Arthropod-borne Disease Research Articles

Dengue virus downregulates TNFR1- and TLR3-stimulated NF-κB activation by targeting RIPK1.

Dengue virus (DENV) infection is the most prevalent arthropod-borne virus disease and is endemic in more than 100 countries. Several DENV proteins have been shown to target crucial human host proteins to evade innate immune responses and establish a productive infection. Here we report that the DENV NS3 protein targets RIPK1 (Receptor Interacting Protein Kinase I), a central mediator of inflammation and cell death, and decreases intracellular RIPK1 levels during DENV infection. The interaction of NS3 with RIPK1 results in the inhibition of NF-κB activation in response to TNFR or TLR3 stimulation. Also, we observed that the effects of NS3 on RIPK1 were independent of NS3 protease activity. Our data demonstrate a novel mechanism by which DENV suppresses normal cellular functions to evade host innate immune responses

Overview of Aedes aegypti and Use in Laboratory Studies.

The yellow fever mosquito Aedes aegypti is a prolific disease vector. This mosquito has been the subject of scientific investigation for more than a century. Continued research into Aedes aegypti biology is crucial for understanding how to halt the suite of major arthropod-borne viral diseases this mosquito transmits. Here, we provide an introductory overview of Aedes aegypti life cycle; evolutionary history, biology, and ecology; genetics and sex differences; vector competence; and laboratory colonization and considerations for rearing this robust mosquito species for use in laboratory research.

Identification and characterization of bluetongue virus in Culicoides spp. and clinically healthy livestock in southeastern Kazakhstan

ObjectiveBluetongue is an arthropod-borne disease of ruminants. Here, we investigated the seroprevalence of bluetongue virus (BTV) in livestock and performed the first genetic characterization of BTV isolated from sheep and Culicoides midges in the southeastern region of Kazakhstan. MethodsBlood samples were collected from 1241 asymptomatic livestock. In addition, 497 Culicoides midges were collected. Samples were analyzed for specific anti-BTV antibodies and BTV RNA by ELISA and conventional RT-PCR, respectively. ResultsThe overall seroprevalence of BTV antibodies was shown to be 4.3 % (46/1079) in small ruminant and 1 % (1/82) in cattle. Anti-BTV antibodies were not detected in camels (0/80). The minimum infection rate of BTV in Culicoides was shown to be 0.24 %. Seg-2 and Seg-10 sequence analysis demonstrated that all isolates belonged to the ‘western’ topotype of the BTV-9 strain. ConclusionThe present data confirm circulation of BTV in southeastern Kazakhstan.

DENGUE and its Prevalence

About 2.5 billion individuals worldwide are infected with the dengue virus (DENV), an important arthropod-borne viral disease, of which 975 million reside in both large and small cities in tropical and subtropical regions of Southeast Asia, the Pacific, and the America. Dengue is presently endemic in more than 100 countries as a result of a sharp increase in incidence over the past few decades [1]. Aedes genus mosquitoes, particularly Aedes aegypti or Aedes albopictus, which are infected females and transmit the dengue virus, which is a member of the Flaviviridae family, infect people. Primary infection and secondary infection are the two types of diseases brought on by the dengue virus. A complicated immune response clears dengue fever (DF), an acute febrile sickness brought on by a primary infection, in about seven days. Haemorrhagic fever (DHF) or dengue shock syndrome (DSS) are the effects of a secondary infection that is more severe. Pakistan is at a significant risk for dengue endemics because of its congested cities, contaminated water, poor sanitation, huge refugee population, and low immunisation rates [2]. Dengue fever (DF), as well as more severe DHF/DSS, can be brought on by the dengue virus. Within three to five days of an infection, DF might result in a fever, which is accompanied by thrombocytopenia, relative leucopenia, headache, joint discomfort, and skin rashes. Other etiologies, including non-dengue flavivirus infections, should be ruled out based on the patient's place of origin [3]. Dengue virus infection can be diagnosed in a lab by examining a specific virus, viral antigen, genomic sequence, and/or antibodies. Due to the four viral serotypes, there is currently no vaccination for the prevention of Dengue virus infection. In the most severe cases, dengue infection can result in patient death. To combat dengue virus infection, numerous antiviral compounds are being explored, but an effective, affordable, and secure vaccine that can neutralise all four dengue virus serotypes is still required. However, a patient with dengue fever can be saved with supportive care and therapy. Antipyretics like paracetamol can be used to treat fever. Drugs that reduce pain, such as analgesics, can be used to alleviate joint pain. Patients with DHF/DSS must be hospitalised. Oral rehydration therapy can reduce dehydration, and intravenous fluid replacement can reduce shock in infected individuals if oral intake is impossible. A platelet transfusion is advised if the patient's platelet count falls below 20,000 or if there is substantial bleeding. Aspirin, Brevrin, and non-steroidal anti-inflammatory drugs should be avoided as they may exacerbate the tendency to bleed [4].

