Mosquito-borne Infection Research Articles

Incidence of Dengue fever, serotypes, clinical features, and laboratory markers: a case study of 2019 outbreak at district Shangla, KP, Pakistan.

Dengue is a widely spread mosquito-borne infection in humans, which in recent decades declared is public health problem globally. The dengue virus contains 4 different serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) which belong to the genus Flavivirus. A descriptive experimental study was conducted to determine the epidemiology, types of Dengue serotypes, clinical features, laboratory probe, and markers for primary diagnosis of dengue virus infection in hospitalized patients. A total of 691 suspects were diagnosed from August to October 2019 in district Shangla KP, Pakistan. Serological tests were used for nonstructural protein-1 antigen (NS1), and antibodies (immunoglobulin-M (IgM) & Immunoglobulin-G (IgG)) while real-time PCR was used to confirm the cases. The data was statistically analyzed using IBM-SPSS Statistics 20 version. The dengue virus infection was more prevalent in the male group (68.09%) than the female group (31.1%). A large number of patients were from rural areas (63.5%) while from urban areas were (36.4%), whereas Besham tehsil was found the most affected compared to other regions. The most prevalent serotype observed in our study was DENV-3 (56.60%) while DENV-4 was the least prevalent serotype (1.88%). Among the age-wise analysis of dengue-virus-infected individuals, the age group of 19-37 years (64.07%) was found the most affected group. The month-wise analysis revealed that the highest number of infections (49.8%) were recorded in September. Significant differences were noticed among blood parameters. The possible reasons for the dengue overwhelming in the study area could be less or lack of awareness particularly regarding the transmission of viral infections, improper sewage management, and no effective vector control strategies that lead the dengue outbreaks in the study population.

Densovirus Oil Suspension Significantly Improves the Efficacy and Duration of Larvicidal Activity against Aedes albopictus.

Aedes albopictus is the sole vector for various mosquito-borne viruses, including dengue, chikungunya, and Zika. Ecofriendly biological agents are required to reduce the spread of these mosquito-borne infections. Mosquito densoviruses (MDVs) are entomopathogenic mosquito-specific viruses, which can reduce the capacity of isolated vectors and decrease mosquito-borne viral disease transmission. However, their variable pathogenicity restricts their commercial use. In the present study, we developed a series of novel larvicide oil suspensions (denoted Bacillus thuringiensis (Bti) oil, Ae. albopictus densovirus (AalDV-5) oil, and a mixture of AalDV-5+Bti oil), which were tested against Ae. albopictus larvae under experimental semi-field and open-field conditions. The effect of AalDV-5 on non-target species was also evaluated. The combined effect of AalDV-5+Bti was greater than that of individual toxins and was longer lasting and more persistent compared with the laboratory AalDV-5 virus strain. The virus was quantified on a weekly basis by quantitative polymerase chain reaction (qPCR) and was persistently detected in rearing water as well as in dead larvae. Wildtype densovirus is not pathogenic to non-target organisms. The present findings confirm the improved effect of a mixed microbial suspension (AalDV-5+Bti oil) larvicide against Ae. albopictus. The development and testing of these products will enable better control of the vector mosquitoes.

A Study to Assess the Effectiveness of Planned Health Teaching Program on Knowledge regarding use of Papaya Leaf in Dengue Fever among people of selected Rural Community area of Mehsana

