The Chikungunya virus: An emerging US pathogen.
Nappe Thomas M,Chuhran Craig M,Johnson Steven A
World journal of emergency medicine
BACKGROUND:The Chikungunya (CHIK) virus was recently reported by the CDC to have spread to the United States. We report an early documented case of CHIK from the state of Pennsylvania after a patient recently returned from Haiti in June of 2014. METHODS:A 39-year-old man presented to the emergency department complaining of fever, fatigue, polyarthralgias and a diffuse rash for two days. Four days before, he returned from a mission trip to Haiti and reported that four of his accompanying friends had also become ill. A CHIK antibody titer was obtained and it was found to be positive. During his hospital stay, he responded well to supportive care, including anti-inflammatories, intravenous hydration and anti-emetics. RESULTS:His condition improved within two days and he was ultimately discharged home. CONCLUSIONS:Manifestations of CHIK can be similar to Dengue fever, which is transmitted by the same species of mosquito, and occasionally as a co-infection. Clinicians should include Chikungunya virus in their differential diagnosis of patients who present with fever, polyarthralgia and rash with a recent history of travel to endemic areas, including those within the United States.
Prevalence of Post-Chikungunya Infection Chronic Inflammatory Arthritis: A Systematic Review and Meta-Analysis.
Rodríguez-Morales Alfonso J,Cardona-Ospina Jaime A,Fernanda Urbano-Garzón Sivia,Sebastian Hurtado-Zapata Juan
Arthritis care & research
OBJECTIVE:To determine the percentage of patients who would develop chronic inflammatory rheumatism (CIR) following chikungunya (CHIK) virus disease. METHODS:We conducted a systematic review of the literature in 3 databases (PubMed, Science Citation Index, and Scopus) to identify studies assessing the proportion of patients who progress to CHIK-CIR. We performed a random-effects model meta-analysis to calculate the pooled prevalence and 95% confidence intervals (95% CIs). A 2-tailed alpha level of 5% was used for hypothesis testing. Measures of heterogeneity, including Cochran's Q statistic, the I index, and the tau-squared test, were calculated and reported. Subgroup analyses were conducted by type of study and country, by studies evaluating chronic arthritis, and by studies with ≥200 patients and followup ≥18 months. Publication bias was assessed using a funnel-plot. RESULTS:Up to June 15, 2015, our literature search yielded 578 citations. The pooled prevalence of CHIK-CIR in 18 selected studies among 5,702 patients was 40.22% (95% CI 31.11-49.34; τ = 0.0838). From studies derived from India, prevalence was 27.27% (95% CI 15.66-38.88; τ = 0.0411), while from France, prevalence was 50.25% (95% CI 25.38-75.12; τ = 0.1797). The prevalence of CHIK chronic arthritis was 13.66% (95% CI 9.31-18.00; τ = 0.0060). Considering just those studies with ≥200 patients assessed, prevalence was 34.14% (95% CI 23.99-44.29; τ = 0.0525). In studies with a followup ≥18 months, prevalence was 32.13% (95% CI 22.21-42.04; τ = 0.0453). CONCLUSION:According to our results in the most conservative scenario, approximately 25% of CHIK cases would develop CHIK-CIR (34% if we just consider the most representative studies), and 14% would develop chronic arthritis.
Congenital and Neonatal Chikungunya in Colombia.
Alvarado-Socarras J L,Ocampo-González M,Vargas-Soler J A,Rodriguez-Morales A J,Franco-Paredes C
Journal of the Pediatric Infectious Diseases Society
In Latin America and the Caribbean (LAC), chikungunya (CHIK) viral infection has emerged as a significant arboviral disease. This rapidly expanding vector-borne viral illness is associated with a substantial burden of disease in terms of acute illness and also in terms of long-term sequelae. In addition, this viral pathogen has the ability to impact different populations including pregnant women and newborns. Despite the growing threat of this arboviral infection to the region, there are insufficient reports or studies attempting to delineate the clinical and epidemiological features of congenital and neonatal cases of CHIK in LAC. In this study, we present a case of congenital CHIK and a case of neonatal CHIK infection identified in Santander, Colombia. We discuss the potential neurological impact and sequelae of CHIK infection acquired during the neonatal period. There is an urgent need for further epidemiological and clinical studies to better understand the impact of CHIK in endemic areas in LAC.
A case of consecutive infection with Zika virus and Chikungunya virus in Bora Bora, French Polynesia.
Kutsuna Satoshi,Kato Yasuyuki,Nakayama Eri,Taniguchi Satoshi,Takasaki Tomohiko,Yamamoto Kei,Takeshita Nozomi,Hayakawa Kayoko,Kanagawa Shuzo,Ohmagari Norio
Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy
Chikungunya fever (CHIK) and Zika virus (ZIKV) infection have similar endemic areas and clinical manifestations. We report a case of CHIK at 1 year after a ZIKV infection in Bora Bora (French Polynesia), which we diagnosed based on IgM to the CHIK virus and neutralizing antibodies to ZIKV.
Spectrum of neurological complications in chikungunya fever: experience at a tertiary care centre and review of literature.
Anand Kuljeet Singh,Agrawal Arun Kumar,Garg Jyoti,Dhamija Rajinder K,Mahajan Rakesh Kumar
Chikungunya (CHIK) has re-emerged as a potential neurotropic virus, with outbreaks recently being reported from many parts of India. The present study was conducted to study the spectrum and outcome of neurological complications in patients of CHIK during the 2016 outbreak in Delhi. A total of 42 cases seropositive for IgM CHIK antibodies by MAC-ELISA and developing neurological complications were enrolled. The male:female ratio was 1:2 (age range = 18-90 years). The neurological manifestations observed were encephalitis (n = 12), bulbar palsy (n = 3), acute disseminated encephalomyelitis (n = 1), cerebellitis (n = 1), myelopathy (n = 1), radiculoneuropathy (n = 3), carpal tunnel syndrome (n = 9) and tremors (n = 1). Ten patients reported worsening of pre-existing neuropathic symptoms of diabetic peripheral neuropathy (n = 4) and carpal tunnel syndrome (n = 6). One patient had aggravation of myasthenia gravis leading to respiratory failure. The majority of patients (n = 32) showed a good outcome; ten had a poor prognosis, out of which four died, all from the encephalitis group, particularly the elderly with co-morbidities.
Rare variant of Guillain-Barré syndrome after chikungunya viral fever.
Hameed Sajid,Khan Sara
BMJ case reports
Chikungunya (CHIK) viral fever is a self-limiting illness that presents with severe debilitating arthralgia, myalgia, fever and rash. Neurological complications are rare. We present a case of a 36-year-old woman who presented with acute onset progressive difficulty swallowing and left arm weakness. She was diagnosed with CHIK viral fever 4 weeks prior to admission. After investigations, she was diagnosed with a pharyngeal-cervical-brachial variant of Guillain-Barré syndrome. In hospital, she required ventilator support. Her condition improved after five sessions of intravenous immunoglobulin with almost complete resolution within 6 months of symptom onset. With frequent CHIK outbreaks, the neurological complications are increasingly seen in the emergency department. The knowledge of these associations will result in early diagnosis and treatment.