African horse sickness: an ancient disease for a current threat

African horse sickness (AHS) is a major arthropod-borne disease that causes significant losses in horses in sub-Saharan Africa. It is caused by the African horse sickness virus (AHSV), which is transmitted during a blood meal by Culicoides biting midges. The distribution of historical African culicoid vectors increases due to global warming. In addition, recent (Thailand, 2020) and earlier (Iberian Peninsula, 1965-66/1987-90) AHS outbreaks outside Africa demonstrate the adaptation of the virus to endogenous species in AHS-free regions, similar to what has been observed for bluetongue disease in recent decades. Therefore, many regions are considered at risk of introduction of AHS which could have important economic consequences for the equine industry. Overall, this prone the European Union to launch research programs to get better diagnostic and prophylactic tools.

Clinico-hematological and Biochemical Studies on Naturally Infected Buffaloes with Trypanosomiasis in Deepor Beel Area of Assam

Background: Trypanosomiasis, an arthropod-borne blood protozoan disease commonly known as Surra, has an adverse influence on the health and working capability of infected animals. Monitoring and identification of blood-borne parasitic infections in dairy animals are of vital importance to get the optimum production. There was a lake of the scientific report of incidence of trypanosomiasis in buffalo in the northeast region. Methods: In the present study, a total of 100 buffalo was screened in the Deepor Beel area of Assam and 25 animals were suspected of trypanosomiasis based on clinical signs. The diagnosis was confirmed by microscopic examination and formol gel slide test which was further confirmed by PCR. The blood from twenty-one buffalo tested positive for the presence of Trypanosoma evansi was evaluated for clinico-haemato-biochemical alterations. Result: The outbreak in the affected animals exhibiting high fever (105±1.0°F), hyperemic mucosa of eyes, corneal opacity, incoordination of the hindquarter, wasting condition of body and death, was confirmed based on examination of Wright-Giemsa stained blood smears, formol gel slide test and by polymerase chain reaction by using T. evansi specific primers yielding species-specific 227 bp PCR product. The infected bovines showed marked anaemic tendency as revealed by a significant decrease in Hb, PCV, RBC, Lymphocytopenia and leukocytosis along with marked thrombocytopenia. There is a marked increase in BUN, creatinine and total bilirubin level while random blood sugar shows a decreased level.

Autophagy Activation Induces p62-Dependent Autophagic Degradation of Dengue Virus Capsid Protein During Infection.

