Rationale:Transmitted to humans via the Aedes mosquito,Chikungunya virus(CHIKV)is associated with multi-system complications,sometimes collectively referred to as“atypical features.”However,a disorder of the nervous...Rationale:Transmitted to humans via the Aedes mosquito,Chikungunya virus(CHIKV)is associated with multi-system complications,sometimes collectively referred to as“atypical features.”However,a disorder of the nervous system appears to be the most common severe complication of CHIKV infection.Patient’s Concern:A seventy-five-year-old patient from India presented to the hospital with fever,chills,rigors,and multiple joint pains for which he was worked up.Diagnosis:CHIKV encephalitis.Interventions:The patient was treated initially on supportive therapy with antipyretics,intravenous fluids;however,during his hospital stay,the patient had altered sensorium during which he was managed in the intensive care unit;required mechanical ventilation.Outcomes:The patient sccumbed to his illness.Lessons:Treating clinicians should keep CHIKV disease in the differential diagnosis in cases of febrile exanthems associated with disabling arthritis,especially in a CHIKV-endemic country like India.展开更多
Chikungunya fever(CF)is caused by an arbovirus whose manifestations are extremely diverse,and it has evolved with significant severity in recent years.The clinical signs triggered by the Chikungunya virus are similar ...Chikungunya fever(CF)is caused by an arbovirus whose manifestations are extremely diverse,and it has evolved with significant severity in recent years.The clinical signs triggered by the Chikungunya virus are similar to those of other arboviruses.Generally,fever starts abruptly and reaches high levels,followed by severe polyarthralgia and myalgia,as well as an erythematous or petechial maculopapular rash,varying in severity and extent.Around 40%to 60%of affected individuals report persistent arthralgia,which can last from months to years.The symptoms of CF mainly represent the tissue tropism of the virus rather than the immunopathogenesis triggered by the host's immune system.The main mechanisms associated with arthralgia have been linked to an increase in T helper type 17 cells and a consequent increase in receptor activator of nuclear factor kappa-Βligand and bone resorption.This review suggests that persistent arthralgia results from the presence of viral antigens post-infection and the constant activation of signaling lymphocytic activation molecule family member 7 in synovial macrophages,leading to local infiltration of CD4+T cells,which sustains the inflammatory process in the joints through the secretion of pro-inflammatory cytokines.The term"long chikungunya"was used in this review to refer to persistent arthralgia since,due to its manifestation over long periods after the end of the viral infection,this clinical condition seems to be characterized more as a sequel than as a symptom,given that there is no active infection involved.展开更多
Mosquito-borne infections are of global health concern because of their rapid spread and upsurge,which creates a risk for coinfections.chikungunya virus(CHIKV),an arbovirus disease transmitted by Aedes aegypti or A.al...Mosquito-borne infections are of global health concern because of their rapid spread and upsurge,which creates a risk for coinfections.chikungunya virus(CHIKV),an arbovirus disease transmitted by Aedes aegypti or A.albopictus,and malaria,a parasitic disease transmitted by Anopheles gambiae,are prevalent in Nigeria and neighbouring countries,but their burden and possible coinfections are poorly understood.In this study,we investigated the antibody seropositivity and endemicity of chikungunya and Zika viruses(ZIKV)in three regions of Nigeria.A cross-sectional serosurvey was conducted on 871 participants.Samples were collected from outpatients by simple random sampling.Analyses of the samples were performed using recomLine Tropical Fever for the presence of antibody serological marker IgG immunoblot with CHIKV VLP(virus like particle),ZIKV NS1 and ZIKV Equad according to manufacturers’instructions and malaria RDT for malaria parasite.There was a significantly higher antibody seropositivity against CHIKV in the central region than in the northern and southern regions(69.5%,291/419),while ZIKV-seropositivity(22.4%,34/152)and CHIKV-ZIKV co-circulating antibody seropositivity(17.8%,27/152)were notably higher in the southern region than in the central and northern regions.This investigation revealed an unexpectedly high antibody seropositivity and concealed endemicity of CHIKV and ZIKV in three Nigerian regions.The seropositivity of detectable antibodies differed among the three geographical locations.展开更多
Rationale: Parsonage-Turner syndrome is a rare syndrome of unknown etiology, affecting mainly the lower motor neurons of the brachial plexus.Chikungunya fever is a mosquito-borne viral disease characterized by acute f...Rationale: Parsonage-Turner syndrome is a rare syndrome of unknown etiology, affecting mainly the lower motor neurons of the brachial plexus.Chikungunya fever is a mosquito-borne viral disease characterized by acute fever and polyarthritis/polyarthralgia.Patient concerns: A 54-year-old Brazilian male patient who presented with a 2-day history of fever(temperature 38.8 ℃), arthralgia, erythematous rash, diffuse osteomuscular pain and headache, which evolved into left shoulder pain associated with morning stiffness.Diagnosis: Parsonage-Turner syndrome and chikungunya fever.Interventions: Symptomatic treatment(a combination of short-acting dypirone(500 mg every 6 h) and slow-release opioids(tramadol 100 mg every 4 h) and physiotherapy/rehabilitation with improvement.Outcomes: The patient was improved and discharged, remaining with symptomatic treatment and physiotherapy/rehabilitation.Lessons: To the best of our knowledge, there were no reports of Parsonage-Turner syndrome following chikungunya virus infection.Awareness of the possibility of this rare association is important.The present case report highlights the importance of awareness of this association as a new cause of morbidity in patients with chikungunya virus infection.展开更多
Objective:To obtain Iuteolin and apigenin rich fraction from the ethanolic extract of Cynodon dactylon(L.)(C.dactylon) Pers and evaluate the fraction's cytotoxicity and anti-Chikungunya potential using Vero cells....Objective:To obtain Iuteolin and apigenin rich fraction from the ethanolic extract of Cynodon dactylon(L.)(C.dactylon) Pers and evaluate the fraction's cytotoxicity and anti-Chikungunya potential using Vero cells.Methods:The ethanolic extract of C.dactylon was subjected to silica gel column chromatography to obtain anti-chikungunya virus(CHIKV) fraction.Reverse phase-HPLC and GC-MS studies were carried out to identily the major phytochemicals in the fraction using phylochemical standards.Cytotoxicity and the potential of the fraction against CHIKV were evaluated in vitro using Vero cells.Reduction in viral replication was assessed by reverse transcriptase-polymerase chain reaction(RT-PCR) after treating the viral infected Vero cells with the fraction.Results:Reverse Phase-HPLC and GC-MS studies confirmed the presence of flavonoids,luteolin and apigenin as major phytochemicals in the anti-CHIKV ethanolic fraction of C.dactylon- The fraction was found to exhibit potent viral inhibitory activity(about 98%) at the concentration of 50 μg/mL as observed by reduction in cytopathic effect,and the cytotoxic concentration of the fraction was found to be 250 μg/mL.RT-PCR analyses indicated that the reduction in viral mRNA synthesis in fraction treated infected cells was much higher than the viral infected control cells.Conclusions:Luteolin and apigenin rich ethanolic fraction from C.dactylon can be utilized as a potential therapeutic agent against CHIKV infection as the fraction does not show cytotoxicity while inhibiting the virus.展开更多