Adverse event following live attenuated chikungunya vaccine in a cynomolgus macaque with pre-existing chronic hydrocephalus.
Peterson Tiffany A,MacLean Andrew G,Russell-Lodrigue Kasi E,Didier Peter J,Weaver Scott C,Roy Chad J
Journal of medical primatology
A cynomolgus macaque (Macaca fascicularis) with a pre-existing, undiagnosed, subclinical but severe cerebral hydrocephalus was enrolled in a study of long-term immunogenicity of the IRES/CHIK vaccine. The animal began showing signs of neurological dysfunction post-vaccination, which progressed and ultimately resulted in euthanasia. The underlying brain abnormality was revealed at necropsy and was subsequently investigated with gross and microscopic examination. This becomes the first reported case of an adverse event following administration of a live attenuated vaccine and suggests the possibility of an increased susceptibility risk of unwanted adverse outcome associated with vaccination in populations with pre-existing conditions such as hydrocephalus.
The chik sign in dengue.
Bhatia Shibani S,Shenoi Shrutakirthi D,Hebbar Shrikiran A,Kayarkatte Manasa N
The "chik sign" is considered to be one of the most common cutaneous features of chikungunya fever and has been considered unique to this disorder. It consists of brownish hyperpigmentation involving the nose. We report a case of a 3-year-old boy with dengue infection who presented with macular hyperpigmentation of nose simulating the chik sign. Hyperpigmentation is an unusual cutaneous manifestation in cases of dengue.
Immunogenicity, safety, and tolerability of the measles-vectored chikungunya virus vaccine MV-CHIK: a double-blind, randomised, placebo-controlled and active-controlled phase 2 trial.
Reisinger Emil C,Tschismarov Roland,Beubler Eckhard,Wiedermann Ursula,Firbas Christa,Loebermann Micha,Pfeiffer Andrea,Muellner Matthias,Tauber Erich,Ramsauer Katrin
Lancet (London, England)
BACKGROUND:Chikungunya fever is an emerging viral disease and substantial threat to public health. We aimed to assess the safety, tolerability, and immunogenicity of a live-attenuated, measles-vectored chikungunya vaccine (MV-CHIK). METHODS:In this double-blind, randomised, placebo-controlled and active-controlled phase 2 trial, we enrolled healthy volunteers aged 18-55 years at four study sites in Austria and Germany. Participants were randomly assigned to receive intramuscular injections with MV-CHIK (5 × 10 or 5 × 10 50% tissue culture infectious dose), control vaccine, or measles prime and MV-CHIK, in two different administration regimens. Randomisation was done by use of three-digit randomisation codes in envelopes provided by a data management service. The participants and investigators were masked to treatment assignment, which was maintained by use of sterile saline as a placebo injection. The primary endpoint was immunogenicity, defined as the presence of neutralising antibodies against chikungunya virus, at day 56, which is 28 days after one or two immunisations. The primary endpoint was assessed in all participants who completed the study without major protocol deviations (per-protocol population) and in all randomised participants who received at least one study treatment (modified intention-to-treat population). The safety analysis included all participants who received at least one study treatment. This trial is registered with ClinicalTrials.gov (NCT02861586) and EudraCT (2015-004037-26) and is completed. FINDINGS:Between Aug 17, 2016, and May 31, 2017, we randomly assigned 263 participants to receive control vaccine (n=34), MV-CHIK (n=195), or measles prime and MV-CHIK (n=34). 247 participants were included in the per-protocol population. Neutralising antibodies against chikungunya virus were detected in all MV-CHIK treatment groups after one or two immunisations, with geometric mean titres ranging from 12·87 (95% CI 8·75-18·93) to 174·80 (119·10-256·50) and seroconversion rates ranging from 50·0% to 95·9% depending on the dose and administration schedule. Adverse events were similar between groups, with solicited adverse events reported in 168 (73%) of 229 participants assigned to MV-CHIK and 24 (71%) of 34 assigned to control vaccine (p=0·84) and unsolicited adverse events in 116 (51%) participants assigned to MV-CHIK and 17 (50%) assigned to control vaccine (p=1·00). No serious adverse events related to the vaccine were reported. INTERPRETATION:MV-CHIK showed excellent safety and tolerability and good immunogenicity, independent of pre-existing immunity against the vector. MV-CHIK is a promising candidate vaccine for the prevention of chikungunya fever, an emerging disease of global concern. FUNDING:Themis.
Chikungunya in Mississippi: The Health Department Response to Imported Cases.
Goddard Jerome,Varnado Wendy C,Hand Sheryl,Meyer Florencia
Journal of the Mississippi State Medical Association
Chikungunya (CHIK), a newly recognized mosquito-borne disease in the Western Hemisphere, has resulted in well over a million cases since December 2013. Only about a dozen locally-acquired cases thus far have been reported in the U. S. (Florida), but approximately 1500 imported cases have been seen in returning travelers from the Caribbean and Central and South America. Public health officials are concerned that imported cases may lead to infection of local mosquitoes and, thus disease transmission. This paper documents 9 confirmed CHIK cases in Mississippi: 5 resulting from travel to the Dominican Republic, 2 from Haiti, 1 from Honduras, and 1 from Puerto Rico. In addition, the Mississippi State Department of Health response to those cases is presented and discussed.
Vertical transmission of Indian Ocean Lineage of chikungunya virus in Aedes aegypti and Aedes albopictus mosquitoes.
Chompoosri Jakkrawarn,Thavara Usavadee,Tawatsin Apiwat,Boonserm Rungfar,Phumee Atchara,Sangkitporn Somchai,Siriyasatien Padet
Parasites & vectors
BACKGROUND:The re-emergence of chikungunya (CHIK) fever in Thailand has been caused by a novel lineage of chikungunya virus (CHIKV) termed the Indian Ocean Lineage (IOL). The Aedes albopictus mosquito is thought to be a primary vector of CHIK fever in Thailand, whereas Ae. aegypti acts as a secondary vector of the virus. The vertical transmission is believed to be a primary means to maintain CHIKV in nature and may be associated with an increased risk of outbreak. Therefore, the goal of this study was to analyze the potential of these two Thai mosquito species to transmit the virus vertically and to determine the number of successive mosquito generations for the virus transmission. METHODS:Two-hundred-and-fifty female Ae. aegypti and Ae. albopictus mosquitoes were artificially fed a mixture of human blood and CHIKV IOL. Mosquito larvae and adults were sampled and screened for CHIKV by one-step qRT-PCR. LLC-MK2 cell line was used to isolate CHIKV in the mosquitoes each generation. The virus isolate was identified by immunocytochemical staining and was confirmed by sequencing. Both mosquito species fed on human blood without CHIKV and uninfected LLC-MK2 cells were used as controls. RESULTS:Aedes aegypti and Ae. albopictus mosquitoes were able to transmit CHIKV vertically to F5 and F6 progenies, respectively. The virus isolated from the two mosquito species caused cytopathic effect in LLC-MK2 cells by 2 days post-infection and immunocytochemical staining showed the reaction between CHIKV IOL antigen and specific monoclonal antibody in the infected cells. DNA sequence confirmed the virus transmitted vertically as CHIKV IOL with E1-A226V mutation. No CHIKV infection was observed in both mosquito species and LLC-MK2 cells from control groups. CONCLUSIONS:The study demonstrated that Ae. aegypti and Ae. albopictus mosquitoes from Thailand are capable of transmitting CHIKV IOL vertically in the laboratory. Our results showed that Ae. albopictus is more susceptible and has a greater ability to transmit the virus vertically than Ae. aegypti. This knowledge would be useful for risk assessments of the maintenance of CHIKV in nature, which is crucial for disease surveillance, vector control and the prevention of potential CHIKV epidemics.