In the past decade, dengue virus infection is one of the most prevalent and rapidly spreading arthropod-borne diseases worldwide with about 400 million infections every year. Although it has been reported that the dengue virus could take advantage of autophagy to promote its propagation, the association between selective autophagy and the dengue virus remains largely unclear. Here, we demonstrated that dengue virus capsid protein, the key viral protein for virus assembly, maturation, and replication, underwent autophagic degradation after autophagy activation. Autophagy cargo receptor p62 delivered ubiquitinated capsid protein to autophagosomes for degradation, which could be enhanced by Torin 1 treatments. Further study revealed that the association between p62 and viral capsid protein was dependent on the ubiquitin-binding domain of p62, and the poly-ubiquitin conjugated at lysine 76 of capsid protein served as a recognition signal for autophagy. Consistently, p62 deficiency in Huh7 cells led to the enhancement of dengue virus replication. Our study revealed that p62 targeted dengue virus capsid protein for autophagic degradation in a ubiquitin-dependent manner, which might uncover the potential roles of p62 in restricting dengue virus replication.

HIGH FLUORESCENCE LYMPHOCYTE COUNT AS AN EARLY PREDICTOR OF SEVERE THROMBOCYTOPENIA IN DENGUE INFECTION

Objective: Dengue infection (DI) is the most common arthropod-borne viral disease with symptoms ranging from mild flu like illness to fatal hemorrhagic fever. Thrombocytopenia is one of the common manifestations of dengue which can lead to life threatening bleeding. Currently, there is no validated test available that can predict the severity of thrombocytopenia in a dengue patient. Dengue has been well associated with presence of high fluorescence lymphocytes in the peripheral blood. High fluorescence lymphocyte count (HFLC) is a parameter generated at no extra cost when an automated complete blood count (CBC) is performed on Sysmex XN-1000 automated hematology analyzer. We aim to assess the significance and correlation of the HFLC with thrombocytopenia during the course of dengue infection especially during day 1 to 5 of the infection. Material and Methods: This is a cross sectional study and was conducted at Chughtai Institute of Pathology from August 2021 to October 2021. Total 312 patients, both males and females, who had NS1 positive confirmed dengue infection were included in the study. Their platelet count and HFLC were noted at the time of diagnosis using Sysmex XN-1000. Follow up CBC were analyzed for next 5 days to observe the severity of thrombocytopenia. Results: There is significant negative correlation between absolute HFLC and platelet count on day one to five of the infection. On receiver operator characteristic curve analysis, we found that HFLC < 0.5 x103/µL had 60% sensitivity and 71.8% specificity for severe thrombocytopenia (platelet count less than 50 x 103/µL on day 5 of the infection. Conclusion: HFLC is a negative predictive factor for severe thrombocytopenia and therefore can be used as an early predictor of disease progression. Key Words: Dengue infection, NS1 antigen, High fluorescence lymphocyte count, Thrombocytopenia, Automated hematology analyzer.

Fulminant Myocarditis: A Very Rare Manifestation of Dengue Fever

Dengue is a highly prevalent arthropod-borne viral disease in tropical and subtropical areas of the globe. The majority of dengue cases are benign but rare complications and presentations are seen increasingly due to the rising burden of the disease mainly in tropical countries. In dengue, clinical manifestations vary from asymptomatic infection to severe disease. Dengue fever is characterised by fever, myalgia, arthralgia, headache and bleeding manifestations. We report a rare case of dengue fever complicated with acute myocarditis. The patient recovered gradually with supportive care.

Ambivalent Roles of Oxidative Stress in Triangular Relationships among Arthropod Vectors, Pathogens and Hosts.

Blood-feeding arthropods, particularly ticks and mosquitoes are considered the most important vectors of arthropod-borne diseases affecting humans and animals. While feeding on blood meals, arthropods are exposed to high levels of reactive oxygen species (ROS) since heme and other blood components can induce oxidative stress. Different ROS have important roles in interactions among the pathogens, vectors, and hosts. ROS influence various metabolic processes of the arthropods and some have detrimental effects. In this review, we investigate the various roles of ROS in these arthropods, including their innate immunity and the homeostasis of their microbiomes, that is, how ROS are utilized to maintain the balance between the natural microbiota and potential pathogens. We elucidate the mechanism of how ROS are utilized to fight off invading pathogens and how the arthropod-borne pathogens use the arthropods’ antioxidant mechanism to defend against these ROS attacks and their possible impact on their vector potentials or their ability to acquire and transmit pathogens. In addition, we describe the possible roles of ROS in chemical insecticide/acaricide activity and/or in the development of resistance. Overall, this underscores the importance of the antioxidant system as a potential target for the control of arthropod and arthropod-borne pathogens.