Background: Dengue is fast emerging pandemic-prone viral disease in many parts of the world. Dengue flourishes in urban poor areas, suburbs and the countryside but also affects more affluent neighbourhoods in tropical and subtropical countries. Dengue is a mosquito-borne viral infection causing a severe flu-like illness and, sometimes causing a potentially lethal complication called severe dengue. The incidence of dengue has increased 30-fold over the last 50 years. Up to 50-100 million infections are now estimated to occur annually in over 100 endemic countries, putting almost half of the world’s population at risk. Severe dengue (previously known as dengue haemorrhagic fever) was first recognized in the 1950s during dengue epidemics in the Philippines and Thailand. Today it affects Asian and Latin American countries and has become a leading cause of hospitalization and death among children and adults in these regions. The full life cycle of dengue fever virus involves the role of mosquito as a transmitter (or vector) and humans as the main victim and source of infection. The dengue virus (DEN) comprises four distinct serotypes (DEN-1, DEN-2, DEN-3 and DEN-4) which belong to the genus Flavivirus, family Flaviviridae.1 Aims and Objectives: To assess knowledge regarding use of papaya leaf in dengue fever among the selected rural community. To evaluate effectiveness of plan teaching on knowledge regarding use of papaya leaf in dengue fever among rural community of mehsana. To find out the association with knowledge score with their selected demographic variables. Result: Regarding level of knowledge, in pre-test 66.66 % of respondents belong to poor knowledge 16.66% of respondents belong to average knowledge and 16.66% of responds belong to good knowledge before intervention. In post-test, 20% of responds belong to poor knowledge 46.66% of respondents belongs to averages knowledge and 33.33%of respondents belong to good knowledge after intervention. During pre-test the mean level of knowledge was 7.54%during post-test the mean level of knowledge was 10.67%, which is apparently higher than pre-test knowledge scoreWith regard to effectiveness of planned teaching programme regarding use of papaya leaf in dengue fever among people of selected rural community area of mehsana. With regard to the association between the level of knowledge among the people with their demographic variables was significant. Conclusion- The main conclusion from this present study is that most of the people head poor level of knowledge regarding use of papaya leaf in dengue fever in pre –test and their level of knowledge regarding use of papaya leaf in dengue fever head improved to a great extent after planned teaching program which was revealed in post-test. This shows the imperative need to understand the utilities of planned teaching programme in improvement of knowledge regarding use of papaya leaf in dengue fever and it will improve the people knowledge.

Mathematical models for dengue fever epidemiology: A 10-year systematic review.

Mathematical models have a long history in epidemiological research, and as the COVID-19 pandemic progressed, research on mathematical modeling became imperative and very influential to understand the epidemiological dynamics of disease spreading.Mathematical models describing dengue fever epidemiological dynamics are found back from 1970. Dengue fever is a viral mosquito-borne infection caused by four antigenically related but distinct serotypes (DENV-1 to DENV-4). With 2.5 billion people at risk of acquiring the infection, it is a major international public health concern. Although most of the cases are asymptomatic or mild, the disease immunological response is complex, with severe disease linked to the antibody-dependent enhancement (ADE) - a disease augmentation phenomenon where pre-existing antibodies to previous dengue infection do not neutralize but rather enhance the new infection. Here, we present a 10-year systematic review on mathematical models for dengue fever epidemiology. Specifically, we review multi-strain frameworks describing host-to-host and vector-host transmission models and within-host models describing viral replication and the respective immune response.Following a detailed literature search in standard scientific databases, different mathematical models in terms of their scope, analytical approach and structural form, including model validation and parameter estimation using empirical data, are described and analyzed.Aiming to identify a consensus on infectious diseases modeling aspects that can contribute to public health authorities for disease control, we revise the current understanding of epidemiological and immunological factors influencing the transmission dynamics of dengue. This review provide insights on general features to be considered to model aspects of real-world public health problems, such as the current epidemiological scenario we are living in.

The fabrication and assessment of mosquito repellent cream for outdoor protection

Mosquito-borne infections like dengue, malaria, chikungunya, etc. are a nuisance and can cause profound discomfort to people. Due to the objectional side effects and toxicity associated with synthetic pyrethroids, N,N-diethyl-3-methylbenzamide (DEET), N,N-diethyl phenylacetamide (DEPA), and N,N-di ethyl benzamide (DEBA) based mosquito repellent products, we developed an essential oil (EO) based mosquito repellent cream (EO-MRC) using clove, citronella and lemongrass oil. Subsequently, a formulation characterization, bio-efficacy, and safety study of EO-MRC were carried out. Expression of Anti-OBP2A and TRPV1 proteins on mosquito head parts were studied by western blotting. In-silico screening was also conducted for the specific proteins. An FT-IR study confirmed the chemical compatibility of the EOs and excipients used in EO-MRC. The thermal behaviour of the best EOs and their mixture was characterized by thermogravimetric analysis (TGA). GC–MS examination revealed various chemical components present in EOs. Efficacy of EO-MRC was correlated with 12% N,N-diethyl benzamide (DEBA) based marketed cream (DBMC). Complete protection time (CPT) of EO-MRC was determined as 228 min. Cytotoxicity study on L-132 cell line confirmed the non-toxic nature of EO-MRC upon inhalation. Acute dermal irritation study, acute dermal dose toxicity study, and acute eye irritation study revealed the non-toxic nature of EO-MRC. Non-target toxicity study on Danio rerio confirmed EO-MRC as safer for aquatic non-target animals. A decrease in the concentration of acetylcholinesterase (AChE) was observed in transfluthrin (TNSF) exposed Wistar rats. While EO-MRC did not alter the AChE concentrations in the exposed animals. Results from western blotting confirmed that Anti-OBP2A and TRPV1 proteins were inhibited in TNSF exposed mosquitoes. Mosquitoes exposed to EO-MRC showed a similar expression pattern for Anti-OBP2A and TRPV1 as the control group. In silico study revealed eight identified compounds of the EOs play significant roles in the overall repellency property of the developed product. The study emphasizes the mosquito repellent activity of EO-MRC, which could be an effective, eco-friendly, and safer alternative to the existing synthetic repellents for personal protection against mosquitoes during field conditions.