Expression and Characterization of Yeast Derived Chikungunya Virus Like Particles (CHIK-VLPs) and Its Evaluation as a Potential Vaccine Candidate.
Saraswat Shweta,Athmaram T N,Parida Manmohan,Agarwal Ankita,Saha Amrita,Dash Paban Kumar
PLoS neglected tropical diseases
Chikungunya virus (CHIKV) has emerged as a global health concern due to its recent spread in both old and new world. So far, no CHIKV specific drug or vaccine is licensed for human use. In this study, we report production of Chikungunya virus like particles (CHIK-VLPs) using novel yeast expression system (Pichia pastoris) and its evaluation as vaccine candidate. The gene encoding structural polyprotein of CHIKV from a recent epidemic strain was cloned into yeast expression system. The multicopy integrants were processed for expression of CHIK-VLPs. The VLPs were purified and confirmed through electron microscopic analysis for their morphological identity with CHIKV. The in vitro and in vivo evaluation of CHIK-VLPs as vaccine candidate was determined in Balb/c mice. Induction of both humoral and cellular immune response was observed with different doses of CHIK-VLPs. The humoral immune response was studied through different techniques like enzyme linked immunosorbent assay, IgG Isotyping and plaque reduction neutralization test. CHIK-VLPs were found to elicit high titer of antibodies that are able to recognize native CHIKV. Higher level of IgG2a and IgG1 subtypes was identified suggestive of balanced Th1/Th2 response. Both in vitro and in vivo neutralization activity of CHIK-VLPs antibodies was observed even with low concentration, which shows its high specificity and neutralizing activity against two different CHIKV strains. Neonatal mice receiving anti-CHIK-VLPs antibodies were protected from CHIKV challenge. Induction of cellular immune response was confirmed through higher level of TNF-α, IL-10 and substantial level of IL-2, IL-4 and IFN-γ indicating a balanced response. This is the first report, where CHIK-VLPs has been expressed by Pichia pastoris and evaluated for neutralizing activity against CHIKV. These promising results indicate the utility of CHIK-VLPs as a promising vaccine candidate against emerging CHIKV.
Comparison between silver- and copper-modified zeolite-rich tuffs as microbicide agents for Escherichia coli and Candida albicans.
Rossainz-Castro L G,De-La-Rosa-Gómez I,Olguín M T,Alcántara-Díaz D
Journal of environmental management
Zeolite-rich tuff from the State of Chihuahua was modified with silver or copper ions (ZChAg and ZChCu) to evaluate its microbicidal effect against Escherichia coli (E. coli) and Candida albicans (C. albicans) suspended in an aqueous solution in order to compare the microbial disinfection kinetics between bacteria and yeast. The zeolite-rich tuff was treated with AgNO or CuCl solutions. The materials obtained were characterized using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD) and the textural properties were also determined by BET-analyses. The concentration of Ag and Cu was verified in the zeolitic materials using neutron activation analysis. The experimental data were adjusted to both Chick and Chik-Watson models to describe the kinetic behavior of the process. It was found that when the mass of ZChAg increased, the survival microorganisms notably decreased. The E. coli and C. albicans showed higher resistance in contact with ZChCu even when the mass of such material was 10-20 times higher than the mass of ZChAg. Chick and Chik-Watson constants showed that the kinetics of the disinfection process depended on the desorption of the exchange ion that modified the structure of the zeolitic material, its concentration in aqueous medium, its oligodynamic properties, and each microorganism's characteristics (Gram-negative bacteria and yeast). The kinetic desorption of Ag and Cu from the corresponding modified-zeolite-rich tuffs was also considered in this work. In this case, the Higuchi and Korsmeyer-Peppas models were applied.
Vaccination with a chikungunya virus-like particle vaccine exacerbates disease in aged mice.
Arévalo Maria T,Huang Ying,Jones Cheryl A,Ross Ted M
PLoS neglected tropical diseases
INTRODUCTION:Chikungunya virus (CHIKV) is a re-emerging pathogen responsible for causing outbreaks of febrile disease accompanied with debilitating joint pain. Symptoms typically persist for two weeks, but more severe and chronic chikungunya illnesses have been reported, especially in the elderly. Currently, there are no licensed vaccines or antivirals against CHIKV available. In this study, we combined a CHIK virus-like particle (VLP) vaccine with different adjuvants to enhance immunogenicity and protection in both, adult and aged mice. METHODS:CHIK VLP-based vaccines were tested in 6-8-week-old (adult) and 18-24-month-old (aged) female C57BL/6J mice. Formulations contained CHIK VLP alone or adjuvants: QuilA, R848, or Imject Alum. Mice were vaccinated three times via intramuscular injections. CHIKV-specific antibody responses were characterized by IgG subclass using ELISA, and by microneutralization assays. In addition, CHIKV infections were characterized in vaccinated and non-vaccinated adult mice and compared to aged mice. RESULTS:In adult mice, CHIKV infection of the right hind foot induced significant swelling, which peaked by day 7 post-infection at approximately 170% of initial size. Viral titers peaked at 2.53 × 1010 CCID50/ml on day 2 post-infection. Mice vaccinated with CHIK VLP-based vaccines developed robust anti-CHIKV-specific IgG antibody responses that were capable of neutralizing CHIKV in vitro. CHIK VLP alone or CHIK plus QuilA administered by IM injections protected 100% of mice against CHIKV. In contrast, the antibody responses elicited by the VLP-based vaccines were attenuated in aged mice, with negligible neutralizing antibody titers detected. Unvaccinated, aged mice were resistant to CHIKV infection, while vaccination with CHIKV VLPs exacerbated disease. CONCLUSIONS:Unadjuvanted CHIK VLP vaccination elicits immune responses that protect 100% of adult mice against CHIKV infection. However, an improved vaccine/adjuvant combination is still necessary to enhance the protective immunity against CHIKV in the aged.
Imported cases of Chikungunya virus in Iran.