Infectious diseases are indeed a lifelong threat to everyone irrespective of age, sex, lifestyle and socio-economic status. The infectious diseases have persisted among the prominent causes of death globally. Recently...Infectious diseases are indeed a lifelong threat to everyone irrespective of age, sex, lifestyle and socio-economic status. The infectious diseases have persisted among the prominent causes of death globally. Recently, re-emergence of Chikungunya viral infection harmed many in Asian and African countries. Chikungunya was considered as a major threat in developing and underdeveloped countries; the recent epidemiological outbreak of Chikungunya in La Reunion urges the global researchers to develop effective vaccine against this viral disease. In this review, Chikungunya, pathogenesis and epidemiology were briefly described.展开更多
Objective:To develop diagnostic test for detection chikungunya virus(CHIKV and Dengue virus (DENV) infection.Methods:We have performed a rapid,accurate laboratory confirmative method to simultaneously detect,quantify ...Objective:To develop diagnostic test for detection chikungunya virus(CHIKV and Dengue virus (DENV) infection.Methods:We have performed a rapid,accurate laboratory confirmative method to simultaneously detect,quantify and differentiate CHIKV and DENV infection by single-step multiplex real-time RT-PCR.Results:The assay’s sensitivity was 97.65%,specificity was 92.59% and accuracy was 95.82%when compared to conventional RT-PCR.Additionally,there was no cross-reaction between CHIKV,DENV,Japanese encephalitis virus,hepatitis C,hepatitis A or hepatitis E virus.Conclusions:This rapid and reliable assay provides a means for simultaneous early diagnosis of CHIKV and DENV in a single-step reaction.展开更多
Objective:To investigate the efficacy of ethanolic extract of nilavembu kudineer choornam (EENKC) in inflammation,pain and fever using animal models to support its actions.Methods: Acute toxicity study of EENKC was pe...Objective:To investigate the efficacy of ethanolic extract of nilavembu kudineer choornam (EENKC) in inflammation,pain and fever using animal models to support its actions.Methods: Acute toxicity study of EENKC was performed in mice to fix the effective dose.The antipyretic, anti-inflammatory and analgesic activity of EENKC was evaluated in brewer’s yeast induced pyrexia in rats,carrageenan-induced inflammation in rats and acetic-acid induced writhing in mice model.Results:Acute toxicity revealed that EENKC didn’t show death and toxic signs up to 2 000 mg/kg.In brewer’s yeast induced pyrexia and carrageenan-induced inflammation EENKC at the doses of 200 and 400 mg/kg inhibited fever and inflammation significantly(P【0.01 and【0.05) compared to control animals.In mice,the number of writhing induced by acetic-acid was significantly(P【0.01) reduced after treatment with both the dose of EENKC than control animals. EENKC 200 mg/kg inhibits inflammation higher level in carrageenan-induced paw edema,but there is no significant difference when compared to indomethacin 10 mg/kg.Conclusions:The present findings revealed that EENKC possesses antipyretic,anti-inflammatory and analgesic activity which supports nilavembu kudineer choornam efficacy in chikungunya fever.展开更多
Objective: To investigate the association between TLR3 and TLR7 polymorphisms with susceptibility and clinical manifestations of Chikungunya Fever.Methods: A total of 177 individuals were studied: 73 patients with a c...Objective: To investigate the association between TLR3 and TLR7 polymorphisms with susceptibility and clinical manifestations of Chikungunya Fever.Methods: A total of 177 individuals were studied: 73 patients with a confirmed diagnosis for Chikungunya virus and 104 non-infected individuals. Polymorphisms were determined by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism(PCR-RFLP).Results: Our analysis showed an increased CC genotype frequency of the TLR7 rs3853839 polymorphism in male patients compared to control(29% versus 2%,respectively; OR=20.69; 95% CI=2.55-167.36; P<0.001). Furthermore,arthritis(acute and chronic) was frequently found in CC male patients. On the contrary,65% of CG carriers were no-infected males(29% versus 65%,respectively; OR=0.23,95% CI=0.48-3.04; P=0.002). Finally,we observed a higher frequency of lymphopenia in CG male patients(CG=666.86±233.77,GG=1,314.27±752.29 cells/mm3,P=0.047). Conclusions: Our results suggest the TLR7 rs3853839 polymorphism is associated with lymphopenia and increased susceptibility to Chikungunya Fever in males.展开更多
A number of re-emerging and emerging infectious diseases including chikungunya, West Nile, yellow fever, Zika, dengue, Japanese encephalitis, and others have increased in recent years, which threaten the public health...A number of re-emerging and emerging infectious diseases including chikungunya, West Nile, yellow fever, Zika, dengue, Japanese encephalitis, and others have increased in recent years, which threaten the public health across the globe. Chikungunya is a neglected re-emerging arboviral infection caused by chikungunya virus. Arboviral infections such as chikungunya, Zika and dengue have similar epidemiology, transmission cycles and clinical symptoms, which makes it difficult to diagnose these three infections. Moreover, there is no commercial vaccine or licensed therapy available for chikungunya infection, thus causing severe burden worldwide. Vector control may reduce the disease risk; however, this remains a challenge due to many factors including, but not limited to, evolution of insecticide resistance in mosquitoes, gaps in vector control tools, urbanization, environmental and demographic changes. Effective integrated vector control strategies and surveillance measures along with affordable vaccine development or anti-viral therapy are essential to control the infection. In this review, we discuss the epidemiology of mosquito-borne infection chikungunya which has re-emerged as an international concern in recent decades.展开更多
Objective: To investigate the therapeutic efficacy of andrographolide, a plant derived compound, against chikungunya virus(CHIKV) infection. Methods: Using flow cytometry and immunoblotting assay, in vitro viral prote...Objective: To investigate the therapeutic efficacy of andrographolide, a plant derived compound, against chikungunya virus(CHIKV) infection. Methods: Using flow cytometry and immunoblotting assay, in vitro viral protein expression was studied in THP-1 cells line. In Balb/c mouse neonates, viral RNA copy number was determined by real time PCR. Results:The results showed reduced CHIKV protein expression on andrographolide treatment in CHIKV-infected human peripheral blood mononuclear cells, Vero cells and THP-I cell line.In vivo, andrographolide treatment to CHIKV-infected neonates reduced viral RNA copy number. Further. andrographolide also increased cytotoxic T lymphocytes both in vitro and in vivo. Andrographolide also activated host innate immune pathways, viz., protein kinase R.phosphorylated eukaryotic initiation factor 2 α, retinoic acid inducible gene-Ⅰ and interferon regulatory factor 3/7, thereby increasing IFN-a secretion. CHIKV-induced nuclear factor κlight chain enhancer of activated B cells and tumor necrosis factor-a was also reduced on andrographolide treatment. Conclusion: Andrographolide inhibits CHIKV by suppressing viral protein expression and up-regulating host innate immunity and hence could be an effective therapeutic agent against CHIKV infection.展开更多