Hantavirus Pulmonary Syndrome Coexistent with Dengue

Dengue is an arthropod-borne disease caused by viruses of Flaviviridae family. It poses a major public health burden in tropical and sub-tropical regions. Clinical features of dengue vary from a mild flu-like disease and rash, to a potentially lethal haemorrhagic fever or shock syndrome. Hantavirus pulmonary syndrome is a rodent-born disease emerging in the American continent and is caused by viruses of the Bunyaviridae family. Potential reservoirs of these agents were described in Brazilian Central Plateau. Dengue infection is transmitted by mosquitoes, while hantaviruses are acquired by contact or inhalation of aerosolised excreta of infected rodents. Dengue and hantavirus infections have also been considered as emerging public health problems in some Indian areas; moreover, other infections mixed with dengue have been documented. The case of a Brazilian patient with hantavirus pulmonary syndrome and serologic evidence of dengue infection is described.

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.
 HIGHLIGHTS
 
 Dengue is a mosquito-transmitted virus cause of arthropod-borne viral disease
 The discovery of peptides became a potential agent for dengue virus and previously peptide NRRRRSAGMI has been reported as starting linear heptapeptide RRRSAGM
 A computational alanine scanning based on the peptide RRRSAGM has been performed
 S1 and S2 pockets show strong preferences for basic amino acids, whereas the S3 pocket is less selective for basic residue
 The arginine at P1 and P2 positions of the heptapeptide substrate contribute significantly to the substrate binding affinity
 
 GRAPHICAL ABSTRACT

A Combination of Forward Chaining and Certainty Factor Methods for Early Detection of Fever : Dengue Hemorrhagic Fever, Malaria and Typhoid

Abstract. Purpose: Dengue Hemorrhagic and Malaria fevers are the most common arthropod-borne diseases caused by mosquito bites and they also have similar signs and symptoms. Based on the problems, the researcher makes an expert system that aims to help people early detect fever diseases. This system is expected to help and support the infectious disease prevention and control program by the Ministry of Health of the Republic of Indonesia.Methods: This study uses an expert system with a combination of Forward Chaining and Certainty Factor to detect the symptoms of fever. Forward Chaining is a technique that begins with gathering information related to known facts, then combining rules to produce conclusions. The certainty Factor method is used to define a measure of certainty against a fact or rule and to describe the level of expert confidence in dealing with problems. There are 32 symptoms of the disease consisting of dengue fever, malaria and typhoid, it was obtained based on the literature and interviews with internal medicine specialist with 20 case datasets.Result: Based on 20 test data, obtained one data that does not match the test results and the desired target so that the system accuracy obtained is 95%. In addition, the combination of Forward Chaining and Certainty factor has better accuracy when compared to expert systems in previous studies.Novelty: Forward Chaining to find three rules and assigning weights to the Certainty Factor that has been set by the expert makes the combination of the two methods produce better accuracy.

Chest Pain in a Patient with Dengue Fever Resembling Acute Myocardial Infarction: A Case Report

Dengue is an arthropod-borne viral disease. Dengue fever may present with dengue hemorrhagic fever/dengue shock syndrome. Now a days some atypical and rare manifestations are noticed involving liver, central nervous system and heart. Here we reported a case of dengue fever in 25 years young man having high level of cardiac biomarkers and ECG changes mimicking myocardial infarction initially but later on further evaluation of the case confirmed as acute myocarditis due to dengue fever. JAFMC Bangladesh. Vol 17, No 2 (December) 2021: 99-102

Variation in White Blood Cell Differential Fluorescence Scattergram: A Clue for Automated Malaria Diagnosis