Pouriayevali Mohammad Hassan,Rezaei Farshid,Jalali Tahmineh,Baniasadi Vahid,Fazlalipour Mehdi,Mostafavi Ehsan,Khakifirouz Sahar,Mohammadi Tahereh,Fereydooni Zahra,Tavakoli Mahsa,Azad-Manjiri Sanam,Hosseini Motahareh,Ghalejoogh Mahsa,Gouya Mohammad Mehdi,Failloux Anna-Bella,Salehi-Vaziri Mostafa
BMC infectious diseases
BACKGROUND:Chikungunya virus (CHIKV) is a widespread mosquito-borne virus representing a serious challenge to public health. The largest outbreak in the Middle-East was recorded in 2016-2017 in Pakistan. Sistan and Baluchistan Province of Iran shares a wide border with Pakistan; accordingly, introduction of CHIKV from Pakistan to Iran seems to be probable. The current study is aimed at investigating CHIKV infection in Sistan and Baluchistan Province. METHODS:Between April 2017 and June 2018, a total of 159 serum samples of CHIK suspected cases from 10 cities of Sistan and Baluchistan Province were tested by molecular and serological assays. Samples obtained up to 4 days after onset of illness were tested by real time PCR (n = 8). Samples collected 5-10 days after disease onset were subjected to ELISA, as well as real time PCR tests (n = 72). Samples obtained after the 10th day of disease onset were tested by only ELISA (n = 79). Phylogenetic analysis of real time PCR positive samples was carried out by sequencing of a 1014-bp region of Envelope 1 gene (E1 gene). Chi-square and independent t tests were used to evaluate the association between variables and CHIKV infection. RESULTS:In total, 40 (25.1%) out of 159 samples tested positive either by real time PCR or ELISA tests.Out of 151 samples serologically analyzed, 19 (12.6%) and 28 (18.6%) cases were positive for anti-CHIKV IgM and anti-CHIKV IgG antibodies, respectively. Of 80 samples tested by real time PCR, CHIKV RNA was detected in 11 (13.7%) sera, all of them had recent travel history to Pakistan. Additionally, phylogenetic analysis of 5 samples indicated their similarity with recent isolates of Pakistan outbreak 2016-2017 belonging to Indian Ocean sub-lineage of ECSA genotype. A significant correlation between abroad travel history and CHIKV infection was observed (P < 0.001). The most common clinical symptoms included fever, arthralgia/arthritis, myalgia, headache, and chill. CONCLUSIONS:These results present substantial evidence of CHIKV introduction to Iran from Pakistan and emphasize the need for the enhancement of surveillance system and preventive measures.
Zika virus: Indian perspectives.
Mourya Devendra T,Shil Pratip,Sapkal Gajanan N,Yadav Pragya D
The Indian journal of medical research
The emergence of Zika virus (ZiV), a mosquito borne Flavivirus like dengue (DEN) and chikungunya (CHIK), in Brazil in 2014 and its spread to various countries have led to a global health emergency. Aedes aegypti is the major vector for ZiV. Fast dissemination of this virus in different geographical areas posses a major threat especially to regions where the population lacks herd immunity against the ZiV and there is abundance of Aedes mosquitoes. In this review, we focus on current global scenario, epidemiology, biology, diagnostic challenges and remedial measures for ZiVconsidering the Indian perspective.
Chikungunya Fever Presenting as a Systemic Disease with Fever. Arthritis and Rash: Our Experience in Israel.
The Israel Medical Association journal : IMAJ
Chikungunya fever (CHIK-F) has been increasingly documented among Western travelers returning from areas with chikungunya virus transmission, which are also popular tourist sites. We present three Israeli travelers who developed fever, maculopapular rash and long-standing arthralgias while visiting northern Indian states not known to be involved in the chikungunya fever epidemic. We also present an epidemiological review of the chikungunya epidemic over the past decades. Rare systemic manifestations of this disorder, like catastrophic antiphospholipid syndrome (CAPS) and adult-onset Still's syndrome, are discussed. The present era of international travel poses a new diagnostic and epidemiologic challenge that demands increased awareness to the possibility of an exotic tropical infectious disease.
The Clinical Features, Pathogenesis and Methotrexate Therapy of Chronic Chikungunya Arthritis.
Amaral J Kennedy,Taylor Peter C,Teixeira Mauro Martins,Morrison Thomas E Tem,Schoen Robert T
Chikungunya fever (CHIKF) is an emerging viral infection that has spread widely, along with its vectors, throughout the tropics and beyond, causing explosive epidemics of acute illness and persistent disabling arthritis. The rheumatic symptoms associated with chikungunya virus (CHIKV) infection include polyarthralgia, polyarthritis, morning stiffness, joint edema, and erythema. Chronic CHIK arthritis (CCA) often causes severe pain and associated disability. The pathogenesis of CCA is not well understood. Proposed hypotheses include the persistence of a low level of replicating virus in the joints, the persistence of viral RNA in the synovium, and the induction of autoimmunity. In this review, we describe the main hypotheses of CCA pathogenesis, some of which support methotrexate (MTX) treatment which has been shown to be effective in preliminary studies in CCA.
[First case of chikungunya fever in Hermosillo, Sonora, Mexico].
Martínez-Medina Miguel Ángel,Cañedo-Dorame Ismael Antonio
Revista medica del Instituto Mexicano del Seguro Social
The Chikungunya is an arbovirus first described during a 1952 outbreak of febrile exantematic disease in southern Tanganyika (now Tanzania). It is a virus within the alphavirus genus of the Togaviridae family, it is usually transmitted to humans by Aedes mosquitoes. Typically, the disease manifests as acute onset of fever and joint pains. This study describes the clinical characteristics the first imported case infected with chikungunya fever (CHIK) in Hermosillo, Sonora, Mexico. We report the case of a 30 years old man seen in our emergency department due to fever, polyarthralgia, rash and headache. This patient has been in Tapachula, Chiapas, a jungle area in southern México, and he returned from a 45 days trip before the onset his symptoms. The chikungunya viral infection (CHIK) was diagnosed by RT-PCR procedure. Paracetamol therapy was administered and his clinical course was self-limited. We concluded that with the increase of mosquito´s habitat by global warming and frequent traveling, CHIK reemerged and showed global distribution recently. This disease must be suspected in patients with compatible clinical symptoms returning from epidemic/endemic areas. CHIK must be diagnosed on the basis of clinical, epidemiological and laboratory criteria.
Chikungunya and diabetes, what do we know?
de Almeida Barreto Francisca Kalline,Montenegro Renan Magalhães,Fernandes Virginia Oliveira,Oliveira Rhaquel,de Araújo Batista Lívia Aline,Hussain Akhtar,de Góes Cavalcanti Luciano Pamplona
Diabetology & metabolic syndrome
Background:Chikungunya (CHIK) is a viral disease transmitted by mosquitoes. The first cases in Brazil were confirmed in 2014. Between 2016 and 2017, over 300,000 cases were identified during this period, with nearly 300 deaths. The clinical manifestations, pathogenesis and risk factors for occurrence of severe cases are not yet well understood, although it is known that the severity of the cases is associated with the presence of comorbidities, especially diabetes mellitus (DM). Objective:To review the medical literature for the associations between DM and CHIK and to understand the potential impact on metabolic state and its complications. Methods:Literature review was carried out to search for articles (English, Portuguese and Spanish) in Medline and Virtual Health Library databases for the period between 1952 and 2017, with the following keywords: "Chikungunya fever", "Chikungunya virus", "diabetes mellitus", "diabetes", "diabetes complications "and "multi-morbidities (MeSH) "with interposition of the Boolean operator "AND". Results:After removal of duplicities and following exclusion criteria, 11 articles were selected. Our results showed that the patients of CHIK with DM had more severe and prolonged symptoms of CHIK and more frequently required hospitalization. No study investigated the biological process to explain how hyperglycemic state worsened the clinical manifestations of Chikungunya in diabetic patients. Conclusion:An important association between DM and the severity of CHIK is observed. Prospective and more rigorous controlled studies are required to generate evidence that might y elucidate the causes of this relationship. Given the fast expanding viral infection of Chikungunya in Central and South America, Asia and Africa in recent years in the context of exponential increase in diabetes globally, the issue deserves global attention.