In recent decades, the issue of emerging and reemerging infectious diseases, especially those related to viruses, has become an increasingly important area of concern in public health. It is of significance to anticip...In recent decades, the issue of emerging and reemerging infectious diseases, especially those related to viruses, has become an increasingly important area of concern in public health. It is of significance to anticipate future epidemics by accumulating knowledge through appropriate research and by monitoring their emergence using indicators from different sources. The objective is to alert and respond effectively in order to reduce the adverse impact on the general populations. Most of the emerging pathogens in humans originate from known zoonosis. These pathogens have been engaged in long-standing and highly successful interactions with their hosts since their origins are exquisitely adapted to host parasitism. They developed strategies aimed at:(1) maximizing invasion rate;(2) selecting host traits that can reduce their impact on host life span and fertility;(3) ensuring timely replication and survival both within host and between hosts; and(4) facilitating reliable transmission to progeny. In this context, Arboviruses(or ARthropod-BOrne viruses), will represent with certainty a threat for the coming century. The unprecedented epidemic of Chikungunya virus which occurred between 2005 and 2006 in the FrenchReunion Island in the Indian Ocean, followed by several outbreaks in other parts of the world, such as India and Southern Europe, has attracted the attention of medical and state authorities about the risks linked to this re-emerging mosquito-borne virus. This is an excellent model to illustrate the issues we are facing today and to improve how to respond tomorrow.展开更多
Objective: To investigate cytokine profile in patients with chikungunya virus (CHIKV) infection. Methods: Twenty eight pairs of serum samples collected from CHIKV infected patients during the outbreak of chikungunya f...Objective: To investigate cytokine profile in patients with chikungunya virus (CHIKV) infection. Methods: Twenty eight pairs of serum samples collected from CHIKV infected patients during the outbreak of chikungunya fever in South Thailand in 2008 were obtained. A multiple cytokine assay for detection of 17 cytokines was performed. Results: In the acute stage of CHIKV infection, the patients had significantly higher levels of interleukin-6, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein 1 and tumor necrosis factor alpha than the control ( P<0.001, P=0.023, P=0.015, P <0.001 and P=0.024, respectively). When the disease developed to the recovery stage, the patients had significantly lower levels of interleukin-6, granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein 1 and macrophage inflammatory protein beta than in the acute stage ( P<0.001). Conclusions: This study provides additional information that these cytokines could play roles in pathogenesis of CHIKV infection and could be used as disease biomarkers or drug targets.展开更多
Objective:The study involved survey and screening of areas suspected of chikungunya virus (CHIKV) infection,characterizing the causative agent and identifying the circulating CHIKV genotype.Methods:Acute phase samples...Objective:The study involved survey and screening of areas suspected of chikungunya virus (CHIKV) infection,characterizing the causative agent and identifying the circulating CHIKV genotype.Methods:Acute phase samples were screened by the use of RTPCR using primer set DVRChk-F/DVRChk-R whereas convalescent samples were tested by CHIKV IgM strips. Results:Two hundred and seventy five acute phase samples were screened by RT-PCR.of which 149(54.18%) showed positivity for CHIKV.Later on 192 convalescent phase samples were tested for CHIKV specific antibodies in which 125(65.10%) samples were found to be positive.Four CHIKV strains were selected and subjected to cloning followed by nucleotide sequencing and were submitted to the Genbank DMA database with the Accession numbers(GQ119362,GQ119363, GQl 19364,and FJ225403).The Sequence analysis of "CHIK-Kadapa" strain(GQ119362) with other CHIKV isolates suggested that the present CHIKV strain has(99.23±0.52)%and 100%identity with Central East South African isolates(CESA) at nucleotide and amino acid levels respectively.Two unique non synonymous mutations S168L and D183V were depicted in El gene of the selected strains of the present study.Conclusions:The 14 months survey revealed the circulation of CHIKV in 2008-2009 in Andhra Pradesh and the causative agent is identified to be of Central East South African(CESA) origin.The importance of the non synonymous mutations(S168L and D183V) and their role in the mobility and strength of the El-El and E1-E2 interactions needs further investigations.The study also urges the need for intensifying the epidemiological and entomological surveillance to combat any such CHIKV outbreak in the near future.展开更多
Objective:To understand the epidemiology of the East,Central and South African(ECSA) genotype of Chikungunya virus(CHIKV) in terms of emerging and re-emerging infections,this study has been aimed at investigating the ...Objective:To understand the epidemiology of the East,Central and South African(ECSA) genotype of Chikungunya virus(CHIKV) in terms of emerging and re-emerging infections,this study has been aimed at investigating the evolutionary parameters,genomic signatures and molecular tracking of the CHIKV ECSA genotype in South-east Asia and coastal areas of the Indian Ocean between 2006 and 2009 by using phylogenetie analysis and the Bayesian Markov Chain Monte Carlo(BMCMC) evolutionary estimation.Methods:Nearly complete genome sequences of 53 CHIKV isolates from all genotypes were subjected to phylogenetie analysis and evolutionary parameter estimation.The amino acids of 67 of ECSA genotype during 2006 to 2009 were compared for finding molecular signature tracking.The ECSA genotype signatures were visualized to find the possible transmission root was projected onto a geographic map.Results: Phylogenetie analysis showed the ECSA genotype was divided into 2 groups.The first group comprises viruses from India and Southeast Asian countries.The second group consists of strains typically circulating in Sri Lanka in 2008.The evolutionary parameters of these groups depicted the time of the most recent common ancestor at approximately 7.5 years ago.The genomic signatures revealed the positions of amino acid variation in each group.Conclusions:The molecular evolution projected onto a geographical map showed the routes of CHIKV transmission from 2006 to 2009.Molecular tracking will assist in understanding transmission routes, epidemiology and molecular evolution of CHIKV.展开更多
Objective:To identify the chikungunya outbreaks in both indoor and outdoor patients in some selected hospitals in our locality and the burden and magnitude of the disease,to compare different system of medicines(allop...Objective:To identify the chikungunya outbreaks in both indoor and outdoor patients in some selected hospitals in our locality and the burden and magnitude of the disease,to compare different system of medicines(allopathic,Ayurvedic,homeopathy etc) and to explore the knowledge,attitude and practices of pharmacists and other health care professionals in the treatment of chikungunya.Methods:A six-month study was carried out.Detailed history was taken from the case history,personal interview of doctors and suspected cases.Personal data such as name age,sex,location,date of onset of illness,medical history,general/systemic examination features,drugs used(allopathy,Ayurveda,homeopathy,or traditional) for the treatment,etc.were noted down.A simple questionnaire was prepared and distributed to various doctors practicing various systems of medicines.Results:A total of 209 suspected cases were identified from July to December,2009.People in the age group of 20-40 years were more affected.The study revealed that females were more affected than males.The Grade-Ⅲ(58.73%) population was more prone to chikungunya than Grade-Ⅱ(38.75%) and Grade-Ⅰ(2.87%).It showed that fever,pain in muscles, and sleeping disturbances were the intense symptoms of chikungunya.Myocarditis and arthritis were concomitant diseases which worsened chikungunya symptoms.It also indicated the effective medicine for compliance is nonsteroidal antiinflammatory drugs(NSAIDS).Conclusions:From our study we found that in some places there is no proper documentation,even though there are proper guidelines framed by the relevant authorities.It can be concluded from the study that all the systems of medicine are equally important for the management of chikungunya.Additional effort in promoting the guidelines at local level and proper documentation helps to achieve the goal of curbing the chikungunya.It is high time to increase our effort and promote these messages at grassroot level which benefits the society/ community as a whole.展开更多