Background: Malaria is an arthropod-borne disease caused by Plasmodium. Malaria is a significant public health challenge with about 3.3 billion human lives at risk in 97 countries with two hundred million estimated malaria cases and 600,000 fatalities. Timely diagnosis can prevent disease spread, loss of human lives, and its harmful impact on the economy therefore malaria diagnosis by automated hematology analyzer is of great value. Objective: To assess identification of scattergram abnormalities in malaria samples and to compare its performance with Microscopy, RDTs & PCR. Study Design: Descriptive and cross-sectional study Place and Duration of Study: Department of Pathology, Liaquat University of Medical & Health Sciences Jamshoro, 06 months from May 2020 to October 2020. Methodology: Eighty seven malaria suspected samples were included. CBC performed on Sysmex XN1000i followed by Microscopy of thin blood film, RDTs by using STANDARDTM Q Malaria P.f/Pan Ag Test, DNA extracted by QIAamp DNA mini kit, PCR performed by GenoAmp Real-time qPCR Malaria. Results: The median age of patients was 24+13.93 years. WDF Scattergram abnormalities were observed in 95.4 %of samples with sensitivity of 97.6% and specificity of 100% respectively. PPV was 100% and NPV was 99.8%. 96.4% of patients were malaria positive by microscopy. ICT was positive in 96.6% of samples while PCR confirmed plasmodium presence in 97.7% samples. Conclusion: Automated hematology analyzer provides high sensitivity and specificity for malaria diagnosis. The Sysmex XN-1000i can detect certain abnormalities in WDF scattergrams in malaria patients. As a result, the appearance of an abnormal WDF scattergram in a patient with a history of febrile illness, aids the pathologist in confirming a malaria diagnosis. Keywords: Malaria, Plasmodium Vivax, Plasmodium Falciparum, WDF scattergram, ICT, RT qPCR

Insight on Bluetongue virus transmission in small ruminants in Senegal

Bluetongue (BT) is an infectious, arthropod-borne viral disease of domestic and wild ruminants. The disease causes animal mortality, production decrease and commercial limits for herds. Despite the active circulation of the disease in the world, few studies have been carried out in Senegal. The objective of this study was to assess the current prevalence of BT in small ruminants and the serotypes circulating in Senegal. A cross-sectional study was conducted in the fourteen regions of Senegal. After the sampling campaign, sera collected in sheep and goats herds were screened for the presence of Bluetongue virus (BTV) specific antibodies using c-Elisa. The whole blood of seropositive animals was further analyzed by RT-qPCR and positive samples were typed to identify BTV serotypes. Analysis of several risk factors such as age, sex and species of animals was performed using logistic regression. The overall seroprevalence of BTV in Senegal was 72.6% (95% CI: 70.3–74.9%) with 75.9% (95% CI: 72.2–79.5%) in goat and 70.6% (95% CI: 67.5–73.6%) in sheep. Female (prevalence=77.1%) and adult (prevalence=80%) animals showed the highest seropositivity to BTV compared respectively to male (55.7%, p=6.133e-09) and young (49.4%, p < 2.2e-16). The RT-qPCR results showed the presence of BT viral genome in 359 small ruminants. The results obtained from serological and genotyping studies showed an active spread of the Bluetongue virus in domestic ruminants and phylogenetic analysis showed that the BTV-2 is one of the circulating serotypes in Senegal. This study allows having baseline information for controlling Bluetongue in Senegal.

