Borne Viral Disease Research Articles

SERO-PREVALENCE OF DENGUE INFECTION FROM GOVERNMENT HOSPITAL, RAJASTHAN DURING 2022

Background: Viral haemorrhagic fevers are becoming increasingly common in the tropics and subtropics. Dengue fever is currently the most important arthropod‑borne viral disease because of its widespread distribution in more than 100 countries and its potential for extensive outbreaks of life‑threatening disease. Material and Methods: This study was a hospital‑based cross‑sectional study conducted in LaboratoryShrr. R.K.J. Hopsital, Dausa, in Rajasthan, India, between January 2022 to December 2022. The present study included all serum specimens received at laboratory of R.K.J. Hopsital, Dausa, from clinically suspected cases of dengue infection, during this duration. Serum samples were received for serological testing from suspected cases of dengue as advised by consultants from various departments in hospital for laboratory confirmation of suspected cases. Laboratory-confirmed dengue cases were defined as suspected dengue cases with positive dengue serology. Result: The present study analyzed the samples of 1880 of suspected patients during year of 2022. and seropositivity rate of 15% (296/1880) was found out of which 10% (67/648) were seropositive for NS1 antigen and 18% (229/1232) were by IgM ELISA test. The present study revealed trend of cases from August to December 2022 peak of cases was reported in month of September and November. Discussion: The resurgence of dengue has been notable in India and dengue epidemics have been frequently reported in the country both from urban and rural regions. Recent analysis of the past two decades highlighted that, in India, transmission pattern of dengue has changed and widened with shift in peak post-monsoon shifting toward November from October in the recent decade from irregular peak of the previous decade. However, the present pattern in shift of transmission is clear that dengue cannot be considered as a seasonal disease. Conclusions: An alarming rate of increasing emerging and reemerging trends of these arboviral infections are noted in this part of Rajasthan. Hence, the need to focus on proper surveillance, and implementation of prevention and control measure in the country are of utmost priority. Presently, there are no licensed vaccines or antivirals available however, India has initiated several efforts in this direction including traditional medicines. The outcome of this study will help in focusing and improvement of existing surveillance systems and vector control tools, as well as on the development of suitable antiviral agents and formulating candidate vaccine.

Dengue Infection: Frequently Asked Questions by People in the Province of Aklan, Philippines

Dengue virus is the most common mosquito borne viral disease in humans, and poses a major challenge to global public health services. Infection can be caused by any of the 4 DENV serotypes, transmitted by female Aedes aegypti mosquitoes. Presenting features may vary from a mild self-limiting febrile illness to life-threatening symptoms of bleeding, organ impairment, and plasma leakage leading to shock. Early diagnosis and monitoring are critical to reduce mortality, especially in the context of the COVID-19 pandemic. Laboratory tests, such as the serological detection of either antigen or antibodies are useful in the diagnosis. Currently, although a vaccine for DENV is available, it remains a challenge to develop an effective vaccine against 4 discrete serotypes and antiviral drugs effective in reducing morbidity or improving disease outcome.

Management of dengue with co-infections: an updated narrative review.

Dengue is a life-threatening mosquito borne viral disease. We are still in the era of supportive treatment where morbidity and mortality are a major concern. Dengue infection in presence of other co-infections makes this scenario rather worse. Timely recognition and raising alarm to be intensive is the need of the hour for primary care physicians practicing in the community and indoors. This review provides a comprehensive knowledge about the recent trends of coinfection in dengue as well as their management consideration which will be particularly helpful for physicians practicing in rural and remote areas of India.

