heptapeptide R(P3)-R(P2)-R(P1)-S(P1’)-A(P2’)-G(P3’)-M(P4’). This study aimed to investigate the importance and specificity of individual amino acid residue of the heptapeptide substrate on the binding affinity and interaction to NS2B/NS3 dengue protease through computational alanine scanning. It showed that the changing of P1 and P2 arginine to alanine resulted to higher values of binding affinity. Thus, the arginine is an important residue at the P1 and P2 positions for the binding of the substrate peptide to DENV NS2B/NS3 protease, hence the amino acid residues which are essential for the enzyme-substrate interactions can be predicted through computational alanine scanning.&#x0D; HIGHLIGHTS&#x0D; &#x0D; Dengue is a mosquito-transmitted virus cause of arthropod-borne viral disease&#x0D; The discovery of peptides became a potential agent for dengue virus and previously peptide NRRRRSAGMI has been reported as starting linear heptapeptide RRRSAGM&#x0D; A computational alanine scanning based on the peptide RRRSAGM has been performed&#x0D; S1 and S2 pockets show strong preferences for basic amino acids, whereas the S3 pocket is less selective for basic residue&#x0D; The arginine at P1 and P2 positions of the heptapeptide substrate contribute significantly to the substrate binding affinity&#x0D; &#x0D; GRAPHICAL ABSTRACT

Comparation of Elman neural network, long short-term memory, and gated recurrent unit in predicting dengue hemorrhagic fever at DKI Jakarta

Dengue hemorrhagic fever (DHF) is a seasonal disease that has quickly spread throughout the world in the past few years. It is caused by the dengue virus that is transmitted by a biological vector in the form of mosquitoes. In DKI Jakarta, the capital of Indonesia, there were 970 DHF cases at the beginning of 2020, thus placing Jakarta in the red zone for the spread of DHF. Besides, DHF can emerge due to various weather and climate factors such as humidity, rainfall, and temperature. With a significant increase in the number of potentially fatal DHF cases in DKI Jakarta, preventing DHF outbreaks is recommended. This research aims to predict the number of DHF cases in DKI Jakarta using weather and DHF case data. Three machine learning models were employed to predict DHF case numbers: Elman neural network (ENN), long short-term memory (LSTM), and gated recurrent unit (GRU). ENNs have a simplified recurrent neural network (RNN) structure, LSTM is a modified RNN with long-range memory and an activation function for deciding which information should be retained or discarded, and GRUs are modified RNNs that are slightly simpler than LSTMs. These methods were implemented in three different data sets as follows: one with 90% training data and 10% testing data, another with 80% training data and 20% testing data, and finally, one with 70% training data and 30% testing data. A grid search is used to determine the best hyperparameter from all three methods. This will determine the best model for predicting the number of DHF cases in DKI Jakarta (excluding Kepulauan Seribu Regency) according to the data used, RMSE values, and the simulation results. Based on these criteria, LSTM is better suited to predicting the number of DHF cases than ENN or GRU in almost every district in DKI Jakarta.

Risk Factors Associated with Fatal Dengue Hemorrhagic Fever in Adults: A Case Control Study.

Background Dengue is endemic in most parts of the tropics with a significant mortality of 1–5%. Although individual case reports and case series have been published, large-scale case controls studies are few. The objective of this study was to find clinical and laboratory predictors of mortality in dengue. Methods Hospital case record based case control study was performed. Results Twenty fatalities with 80 controls were analyzed. Clinical parameters of postural dizziness (OR 3.2; 95% CI 1.1–8.9), bleeding (OR 31.9; 95% CI 6.08–167.34), presence of plasma leakage (OR 64.6; 95% CI 7.45–560.5), abdominal tenderness (OR 2.24; 95% CI 0.79–6.38), and signs of cardiorespiratory instability at admission increased the risk of dying from dengue. Altered consciousness was exclusively seen in 20% of cases. Laboratory parameters of elevated CRP (OR 1.652; 95% CI 1.28–2.14), AST, or ALT > 500 IU/L (OR 52.5; 95% CI 12.52–220.1) and acute kidney injury (AKI) (OR 103.5; 95% CI 13.26–807.78) during hospital stay increased the odds of dying. Need for assisted ventilation and multiorgan dysfunction (MOD) were exclusively seen in the cases. Multivariate logistic regression revealed bleeding at admission, AKI, and elevated hepatic transaminase >500 IU/L to be independent predictors of mortality. Conclusions This case control study revealed that mortality from dengue could be predicted using clinical parameters at admission and low cost routine laboratory investigations.

