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1.
Although the acute manifestations of Chikungunya virus (CHIKV) illness are well-documented, few data exist about the long-term rheumatic outcomes of CHIKV-infected patients. We undertook between June and September 2006 a retrospective cohort study aimed at assessing the course of late rheumatic manifestations and investigating potential risk factors associated with the persistence of these rheumatic manifestations over 15 months. 147 participants (>16 yrs) with laboratory-confirmed CHIKV disease diagnosed between March 1 and June 30, 2005, were identified through a surveillance database and interviewed by telephone. At the 15-month-period evaluation after diagnosis, 84 of 147 participants (57%) self-reported rheumatic symptoms. Of these 84 patients, 53 (63%) reported permanent trouble while 31 (37%) had recurrent symptoms. Age ≥45 years (OR = 3.9, 95% CI 1.7–9.7), severe initial joint pain (OR = 4.8, 95% CI 1.9–12.1), and presence of underlying osteoarthritis comorbidity (OR = 2.9, 95% CI 1.1–7.4) were predictors of nonrecovery. Our findings suggest that long-term CHIKV rheumatic manifestations seem to be a frequent underlying post-epidemic condition. Three independent risk factors that may aid in early recognition of patients with the highest risk of presenting prolonged CHIKV illness were identified. Such findings may be particularly useful in the development of future prevention and care strategies for this emerging virus infection.  相似文献   

2.
BackgroundSince 2003, the tropical arthritogenic chikungunya (CHIK) virus has become an increasingly medical and economic burden in affected areas as it can often result in long-term disabilities. The clinical spectrum of post-CHIK (pCHIK) rheumatic disorders is wide. Evidence-based recommendations are needed to help physicians manage the treatment of afflicted patients.ResultsWe reviewed 159 patient medical files. Ninety-four patients (59%) who were free of any articular disorder prior to CHIK met the CIR criteria: rheumatoid arthritis (n=40), spondyloarthritis (n=33), undifferentiated polyarthritis (n=21). Bone lesions detectable by radiography occurred in half of the patients (median time: 3.5 years pCHIK). A positive therapeutic response was achieved in 54 out of the 72 patients (75%) who were treated with methotrexate (MTX). Twelve out of the 92 patients (13%) received immunomodulatory biologic agents due to failure of contra-indication of MTX treatment. Other patients mainly presented with mechanical shoulder or knee disorders, bilateral distal polyarthralgia that was frequently associated with oedema at the extremities and tunnel syndromes. These pCHIK musculoskeletal disorders (MSDs) were managed with pain-killers, local and/or general anti-inflammatory drugs, and physiotherapy.ConclusionRheumatologists in Reunion Island managed CHIK rheumatic disorders in a pragmatic manner following the outbreak in 2006. This retrospective study describes the common mechanical and inflammatory pCHIK disorders. We provide a diagnostic and therapeutic algorithm to help physicians deal with chronic patients, and to limit both functional and economic impacts. The therapeutic indication of MTX in pCHIK CIR could be approved in future efficacy trials.  相似文献   

3.
BackgroundChikungunya fever is considered an abrupt onset arbovirus transmitted by mosquitoes, mainly Aedes aegypti and Aedes albopictus. The disease has a significant impact on the quality of life of affected persons, and many of its numerous symptoms have not yet been properly clarified, such as the manifestations that can occur in the oral cavity. The aim of this study was to identify the main oral manifestations related to chikungunya fever, as well as describe the demographic characteristics of patients, by conducting a systematic review of the literature.Methods and findingsSearches were performed in MEDLINE (PubMed), Embase (Elsevier), LILACS (VHL), Cochrane Library, Scopus, and CAPES electronic databases for theses and dissertations published up to January 16, 2021 without language and date restrictions. Additional manual searches of gray literature, reference list, and Google Scholar were carried out. We included 27 studies highlighting mainly oral manifestations that cause masticatory discomfort such as ulcers and oral thrush, gingival bleeding, pain and burning of the oral mucous membranes, temporomandibular joint (TMJ) arthralgia, opportunistic infections, and changes in taste.ConclusionsThere seems to be a predominance of oral manifestations that cause discomfort when chewing, such as ulcerations in the acute phase of the disease, with complete remission within 3 to 10 days after the onset, apparently mostly affecting women and older persons. These oral manifestations can be compatible with basic viral infections related to inflammatory response and transitory immunosuppression.  相似文献   

4.