English

BACKGROUND Dengue is a major public health concern in tropical Asian countries and a most rapidly spreading mosquito borne viral disease with a 30 fold increase in global incidence over the last five decades. Dengue is among the ten leading causes of death in children ranging from 1 to 15 years of age in tropical Asian countries. Complications of dengue fever are common in children. But very limited studies are available on paediatric populations. The virus or non-structural protein (NS1) interacts with platelets and coagulation factors. A combined effect of mild disseminated intravascular coagulation, liver damage and platelet dysfunction results in bleeding in dengue fever. With this scientific knowledge background, the present study was undertaken to identify and document the changing pattern of dengue infection in paediatric age group with a special emphasis on laboratory findings of dengue cases in paediatric age group. METHODS The present descriptive study was conducted for two years in a state run paediatric referral hospital. The sample was purposive by design and consisted of patients who have been diagnosed as having dengue fever with warning signs and admitted. RESULTS Fever was typically high grade (> 103 F) and most patients presented with warning signs within 5 days of illness (64.2 % in year 2016 and 76.6 % in year 2017). Persistent vomiting and abdominal pain were the most common warning signs in both the years. Thrombocytopenia was the commonest laboratory finding. Bleeding in study subjects lead to < 50000 / cu mm platelet count. Most common bleeding was gastrointestinal bleeding (39.2 % of study subjects with platelet count < 50000 / cu mm presented with G. I bleeding). CONCLUSIONS Dengue illness comes with varied presentation. Atypical presentations can delay the diagnosis. Early recognition of warning signs keeping the atypical presentation in mind is important. KEYWORDS Dengue Fever, Paediatric Age Group, Non-Structural Protein (NS1), Thrombocytopenia

DEVELOPMENT OF NANOEMULSION AND ITS CHARACTERIZATION FOR ANTI BIOFILM AND LARVICIDAL ACTIVITY

Dengue is a mosquito borne viral disease and the main root cause vector is Aedes aegypti. Hence in this work a rapid measure was taken to eradicate the vector using nanoemulsion. Plant essential oil based nanoemulsions was formulated by ultrasonic emulsification method. In the current study, nanoemulsion (O/W) was developed using oil extracted from the leaves of a Tulsi, Neem and Nochi. The emulsions were prepared in different ratios of oil and surfactant (Tween 80) and evaluated for their mechanical and thermal stability. After the confirmation of stable nanoemulsion formation, it was evaluated for its antibiofilm activity. Results revealed that the formulated mixed oil nanoemulsion exhibited enhanced antibiofilm activity against isolated microorganisms from contaminated wall samples. Further the biofilm forming capability of bacterial culture was indirectly assessed by staining with 1% crystal violet and measured absorbance using ethanol as a destaining solution. The mean biofilm production of S3 bacterial isolates significantly greater than that observed for S1 & S2. In addition, antibiofilm activity of the emulsion NE3 was higher against bacterial culture S3. Different concentration of mixed oil nanoemulsiom (NE3) treated group was subjected to evaluate the larvicidal activity against Aedes aegypti between 1 to 12 hours respectively. It was observed that an increase in the nanoemulsion concentration (NE3) to 25 ppm and 50 ppm resulted in complete loss of larval viability in 5 hr and 6 hr respectively. There is no significant difference in larval viability after 6 hr and 12 hr in all the treatment groups. Hence the above findings suggest the applicative potential of mixed nanoemulsion formulation for various applications including mosquito larval control and antibiofilm activity.

Co-circulation of all the Four Serotype of Dengue Virus in Endemic Region of Saurashtra, Gujarat during 2019-2020 Season