Dengue Management in Triage using Ultrasound in children from Cambodia: a prospective cohort study

SummaryBackgroundDengue is a mosquito-borne viral infection with increasing global prevalence. It is endemic in more than 100 countries, with a heavy burden in Asia. Ultrasound findings including gallbladder wall thickening, ascites, and pleural effusions secondary to plasma leakage have been described in dengue. We aimed to determine if the presence of point-of-care ultrasound findings early in suspected dengue could predict clinical worsening in ambulatory pediatric patients.MethodsWe did a prospective, single-blinded, observational cohort study at a children's hospital in Siem Reap, Cambodia during periods of dengue outbreak. Ambulatory patients were screened and children ages > 3 month and ≤ 16 years with suspected acute, non-severe dengue were enrolled. Subjects had chest and abdominal ultrasound exams. Independently, subjects were evaluated by a blinded physician who determined a treatment plan as per usual practice. Follow-up was conducted 7-10 days after the initial visit. Analysis of ultrasound findings was performed to determine their relationship with outcome measures including need for unplanned hospital visits or admissions.FindingsA total of 2,186 children were screened during periods of national dengue outbreak in Cambodia in consecutive years 2018-2019, and 253 children met eligibility criteria. Results showed patients with gallbladder wall thickening (> 3·0 mm) who were discharged had a significantly more likely need for unplanned visit or hospitalization than those with normal gallbladder wall, 67% (95% CI 44 – 84) versus 17% (95% CI 12 – 24), p < 0.0001. Subjects with any abnormal ultrasound finding were more likely to be directly admitted versus discharged upon initial presentation, 62·2% (95% CI 46.1 – 76.0) versus 19.5% (95% CI 14.8 – 25.4), p < 0.0001.InterpretationPoint-of-care ultrasound findings, particularly gallbladder wall thickening, in suspected early dengue can help predict disease progression in ambulatory patients. Ultrasound has potential to help guide management of suspected dengue patients and resource management during periods of dengue outbreak.FundingSociety for Academic Emergency Medicine Foundation.

Autochthonous Human Dirofilaria repens Infection in Austria

PurposeThis report describes a rare autochthonous case of human D. repens infection in Austria. Dirofilariosis is a mosquito-borne parasitic infection that predominantly affects dogs. Human D. repens infections have primarily been reported in Mediterranean countries, but are emerging throughout Central and Northern Europe.MethodsThe worm was removed surgically and identified using PCR and DNA sequencing. The consensus sequences were compared against reference sequences of Dirofilaria repens from GenBank.ResultsThe 56-year-old woman acquired the infection, which presented as a subcutaneous nodule, in Vienna, Austria. This is the second autochthonous case of human D. repens infection in Austria.ConclusionThe reasons for the emergence of D. repens and other parasitic infections in Central and Northern Europe are manifold, including climate change and globalization. This case demonstrates that with the growing number of D. repens infections, health care professionals must place further emphasis on emerging infectious diseases to ensure appropriate diagnostics and treatment in the future.

Trend analysis in seroprevalence of dengue, chikungunya and malaria: A seven-year serological study from a tertiary care hospital of Maharashtra, India.