Dengue Hemorrhagic Fever and Non Immune Hemolytic Anemia: Two Recherché in Alliance

Dengue is a prevalent arthropod-borne viral disease in tropical and subtropical areas of the globe. Dengue clinical manifestations include asymptomatic infections; undifferentiated fever; dengue fever, which is characterized by fever, headache, retro orbital pain, myalgia, and arthralgia; and a severe form of the disease denominated dengue hemorrhagic fever/dengue shock syndrome, characterized by hemoconcentration, thrombocytopenia, and bleeding tendency. However, atypical manifestations, such as liver, central nervous system, and cardiac involvement, have been increasingly reported called expanded dengue syndrome. We report a 42 years old lady with atypical and rare presentation of dengue disease marked by non immune hemolysis following the critical phase of infection. Condition improved after conservative treatment. Hematological complications in dengue are now increasingly observed with the most common case is cytopenias and bleeding. Non immune hemolytic anemia in dengue is self-limiting in almost all cases. The main mechanism of hemolysis is still unknown though both direct viral infection and immune mediated damage have been suggested to be the cause. To avoid otherwise preventable morbidity and mortality, physicians should have a high index of suspicion for hematological complications in patients with dengue illness and should manage this accordingly.

COVID-19: A Veterinary and One Health Perspective.

Interface with animals has been responsible for the occurrence of a major proportion of human diseases for the past several decades. Recent outbreaks of respiratory, haemorrhagic, encephalitic, arthropod-borne and other viral diseases have underlined the role of animals in the transmission of pathogens to humans. The on-going coronavirus disease-2019 (COVID-19) pandemic is one among them and is thought to have originated from bats and jumped to humans through an intermediate animal host. Indeed, the aetiology, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can infect and cause disease in cats, ferrets and minks, as well as be transmitted from one animal to another. The seriousness of the pandemic along with the zoonotic origin of the virus has been a red alert on the critical need for collaboration and cooperation among human and animal health professionals, as well as stakeholders from various other disciplines that study planetary health parameters and the well-being of the biosphere. It is therefore imminent that One Health principles are applied across the board for human infectious diseases so that we can be better prepared for future zoonotic disease outbreaks and pandemics.

A new record of Rickettsia japonica in ticks infesting a Burmese ferret-badger in Thailand.

Ticks are important vectors of arthropod-borne diseases and they can transmit a wide variety of zoonotic pathogens to humans, domestic and wild animals. Rickettsia japonica is a member of SFG rickettsiae causing Japanese spotted fever (JSF) and can transmit to humans via infected ticks. In this study, we report the first case of Rickettsia japonica in Haemaphysalis hystricis tick collected from a roadkill Burmese ferret-badger ( Melogale personata ) in Loei province, northeastern Thailand. According to the DNA sequences and phylogenetic analyses of the outer membrane protein A and B genes ( ompA and ompB), the detected R. japonica was identical to those found in JSF patients in Korea, Japan, and China, and closely related to Rickettsia detected by ompA in a tick from Thailand. Further study on the prevalence of R. japonica and diversity of mammalian reservoir hosts will be useful to gain a better understanding of JSF epidemiology.

Assessing Prevalence and Transmission Rates of Malaria through Simultaneous Profiling of Antibody Responses against Plasmodium and Anopheles Antigens.

Reliably assessing exposure to mosquitoes carrying malaria parasites continues to be a challenge due to the lack of reliable, highly sensitive diagnostics with high-throughput potential. Here, we describe an approach that meets these requirements by simultaneously measuring immune responses to both disease vector and pathogen, using an electro-chemiluminescence-based multiplex assay platform. While using the same logistical steps as a classic ELISA, this platform allows for the multiplexing of up to ten antigens in a single well. This simple, reproducible, quantitative readout reports the magnitude, incidence, and prevalence of malaria infections in residents of malaria-endemic areas. By reporting exposure to both insect vectors and pathogen, the approach also provides insights into the efficacy of drugs and/or other countermeasures deployed against insect vectors aimed at reducing or eliminating arthropod-borne diseases. The high throughput of the assay enables the quick and efficient screening of sera from individuals for exposure to Plasmodium even if they are taking drug prophylaxis. We applied this assay to samples collected from controlled malaria infection studies, as well as those collected in field studies in malaria-endemic regions in Uganda and Kenya. The assay was sensitive to vector exposure, malaria infection, and endemicity, demonstrating its potential for use in malaria serosurveillance.