Emergence and treatment of chikungunya arthritis.
Sutaria Ravi B,Amaral Jose K,Schoen Robert T
Current opinion in rheumatology
PURPOSE OF REVIEW:To review the emergence, clinical features, pathogenesis, and treatment of acute chikungunya (CHIK) fever and chronic CHIK arthritis. RECENT FINDINGS:Since 2004, CHIK, an arboviral infection, has spread throughout the world, infecting millions of people. The illness occurs in two phases: an acute viremic infection followed by chronic arthritis. In less developed countries, there are limited resources and effective treatment. For acutely ill CHIK fever patients, management is symptomatic. The treatment of chronic CHIK arthritis should be determined by an understanding of pathogenesis. Is chronic CHIK arthritis a persistent viral infection or a postinfectious inflammatory process? Multiple proinflammatory cytokines, chemokines, and growth factors have been identified in chronic CHIK arthritis. Attempts to isolate CHIK virus from synovial fluid have been unsuccessful. Given pathogenetic similarities (as well as differences) compared with rheumatoid arthritis and the painful, disabling nature of the arthritis, it is not surprising that disease-modifying antirheumatic drugs such as methotrexate have begun to be used. SUMMARY:CHIK infection has emerged with major arthritic epidemics for which evidence-based therapy is limited. But there is an opportunity to improve the treatment of chronic CHIK arthritis and, from this disease, to gain understanding of the pathogenesis and treatment of inflammatory arthritis more generally.
Atypical Neurological Manifestations of Chikungunya Fever: Two Case Reports.
Mahto Subodh Kumar,Gupta Pulin Kumar,Singh Akanksha,Meena Ramesh Chand
Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine
Chikungunya fever (CHIK) is an arboviral disease which is transmitted by a mosquito bite (). Fever, polyarthralgia, and maculopapular rash are hallmark clinical manifestations of this disease. These manifestations are self-liming and complete recovery is seen in most of the cases. However, atypical and lethal complications such as myocarditis, hepatitis, Guillain-Barre syndrome (GBS), and meningoencephalitis have been reported in few cases of CHIK. We hereby report two cases of chikungunya infection where rare and atypical manifestations of CHIK, i.e., GBS with bilateral lower motor facial nerve palsy, and meningoencephalitis with epidermal necrosis were seen.
Chikungunya Infection: A Re-emerging Epidemic.
Paul Binoy J,Sadanand Shajit
Rheumatology and therapy
Chikungunya (CHIK) is an arboviral infection caused by the chikungunya virus. An unusual feature of CHIK is its long periods of quiescence followed by an epidemic of devastating severity that can involve millions of people. Manifestations of CHIK range from a mild self-limiting febrile illness with arthralgia and rash to crippling acute and lingering debilitating arthritis. In about 10-60% of patients, musculoskeletal symptoms may persist for up to 3-5 years. Management is mainly symptomatic, with analgesics, antipyretics and non-steroidal anti-inflammatory agents. Ecological changes together with alterations in the viral genome facilitate the development of newer variants with greater pathogenicity, a matter of great concern. The social and economic burdens to a society as a result of CHIK epidemics have generated a considerable interest in the scientific community to decipher the reasons underlying myriad manifestations and to develop management strategies for tackling the menace of CHIK across the globe.
Neuromodulation treats Chikungunya arthralgia: a randomized controlled trial.
Silva-Filho Edson,Okano Alexandre H,Morya Edgard,Albuquerque Jessica,Cacho Enio,Unal Gozde,Bikson Marom,Pegado Rodrigo
The Chikungunya (CHIK) virus is epidemic in Brazil, with 170,000 cases in the first half of 2016. More than 60% of patients present relapsing and remitting chronic arthralgia with debilitating pain lasting years. There are no specific therapeutic agents to treat and rehabilitee infected persons with CHIK. Persistent pain can lead to incapacitation, requiring long-term pharmacological treatment. Advances in non-pharmacological treatments are necessary to promote pain relief without side effects and to restore functionality. Clinical trials indicate transcranial direct current stimulation (tDCS) can treat a broad range of chronic pain disorders, including diffuse neuromuscular pain and arthralgia. Here, we demonstrate that the tDCS across the primary motor cortex significantly reduces pain in the chronic phase of CHIK. High-resolution computational model was created to analyze the cortical electric field generated during tDCS and a diffuse and clustered brain current flow including M1 ipsilateral and contralateral, left DLPFC, nucleus accumbens, and cingulate was found. Our findings suggest tDCS could be an effective, inexpensive and deployable therapy to areas lacking resources with a significant number of patients with chronic CHIK persistent pain.
An analysis of community perceptions of mosquito-borne disease control and prevention in Sint Eustatius, Caribbean Netherlands.
Leslie Teresa E,Carson Marianne,Coeverden Els van,De Klein Kirsten,Braks Marieta,Krumeich Anja
Global health action
BACKGROUND:In the Caribbean, mosquito-borne diseases are a public health threat. In Sint Eustatius, dengue, Chikungunya and Zika are now endemic. To control and prevent mosquito-borne diseases, the Sint Eustatius Public Health Department relies on the community to assist with the control of Aedes aegypti mosquito. Unfortunately, community based interventions are not always simple, as community perceptions and responses shape actions and influence behavioural responses Objective: The aim of this study was to determine how the Sint Eustatius population perceives the Aedes aegypti mosquito, mosquito-borne diseases and prevention and control measures and hypothesized that increased knowledge of the virus, vector, control and prevention should result in a lower AQ1 prevalence and incidence of mosquito-borne diseases. METHODS:This study was conducted in Sint Eustatius island in the Eastern Caribbean. We combined qualitative and quantitative designs. We conducted interviews and focus groups discussions among community member and health professional in 2013 and 2015. We also conducted cross-sectional survey to assess local knowledge on the vector, virus, and control and prevention. RESULTS:The population is knowledgeable; ©however, mosquito-borne diseases are not the highest health priority. While local knowledge is sometimes put into action, it happens on the 20 household/individual level as opposed to the community level. After the 2014 CHIK outbreak, there was an increase in knowledge about mosquito control and mosquito-borne diseases. DISCUSSION:In the context of Sint Eustatius, when controlling the Aedes population it may be a strategic option to focus on the household level rather than the community and build collaborations with households by supporting them when they actively practice mosquito 25 control. To further increase the level of knowledge on the significance of mosquito-borne diseases, it may also be an option to contextualize the issue of the virus, vector, prevention and control into a broader context. CONCLUSION:As evidenced by the increasing number of mosquito-borne diseases on the island, it appears that knowledge amongst the lay community may not be transferred into 30 action. This may be attributed to the perception of the Sint Eustatius populations that mosquitoes and the viruses they carry are not a high priority in comparison to other health concerns.
Entomological Investigations During Early Stages of A Chikungunya Outbreak In the United States Virgin Islands, 2014.