Objective: To detect the prevalence pattern of Chikungunya virus in three states of Northeast India. Methods: A total of 1 510 samples were collected from different private and government hospitals of Assam, Arunachal...Objective: To detect the prevalence pattern of Chikungunya virus in three states of Northeast India. Methods: A total of 1 510 samples were collected from different private and government hospitals of Assam, Arunachal Pradesh and Meghalaya. Serum was tested for the presence of IgM antibodies against Chikungunya virus followed by RT-PCR for amplification of Chikungunya E1 gene region using specific primers. Results: Overall, 11.83%(172/1 454) clinical samples were positive by MAC-ELISA and/or RT-PCR assay. Asymptomatic infection was seen in 17.86%. Males were more affected than females and age group 16-30 years was mostly affected. Fever(100.00%) was the primary symptom followed by headache(72.03%) and arthralgia(41.53%). Only 118 Chikungunya positive cases could be traced, of which 25.42% complained about sequelae of infection. In entomological investigation, Aedes aegypti was more predominant(92.10%) than Aedes albopictus(7.90%). No mosquito pools could be incriminated for Chikungunya virus. Conclusions: In this study, Chikungunya was observed to be prevalent in Assam, Arunachal Pradesh and Meghalaya. Though Chikungunya is a selflimiting infection, increasing morbidity by CHIKV infection is affecting social and economic status of individual. Thus, a community empowerment to effectively control mosquito population by employing different mosquito control measures along with personal protection is mandatory to tackle future outbreak of the disease.展开更多
Objective:To establish a surveillance in Dong Thap,at the border with Cambodia by assessing the presence of DHNV serotypes and CHIKV among patients hospitalized at Dong Thap general hospital.Methods:Cross-sectional de...Objective:To establish a surveillance in Dong Thap,at the border with Cambodia by assessing the presence of DHNV serotypes and CHIKV among patients hospitalized at Dong Thap general hospital.Methods:Cross-sectional descriptive analysis was conducted on a cohort of 131 patients hospitalized with acute fever and symptoms compatible with dengue or chikungunya.The study was conducted from January 2012 to February 2013.The full clinical picture was established as well as serological and molecular detection.Serological analysis was sequentially performed on blood samples collected on admission and an average of seven days after admission.The detection of IgM antibody to DENV was performed by IgM capture ELTSA and the detection of DENV and CHIKV RNA was done by reverse-transcription multiplex PCR.Results:101 patients out of 131(77%) were confirmed with dengue.All four dengue serotypes were detected with a predominance of DENV2 and DENV4.No chikungunya infection was detected although reported in neighboring Cambodia.A differential efficiency of serological dengue detection was observed.Efficiency was 29%upon admission and 53%after seven days on the same patients.30 patients out of 131(23%) were negative with both DENV and CHIKV.Conclusions:Dengue is at risk of being underestimated and chikungunya is not systematically detected.Changes in detection and surveillance procedures are therefore discussed to increase efficiency of dengue detection and continue the monitoring the emergence of CHIKV in Dong Thap province and in Vietnam.展开更多
Chikungunya fever(CHIKF)is an arboviral disease that typically consists of an acute illness with fever,skin rash,and incapacitating arthralgia.The causative agent of CHIKF is Chikungunya virus(CHIKV),an alphavirus tha...Chikungunya fever(CHIKF)is an arboviral disease that typically consists of an acute illness with fever,skin rash,and incapacitating arthralgia.The causative agent of CHIKF is Chikungunya virus(CHIKV),an alphavirus that is transmitted by the Aedes mosquitoes.Despite the re-emergence of CHIKV as an epidemic threat,there is no approved effective anti-viral treatment currently available for CHIKV.In our preliminary studies,selected small molecule inhibitors of arboviruses related to CHIKV were investigated and this led us to identify compounds with thieno[3,2-b]pyrrole scaffold as hits.Building on the discovery of our best hit compounds,5-carboxylic acid thieno[3,2-b]pyrrole 1 and 5-carboxamide thieno[3,2-b]pyrrole 2,the main aim of this study is to optimize their anti-viral activities by synthesizing analogs of thieno[3,2-b]pyrroles 1 and 2 and examine their activities against CHIKV.In these two parallel optimization studies,we synthesized two series of thieno[3,2-b]pyrroles,namely the 5-carboxylic acids and 5-carboxamides that possessed a variety of substituents at N4,C2,C6 or C5positions of the thieno[3,2-b]pyrrole scaffold.These compounds were then examined for their cytotoxicity effects and anti-viral activities using a luminescence-labelled CHIKV infectious clone.The most potent compound in our studies was found in the 5-carboxamide series.The synthesis,biological activity and structure-activity relationship(SAR)will be presented and discussed in detail.展开更多
Objective:To describe the prognostic and clinical profile of hospitalized patients with chikungunya virus(CHIKV)infection focusing on renal outcomes.Methods:This is a cross-sectional study including all patients with ...Objective:To describe the prognostic and clinical profile of hospitalized patients with chikungunya virus(CHIKV)infection focusing on renal outcomes.Methods:This is a cross-sectional study including all patients with confirmed chikungunya fever(CHIKF)admitted to 3 different highcomplexity hospitals in Fortaleza,Brazil between January 2016 and June 2017.Data analysis was carried out to evaluate correlation between clinical profile and outcomes.Results:Fifty-five patients were included,with a median age of 77(IQR=21)years,and 23(41.82%)were male.Twenty-five patients(45.45%,25/55)developed acute kidney injury(AKI),and 15(60.00%,15/25)were classified as KDIGO 1,1(4.00%)as KDIGO 2,and 9(36.00%)as KDIGO 3.The overall mortality was 34.54%whilst AKI-related mortality was 64.00%(16/25).Both AKI and encephalitis were associated with higher mortality.Patients who died were significantly older[82(IQR=12)years vs.70(IQR=28.75)years,P<0.001].In the multivariate analysis,abdominal pain was associated with an increased risk of severe AKI(OR=5.33,95%CI=1.11–25.64,P=0.037)and AKI was an independent risk factor of death(OR=12.06,95%CI=2.55–57.15,P=0.002).Recovery of renal function was similar among the different age groups.Conclusions:AKI is present in half of the study population and is an independent risk factor of death.Thus,renal function should be carefully monitored in hospitalized patients with CHIKV infection.展开更多
文摘Rationale:Transmitted to humans via the Aedes mosquito,Chikungunya virus(CHIKV)is associated with multi-system complications,sometimes collectively referred to as“atypical features.”However,a disorder of the nervous system appears to be the most common severe complication of CHIKV infection.Patient’s Concern:A seventy-five-year-old patient from India presented to the hospital with fever,chills,rigors,and multiple joint pains for which he was worked up.Diagnosis:CHIKV encephalitis.Interventions:The patient was treated initially on supportive therapy with antipyretics,intravenous fluids;however,during his hospital stay,the patient had altered sensorium during which he was managed in the intensive care unit;required mechanical ventilation.Outcomes:The patient sccumbed to his illness.Lessons:Treating clinicians should keep CHIKV disease in the differential diagnosis in cases of febrile exanthems associated with disabling arthritis,especially in a CHIKV-endemic country like India.