Dengue, chikungunya and malaria are mosquito-borne infections, which have shared endemicity and similar clinical presentation. Simultaneous co-infection with more than one infectious agent complicates the diagnosis and further course of treatment. This study aims to determine the seroprevalence and trend of malaria, dengue and chikungunya from 2014-2020 in a tertiary care hospital of western India. The present study was retrospective descriptive record-based. Serum samples from clinically suspected dengue and chikungunya were subjected to both IgM antibody capture ELISA kits produced by National Institute of Virology (NIV), Pune, India. They were also subjected to ELISA based NS1Ag testing. In Suspected malaria cases, blood collected in EDTA tubes was subjected for Rapid Malaria antigen testing. Statistical analysis was performed using MS Excel and JMP Software. Seropositivity of malaria was comparatively higher in 2014 (5.53%) and a decreasing trend was observed in subsequent years. Majority of malarial infections were caused by Plasmodium vivax (81.67%). There is drastic increase in seropositivity of chikungunya from 2016 (23.67%) and thereafter as compared to 2014 (6.57%) and 2015 (7.29%) indicating its re-emergence. The dengue seropositivity in 2019 (40.19%) was highest in last seven years. Males were predominantly affected, and most affected age group was 21-30 years. Peak transmission was observed in post-monsoon seasons. Dengue and chikungunya co-infection was observed to be 5.79%. This study emphasizes the importance of surveillance studies to understand the trend of vector-borne diseases for prompt diagnosis, management of patients in hospital setup and for early detection and curtailment of outbreaks and epidemics by public health sectors through appropriate vector control programs.

In silico study of six FDA approved anti-HCV drugs as inhibitors for NS5 methyltransferase of dengue virus type 2

Background & objectives: Dengue virus infection has become a major health threat. Dengue is a mosquito-borne viral infection caused by a viral RNA of the family Flaviviridae and spread by Aedes mosquitoes. Dengue NS5 methyltransferase is used as a drug target for the disease. Six FDA approved anti-HCV drugs were tested as potential dengue virus type 2 methyltransferase inhibitors using molecular docking analysis seeking potential treatment. Methods: Molecular docking analysis tested six FDA approved anti-HCV drugs, including Elbasvir, Daclatasvir, Ledipasvir, Pibrentasvir, Velpatasvir, and Ombitasvir. Results: 1000 ps molecular dynamics simulation of protein-complex validates its stability. Interpretation & conclusion: The analysis indicates the binding of Ombitasvir with the protein drug target with optimal binding features for further in vitro and in vivo evaluations. Ombitasvir was the optimum candidate ligand compound with binding affinity value (-11.56 ΁ 0.46 kcal/mol) with 2P3Q. Interactions of Ombitasvir with the active site residues of 2P3Q revealed good results for experimental drug testing.

Molecular characterization of dengue viruses during an outbreak in Kolkata: A hospital-based study

Context: Dengue, a mosquito-borne viral infection in the tropical regions of the world, has recently become a major public health concern. In West Bengal, several outbreaks of dengue fever occurred in the past few years. In the present study, serological analysis, molecular detection, and serotyping of dengue virus were done to identify the serotype/s presently circulating in the region. Methods: The present study was conducted for a period of 1 year from November 2017 to October 2018 in the Department of Microbiology, ID and BG Hospital, Kolkata. 5240 blood samples collected from clinically suspected dengue fever cases were screened for dengue specific immunoglobulin M (IgM) antibody by MAC-ELISA and NS1 antigen by NS1 ELISA according to the duration of fever as per the National Vector Borne Disease Control Program guidelines. Molecular detection and serotyping were done in 70 NS1 positive samples by nested reverse transcription-polymerase chain reaction. Results: Total 5240 samples were tested for dengue. About 30.48% (1597) were serologically reactive for dengue infection (either IgM or NS1). Among these, 80.52% (1286) were NS1 reactive and 19.47% (311) were IgM reactive. Male predominance (66.37%) was observed throughout the study period. A post monsoon season peak was also noted in our study. DEN2 was found as most prevalent serotype presently circulating in the region. Conclusions: Laboratory-based active surveillance system is required which can forecast dengue epidemics by detecting increasing number of dengue cases or changing pattern in the prevalent serotype as a specific serotype (viz.DEN2) is associated with higher incidence of complications. This will help alert the public and physicians to diagnose properly and treat cautiously the complicated dengue cases.