Kenney Joan L,Burkhalter Kristen L,Scott Mariah L,McAllister Janet,Lang Francine E,Webster Stevie,Maduro Dwayne J,Johannes Juanita,Liburd Alistair,Mutebi John-Paul
Journal of the American Mosquito Control Association
During the 2014 chikungunya (CHIK) outbreak in the Caribbean, we performed entomological surveys on 3 United States Virgin Islands (USVI): St. Croix, St. Thomas, and St. John. We aimed to evaluate the potential for chikungunya virus (CHIKV) transmission in the USVI. The surveys took place between June 19, 2014, and June 29, 2014, during the dry season in USVI. A total of 1,929 adult mosquitoes belonging to 4 species- Culex quinquefasciatus (68.4%), Aedes aegypti (29.7%), Ae. mediovittatus (1.3%), and Ae. sollicitans (<1%)-were detected. Environmental investigations showed that between 73% and 87% of the homes had containers that could serve as mosquito larval habitats. In addition, 47% of the homes did not have air conditioning and between 69% and 79% of homes showed evidence of frequent outdoor activity exhibited by residents. Taken together, these observations suggest a high potential for CHIKV transmission in USVI. The relative abundance of Ae. aegypti on St. John's, St. Thomas, and St. Croix was 21.0, 11.0, and 3.0 mosquitoes/trap per day, respectively, suggesting that the former 2 islands were at the highest risk of CHIKV outbreaks. Insecticide resistance testing detected high levels of resistance to malathion and permethrin in several local populations of Ae. aegypti on St. Croix Island, which suggested that these 2 insecticides should not be used during CHIK outbreaks.
Production of a Chikungunya Vaccine Using a CHO Cell and Attenuated Viral-Based Platform Technology.
Eldi Preethi,Cooper Tamara H,Liu Liang,Prow Natalie A,Diener Kerrilyn R,Howley Paul M,Suhrbier Andreas,Hayball John D
Molecular therapy : the journal of the American Society of Gene Therapy
Vaccinia-based systems have been extensively explored for the development of recombinant vaccines. Herein we describe an innovative vaccinia virus (VACV)-derived vaccine platform technology termed Sementis Copenhagen Vector (SCV), which was rendered multiplication-defective by targeted deletion of the essential viral assembly gene D13L. A SCV cell substrate line was developed for SCV vaccine production by engineering CHO cells to express D13 and the VACV host-range factor CP77, because CHO cells are routinely used for manufacture of biologics. To illustrate the utility of the platform technology, a SCV vaccine against chikungunya virus (SCV-CHIK) was developed and shown to be multiplication-defective in a range of human cell lines and in immunocompromised mice. A single vaccination of mice with SCV-CHIK induced antibody responses specific for chikungunya virus (CHIKV) that were similar to those raised following vaccination with a replication-competent VACV-CHIK and able to neutralize CHIKV. Vaccination also provided protection against CHIKV challenge, preventing both viremia and arthritis. Moreover, SCV retained capacity as an effective mouse smallpox vaccine. In summary, SCV represents a new and safe vaccine platform technology that can be manufactured in modified CHO cells, with pre-clinical evaluation illustrating utility for CHIKV vaccine design and construction.
Experimental Zika virus infection in : Susceptibility, transmission & co-infection with dengue & chikungunya viruses.
Mourya Devendra T,Gokhale Mangesh D,Majumdar Triparna D,Yadav Pragya D,Kumar Vimal,Mavale Mangala S
The Indian journal of medical research
Background & objectives:There are reports about the susceptibility of Aedes mosquitoes to ZIKV from various countries, however, no such information is available from Indian sub-continent, although, high level of group cross-reactivity of ZIKV with other flaviviruses has been reported. During outbreak situations, many cases of Dengue (DEN) and Chikungunya (CHIK) are reported. In such scenario, vector mosquitoes are likely to get co-infection/secondary-infection with one or other virus. The present study was carried out to determine the susceptibility of Indian strain of Aedes aegypti to Zika virus (ZIKV) strain (MR-766) and the effect of co-infection/super-infection with either dengue virus (serotype-2) (DENV) or chikungunya virus (CHIKV) on ZIKV replication. Methods:Ae. aegypti mosquitoes used in this study were reared for many generations since 1980 at laboratory colony maintained at the ICMR-National Institute of Virology, Pune, India. Transmissibility of ZIKV from infected mosquitoes to suckling mice was also studied. Mosquitoes were experimentally infected with ZIKV and super-infected with either DENV or CHIKV via membrane-feeding route and incubated for 14 days at 28±2°C and humidity of 85±5 per cent. Replication of these viruses in mosquitoes was confirmed using real-time reverse transcription-polymerase chain reaction and immunofluorescence assay. Twenty infected mosquitoes were allowed to feed upon four suckling CD1 mice for about 30 min. Transmission of the ZIKV by infected mosquitoes to suckling mice was confirmed by the appearance of clinical signs and the presence of viral RNA in different organs. Results:Concomitant infection of mosquitoes with all the three viruses showed simultaneous propagation of all three viruses, confirmed by real time RT-PCR and IFA. Infection of mosquitoes with CHIKV followed by ZIKV showed positivity in individual head squashes (7%) for both viruses using IFA; only 8.3 per cent showed dual positivity with primary infection of ZIKV followed by DENV; 8.3 per cent dual infection positivity was observed when infected with DENV followed by ZIKV; 5 per cent showed dual infection was observed when infected with ZIKV followed by CHIKV. Ae. aegypti was found to be susceptible to ZIKV strain as ZIKV could be detected from the second post-infection day (PID) in infected mosquitoes. Transmission of ZIKV to mice by the bite of infected Ae. aegypti establishes this species as a potential vector. Interpretation & conclusions:From super-infection experiments, it was concluded that ZIKV might have a relative advantage in replication dynamics over DENV. Vertical transmission was not observed for ZIKV in experimentally infected mosquitoes (n=920 larvae). Further studies are required to understand the possibility of silently circulating ZIKV in India, which remain non-detected because of lack of surveillance.
Chikungunya Detection during Dengue Outbreak in Sumatra, Indonesia: Clinical Manifestations and Virological Profile.
Sasmono R Tedjo,Perkasa Aditya,Yohan Benediktus,Haryanto Sotianingsih,Yudhaputri Frilasita A,Hayati Rahma F,Ma'roef Chairin Nisa,Ledermann Jeremy P,Aye Myint Khin Saw,Powers Ann M
The American journal of tropical medicine and hygiene
Chikungunya fever (CHIK) is an acute viral infection caused by infection with chikungunya virus (CHIKV). The disease affects people in areas where certain species mosquito vectors are present, especially in tropical and subtropical countries. Indonesia has witnessed CHIK disease since the early 1970s with sporadic outbreaks occurring throughout the year. The CHIK clinical manifestation, characterized by fever, headache, and joint pain, is similar to that of dengue (DEN) disease. During a molecular study of a DEN outbreak in Jambi, Sumatra, in early 2015, DENV-negative samples were evaluated for evidence of CHIKV infection. Among 103 DENV-negative samples, eight samples were confirmed (7.8%) as positive for CHIKV by both molecular detection and virus isolation. The mean age of the CHIK patients was 21.3 ± 9.1 (range 11-35 years). The clinical manifestations of the CHIK patients were mild and mimicked DEN, with fever and headache as the main symptoms. Only three out of eight patients presented with classical joint pain. Sequencing of the envelope glycoprotein E1 gene and phylogenetic analysis identified all CHIKV isolates as belonging to the Asian genotype. Overall, our study confirms sustained endemic CHIKV transmission and the presence of multiple arboviruses circulating during a DEN outbreak in Indonesia. The co-circulation of arboviruses poses a public health threat and is likely to cause misdiagnosis and underreporting of CHIK in DEN-endemic areas such as Indonesia.