文摘Chikungunya fever(CF)is caused by an arbovirus whose manifestations are extremely diverse,and it has evolved with significant severity in recent years.The clinical signs triggered by the Chikungunya virus are similar to those of other arboviruses.Generally,fever starts abruptly and reaches high levels,followed by severe polyarthralgia and myalgia,as well as an erythematous or petechial maculopapular rash,varying in severity and extent.Around 40%to 60%of affected individuals report persistent arthralgia,which can last from months to years.The symptoms of CF mainly represent the tissue tropism of the virus rather than the immunopathogenesis triggered by the host's immune system.The main mechanisms associated with arthralgia have been linked to an increase in T helper type 17 cells and a consequent increase in receptor activator of nuclear factor kappa-Βligand and bone resorption.This review suggests that persistent arthralgia results from the presence of viral antigens post-infection and the constant activation of signaling lymphocytic activation molecule family member 7 in synovial macrophages,leading to local infiltration of CD4+T cells,which sustains the inflammatory process in the joints through the secretion of pro-inflammatory cytokines.The term"long chikungunya"was used in this review to refer to persistent arthralgia since,due to its manifestation over long periods after the end of the viral infection,this clinical condition seems to be characterized more as a sequel than as a symptom,given that there is no active infection involved.
文摘Mosquito-borne infections are of global health concern because of their rapid spread and upsurge,which creates a risk for coinfections.chikungunya virus(CHIKV),an arbovirus disease transmitted by Aedes aegypti or A.albopictus,and malaria,a parasitic disease transmitted by Anopheles gambiae,are prevalent in Nigeria and neighbouring countries,but their burden and possible coinfections are poorly understood.In this study,we investigated the antibody seropositivity and endemicity of chikungunya and Zika viruses(ZIKV)in three regions of Nigeria.A cross-sectional serosurvey was conducted on 871 participants.Samples were collected from outpatients by simple random sampling.Analyses of the samples were performed using recomLine Tropical Fever for the presence of antibody serological marker IgG immunoblot with CHIKV VLP(virus like particle),ZIKV NS1 and ZIKV Equad according to manufacturers’instructions and malaria RDT for malaria parasite.There was a significantly higher antibody seropositivity against CHIKV in the central region than in the northern and southern regions(69.5%,291/419),while ZIKV-seropositivity(22.4%,34/152)and CHIKV-ZIKV co-circulating antibody seropositivity(17.8%,27/152)were notably higher in the southern region than in the central and northern regions.This investigation revealed an unexpectedly high antibody seropositivity and concealed endemicity of CHIKV and ZIKV in three Nigerian regions.The seropositivity of detectable antibodies differed among the three geographical locations.
文摘Rationale: Parsonage-Turner syndrome is a rare syndrome of unknown etiology, affecting mainly the lower motor neurons of the brachial plexus.Chikungunya fever is a mosquito-borne viral disease characterized by acute fever and polyarthritis/polyarthralgia.Patient concerns: A 54-year-old Brazilian male patient who presented with a 2-day history of fever(temperature 38.8 ℃), arthralgia, erythematous rash, diffuse osteomuscular pain and headache, which evolved into left shoulder pain associated with morning stiffness.Diagnosis: Parsonage-Turner syndrome and chikungunya fever.Interventions: Symptomatic treatment(a combination of short-acting dypirone(500 mg every 6 h) and slow-release opioids(tramadol 100 mg every 4 h) and physiotherapy/rehabilitation with improvement.Outcomes: The patient was improved and discharged, remaining with symptomatic treatment and physiotherapy/rehabilitation.Lessons: To the best of our knowledge, there were no reports of Parsonage-Turner syndrome following chikungunya virus infection.Awareness of the possibility of this rare association is important.The present case report highlights the importance of awareness of this association as a new cause of morbidity in patients with chikungunya virus infection.
文摘Objective:To obtain Iuteolin and apigenin rich fraction from the ethanolic extract of Cynodon dactylon(L.)(C.dactylon) Pers and evaluate the fraction's cytotoxicity and anti-Chikungunya potential using Vero cells.Methods:The ethanolic extract of C.dactylon was subjected to silica gel column chromatography to obtain anti-chikungunya virus(CHIKV) fraction.Reverse phase-HPLC and GC-MS studies were carried out to identily the major phytochemicals in the fraction using phylochemical standards.Cytotoxicity and the potential of the fraction against CHIKV were evaluated in vitro using Vero cells.Reduction in viral replication was assessed by reverse transcriptase-polymerase chain reaction(RT-PCR) after treating the viral infected Vero cells with the fraction.Results:Reverse Phase-HPLC and GC-MS studies confirmed the presence of flavonoids,luteolin and apigenin as major phytochemicals in the anti-CHIKV ethanolic fraction of C.dactylon- The fraction was found to exhibit potent viral inhibitory activity(about 98%) at the concentration of 50 μg/mL as observed by reduction in cytopathic effect,and the cytotoxic concentration of the fraction was found to be 250 μg/mL.RT-PCR analyses indicated that the reduction in viral mRNA synthesis in fraction treated infected cells was much higher than the viral infected control cells.Conclusions:Luteolin and apigenin rich ethanolic fraction from C.dactylon can be utilized as a potential therapeutic agent against CHIKV infection as the fraction does not show cytotoxicity while inhibiting the virus.