Introduction: Dengue has rapidly emerged as a vector - borne viral disease in recent years and also endemic in all continents. The agent of dengue, i.e., dengue viruses, are categorised under the genus Flavivirus, with the four dengue virus serotypes: designated as DENV-1, DENV-2, DENV-3 and DENV-4. These all four serotypes are in circulation either singly, or more than one at the same time. Aim: To study the epidemiological update of dengue with circulating serotype and co-infection in Saurashtra region, Gujarat, India. Materials and Methods: A cross-sectional study was conducted during January 2019 to December 2020 and total samples received were 12,563 which were clinically suspected dengue samples case. After receiving blood samples, serum was separated and proceeded for Dengue NS1Ag (nonstructural protein 1 antigen), and Dengue IgM Ab (Immunoglobulin M antibody). After serological confirmation, 151 samples from different geographical area were selected for Dengue specific Reverse Transcriptase- Polymerase Chain Reaction (RT-PCR) for serotyping. results: Total 4069 (32%) had confirmed dengue positive by Enzyme Linked Immunosorbent Assay (ELISA). The ratio of male cases was higher than female, and in age group 21-35 year (47%). Seasonal trend showed a gradual increase in positivity from June with high peak in October. Circulation of all the four serotypes in area, higher monotypic infection by DENV-1 serotype (41%), followed by DENV-4, DENV-2 and DENV-3. Co-infection of different serotypes were also found. conclusion: The present study concluded that all four serotypes circulate with predominant being DENV-1 type and co-infection of different serotypes in the saurashtra region. Dengue mainly affected adult male population, and seasonal peak during monsoon and post-monsoon period.

WATER RESOURCES HELPS İN THE EXPANSİON OF MOSQUİTOES COLONİES

In Pakistan, water storage bodies are often the most plentiful and active habitats of immature stages of mosquitoes. Mosquitoes are blood feeding type of vectors that bite a particular host and suck blood. As a result, these vectors transmit disease causing agents to the host system. The most common mosquitoes borne viral diseases in Pakistan are Chicken gunya, Dengue fever, west nile and Zika fever. These diseases are common in low and poor living standard areas. Death rate increases due to more attack of these fatal diseases. Mosquitoes breeding sites are water bodies, discarded tyres, water tanks, bottles, cups and ant traps. Various environmental agents i.e. temperature fluctuations and water resources, now increase the rate of mosquitos in most areas of Pakistan. There is a lack of basic medical education and knowledge about its pervention techniques in mosquito affected areas in Pakistan. The purpose of this review is to highlight the current status of emerging mosquito borne viral diseases in Pakistan, i.e. Chicken gunya, Dengue fever, est nile and Zika fever. There is more need of prevention strategies and understanding about factors involved in spreading of mosquito borne diseases.

Inhibition studies of methyltransferase domain of dengue virus protein NS-5 by a poly herbal extract- An Insilico Apporach.

Dengue is a mosquito borne viral disease mainly transmitted by Aedes aegypti and, to a lesser extent, Ae. albopictus. The global incidence of Dengue is grown dramatically in recent decades. Dengue is endemic in over 100 countries and there are an estimated 100-400 million infections every year. Currently no antiviral drugs are available against Dengue. This urges a strong need to develop therapeutic strategies that can tackle this life threatening disease. In this study, the efficiency of nine bioactive chemical entities from Nilavembu Kudineer, a popularly known traditional Siddha formulation have been analyzed for their in silico docking potentials against NS-5 methyltransferase of Dengue virus. Methyltransferase is responsible for capping the nascent genomic RNA of Dengue Virus, using S-Adenosyl methionine as a methyl group donar, this methylation of viral RNA plays a major role allowing the virus to escape the immune response. A graphical automated drug discovery system called iGEMDOCK is used for integrating docking, screening, post analysis and visualization. Current investigation clearly focuses on pharmacological interactions of polyherbal drug in preventing the capping of mRNA, thereby inhibiting RNA dependent RNA polymerase (RdRp), ultimately hindering the post transcriptional modifications. Out of the nine ligands screened for its antiviral activity, Monolinolein and Palmitic acid showed binding energies >90 Kcal/mol towards the binding site of NS-5 methyltransferase and could be the active pharmaceutical ingredients of Nilavembu kudineer.