Patterns of occurrence of dengue and chikungunya, and spatial distribution of mosquito vector Aedes albopictus in Swabi district, Pakistan.
Hira Fatima Syeda,Asad Ali,Farrah Zaidi,Basit Rasheed Syed,Mehreen Fatima,Muhammad Khisroon
Tropical medicine & international health : TM & IH
OBJECTIVE:Two principal vector species, Aedes aegypti and Aedes albopictus, are known for transmission of dengue (DEN) and chikungunya (CHK) in Pakistan. We aimed to investigate their spatial and temporal distribution. METHODS AND RESULTS:The Maximum Entropy algorithm revealed current climatic suitability of A. albopictus by highlighting variables contributing to its spatial distribution: Land use cover was the most important environmental factor (63.1%) followed by elevation-normalised difference vegetation index (10.9%), NDVI (8.5%) and annual precipitation (7.9%). As per Normalized Difference Vegetation Index values, the vector's presence was highly likely in areas with little vegetation such as built-up spaces or uncultivated fields, and in areas with sparse vegetation such as grasslands and cultivated fields. Temperature variables showed differing effects on vector ecology with annual temperature being the most important. Logistic regression models showed that presence of the vector, build-up and distance to roads contributed significantly to the distribution of both DEN and CHIK. CONCLUSION:In Swabi, the mean temperatures of warmest and driest quarters are more important in the spatial distribution of A. albopictus than mean temperatures of the wettest and coldest quarters. Finally, disease modelling reflects a high probability for both DEN and CHIK in the same regions over a huge area.
Ultrastructural Analysis of Chikungunya Virus Dissemination from the Midgut of the Yellow Fever Mosquito, .
Kantor Asher M,Grant DeAna G,Balaraman Velmurugan,White Tommi A,Franz Alexander W E
The transmission cycle of chikungunya virus (CHIKV) requires that mosquito vectors get persistently infected with the virus, following its oral acqsuisition from a vertebrate host. The mosquito midgut is the initial organ that gets infected with orally acquired CHIKV. Following its replication in the midgut epithelium, the virus exits the midgut and infects secondary tissues including the salivary glands before being transmitted to another host. Here, we investigate the pattern of CHIKV dissemination from the midgut of at the ultrastructural level. Bloodmeal ingestion caused overstretching of the midgut basal lamina (BL), which was disrupted in areas adjacent to muscles surrounding the midgut as shown by scanning electron microscopy (SEM). Using both transmission electron microscopy (TEM) and focused ion beam scanning electron microscopy (FIB-SEM) to analyze midgut preparations, mature chikungunya (CHIK) virions were found accumulating at the BL and within strands of the BL at 24⁻32 h post-infectious bloodmeal (pibm). From 48 h pibm onwards, virions no longer congregated at the BL and became dispersed throughout the basal labyrinth of the epithelial cells. Ingestion of a subsequent, non-infectious bloodmeal caused mature virions to congregate again at the midgut BL. Our study suggests that CHIKV needs a single replication cycle in the midgut epithelium before mature virions directly traverse the midgut BL during a relatively narrow time window, within 48 h pibm.
Regulatory considerations in development of vaccines to prevent disease caused by Chikungunya virus.
Yang Sixun,Fink Doran,Hulse Andrea,Pratt R Douglas
Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus. Chikungunya disease (CHIK) in humans is characterized by sudden onset of high fever, cutaneous rash, myalgia and debilitating polyarthralgia. Until recently the virus was considered endemic to only Africa and Asia, but since 2004 CHIK has spread to previously non-endemic regions, including Europe and the Americas, thereby emerging as a global health threat. Although a variety of CHIKV vaccine candidates have been tested in animals, and a few have advanced to human clinical trials, no licensed vaccine is currently available for prevention of disease. In this article, we review recent efforts in CHIKV vaccine development and discuss regulatory considerations for CHIKV vaccine licensure under U.S. FDA regulations. Several licensure pathways are available, and the most appropriate licensure pathway for a CHIK vaccine will depend on the type of evidence that can be generated to demonstrate the vaccine's effectiveness. If "traditional approval" following demonstration of direct benefit in adequate and well-controlled clinical disease endpoint studies is not possible, the Accelerated Approval and Animal Rule pathways are potential alternatives. In terms of vaccine safety, the potential for vaccine associated arthralgia and antibody-dependent enhancement of infectivity and disease severity are important issues that should be addressed in both pre-clinical and clinical studies. CHIK vaccine developers are encouraged to communicate with the FDA during all stages of vaccine development.
Management of chikungunya arthritis.
Kennedy Amaral Pereira J,Schoen Robert T
Chikungunya fever (CHIKF) is an emerging viral infection that has spread widely, along with its Aedes vectors, throughout the tropics and beyond, causing explosive epidemics of both acute illness and persistent disabling arthritis. There is an urgent need to mitigate the devastating impact of this illness, through vector control, personal protection, and possibly vaccine development. There is also a need to improve treatment for both acute illness and chronic arthritis. In this review, we will review the emergence of CHIK, what is known about pathogenesis and clinical manifestations, and then focus on current understanding of how to treat individual patients, in particular, those who develop chronic arthritis.
Treatment of chikungunya chronic arthritis: A systematic review.
Sales Gabriella Maria Pitt Gameiro,Barbosa Izabel Crystine Pereira,Canejo Neta Laura Maia Sampaio,Melo Paloma Lopes de,Leitão Raphael de Azevedo,Melo Hugo Moura de Albuquerque
Revista da Associacao Medica Brasileira (1992)
INTRODUCTION:Chikungunya (CHIK) is a tropical arbovirus, transmitted by the female mosquito Aedes aegypti and Aedes albopictus. In Brazil, there have been cases reported since 2014. The initial manifestations of this virus are sudden onset high fever, headache, chills, rashes, myalgia and intense joint pain. Usually, CHIK presents the acute and chronic phases, the latter characterized by bilateral polyarthralgia, which can last for months or even years. During this period, autoimmune diseases can be triggered, making the picture even more complicated. METHOD:A systematic review was performed on the PubMed and Scielo databases in January 2017. Clinical trials, cohorts, case-control and case reports were included in the study. Expert opinions, societal consensuses and literary reviews were exclusion criteria. Studies were conducted in English, Spanish and Portuguese. The studies were descriptively analyzed and the data was grouped according to methodological similarity. RESULTS:Twenty-four (24) articles were selected and, in compliance with the inclusion and exclusion criteria, 18 were eliminated, with six studies remaining in the present review: five clinical trials and one case report. CONCLUSION:When the manifestations of CHIK become chronic and, the longer they last, more complications arise. Polyarthralgia can be immaterial, distancing individuals from their daily-life activities. Anti-inflammatory drugs (either steroid or not), in addition to immunosuppressants, homeopathy and physiotherapy are measures of treatment that, according to the literature, have been successful in relieving or extinguishing symptoms. However, it is fundamental that studies of CHIK treatment be further developed.