Background

Arthritogenic alphaviruses, including Chikungunya virus (CHIKV), are responsible for acute fever and arthralgia, but can also lead to chronic symptoms. In 2006, a Chikungunya outbreak occurred in La Réunion Island, during which we constituted a prospective cohort of viremic patients (n = 180) and defined the clinical and biological features of acute infection. Individuals were followed as part of a longitudinal study to investigate in details the long-term outcome of Chikungunya.

Methodology/Principal Findings

Patients were submitted to clinical investigations 4, 6, 14 and 36 months after presentation with acute CHIKV infection. At 36 months, 22 patients with arthralgia and 20 patients without arthralgia were randomly selected from the cohort and consented for blood sampling. During the 3 years following acute infection, 60% of patients had experienced symptoms of arthralgia, with most reporting episodic relapse and recovery periods. Long-term arthralgias were typically polyarthralgia (70%), that were usually symmetrical (90%) and highly incapacitating (77%). They were often associated with local swelling (63%), asthenia (77%) or depression (56%). The age over 35 years and the presence of arthralgia 4 months after the disease onset are risk factors of long-term arthralgia. Patients with long-term arthralgia did not display biological markers typically found in autoimmune or rheumatoid diseases. These data helped define the features of CHIKV-associated chronic arthralgia and permitted an estimation of the economic burden associated with arthralgia.

Conclusions/Significance

This study demonstrates that chronic arthralgia is a frequent complication of acute Chikungunya disease and suggests that it results from a local rather than systemic inflammation.  相似文献   

5.
6.
《Endocrine practice》2022,28(9):842-846
ObjectiveThyroid eye disease (TED) is an autoimmune, inflammatory disease resulting in retro-orbital fat and extraocular muscle expansion. TED quiets (“inactivates”) as inflammation wanes; however, signs/symptoms often persist. Signs/symptoms of the disease and the impact on quality of life (QoL) were examined in noninflammatory and inflammatory TED.MethodsData of patients with moderate-to-severe TED were collected from treating physicians. Clinical activity score (CAS, 6/7 measures available) was used to classify TED as inflammatory (CAS ≥ 3) or noninflammatory (CAS = 0 or 1). QoL impact was scored as 1 = “not at all impaired” to 7 = “extremely impaired.” Patients with noninflammatory TED were further grouped into longer (>3 years) and shorter (≤3 years) disease courses.ResultsPatients with inflammatory (N = 307) and noninflammatory (N = 281) TED had comparable age (50.0 ± 13.3 years vs 48.3 ± 13.8 years), gender (66% men vs 64% women), TED duration (4.0 ± 4.9 years vs 4.6 ± 5.5 years), and proportion of smokers (15% vs 11%). The most common signs/symptoms of noninflammatory TED included ocular dryness/grittiness (77%), proptosis (56%), excessive tearing (43%), soft tissue edema (42%), conjunctival redness (24%) decreased vision (24%), and eye muscle involvement (22%; 14% had diplopia). All signs/symptoms were less frequently reported in these patients than in those with inflammatory TED. QoL was impacted by noninflammatory TED, although to a lesser degree than the inflammatory disease (3.6 ± 1.5 vs 4.7 ± 1.4). However, mental health issues were similarly reported. Patients with noninflammatory TED with a longer disease course (9.0 ± 6.0 years) had similar QoL impact, mental health diagnoses, and TED signs/symptoms as those with a shorter disease course (1.4 ± 1.0 years).ConclusionThe signs/symptoms of TED often chronically persist long after TED has “quieted,” continuing to impact a patient’s QoL and mental health. These data suggest that moderate-to-severe TED should be thought of as a robust symptomatic chronic disease, regardless of its inflammatory status.  相似文献   