基金The Department of Biotechnology,Bharathiar University,Coimbatore,Tamil Nadu,India for supporting this research through DST-FIST (SR/FST/LST-299/2006 Dt:31-01-2007)UGC-SAP (F.No.3-9/2007 (SAP-II) February 2007)
文摘Infectious diseases are indeed a lifelong threat to everyone irrespective of age, sex, lifestyle and socio-economic status. The infectious diseases have persisted among the prominent causes of death globally. Recently, re-emergence of Chikungunya viral infection harmed many in Asian and African countries. Chikungunya was considered as a major threat in developing and underdeveloped countries; the recent epidemiological outbreak of Chikungunya in La Reunion urges the global researchers to develop effective vaccine against this viral disease. In this review, Chikungunya, pathogenesis and epidemiology were briefly described.
基金supported by the Center of Excellence in Clinical Virology.Chulalongkorn University,CU Centenary Academic Development ProjectKing Chulalongkorn Memorial Hospital,the National Research University Project of CHEthe Ratchadaphiseksonphot Endowment Fund(HR1155A)
文摘Objective:To develop diagnostic test for detection chikungunya virus(CHIKV and Dengue virus (DENV) infection.Methods:We have performed a rapid,accurate laboratory confirmative method to simultaneously detect,quantify and differentiate CHIKV and DENV infection by single-step multiplex real-time RT-PCR.Results:The assay’s sensitivity was 97.65%,specificity was 92.59% and accuracy was 95.82%when compared to conventional RT-PCR.Additionally,there was no cross-reaction between CHIKV,DENV,Japanese encephalitis virus,hepatitis C,hepatitis A or hepatitis E virus.Conclusions:This rapid and reliable assay provides a means for simultaneous early diagnosis of CHIKV and DENV in a single-step reaction.
文摘Objective:To investigate the efficacy of ethanolic extract of nilavembu kudineer choornam (EENKC) in inflammation,pain and fever using animal models to support its actions.Methods: Acute toxicity study of EENKC was performed in mice to fix the effective dose.The antipyretic, anti-inflammatory and analgesic activity of EENKC was evaluated in brewer’s yeast induced pyrexia in rats,carrageenan-induced inflammation in rats and acetic-acid induced writhing in mice model.Results:Acute toxicity revealed that EENKC didn’t show death and toxic signs up to 2 000 mg/kg.In brewer’s yeast induced pyrexia and carrageenan-induced inflammation EENKC at the doses of 200 and 400 mg/kg inhibited fever and inflammation significantly(P【0.01 and【0.05) compared to control animals.In mice,the number of writhing induced by acetic-acid was significantly(P【0.01) reduced after treatment with both the dose of EENKC than control animals. EENKC 200 mg/kg inhibits inflammation higher level in carrageenan-induced paw edema,but there is no significant difference when compared to indomethacin 10 mg/kg.Conclusions:The present findings revealed that EENKC possesses antipyretic,anti-inflammatory and analgesic activity which supports nilavembu kudineer choornam efficacy in chikungunya fever.
文摘Objective: To investigate the association between TLR3 and TLR7 polymorphisms with susceptibility and clinical manifestations of Chikungunya Fever.Methods: A total of 177 individuals were studied: 73 patients with a confirmed diagnosis for Chikungunya virus and 104 non-infected individuals. Polymorphisms were determined by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism(PCR-RFLP).Results: Our analysis showed an increased CC genotype frequency of the TLR7 rs3853839 polymorphism in male patients compared to control(29% versus 2%,respectively; OR=20.69; 95% CI=2.55-167.36; P<0.001). Furthermore,arthritis(acute and chronic) was frequently found in CC male patients. On the contrary,65% of CG carriers were no-infected males(29% versus 65%,respectively; OR=0.23,95% CI=0.48-3.04; P=0.002). Finally,we observed a higher frequency of lymphopenia in CG male patients(CG=666.86±233.77,GG=1,314.27±752.29 cells/mm3,P=0.047). Conclusions: Our results suggest the TLR7 rs3853839 polymorphism is associated with lymphopenia and increased susceptibility to Chikungunya Fever in males.
基金supported by the Department of Biotechnology,Bharathiar University,Coimbatore,Tamil Nadu,India through DST-FIST,UGC-SAP and UKIERI
文摘A number of re-emerging and emerging infectious diseases including chikungunya, West Nile, yellow fever, Zika, dengue, Japanese encephalitis, and others have increased in recent years, which threaten the public health across the globe. Chikungunya is a neglected re-emerging arboviral infection caused by chikungunya virus. Arboviral infections such as chikungunya, Zika and dengue have similar epidemiology, transmission cycles and clinical symptoms, which makes it difficult to diagnose these three infections. Moreover, there is no commercial vaccine or licensed therapy available for chikungunya infection, thus causing severe burden worldwide. Vector control may reduce the disease risk; however, this remains a challenge due to many factors including, but not limited to, evolution of insecticide resistance in mosquitoes, gaps in vector control tools, urbanization, environmental and demographic changes. Effective integrated vector control strategies and surveillance measures along with affordable vaccine development or anti-viral therapy are essential to control the infection. In this review, we discuss the epidemiology of mosquito-borne infection chikungunya which has re-emerged as an international concern in recent decades.
基金Defence Research & Development Organmzation (DRDO)is gratefully acknowledged for the financial support in the form NBC subproject
文摘Objective: To investigate the therapeutic efficacy of andrographolide, a plant derived compound, against chikungunya virus(CHIKV) infection. Methods: Using flow cytometry and immunoblotting assay, in vitro viral protein expression was studied in THP-1 cells line. In Balb/c mouse neonates, viral RNA copy number was determined by real time PCR. Results:The results showed reduced CHIKV protein expression on andrographolide treatment in CHIKV-infected human peripheral blood mononuclear cells, Vero cells and THP-I cell line.In vivo, andrographolide treatment to CHIKV-infected neonates reduced viral RNA copy number. Further. andrographolide also increased cytotoxic T lymphocytes both in vitro and in vivo. Andrographolide also activated host innate immune pathways, viz., protein kinase R.phosphorylated eukaryotic initiation factor 2 α, retinoic acid inducible gene-Ⅰ and interferon regulatory factor 3/7, thereby increasing IFN-a secretion. CHIKV-induced nuclear factor κlight chain enhancer of activated B cells and tumor necrosis factor-a was also reduced on andrographolide treatment. Conclusion: Andrographolide inhibits CHIKV by suppressing viral protein expression and up-regulating host innate immunity and hence could be an effective therapeutic agent against CHIKV infection.