Computer-Aided Structure Based Drug Design Approaches for the Discovery of New Anti-CHIKV Agents.
Jadav Surender Singh,Sinha Barij Nayan,Hilgenfeld Rolf,Jayaprakash Venkatesan
Current computer-aided drug design
BACKGROUND:Chikungunya is a viral infection caused by Chikungunya virus (CHIKV), an arbovirus transmitted through mosquito (Aedes aegypti and Aedes albopictus) bite. The virus from sylvatic cycle in Africa mutated to new vector adaptation and became one of the major emerging and re-emerging viral infections in the past decade, affecting more than 40 countries. Efforts are being made by many researches to develop means to prevent and control the infection through vaccines and vector control strategy. On the other hand, search for novel chemotherapeutic agents for the treatment of infected patients is on. Approach of repurposed drug is one way of identifying an existing drug for the treatment of CHIKV infection. OBJECTIVE:Review the history of CHIKV nsp2 protease inhibitors derived through structure-based computer-aided drug design along with phytochemicals identified as anti-CHIKV agents. METHODS:A survey on CHIKV inhibitors reported till date has been carriedout. The data obtained were organized and discussed under natural substances and synthetic derivatives obtained as result of rational design. RESULTS:The review provides a well organized content in chronological order that has highly significant information for medicinal chemist who wish to explore the area of Anti-CHIKV drug design and development. Natural compounds with different scaffolds provides an opportunity to explore Ligand based drug design (LBDD), while rational drug design approaches provides opportunity to explore the Structure based drug design. CONCLUSION:From the presented mini-review, readers can understand that this area is less explored and has lots of potential in anti-CHIKVviral drug design & development. of reported literature inferred that, unlike other viral proteases, the nsP2 protease can be targeted for CHIKV viral inhibition. The HTVS process for the identification of anti-CHIK agents provided a few successive validated lead compounds against CHIKV infections.
Chikungunya: A rheumatologist's perspective.
Sharma Shefali Khanna,Jain Sanjay
International journal of rheumatic diseases
Chikungunya (CHIK), a viral infection, is transmitted by Aedes mosquitoes. It is characterized by a phase of acute infection, which is sometimes followed by chronic rheumatisim in the form of arthralgia or myalgia that can last for months and even years. Several studies have been conducted to understand the mechanisms underlying inflammation associated with CHIK infection, persistence of viruses in monocytes-macrophages, and their relationship to the chronic symptoms. Chronic arthritis is one of the serious complications of CHIK infection, which is characterized by swelling and acute pain that poorly responds to treatment with analgesics. Such debilitating chronic joint pain mimics that of rheumatic arthritis and significantly compromises the quality of life. Diagnosis is primarily based on the initial viral detection using molecular methods or the use of virus culture, and on the basis of an immune response in the later stages. In the absence of published guidelines, physicians are often limited to prescribing analgesics and steroids for symptomatic care, as there is no accurate approach for the treatment and management of pain. This review aims to focus on the need for appropriate guidelines that will aid in developing suitable pharmacologic treatment to manage pain associated with post-CHIK chronic inflammatory rheumatism.
Chikungunya in kidney transplant recipients: A series of cases.
Pierrotti Lígia Camera,Lopes Max Igor Banks Ferreira,Nascimento Ana Patrícia do,Caiaffa-Filho Hélio,Lemos Francine Brambate Carvalhinho,Reusing José Otto,Sejas Odeli Nicole Encinas,David-Neto Elias,Azevedo Luiz Sergio
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
Chikungunya (CHIK) is a mosquito-borne virus (CHIKV) infection that recently appeared in the Americas and thousands of confirmed cases have been reported in Brazil since the first autochthonous cases were reported in September 2014. We reported four cases of CHIK in kidney transplant recipients. The diagnosis was confirmed by positive CHIKV real-time polymerase chain reaction in two cases and positive CHIKV-IgM serology in two patients. The time between transplantation and CHIKV infection ranged from 2 to 11 years. All of them had arthralgia, and 3 of them had fever. Other symptoms were mild conjunctivitis, rash, and retro-orbital pain. Kidney function remained stable in all cases. In three patients prednisone doses were temporally increased and the symptoms disappeared concurrently with the increase of the dose. As for the fourth patient, the prednisone dose remained unchanged and yet she improved. Other immunosuppressive drugs were not changed for the four cases. As far as we know, there are only two previously reported cases of CHIK among solid organ transplant recipients besides the four cases reported here. Despite the small number of cases, we can speculate that the use of immunosuppression might have played a role in the paucity of symptoms and the gradual complete recovery with no complication.
Chikungunya virus: a rheumatologist's perspective.
Runowska Marta,Majewski Dominik,Niklas Karolina,Puszczewicz Mariusz
Clinical and experimental rheumatology
Chikungunya virus (CHIKV) is an arthropod-borne alphavirus, transmitted by Aedes aegypti and Aedes albopictus mosquitoes. It is responsible for a febrile illness, typically accompanied by maculopapular rash and severe, incapacitating arthralgia. The disease, although generally self-limiting, frequently evolves into a long-lasting, debilitating rheumatic disorder, which shares many clinical features with rheumatoid arthritis (RA). The underlying mechanism by which CHIKV induces persistent arthritis remains under investigation, however, currently, attention is drawn to the fact, that chronic chikungunya (CHIK) and RA have many common cellular and cytokine pathways involved in their pathogenesis. Over the past decades, the virus has dispersed unexpectedly from tropical and subtropical regions of Africa and Asia, affecting millions of people worldwide. No licensed vaccine, nor antiviral drug against CHIKV is yet available. Treatment of acute CHIK is symptomatic, whereas in chronic stages, different disease-modifying anti-rheumatic drugs (DMARDs) have been used with variable success. Hence, chronic CHIK is an emerging rheumatic condition that rheumatologists have to deal with. This review provides brief insights into the epidemiology, pathogenesis, clinical features and management of Chikungunya disease, with special regard to post-chikungunya rheumatic disorder and its relationship with RA.
[Co-infection by Chikungunya virus (CHIK-V) and dengue virus (DEN-V) during a recent outbreak in Cali, Colombia: Report of a fatal case].
Rosso Fernando,Pacheco Robinson,Rodríguez Sarita,Bautista Diego
Revista chilena de infectologia : organo oficial de la Sociedad Chilena de Infectologia
The recent outbreaks of Chikungunya (CHIK-V) virus in endemic areas of dengue (DEN-V) could increase the risk of co-infection. CHIK infection has been considered not severe and with very unusual mortality, however DEN is associated with severe manifestations and increased mortality. Little is known about coinfection. It is possible that co-infection could generate severe cases. We present a case report of co-infection DEN-V -3 and CHIK-V in an elderly patient who developed acute renal failure, dengue shock syndrome (DSS), progresses to multiple organ failure and died. With the recent emergence of CHIK-V in Colombia, the possibility of co-infection with DEN-V should be suspected, especially in severe cases.