Fiery Fevers - An Epidemiological Evaluation and Management Strategies Experience from a Community Based Day Care Centre

Telangana has a long association with fiery fevers caused by mosquito bites. It is in fact in Telangana that Sir Ronald Ross discovered the malarial parasite in mosquito’s gut in the month of August 1897 for which he was later awarded Nobel Prize in 1902. Malaria has been high on the differential diagnosis in patients presenting with fever in this region. However, over the last two decades there has been an increased incidence of mosquito borne viral diseases with India becoming endemic for Dengue and Chikungunya. The prevalence of these has been on a rise and Telangana region has been no exception. An unpredictable and sudden outbreak of fever cases prevailed from August to October 2019 in Hyderabad, most of them were viral fevers and among them Dengue emerged as a major toll, to a lesser extent Chikungunya and others. Objective of this study is to present a clear and comprehensive picture of the prevailing causes of such a fever outbreak in this specified time frame in our Diagnostics and Day care centre. Serum samples were collected from all fever cases and sent to laboratory and analysed according to the following criteria –age, gender, presenting complaints, lab evaluation etc. The results have been interpretated in the form of tables, figures and graphs reflecting the predominant cause of fevers. The study showed that majority of the cases were in the age group 20–30 years with a male predilection and significant number of patients showed leucopenia and thrombocytopenia even in non dengue and non chikungungya patients. This sudden emergence is being attributed to sparkling vector transmission due to an incessant rainfall during this time inhabiting breeders in stagnant waters. It also reemphasizes the need for regular public health maintenance programmes including removing of stagnant water, mosquito control, regular public awareness camps. Need of the hour would be for both governmental and nongovernmental agencies to work in coordination to reduce the disease burden.

Seroprevalence of West Nile fever virus in horses in the Belgrade epizootiological area

West Nile fever is a vector borne viral disease that can affect humans, horses, birds and sometimes other species of animals. Every year West Nile fever is detected in the human population in Serbia. The disease often occurs in a subclinical form, but most clinically evident cases occur in horses. Therefore, horses are recommended as a sentinel species for monitoring the general incidence of West Nile fever in a specific territory. Our goal was to determine the prevalence of antibodies against West Nile fever virus in horses in the Belgrade epizootiological area. We examined serum samples from 77 horses to determine the seroprevalence of West Nile fever virus in horses throughout the city of Belgrade. Sera were tested by commercial ELISA tests for detection of specific IgG-class antibodies to West Nile fever virus and for the detection of specific IgM-class antibodies to confirm the presence of old and acute (recent) infections in horses. The results confirmed that West Nile fever virus is widespread, detected in 70.1% of the surveyed horse population in Belgrade, and we also detected 5.1% of acute cases had occurred due to horses being infected in 2019. The seroprevalence of West Nile virus in the horse population in the municipality of Belgrade is increasing.

Status of Animal Health with Emphasis of Blue Tongue Virus Disease in Kalat Region, Balochistan

Bluetongue is non contagious vector borne viral disease of small ruminants. It transmits by biting of culicoids midges and causes severe economic losses to animal owner in term of high morbidity, decreased production and impaired reproduction. Balochistan, being largest province of the country have scattered population in far remote areas. About 70% of the provincial population rely upon livestock rearing for their livelihood. Kalat is largest division of the province that stretches from Kalat city upto Lasbella including Khuzdar, Kharan and Awaran. It is located on main RCD route that will ultimately boost the animal marketing and their easy access to main market. Although different vaccines are practiced throughout the province but no such vaccine is available against BTV in the country. That’s why animals are facing problems of some undiagnosed diseases. This review provides necessary information about disease in the region. It is need of the time to educate farmer and strict vigilance may be practiced for proper and timely vaccination of all animals to curtail deadliest diseases in the region.