The Classification Performance using Support Vector Machine for Endemic Dengue Cases

Dengue fever (DF) and the potentially fatal dengue haemorrhagic fever (DHF) are continue to be a crucial public health concern in Malaysia. This paper proposes a prediction model that incorporates Support Vector Machine (SVM) in predicting future dengue outbreak. Datasets used in the undertaken study includes data on dengue cases provided by the Health Department in Kelantan, Malaysia. Data scaling were applied to normalize the range of features before being fed into the training model. In this regard, SVM models built on the basis of three different kernel functions including Gaussian radial basis function (RBF), polynomial function and linear function. The SVM with RBF kernel function was superior to the other techniques because it obtains the highest prediction accuracy of 85%. The polynomial is an alternative model that can achieve a high prediction performance in terms of sensitivity (76%) and specificity (87%).

Ultrastructural Features of Human Liver Specimens from Patients Who Died of Dengue Hemorrhagic Fever.

Recent advances in electron microscopy and tomography have revealed distinct virus-induced endoplasmic reticulum (ER) structures unique for dengue virus (DV) and other flaviviruses in cell culture models, including hepatocytes. These altered ultrastructures serve as sites for viral replication. In this study, we used transmission electron microscopy to investigate whether such structures were present in the liver of fatal dengue hemorrhagic fever (DHF) autopsy cases. In parallel, electron microscopic examination of suckling mouse brains experimentally infected with DV was performed as an in vivo model of acute DV infection. Typical features of ER changes containing abundance of replicative virions were observed in neurons and microglia of DV-infected suckling mouse brains (SMB). This indicated that the in vivo DV infection could induce similar viral replication structures as previously described in the in vitro DV-infected cell model. Nevertheless, liver tissues from autopsy of patients who died of DHF showed scant changes of ER membrane structures and rare particles of virions in hepatocytes, despite overwhelming evidence for the presence of viral antigens and RNA–indicating active virus replication. Instead hepatocytes contained an abundance of steatotic vesicles and structural damages. This lack of structural changes indicative of virus replication in human hepatocytes is discussed.

Assessment of dengue mosquito breeding sources and source reduction at a coastal village in Puducherry

Background: Dengue virus can cause a wide range of illness in humans, from unapparent infection, to classic dengue fever and to fatal dengue haemorrhagic fever. Until a vaccine becomes available for public health use, primary prevention of transmission is crucial to decrease the burden of dengue, and control of Aedes is the only available strategy.Methods: The mosquito larval survey was carried out in the month of November 2017 in Echangadu, a coastal village in Puducherry to assess mosquito breeding sources for the presence of dengue vector species. The survey was performed by selecting houses where freshwater was available. For each household, the presence or absence of possible breeding sources were recorded, as well as the presence or absence of mosquito larvae.Results: Of the 102 houses surveyed, 20 of the houses were infested with Aedes larvae. A total of 182 containers were found in these households of which 47 containers were positive for Aedes larvae. Coconut shells, plastic, metal and discarded containers were the most often found breeding sites.Conclusions: The larval surveillance indicators among the households surveyed revealed a very high risk of future dengue outbreak in the village. All the containers examined including those positive for Aedes larvae were safely disposed.

Selection-based design of in silico dengue epitope ensemble vaccines.