West Nile Virus in Germany: An Emerging Infection and Its Relevance for Transfusion Safety

West Nile virus (WNV) is an arthropod-borne virus (arbovirus). It circulates in an enzootic cycle between ornithophilic mosquitoes as vectors and reservoirs and avian host species for amplification, but humans can be infected as accidental hosts. In most individuals, WNV infection remains silent, while 20% develop mild symptoms of West Nile fever, and only 1% develop neuroinvasive disease (WNND). Human WNV cases have been identified in Southern and Eastern Europe for more than 20 years, but until 2018, Germany was considered to be a non-endemic country. This changed when in the exceptionally warm summer of 2018, conditions for viral replication in mosquitoes were ideal, and the first WNV cases among birds and horses were identified. The widespread domestic Culexmosquitoes are efficient vectors for WNV. Autochthonous mosquito-borne WNV infections in humans were reported in all following years, indicating a continuous circulation in the affected areas of Central-East Germany. So far, no clear expansion of the affected areas is discernible but may develop. WNV is a transfusion-transmissible-infection, and donor deferral or testing of donations after a stay in an affected area are effective means to ensure transfusion safety. WNV transmissions via blood products often result in WNND due to the predisposing underlying medical conditions of transfusion recipients. From 2020 onwards, roughly 80% of all blood establishments in Germany tested their donations for WNV using nucleic acid amplification techniques in the transmission season. Altogether, 19 confirmed WNV infections were identified from 2020–2021. As long as effective and affordable pathogen reduction is not available for all blood components, WNV testing or donor deferral will be essential. In order to timely identify affected areas, combined results of human and veterinary surveillance are needed. Partnerships between public health experts, transfusion medicine specialists, veterinarians, and entomologists should be strengthened to ensure a One Health approach.

Genomic characterization and evolutionary analysis of dengue virus from Aedes mosquitoes in Telangana, India.

Entomological surveillance for mosquito-borne viruses is vital for monitoring disease transmission and vector control programs. The vector control program is reliant not only on vector density but also on the timely detection of mosquito-borne infections. In the present study, we conducted an entomological surveillance in different locations of Hyderabad, Telangana, India during 2017-2018 and the collected mosquitoes were screened for dengue virus. Reverse transcriptase polymerase chain reaction (RT-PCR) was used for the identification and serotyping of the dengue virus. Bioinformatics analysis was performed using Mega 6.0 software. Followed by phylogenetic analysis, which was based on CprM structural genome sequence, was performed by using the Maximum-Likelihood method. The TaqMan RT-PCR assay was used to analyze the serotypes of 25 pools of Aedes mosquitoes and found that all four serotypes are circulating in Telangana. DENV1 (50%) was the most commonly detected serotype followed by DENV2 (16.6%), DENV3 (25%), and DENV4 (8.3%). Moreover, DENV1 has the highest MIR (16 per 1000 mosquitoes) compared with DENV2, 3, and 4. The CprM structural gene sequence was used for phylogenetic analysis, revealing that all four strains have a close relationship with strains isolated from India, Pakistan, China and Thailand. Similarly, two variations in amino acid sequence DENV1 at position 43 (K-R) and 86 (S-T) and a single mutation DENV2 at 111 amino acid position were observed. The results of the study provide an in-depth transmission dynamic of the dengue virus and persistence of this emerging pathogen in Telangana, India that needs appropriate prevention programs.

Household-Based Survey on Knowledge, Attitudes, and Practices towards Dengue Infection and Prevention in a Semi-Urban Area (Ja-Ela MOH Area)

Introduction: Dengue is the most prevalent infectious mosquito-borne viral infection in the world. Over time dengue has causedhigh mortality and morbidity. Methods: A cross-sectional study was conducted to assess the level of knowledge, attitude, and practice among 510 residents ofJa-Ela MOH area using an interviewer-administered questionnaire. Ethical clearance was obtained from the National Institute ofHealth Science Kalutara. Results: The majority (50.8%) of the respondents were females, and the mean age of the sample was 43.7±16.7 years. Thestudy results showed that 56.5% (n=288), 52.9% (n=270), and 50.7% (n=257) of the sample had good knowledge, attitudes,and practices (KAP) towards dengue prevention, respectively. Good knowledge is significantly associated with 41-60 years ofage (odds ratio [OR]=2.513, P&lt;0.001), secondary education or higher (OR=1.857, P=0.008), and a monthly income of LKR20000–40000 and more than 40000 (OR=0.477, P=0.016; OR=0.440, P=0.015). Non-Sinhalese nationality (OR=0.180,P=0.033) was associated with poor levels of knowledge. Good attitudes towards the prevention of dengue were found in males(OR=2.095, P=0.001), unemployed individuals (OR=1.759, P=0.018), and individuals with a monthly income of&lt;LKR 20000(OR=2.393, P=0.001). Poor practices towards dengue prevention were found in other nationalities compared to Sinhalese(OR=0.104, P=0.001) while Roman Catholics had poor practices towards dengue prevention (OR=0.677, P=0.041). The studyshows that the experience of dengue is positively associated with better attitudes towards dengue prevention (Mann-Whitney Utest; P&lt;0.001). Conclusion: KAPs were not significantly correlated with each other. Targeted health education and promotion programmesprovided for specific populations should be considered a priority activity.