7.
BackgroundChikungunya and dengue are emerging diseases that have caused large outbreaks in various regions of the world. Both are both spread by Aedes aegypti and Aedes albopictus mosquitos. We developed a dynamic transmission model of chikungunya and dengue, calibrated to data from Colombia (June 2014 –December 2017).Methodology/Principal findingsWe evaluated the health benefits and cost-effectiveness of residual insecticide treatment, long-lasting insecticide-treated nets, routine dengue vaccination for children aged 9, catchup vaccination for individuals aged 10–19 or 10–29, and portfolios of these interventions. Model calibration resulted in 300 realistic transmission parameters sets that produced close matches to disease-specific incidence and deaths. Insecticide was the preferred intervention and was cost-effective. Insecticide averted an estimated 95 chikungunya cases and 114 dengue cases per 100,000 people, 61 deaths, and 4,523 disability-adjusted life years (DALYs). In sensitivity analysis, strategies that included dengue vaccination were cost-effective only when the vaccine cost was 14% of the current price.Conclusions/SignificanceInsecticide to prevent chikungunya and dengue in Colombia could generate significant health benefits and be cost-effective. Because of limits on diagnostic accuracy and vaccine efficacy, the cost of dengue testing and vaccination must decrease dramatically for such vaccination to be cost-effective in Colombia. The vectors for chikungunya and dengue have recently spread to new regions, highlighting the importance of understanding the effectiveness and cost-effectiveness of policies aimed at preventing these diseases.  相似文献   

8.
The recent outbreak of Chikungunya virus in Thailand caused a rheumatic fever associated with considerable morbidity and fatalities. Thus, it is important to identify biomarker(s) of severe disease induced by this threatening arbovirus. Putative biomarkers in cases of chikungunya fever during an outbreak in the southern part of Thailand in 2009-2010 were identified. Sixty-two patients who had developed fever and myalgia, with or without arthralgia/arthritis, were enrolled and grouped into severe chikungunya fever (CHIKF) (n= 15), mild CHIKF (n= 20) and non-CHIKF (n= 27) to investigate circulating immunological mediators that might serve as markers of severity. Blood samples were taken at presentation (day 1) and 30 days later (day 30) and plasma concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-17, tumor necrosis factor-alpha, monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-1, tissue inhibitor of matrix metalloproteinase-1 and viral load were measured by ELISA. On day 1, severe CHIKF and mild CHIKF groups had viral loads of 10(8.5) and 10(8.3) of RNA copies/mL, respectively. At presentation, all CHIKF patients had circulating concentrations of IL-6 and MCP-1 higher than did non-CHIKF patients, whereas amongst the CHKF patients, the severe CHIKF patients had higher IL-6 concentrations than did mild CHIKF patients. Interestingly, severe CHIKF patients had significantly lower concentrations of circulating IL-8 than the other groups of patients, suggesting that high concentrations of IL-6 and MCP-1 with low concentrations of IL-8 may be a determinant of severe chikungunya virus infection.  相似文献   

9.

Background

Chikungunya (CHIKV) has recently seen a re-emergence in India with high morbidity. However, the epidemiology and disease burden remain largely undetermined. A prospective multi-centric study was conducted to evaluate clinical, epidemiological and virological features of chikugunya infection in patients with acute febrile illness from various geographical regions of India.

Methods and Findings

A total of 540 patients with fever of up to 7days duration were enrolled at Karnataka Institute of Medical Sciences (KIMS), Karnataka (South); Sawai Man Singh Medical College (SMS) Rajasthan (West), and All India Institute of Medical Sciences (AIIMS) New Delhi (North) from June 2008 to May 2009. Serum specimens were screened for chikungunya infection concurrently through RT-PCR and serology (IgM). Phylogenetic analysis was performed using Bioedit and Mega2 programs. Chikungunya infection was detected in 25.37% patients by RT-PCR and/or IgM-ELISA. Highest cases were detected in south (49.36%) followed by west (16.28%) and north (0.56%) India. A difference in proportion of positives by RT-PCR/ELISA with regard to duration of fever was observed (p<0.05). Rashes, joint pain/swelling, abdominal pain and vomiting was frequently observed among chikungunya confirmed cases (p<0.05). Adults were affected more than children. Anti-CHIK antibodies (IgM) were detected for more than 60days of fever onset. Phylogenetic analysis based on E1 gene from KIMS patients (n = 15) revealed ∼99% homology clustering with Central/East African genotype. An amino acid change from lysine to glutamine at position 132 of E1 gene was frequently observed among strains infecting children.