Dengue virus affects approximately 130 countries. Twenty-five percentage of infections result in febrile, self-limiting illness; heterotypic infection results in potentially fatal dengue haemorrhagic fever or dengue shock syndrome. Only one vaccine is currently available. Its efficacy is very variable. Thus, to target dengue, we used an innovative immunoinformatics protocol to design a putative epitope ensemble vaccine by selecting an optimal set of highly conserved epitopes with experimentally verified immunogenicity. From 1597 CD4+ and MHC II epitopes, six MHC Class I epitopes (RAVHADMGYW, GPWHLGKLEM, GLYGNGVVTK, NMIIMDEAHF, KTWAYHGSY and WAYHGSYEV) and nine MHC Class II epitopes (LAKAIFKLTYQNKVV, GKIVGLYGNGVVTTS, AAIFMTATPPGSVEA, AAIFMTATPPGTADA, GKTVWFVPSIKAGND, KFWNTTIAVSMANIF, RAIWYMWLGARYLEF, VGTYGLNTFTNMEVQ and WTLMYFHRRDLRLAA) were selected; this candidate vaccine achieved a world population coverage of 92.49%.

Knowledge, awareness and attitude towards dengue fever outbreaks in the summer

Dengue fever is a life-threatening viral infection that has been a public health problem. It is estimated that almost more than one half of the world population live in countries where dengue fever is endemic. Among affected individuals, about 5% develop the fatal dengue shock syndrome and dengue hemorrhagic fever, and almost 20,000 patients die annually with these conditions. Despite the magnitude of the problem, dengue fever is a preventable disease. Prevention can be carried out by elimination of inhabitant mosquitoes, vaccination of vulnerable individuals, and regular health education particularly during outbreaks. Many literatures studies were conducted to evaluate the impact of healthcare education on dengue fever prevention, and many researchers studied the population awareness and attitudes about the disease. Knowledge and awareness varied among different studies, and some factors were reported to influence this knowledge such as gender, socioeconomic status, level of education, and computer literacy. The attitudes also differed among the studies and did not seem to be correlated with the population knowledge about the disease. This article will review the knowledge, awareness, and attitudes among different countries towards dengue fever outbreaks in the summer.

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 tetravalentchimeric denguevaccine, 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.

Human kidney damage in fatal dengue hemorrhagic fever results of glomeruli injury mainly induced by IL17

Acute kidney injury is an unusual complication during dengue infection. The objective of this study was to better identify the characteristics of glomerular changes focusing on in situ immune cells and cytokines. An immunohistochemical assay was performed on 20 kidney specimens from fatal human cases of dengue hemorrhagic fever (DHF). It was observed a lymphomononuclear infiltrate, neutrophils and nuclear fragmentation in the glomeruli, hydropic degeneration, nuclear retraction, eosinophilic tubules and intense acute congestion. Sickle erythrocytes were frequent in glomeruli and inflammatory infiltrate. The glomeruli presented endothelial swelling and mesangial proliferation. Lymphocytes CD4+ predominated over CD8+ T cells, B cells and natural killer cells. There were also an expressive number of macrophagic CD68+ cells. S100, Foxp3 and CD123 cells were not identified. Cells expressing IL17 and IL18+ cytokines predominated in the renal tissues, while IL4, IL6, IL10, IL13, TNF-alpha and IFN-gamma were rarely visualized. The high number of cells expressing IL17 and IL18+ could reflect the acute inflammatory response and possibly contribute to the local lesion. CD8+ T cells could play a role in the cytotoxic response. DHF is a multifactorial disease of capillary leakage associated with a “Tsunami of cytokines expression”. The large numbers of cells expressing IL17 seems to play a role favoring the increased permeability.

Common variants of chemokine receptor gene CXCR3 and its ligands CXCL10 and CXCL11 associated with vascular permeability of dengue infection in peninsular Malaysia

Dengue causes significantly more human disease than any other arboviruses. It causes a spectrum of illness, ranging from mild self-limited fever, to severe and fatal dengue hemorrhagic fever, as evidenced by vascular leakage and multifactorial hemostatic abnormalities. There is no specific treatment available till date. Evidence shows that chemokines CXCL10, CXCL11 and their receptor CXCR3 are involved in severity of dengue, but their genetic association with the susceptibility of vascular leakage during dengue infection has not been reported. We genotyped 14 common variants of these candidate genes in 176 patients infected with dengue. rs4859584 and rs8878 (CXCL10) were significantly associated with vascular permeability of dengue infection (P<0.05); while variants of CXCL11 showed moderate significance of association (P=0.0527). Haplotype blocks were constructed for genes CXCL10 and CXCL11 (5 and 7 common variants respectively). Haplotype association tests performed revealed that, “CCCCA” of gene CXCL10 and “AGTTTAC” of CXCL11 were found to be significantly associated with vascular leakage (P=0.0154 and 0.0366 respectively). In summary, our association study further strengthens the evidence of the involvement of CXCL10 and CXCL11 in the pathogenesis of dengue infection.