基金Institutional funds from the Centre National de la Recherche Scientifique
文摘In recent decades, the issue of emerging and reemerging infectious diseases, especially those related to viruses, has become an increasingly important area of concern in public health. It is of significance to anticipate future epidemics by accumulating knowledge through appropriate research and by monitoring their emergence using indicators from different sources. The objective is to alert and respond effectively in order to reduce the adverse impact on the general populations. Most of the emerging pathogens in humans originate from known zoonosis. These pathogens have been engaged in long-standing and highly successful interactions with their hosts since their origins are exquisitely adapted to host parasitism. They developed strategies aimed at:(1) maximizing invasion rate;(2) selecting host traits that can reduce their impact on host life span and fertility;(3) ensuring timely replication and survival both within host and between hosts; and(4) facilitating reliable transmission to progeny. In this context, Arboviruses(or ARthropod-BOrne viruses), will represent with certainty a threat for the coming century. The unprecedented epidemic of Chikungunya virus which occurred between 2005 and 2006 in the FrenchReunion Island in the Indian Ocean, followed by several outbreaks in other parts of the world, such as India and Southern Europe, has attracted the attention of medical and state authorities about the risks linked to this re-emerging mosquito-borne virus. This is an excellent model to illustrate the issues we are facing today and to improve how to respond tomorrow.
基金supported by the Higher Education Research Promotion and National Research University Project of Thailand, Office of the Higher Education Commission (HR1155A)Thailand Research Fund (DPG5480002)the Commission on Higher Education, Ministry of Education, and the Center of Excellence in Clinical Virology, Chulalongkorn University, Centenary Academic Development Project
文摘Objective: To investigate cytokine profile in patients with chikungunya virus (CHIKV) infection. Methods: Twenty eight pairs of serum samples collected from CHIKV infected patients during the outbreak of chikungunya fever in South Thailand in 2008 were obtained. A multiple cytokine assay for detection of 17 cytokines was performed. Results: In the acute stage of CHIKV infection, the patients had significantly higher levels of interleukin-6, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein 1 and tumor necrosis factor alpha than the control ( P<0.001, P=0.023, P=0.015, P <0.001 and P=0.024, respectively). When the disease developed to the recovery stage, the patients had significantly lower levels of interleukin-6, granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein 1 and macrophage inflammatory protein beta than in the acute stage ( P<0.001). Conclusions: This study provides additional information that these cytokines could play roles in pathogenesis of CHIKV infection and could be used as disease biomarkers or drug targets.
基金University Grants Commission,New Delhi for financial assistance in the form of UGC-JRF in Research Fellowship in Sciences for Meritorious Students Scheme(RFSMS) and Standard Diagnostics,Korea for providing anti CHIKV IgM kits
文摘Objective:The study involved survey and screening of areas suspected of chikungunya virus (CHIKV) infection,characterizing the causative agent and identifying the circulating CHIKV genotype.Methods:Acute phase samples were screened by the use of RTPCR using primer set DVRChk-F/DVRChk-R whereas convalescent samples were tested by CHIKV IgM strips. Results:Two hundred and seventy five acute phase samples were screened by RT-PCR.of which 149(54.18%) showed positivity for CHIKV.Later on 192 convalescent phase samples were tested for CHIKV specific antibodies in which 125(65.10%) samples were found to be positive.Four CHIKV strains were selected and subjected to cloning followed by nucleotide sequencing and were submitted to the Genbank DMA database with the Accession numbers(GQ119362,GQ119363, GQl 19364,and FJ225403).The Sequence analysis of "CHIK-Kadapa" strain(GQ119362) with other CHIKV isolates suggested that the present CHIKV strain has(99.23±0.52)%and 100%identity with Central East South African isolates(CESA) at nucleotide and amino acid levels respectively.Two unique non synonymous mutations S168L and D183V were depicted in El gene of the selected strains of the present study.Conclusions:The 14 months survey revealed the circulation of CHIKV in 2008-2009 in Andhra Pradesh and the causative agent is identified to be of Central East South African(CESA) origin.The importance of the non synonymous mutations(S168L and D183V) and their role in the mobility and strength of the El-El and E1-E2 interactions needs further investigations.The study also urges the need for intensifying the epidemiological and entomological surveillance to combat any such CHIKV outbreak in the near future.
基金supported by the Commission on Higher Education,Ministry of Education,The Center of Excellence Research FundCU Centenary Academic Development Project+1 种基金Chulalongkorn University,King Chulalongkorn Memorial Hospital,MK Restaurant Company Limited and the National Research University Project of CHEthe Ratchadaphiseksomphot Endowment Fund(HR1155A)
文摘Objective:To understand the epidemiology of the East,Central and South African(ECSA) genotype of Chikungunya virus(CHIKV) in terms of emerging and re-emerging infections,this study has been aimed at investigating the evolutionary parameters,genomic signatures and molecular tracking of the CHIKV ECSA genotype in South-east Asia and coastal areas of the Indian Ocean between 2006 and 2009 by using phylogenetie analysis and the Bayesian Markov Chain Monte Carlo(BMCMC) evolutionary estimation.Methods:Nearly complete genome sequences of 53 CHIKV isolates from all genotypes were subjected to phylogenetie analysis and evolutionary parameter estimation.The amino acids of 67 of ECSA genotype during 2006 to 2009 were compared for finding molecular signature tracking.The ECSA genotype signatures were visualized to find the possible transmission root was projected onto a geographic map.Results: Phylogenetie analysis showed the ECSA genotype was divided into 2 groups.The first group comprises viruses from India and Southeast Asian countries.The second group consists of strains typically circulating in Sri Lanka in 2008.The evolutionary parameters of these groups depicted the time of the most recent common ancestor at approximately 7.5 years ago.The genomic signatures revealed the positions of amino acid variation in each group.Conclusions:The molecular evolution projected onto a geographical map showed the routes of CHIKV transmission from 2006 to 2009.Molecular tracking will assist in understanding transmission routes, epidemiology and molecular evolution of CHIKV.