Pharyngeal-cervical-brachial variant of Landry Guillain Barre syndrome after dengue infection: a case report

Dengue is a common mosquito-borne infection in India. We reported a rare Pharyngeal cervical brachial (PCB) variant of Landry Guillain Barre syndrome (LGBS) associated with the dengue virus infection. The pathogenesis seems to be molecular mimicry between gangliosides and microbial lipo-oligosaccharides. PCB usually presents with oropharyngeal or cervicobrachial weakness. Therefore, it must be recognised early and distinguished from conditions presenting with cephalocaudal progressing weakness, such as Myasthenia Gravis, Miller-Fisher syndrome, botulism, diphtheria, porphyria or brain stem stroke. The aim of the study was to add to the limited literature on the PCB variant of LGBS after dengue infection and shed some light on presentation and management options for this rare entity.

Plant-Derived Alkaloids Acting on Dengue Virus and Their Vectors: From Chemistry to Pharmacology

Dengue is a mosquito-borne viral infection, with its prevention and control depending on effective vector control measures. At present, dengue virus (DENV) is an epidemic in more than 100 countries of Southeast Asia, Africa, Eastern Mediterranean, the Americasand the Western Pacific. Several alkaloids isolated from natural herbs can serve as a reservoir for antiDENV drug development. Traditionally, plant extracts rich in alkaloids are used for the treatment of fever and have also revealed antimicrobial activity against various pathogenic bacteria, fungi and virus. The present narrative review collates the literature-based scenario of alkaloids and derivatives acting on DENV. The mechanism of action of such alkaloids with antiDENV and vector activity is also discussed.

Production, Transmission, Pathogenesis, and Control of Dengue Virus: A Literature-Based Undivided Perspective.

Dengue remains one of the most serious and widespread mosquito-borne viral infections in human beings, with serious health problems or even death. About 50 to 100 million people are newly infected annually, with almost 2.5 billion people living at risk and resulting in 20,000 deaths. Dengue virus infection is especially transmitted through bites of Aedes mosquitos, hugely spread in tropical and subtropical environments, mostly found in urban and semiurban areas. Unfortunately, there is no particular therapeutic approach, but prevention, adequate consciousness, detection at earlier stage of viral infection, and appropriate medical care can lower the fatality rates. This review offers a comprehensive view of production, transmission, pathogenesis, and control measures of the dengue virus and its vectors.

Dengue

Dengue is a mosquito-borne flavivirus infection, found in tropical and sub-tropical climates worldwide, mostly in urban and semi-urban areas. There are four distinct dengue virus (DENV) serotypes, meaning that it is possible to be infected four times. While 75% of DENV infections are asymptomatic, 20% of result in mild to moderate disease (Dengue fever [DF]), and 5% can cause severe disease with activation of the coagulation system (Dengue hemorrhagic fever [DHF]), which is usually seen with subsequent DENV infections. Antibody-mediated disease enhancement (ADE) is a phenomenon that has been observed in various in vitro assays: low concentrations of cross-reacting antibodies from a previous DENV infection in a subsequent infection with another serotype do not neutralize DENV. Instead, they bind to the virus and attach to host cells; thus, enabling viral replication. ADE is one hypothesis proposed, among many, to explain sensitization to severe disease. There is no specific treatment for DENV. Early detection of disease progression and access to proper medical care lower fatality rates of DHF from about 2.5% to &lt;1%. Severe dengue is a leading cause of serious illness and death in some Asian and Latin American countries. The global incidence of dengue has grown dramatically in recent decades. About half of the world's population is now at risk. There are an estimated 100–400 million infections each year. Dengue prevention and control relies on effective vector control measures. Sustained community involvement can improve vector control efforts substantially. There is one licensed dengue vaccine, CYD live attenuated tetravalent dengue vaccine (Dengvaxia®) developed by Sanofi Pasteur, which is approved for use in several dengue endemic countries for persons 9–45 years of age living in endemic areas who have had a previously documented dengue virus infection. Several other vaccines are in clinical development.