Clinical profile of Dengue fever in an urban tertiary care hospital in South India

Background: Dengue is among the most common flavivirus infections in the world. Today dengue ranks as the most important mosquito- borne viral disease in the world. Current estimates report that, at least 112 countries are endemic for Dengue and about 40% of the world populations (2.5-3 billion people) are at risk in tropics and subtropics. Annually 100 million cases of dengue fever and half a million cases of DHF occur worldwide. The clinical features are noted to be different in varying demographics of the world outlining the importance of bringing out data from different parts of the world, so clinicians are better equipped to anticipate the problems associated with clinical dengue.Methods: The study was conducted over a period of 2 years at a tertiary care hospital in urban Bengaluru, India. A cross sectional study of a total of 250 patients was done. They were diagnosed to be positive for dengue serology (NS1 or IgM) before including them in the study. Clinical features, haematological, biochemical and radiological parameters were assessed.Results: Out of 250 patients with dengue fever, the most common symptoms were fever (100%), headache (94.4%) and myalgia (97.2%). Bleeding manifestations were noted in 11.6% of the patients. Bradycardia was noted in 14.8% of the study population. Leukopenia was noted in 36% of the study population. Increased SGOT was seen in 59.6% and increased SGPT in 52.8% of the 250 subjects. The clinical outcome of the 250 patients of dengue fever was classical dengue fever in 86.8%, DHF in 11.6%, DSS in 0.8% and death in 0.8%.Conclusions: All patients with dengue fever present with fever. Other common features noted were headache, myalgia. Bleeding manifestations are to be looked out for. Rare but important features that a clinician must be vigilant to look for are bradycardia and leucopenia.

Pharmacophore modeling, molecular docking and molecular dynamics simulation for screening and identifying anti-dengue phytocompounds

Dengue is a fast spreading mosquito borne viral disease that poses a serious threat to human health. Lack of therapeutic drugs and vaccines signify that more resources need to be explored. Accumulated evidence has suggested that plants offer a vast reservoir for antiviral drug discovery which are safe for human consumption. Plant-based drug discovery is a complex and time-consuming process as plants possess rich repository of chemically diverse compounds. Various in silico methods can make this process simple and economic. We, therefore, performed pharmacophore mapping, molecular docking, molecular dynamics (MD) simulations and ADME (absorption, distribution, metabolism, excretion) prediction to screen potential candidates against dengue. In particular, combined pharmacophore mapping and molecular docking were used to prioritize the potentially active ligands from a ligand library. Biological activities of plant based ligands were predicted using 3D-QSAR pharmacophore modeling. Interaction between proteins, namely, envelope G protein, NS2B/NS3 protease, NS5 methyltransferase, NS1, NS5 polymerase and active plant-based ligands (pIC50 > 5.1) were analyzed using molecular docking. Best docked complex, namely, envelope G protein–mulberroside C, NS2B-NS3 protease–curcumin, NS5 methyltransferase–chebulic acid, NS1–mulberroside A, NS5 methyltransferase–punigluconin and NS5 methyltransferase–chebulic acid were further subjected to MD simulations study to assess the fluctuation and conformational changes during protein–ligand interaction. ADME studies were performed to assess their drug-likeness properties. Collectively, these in silico results helped to identify the potential plant-based hits against the various receptors of dengue virus which can be further validated by bioactivity-based experiments.Communicated by Ramaswamy H. Sarma

A mathematical and numerical analysis of a compartmental model for a single strain dengue epidemic in the presence of vaccination

Dengue disease has presently emerged as an alarming public health concern of mounting significance with the unprecedented number of cases reported worldwide annually, especially from the tropics and subtropics. It is currently considered as the most critical vector borne viral disease in the world due to the acute health, social and economic issues that it causes in the endemic countries. Further, human mobility, climate change, rapid urbanization and public unawareness have led to a substantial dissemination of dengue in new geographical settings with explosive outbreaks. Also, the disease burden has aggravated due to the unavailability of specific clinical therapeutics and effective vaccines for the dengue disease. In such a context, this paper intends to investigate the dynamics of dengue disease in the presence of hypothetical vaccination strategies. Thus, we use a classical compartmental model with mathematical and numerical analyses in order to emphasize the importance of vaccination as an effective measure of disease control. We are hence of the belief that this paper will be a source of motivation for the medical scientists involved in the development of vaccine candidates for the dengue disease.

