Multicenter study of the natural history and therapeutic responses of patients with chikungunya, focusing on acute and chronic musculoskeletal manifestations - a study protocol from the clinical and applied research in Chikungunya (REPLICK network).

BACKGROUND: Chikungunya is associated with high morbidity and the natural history of symptomatic infection has been divided into three phases (acute, post-acute, and chronic) according to the duration of musculoskeletal symptoms. Although this classification has been designed to help guide therapeutic decisions, it does not encompass the complexity of the clinical expression of the disease and does not assist in the evaluation of the prognosis of severity nor chronic disease. Thus, the current challenge is to identify and diagnose musculoskeletal disorders and to provide the optimal treatment in order to prevent perpetuation or progression to a potentially destructive disease course. METHODS: The study is the first product of the Clinical and Applied Research Network in Chikungunya (REPLICK). This is a prospective, outpatient department-based, multicenter cohort study in Brazil. Four work packages were defined: i. Clinical research; ii) Translational Science - comprising immunology and virology streams; iii) Epidemiology and Economics; iv) Therapeutic Response and clinical trials design. Scheduled appointments on days 21 (D21) ± 7 after enrollment, D90 ± 15, D120 ± 30, D180 ± 30; D360 ± 30; D720 ± 60, and D1080 ± 60 days. On these visits a panel of blood tests are collected in addition to the clinical report forms to obtain data on socio-demographic, medical history, physical examination and questionnaires devoted to the evaluation of musculoskeletal manifestations and overall health are performed. Participants are asked to consent for their specimens to be maintained in a biobank. Aliquots of blood, serum, saliva, PAXgene, and when clinically indicated to be examined, synovial fluid, are stored at -80° C. The study protocol was submitted and approved to the National IRB and local IRB at each study site. DISCUSSION: Standardized and harmonized patient cohorts are needed to provide better estimates of chronic arthralgia development, the clinical spectra of acute and chronic disease and investigation of associated risk factors. This study is the largest evaluation of the long-term sequelae of individuals infected with CHIKV in the Brazilian population focusing on musculoskeletal manifestations, mental health, quality of life, and chronic pain. This information will both define disease burden and costs associated with CHIKV infection, and better inform therapeutic guidelines.

Chikungunya in Brazil: An epidemic of high cost for private healthcare, 2017.

OBJECTIVE: We evaluated the impact of direct and indirect medical costs incurred through chikungunya infections in patients treated in Fortaleza, Brazil. METHODS: Cross-sectional study about the cost of illness. The valuation method of medical costs was based on the micro-costing approach (bottom-up). The study was carried out in a large general hospital of the private health network. The study population consisted of patients treated as suspected cases of chikungunya and hospital professionals who applied for sick leave due to chikungunya. RESULTS: In 2017, there were 2683 patients treated at this hospital who incurred an estimated cost of $383,514.40. From this amount, $174,322.91 (45.5%) were expended on emergency care, $194,700.59 (50.8%) on hospitalisations. 123 hospital professionals were infected with chikungunya and sick leave duration ranged between 1 and 19 days. Health professionals generated 746 days of absence and an amount of $14,490.90 due to absenteeism from work related to chikungunya. 31 symptoms were reported, especially arthralgia (91.1%) and fever (79.4%). There was a predominance of females (58.8%) and the age group of 20-39 years (42.1%). CONCLUSION: The average cost of admissions was over $2400. Considering the epidemic potential of chikungunya, our data indicate the huge economic burden of this disease to healthcare units in the presence of epidemics. Economic factors, added to the loss of life and the consequences of chronic chikungunya, make this disease a real scourge for countries with fewer material resources.

Fatal Outcome of Chikungunya Virus Infection in Brazil.

BACKGROUND: Chikungunya virus (CHIKV) emerged in the Americas in 2013 and has caused approximately 2.1 million cases and >600 deaths. A retrospective investigation was undertaken to describe clinical, epidemiological, and viral genomic features associated with deaths caused by CHIKV in Ceará state, northeast Brazil. METHODS: Sera, cerebrospinal fluid (CSF), and tissue samples from 100 fatal cases with suspected arbovirus infection were tested for CHIKV, dengue virus (DENV), and Zika virus (ZIKV). Clinical, epidemiological, and death reports were obtained for patients with confirmed CHIKV infection. Logistic regression analysis was undertaken to identify independent factors associated with risk of death during CHIKV infection. Phylogenetic analysis was conducted using whole genomes from a subset of cases. RESULTS: Sixty-eight fatal cases had CHIKV infection confirmed by reverse-transcription quantitative polymerase chain reaction (52.9%), viral antigen (41.1%), and/or specific immunoglobulin M (63.2%). Co-detection of CHIKV with DENV was found in 22% of fatal cases, ZIKV in 2.9%, and DENV and ZIKV in 1.5%. A total of 39 CHIKV deaths presented with neurological signs and symptoms, and CHIKV-RNA was found in the CSF of 92.3% of these patients. Fatal outcomes were associated with irreversible multiple organ dysfunction syndrome. Patients with diabetes appear to die at a higher frequency during the subacute phase. Genetic analysis showed circulation of 2 CHIKV East-Central-South African (ECSA) lineages in Ceará and revealed no unique virus genomic mutation associated with fatal outcome. CONCLUSIONS: The investigation of the largest cross-sectional cohort of CHIKV deaths to date reveals that CHIKV-ECSA strains can cause death in individuals from both risk and nonrisk groups, including young adults.

Chikungunya and diabetes, what do we know?

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.