Conclusions

The study documented re-emergence of chikungunya in high frequencies and severe morbidity in south and west India but rare in north. The study emphasizes the need for continuous surveillance for disease burden using multiple diagnostic tests and also warrants the need for an appropriate molecular diagnostic for early detection of chikungunya virus.  相似文献   

10.

Background

Chikungunya is a highly debilitating febrile illness caused by Chikungunya virus, a single-stranded RNA virus, which is transmitted by Aedes aegypti or Aedes albopictus mosquito species. The pathogenesis and host responses in individuals infected with the chikungunya virus are not well understood at the molecular level. We carried out proteomic profiling of serum samples from chikungunya patients in order to identify molecules associated with the host response to infection by this virus.

Results

Proteomic profiling of serum obtained from the infected individuals resulted in identification of 569 proteins. Of these, 63 proteins were found to be differentially expressed (≥ 2-fold) in patient as compared to control sera. These differentially expressed proteins were involved in various processes such as lipid metabolism, immune response, transport, signal transduction and apoptosis.

Conclusions

This is the first report providing a global proteomic profile of serum samples from individuals infected with the chikungunya virus. Our data provide an insight into the proteins that are involved as host response factors during an infection. These proteins include clusterin, apolipoproteins and S100A family of proteins.  相似文献   

11.
BackgroundChikungunya fever is an emerging disease caused by the chikungunya virus and is now being spread worldwide by the mosquito Aedes albopictus. The infection can cause a persistent severe joint pain and recent reports link high levels of viremia to neuropathologies and fatalities. The viral protein nsP2 is a multifunctional enzyme that plays several critical roles in virus replication. Virus infection induces oxidative stress in host cells which the virus utilizes to aid viral propagation. Cellular oxidative stress also triggers glutathionylation which is a post-translational protein modification that can modulate physiological roles of affected proteins.MethodsThe nsP2 protease is necessary for processing of the virus nonstructural polyprotein generated during replication. We use the recombinant nsP2 protein to measure protease activity before and after glutathionylation. Mass spectrometry allowed the identification of the glutathione-modified cysteines. Using immunoblots, we show that the glutathionylation of nsP2 occurs in virus-infected cells.ResultsWe show that in virus-infected cells, the chikungunya nsP2 can be glutathionylated and we show this modification can impact on the protease activity. We also identify 6 cysteine residues that are glutathionylated of the 20 cysteines in the protein.ConclusionsThe virus-induced oxidative stress causes modification of viral proteins which appears to modulate virus protein function.General significanceViruses generate oxidative stress to regulate and hijack host cell systems and this environment also appears to modulate virus protein function. This may be a general target for intervention in viral pathogenesis.  相似文献   

12.
13.
India was affected by a major outbreak of chikungunya fever caused by Chikungunya virus (CHIKV) during 2006-2007. Kerala was the worst affected state during 2007 with a contribution of 55.8% suspected cases in the country. However, except for clinically reported case records, no systematic information is available on infection status of CHIKV in the region. Hence, we carried out a post-epidemic survey to estimate seroprevalence status [immunoglobulin G (IgG)] in the community using commercially available indirect immunofluorescence test. This methodology had been reported to be highly specific and sensitive for CHIKV infection. The study area selected was the worst affected mid-highlands region of Kerala which harbour vast area of rubber plantations. The study evidenced 68% of the population to be seropositive for CHIKV IgG. Males were found more affected than females (χ2 = 9.86; p = 0.002). Among males, prevalence was significantly higher in the age classes 21-30 (χ2 = 5.46; p = 0.019) and 31-40 (χ2 = 5.84; p = 0.016) years. This may be due to high occupational risk of the male population engaged in plantation activities exposed to infective bites of Aedes albopictus. The current study provides an insight into the magnitude of CHIKV outbreak in Kerala.  相似文献   