Kidenga: Public engagement for detection and prevention of Aedes -borne viral diseases

Objective(1) Early detection ofAedes-borne arboviral disease; (2) improveddata onAe. aegyptiandAe. albopictusdistribution in the UnitedStates (U.S.); and (3) education of clinicians and the public.IntroductionZika, chikungunya, and dengue have surged in the Americas overthe past several years and pose serious health threats in regions of theU.S. whereAe. aegyptiandAe. albopictusmosquito vectors occur.Ae. aegyptihave been detected up to 6 months of the year or longer inparts of Arizona, Florida, and Texas where mosquito surveillance isregularly conducted. However, many areas in the U.S. lack basic dataon vector presence or absence. The Zika, dengue, and chikungunyaviruses range in pathogenicity, but all include asymptomatic or mildpresentations for which individuals may not seek care. Traditionalpassive surveillance systems rely on confirmatory laboratory testingand may not detect emergent disease until there is high morbidity in acommunity or severe disease presentation. Participatory surveillanceis an approach to disease detection that allows the public to directlyreport symptoms electronically and provides rapid visualization ofaggregated data to the user and public health agencies. Several suchsystems have been shown to be sensitive, accurate, and timelierthan traditional surveillance. We developed Kidenga, a mobilephone app and participatory surveillance system, to address someof the challenges in early detection of day-biting mosquitoes andAedes-borne arboviruses and to enhance dissemination of informationto at-risk communities.MethodsKidenga sends a weekly push notification prompting users toreport symptoms, travel history, and day-biting mosquito activity.If an individual reports through Kidenga that they or a family memberhave had symptoms consistent with Zika, dengue, or chikungunya,they receive an email with educational information about the diseases,prevention strategies, and treatment/testing information for clinicians.Upon registration, users can opt in to have additional follow-up viaemail. At any time, users may also view maps of aggregated userreports, confirmed case counts by county from public health partners(in pilot areas),Aedesdistribution maps, information about preventionand control strategies, and news on the diseases and vectors from acurated newsfeed. Users in select pilot areas may also receive pressreleases issued by their state or local public health department relatedto the diseases and their vectors. University of Arizona owns andmaintains the app and its data. Local and state health departmentsthat want more detailed information on user symptoms and mosquitoactivity may request and monitor the data at no cost. A marketingcampaign to recruit a broad user base is being implemented inArizona, Texas, and Florida.ResultsKidenga was developed with significant input from public healthstakeholders and launched in September 2016,accompanied byEnglish and Spanish radio public service announcements in selectArizona markets, press releases, and a social marketing campaign.A Spanish version of the app is under development. We willdescribe the results of user registration and survey submissions,challenges identified during development and deployment of thisnovel surveillance system, plans for data use and evaluation, andcollaborations with public health partners.ConclusionsThe utility of Kidenga as a surveillance system will depend onbroad and consistent participation among diverse user populations,particularly in low-risk areas; strategies to integrate health reports forhigh-risk populations who may not have smartphones; validation ofdata and development of sensitive and specific algorithms for takingpublic health action, and buy-in from public health departments touse the data and advocate for this novel surveillance tool. Kidenga’ssecondary function as an education tool onAedes-borne viruses is lessdependent upon a large user base and can be evaluated separately.Participatory surveillance systems that specifically monitorAedes-borne pathogens are relatively new, and the challenges associatedwith their early detection may differ from those of other diseases.

Dengue-ocular manifestation and disease outcome

Dengue fever is one of the most common arthropod borne viral diseases. A myriad of ocular manifestations, ranging from mild subconjunctival hemorrhage to retinal hemorrhages and rarely to vision threatening complications such as optic neuropathy and panophthalmitis, have been reported. Therefore, this study was undertaken to document the ocular changes among dengue fever patients along with its association on further course of disease outcome and to study the ocular manifestations associated with dengue fever along with its association on further course of disease outcome. An observational Study was conducted in the Departments of Medicine and Ophthalmology, SRMS-IMS, Bareilly, U.P from September 2015 to November 2015 on 100 patients admitted. All patients underwent complete evaluation with respect to systemic and ophthalmic examination. Of 42 patients 10 patients with platelet counts b/w 35–50000 were found to have subconjunctival hemorrhage, rest other have platelet count below 35000. Retinal hemorrhage was not found in any patient having platelet counts above 25000 (at presentation or dropped during daily monitoring during hospital stay). All patient with subconjunctival hemorrhage must go for further ocular (fundus) examination. Retinal hemorrhage if detected early, may prove as a good marker that may further predict course of hemorrhagic complication in a dengue fever patient and also has correlation with platelet counts of patients.