文摘Objective:To identify the chikungunya outbreaks in both indoor and outdoor patients in some selected hospitals in our locality and the burden and magnitude of the disease,to compare different system of medicines(allopathic,Ayurvedic,homeopathy etc) and to explore the knowledge,attitude and practices of pharmacists and other health care professionals in the treatment of chikungunya.Methods:A six-month study was carried out.Detailed history was taken from the case history,personal interview of doctors and suspected cases.Personal data such as name age,sex,location,date of onset of illness,medical history,general/systemic examination features,drugs used(allopathy,Ayurveda,homeopathy,or traditional) for the treatment,etc.were noted down.A simple questionnaire was prepared and distributed to various doctors practicing various systems of medicines.Results:A total of 209 suspected cases were identified from July to December,2009.People in the age group of 20-40 years were more affected.The study revealed that females were more affected than males.The Grade-Ⅲ(58.73%) population was more prone to chikungunya than Grade-Ⅱ(38.75%) and Grade-Ⅰ(2.87%).It showed that fever,pain in muscles, and sleeping disturbances were the intense symptoms of chikungunya.Myocarditis and arthritis were concomitant diseases which worsened chikungunya symptoms.It also indicated the effective medicine for compliance is nonsteroidal antiinflammatory drugs(NSAIDS).Conclusions:From our study we found that in some places there is no proper documentation,even though there are proper guidelines framed by the relevant authorities.It can be concluded from the study that all the systems of medicine are equally important for the management of chikungunya.Additional effort in promoting the guidelines at local level and proper documentation helps to achieve the goal of curbing the chikungunya.It is high time to increase our effort and promote these messages at grassroot level which benefits the society/ community as a whole.
基金supported by Indian Council of Medical Research,New Delhi(No.NER/23/2013-ECD-I)
文摘Objective: To detect the prevalence pattern of Chikungunya virus in three states of Northeast India. Methods: A total of 1 510 samples were collected from different private and government hospitals of Assam, Arunachal Pradesh and Meghalaya. Serum was tested for the presence of IgM antibodies against Chikungunya virus followed by RT-PCR for amplification of Chikungunya E1 gene region using specific primers. Results: Overall, 11.83%(172/1 454) clinical samples were positive by MAC-ELISA and/or RT-PCR assay. Asymptomatic infection was seen in 17.86%. Males were more affected than females and age group 16-30 years was mostly affected. Fever(100.00%) was the primary symptom followed by headache(72.03%) and arthralgia(41.53%). Only 118 Chikungunya positive cases could be traced, of which 25.42% complained about sequelae of infection. In entomological investigation, Aedes aegypti was more predominant(92.10%) than Aedes albopictus(7.90%). No mosquito pools could be incriminated for Chikungunya virus. Conclusions: In this study, Chikungunya was observed to be prevalent in Assam, Arunachal Pradesh and Meghalaya. Though Chikungunya is a selflimiting infection, increasing morbidity by CHIKV infection is affecting social and economic status of individual. Thus, a community empowerment to effectively control mosquito population by employing different mosquito control measures along with personal protection is mandatory to tackle future outbreak of the disease.
文摘Objective:To establish a surveillance in Dong Thap,at the border with Cambodia by assessing the presence of DHNV serotypes and CHIKV among patients hospitalized at Dong Thap general hospital.Methods:Cross-sectional descriptive analysis was conducted on a cohort of 131 patients hospitalized with acute fever and symptoms compatible with dengue or chikungunya.The study was conducted from January 2012 to February 2013.The full clinical picture was established as well as serological and molecular detection.Serological analysis was sequentially performed on blood samples collected on admission and an average of seven days after admission.The detection of IgM antibody to DENV was performed by IgM capture ELTSA and the detection of DENV and CHIKV RNA was done by reverse-transcription multiplex PCR.Results:101 patients out of 131(77%) were confirmed with dengue.All four dengue serotypes were detected with a predominance of DENV2 and DENV4.No chikungunya infection was detected although reported in neighboring Cambodia.A differential efficiency of serological dengue detection was observed.Efficiency was 29%upon admission and 53%after seven days on the same patients.30 patients out of 131(23%) were negative with both DENV and CHIKV.Conclusions:Dengue is at risk of being underestimated and chikungunya is not systematically detected.Changes in detection and surveillance procedures are therefore discussed to increase efficiency of dengue detection and continue the monitoring the emergence of CHIKV in Dong Thap province and in Vietnam.
文摘Chikungunya fever(CHIKF)is an arboviral disease that typically consists of an acute illness with fever,skin rash,and incapacitating arthralgia.The causative agent of CHIKF is Chikungunya virus(CHIKV),an alphavirus that is transmitted by the Aedes mosquitoes.Despite the re-emergence of CHIKV as an epidemic threat,there is no approved effective anti-viral treatment currently available for CHIKV.In our preliminary studies,selected small molecule inhibitors of arboviruses related to CHIKV were investigated and this led us to identify compounds with thieno[3,2-b]pyrrole scaffold as hits.Building on the discovery of our best hit compounds,5-carboxylic acid thieno[3,2-b]pyrrole 1 and 5-carboxamide thieno[3,2-b]pyrrole 2,the main aim of this study is to optimize their anti-viral activities by synthesizing analogs of thieno[3,2-b]pyrroles 1 and 2 and examine their activities against CHIKV.In these two parallel optimization studies,we synthesized two series of thieno[3,2-b]pyrroles,namely the 5-carboxylic acids and 5-carboxamides that possessed a variety of substituents at N4,C2,C6 or C5positions of the thieno[3,2-b]pyrrole scaffold.These compounds were then examined for their cytotoxicity effects and anti-viral activities using a luminescence-labelled CHIKV infectious clone.The most potent compound in our studies was found in the 5-carboxamide series.The synthesis,biological activity and structure-activity relationship(SAR)will be presented and discussed in detail.
文摘Objective:To describe the prognostic and clinical profile of hospitalized patients with chikungunya virus(CHIKV)infection focusing on renal outcomes.Methods:This is a cross-sectional study including all patients with confirmed chikungunya fever(CHIKF)admitted to 3 different highcomplexity hospitals in Fortaleza,Brazil between January 2016 and June 2017.Data analysis was carried out to evaluate correlation between clinical profile and outcomes.Results:Fifty-five patients were included,with a median age of 77(IQR=21)years,and 23(41.82%)were male.Twenty-five patients(45.45%,25/55)developed acute kidney injury(AKI),and 15(60.00%,15/25)were classified as KDIGO 1,1(4.00%)as KDIGO 2,and 9(36.00%)as KDIGO 3.The overall mortality was 34.54%whilst AKI-related mortality was 64.00%(16/25).Both AKI and encephalitis were associated with higher mortality.Patients who died were significantly older[82(IQR=12)years vs.70(IQR=28.75)years,P<0.001].In the multivariate analysis,abdominal pain was associated with an increased risk of severe AKI(OR=5.33,95%CI=1.11–25.64,P=0.037)and AKI was an independent risk factor of death(OR=12.06,95%CI=2.55–57.15,P=0.002).Recovery of renal function was similar among the different age groups.Conclusions:AKI is present in half of the study population and is an independent risk factor of death.Thus,renal function should be carefully monitored in hospitalized patients with CHIKV infection.