From Mosquito Bites to Sexual Transmission: Evaluating Mouse Models of Zika Virus Infection.

Following the recent outbreak of Zika virus (ZIKV) infections in Latin America, ZIKV has emerged as a global health threat due to its ability to induce neurological disease in both adults and the developing fetus. ZIKV is largely mosquito-borne and is now endemic in many parts of Africa, Asia, and South America. However, several reports have demonstrated persistent ZIKV infection of the male reproductive tract and evidence of male-to-female sexual transmission of ZIKV. Sexual transmission may broaden the reach of ZIKV infections beyond its current geographical limits, presenting a significant threat worldwide. Several mouse models of ZIKV infection have been developed to investigate ZIKV pathogenesis and develop effective vaccines and therapeutics. However, the majority of these models focus on mosquito-borne infection, while few have considered the impact of sexual transmission on immunity and pathogenesis. This review will examine the advantages and disadvantages of current models of mosquito-borne and sexually transmitted ZIKV and provide recommendations for the effective use of ZIKV mouse models.

Dengue virus infection among renal transplant recipients in Singapore: a 15-year, single-centre retrospective review.

Dengue is a mosquito-borne viral infection endemic in Singapore. Its impact on renal transplantation is limited to small case series. We aimed to characterise the clinical presentation and outcomes of dengue infection among renal transplant recipients in Singapore. We conducted a 15-year retrospective review of dengue in renal transplant patients treated at Singapore General Hospital between January 2005 and October 2019. The diagnosis of dengue was made if there were a compatible clinical syndrome and a positive dengue diagnostic assay (dengue non-structural 1 antigen, immunoglobulin M or reverse transcriptase-polymerase chain reaction). Of the 31 patients diagnosed with dengue, 18 (58.1%) were deceased donor recipients. The median age was 52 (interquartile range [IQR] 40-61) years; 16 (51.6%) were females. The median time to diagnosis was 99 (IQR 18-169) months from transplant. The most common clinical symptoms were fever (87.1%), myalgia (41.9%), gastrointestinal symptoms (38.7%) and headache (25.8%). Nineteen (61.3%) patients had dengue without warning signs, nine (29.0%) had dengue with warning signs, three (9.7%) had severe dengue and 30 (96.8%) were hospitalised. Seventeen (54.8%) patients had graft dysfunction, 16 (94.1%) of whom had recovery of graft function. One (3.2%) patient required dialysis and subsequently died. There were two cases of donor-derived infections (DDIs) with favourable outcomes. Our experience with dengue in renal transplant recipients is concordant with published data. Although graft dysfunction is common, it is often transient with favourable outcomes. Outpatient management may be considered for mild infections. Although dengue DDIs are uncommon, more stringent donor screening may be considered in endemic regions.

In vitro and in vivo efficacy of Metformin against dengue

Dengue is a prevalent mosquito-borne viral infection in the tropical and sub-tropical regions. Its potential to progress into severe, life-threatening disease, has pressed the research community to develop safe, effective and affordable antivirals. Metformin (MET), a first-line antidiabetic drug and indirect AMP-activated protein kinase (AMPK) activator, has recently emerged as a potential anti-DENV therapeutic candidate, based on some experimental evidence supporting anti-DENV activity in vitro and widely reported anti-inflammatory properties. Here, we examined MET in vitro activity against the four DENV serotypes and in two different mammalian cell lines. MET displayed a poor anti-DENV activity in BHK-21 cells with IC50 in the mM range, which was associated with increased p-AMPKα levels, thereby supporting that MET antiviral activity is mediated through AMPK activation. In contrast, MET exerted a pro-DENV activity in Vero cells that did not correlate with increased AMPK activation, suggesting AMPK-independent effects. Treatment with compound 991, a direct AMPK activator, led to reduced viral titers against all four serotypes and across both mammalian cell lines. In vivo, oral administration of MET did not reduce viremia titers in an asymptomatic mouse model, neither did it improve disease severity and progression in a mouse model of severe dengue. Instead, high dose regimen worsened disease outcome as evidenced by increased mortality, higher viremia and hyper-inflammation. Therefore, while AMPK may represent a potential host target, MET does not seem to hold great promise as a pan-serotype anti-dengue drug.