A historical overview of the distribution of African horse sickness in Namibia

A historical overview of the distribution of African horse sickness in Namibia African horse sickness (AHS) is a noncontagious, vector borne viral disease, mainly affecting Equids and transmitted by Culicoides midges. Data on the occurrence of AHS in arid environments is limited, especially in Namibia where it is underestimated and underreported. In this study the historical profile of AHS and patterns in the distribution thereof is illustrated.

A study to assess injection practices in civil dispensaries

Background: About 16 billion injections are administered each year worldwide, and at least half of them are unsafe. India contributes 25-30% of the global injection load. A majority of curative injections are unnecessary. Estimates suggest that at least 50% of the world’s injections administered each year are unsafe particularly in developing countries. Methods and materials: The Present study was a cross-sectional study done for 3 months in all the Civil Dispensaries to Assess the Knowledge, Skill and Practices of Health Care Providers working at Civil Dispensaries regarding “Safe Injection Practices” and also to compare the differences between the knowledge and actual practices among Health Care providers of District Gwalior. Result: A total of 35 Health Care Providers were taken in the study. All of them knew that the gloves should be worn during injection procedure but only 4 (11.43%) actually worked during the process. 10 (28.57%) knew that the gloves should be worn for both personal and patient safety. 5(14.29%) did not knew anything about blood borne viral diseases i.e. Human Immuno Deficiency Virus, Hepatitis B and Hepatitis C which could be transmitted to the Health Care Providers. Conclusion: There was a great disparity between knowledge and practices of Health Care Providers regarding injection practices. Efforts are to be needed to be done in this regard for the benefit of both Health Care Providers and the patients.

Identification of a novel infection-enhancing epitope on dengue prM using a dengue cross-reacting monoclonal antibody.

BackgroundDengue virus (DENV) infection is the most important arthropod- borne viral disease in human, but antiviral therapy and approved vaccines remain unavailable due to antibody-dependent enhancement (ADE) phenomenon. Many studies showed that pre-membrane (prM)-specific antibodies do not efficiently neutralize DENV infection but potently promote ADE infection. However, most of the binding epitopes of these antibodies remain unknown.ResultsIn the present study, we characterized a DENV cross-reactive monoclonal antibody (mAb), 4D10, that neutralized poorly but potently enhanced infection of four standard DENV serotypes and immature DENV (imDENV) over a broad range of concentration. In addition, the epitope of 4D10 was successfully mapped to amino acid residues 14 to18 of DENV1-4 prM protein using a phage-displayed peptide library and comprehensive bioinformatics analysis. We found that the epitope was DENV serocomplex cross-reactive and showed to be highly immunogenic in Balb/c mice. Furthermore, antibody against epitope peptide PL10, like 4D10, showed broad cross-reactivity and weak neutralizing activtity with four standard DENV serotypes and imDENV but significantly promoted ADE infection. These results suggested 4D10 and anti-PL10 sera were infection-enhancing antibodies and PL10 was infection-enhancing epitope.ConclusionsWe mapped the epitope of 4D10 to amino acid residues 14 to18 of DENV1-4 prM and found that this epitope was infection-enhancing. These findings may provide significant implications for future vaccine design and facilitate understanding the pathogenesis of DENV infection.

Lymphocytic Choriomeningitis Virus Infections among American Indians

Lymphocytic Choriomeningitis Virus Infections among American Indians