Atrial Fibrillation Due to Acute Myocarditis During Dengue Haemorrhagic Fever.

Atrial Fibrillation Due to Acute Myocarditis During Dengue Haemorrhagic Fever.

Histopathological study of Dengue Haemorrhagic Fever

<strong>Introduction:</strong> Dengue Haemorrhagic Fever (DHF) is a severe febrile disease caused by a Flavivirus.Four serotypes of dengue virus (DEN 1-4) are present and the large majority of DHF occurs following a secondary infection with a different serotype. About 0.5 million people in the world develop DHF annually with 24,000 deaths. Pathogenesis of the disease is still not fully understood. Target cells include dendritic reticulum cells, monocytes, lymphocytes, hepatocytes, and vascular endothelial cells.<br /><br /><strong>Objectives:</strong> To describe the histopathological changes in the liver, lungs, heart, brain, spleen, gastrointestinal tract and kidneys in fatal DHF.<br /><br /><strong>Materials and methods: </strong>Tissue from seventeen autopsies following DHF were processed routinely and stained with haematoxylin and eosin. Histopathological changes in the liver, lungs, heart, brain, spleen, gastrointestinal tract and kidneys were studied.<br /><br /><strong>Results:</strong> Fifteen of 17 cases showed a liver pathology which included submassive necrosis (1/15), bridging necrosis (2/15), midzonal (3/15) and centrilobular necrosis (4/15), focal necrosis (2/15), apoptosis (1/15) and macrovesicular steatosis (7/15). Pulmonary haemorrhage was present in 13 cases and pulmonary oedema in 6 cases. Glomerular congestion and haemorrhage were seen in 6 and medullary congestion with haemorrhage was present in 9 cases. Gastrointestinal mucosal haemorrhages were seen in 8. One patient showed myocarditis and one showed myocardial haemorrhages. Cerebral oedema was present in 8 cases In 13 out of 17 cases the spleen showed red pulp congestion and haemorrhage.<br /><br /><strong>Conclusion:</strong> DHF is a systemic viral infection causing multiorgan pathology. Liver, lungs and spleen are the most commonly affected organs.<br /><br />DOI: <a href="http://dx.doi.org/10.4038/jdp.v8i1.6790" target="_blank">http://dx.doi.org/10.4038/jdp.v8i1.6790</a><br /><br />Journal of Diagnostic Pathology 2012 (8); 1:50-58

Simulations to compare efficacies of tetravalent dengue vaccines and mosquito vector control

Infection with dengue, the most prevalent mosquito-borne virus, manifests as dengue fever (DF) or the more fatal dengue haemorrhagic fever (DHF). DHF occurs mainly when an individual who has acquired antibodies to one serotype is inoculated with another serotype. It was reported that mosquito control may have increased the incidence of DF and DHF due to age-dependency in manifesting these illnesses or an immunological mechanism. Tetravalent dengue vaccine is currently being tested in clinical trials. However, seroconversions to all four serotypes were achieved only after three doses. Therefore, vaccines may predispose vaccinees to the risk of developing DHF in future infections. This study employed an individual-based computer simulation, to emulate mosquito control and vaccination, incorporating seroconversion rates reported from actual clinical trials. It was found that mosquito control alone would have increased incidence of DF and DHF in areas of high mosquito density. A vaccination programme with very high coverage, even with a vaccine of suboptimal seroconversion rates, attenuated possible surges in the incidence of DF and DHF which would have been caused by insufficient reduction in mosquito abundance. DHF cases attributable to vaccine-derived enhancement were fewer than DHF cases prevented by a vaccine with considerably high (although not perfect) seroconversion rates. These predictions may justify vaccination programmes, at least in areas of high mosquito abundance. In such areas, mosquito control programmes should be conducted only after the vaccination programme with a high coverage has been initiated.