14.
Alphavirus nsP2 proteins are multifunctional and essential for viral replication. The protease role of nsP2 is critical for virus replication as only the virus protease activity is used for processing of the viral non-structural polypeptide. Chikungunya virus is an emerging disease problem that is becoming a world-wide health issue. We have generated purified recombinant chikungunya virus nsP2 proteins, both full length and a truncated protease domain from the C-terminus of the nsP2 protein. Enzyme characterization shows that the protease domain alone has different properties compared with the full length nsP2 protease. We also show chikungunya nsP2 protease possesses different substrate specificity to the canonical alphavirus nsP2 polyprotein cleavage specificity. Moreover, the chikungunya nsP2 also appears to differ from other alphavirus nsP2 in its distinctive ability to recognize small peptide substrates.  相似文献   

15.
Chikungunya virus is transmitted by mosquitoes and causes severe, debilitating infectious arthritis in humans. The need for an animal model to study the disease process and evaluate potential treatments is imminent as the virus continues its spread into novel geographic locations. Golden hamsters (Mesocricetus auratus) are often used as outbred laboratory animal models for arboviral diseases. Here we demonstrate that hamsters inoculated with chikungunya virus developed viremia and histopathologic lesions in their limbs and joints similar to those seen in human patients. The virus disseminated rapidly and was found in every major organ, including brain, within a few days of infection. Hamsters did not manifest overt clinical signs, and the virus was generally cleared within 4 days, followed by a strong neutralizing antibody response. These results indicate that hamsters are highly susceptible to chikungunya virus infection and develop myositis and tenosynovitis similar to human patients followed by a complete recovery. This animal model may be useful for testing antiviral drugs and vaccines.  相似文献   

16.
BackgroundIn 2014, a first outbreak of chikungunya hit the Caribbean area where chikungunya virus (CHIKV) had never circulated before.Methodology/Principal findingsWe conducted a cross-sectional study to measure the seroprevalence of CHIKV immediately after the end of the 2014 outbreak in HIV-infected people followed up in two clinical cohorts at the University hospitals of Guadeloupe and Martinique. Study patients were identified during the first months of 2015 and randomly selected to match the age and sex distribution of the general population in the two islands. They were invited to complete a survey that explored the symptoms consistent with chikungunya they could have developed during 2014 and to have a blood sample drawn for CHIKV serology.The study population consisted of 377 patients (198 in Martinique and 179 in Guadeloupe, 178 men and 199 women), 182 of whom reported they had developed symptoms consistent with chikungunya. CHIKV serology was positive in 230 patients, which accounted for an overall seroprevalence rate of 61% [95%CI 56–66], with only 153 patients who reported symptoms consistent with chikungunya. Most frequent symptoms included arthralgia (94.1%), fever (73.2%), myalgia (53.6%), headache (45.8%), and skin rash (26.1%).Conclusions/SignificanceThis study showed that the seroprevalence of CHIKV infection was 61% after the 2014 outbreak, with one third of asymptomatic infections.Trial registrationClinicalTrials.gov NCT 02553369.  相似文献   

17.

Introduction

Viral etiologies of fever, including dengue, Chikungunya, influenza, rota and adeno viruses, cause major disease burden in tropical and subtropical countries. The lack of diagnostic facilities in developing countries leads to failure to estimate the true burden of such illnesses, and generally the diseases are underreported. These diseases may have similar symptoms with other causes of acute febrile illnesses including malaria and hence clinical diagnosis without laboratory tests can be difficult. This study aimed to identify viral etiologies as a cause of fever in children and their co-infections with malaria.

Methods

A cross sectional study was conducted for 6 months at Kilosa district hospital, Tanzania. The participants were febrile children aged 2–13 years presented at the outpatient department. Diagnostic tests such as IgM and IgG ELISA, and PCR were used.

Results

A total of 364 patients were enrolled, of these 83(22.8%) had malaria parasites, 76 (20.9%) had presumptive acute dengue infection and among those, 29(38.2%) were confirmed cases. Dengue was more likely to occur in children ≥ 5 years than in <5 years (OR 2.28, 95% CI: 1.35–3.86). Presumptive acute Chikungunya infection was identified in 17(4.7%) of patients. We observed no presenting symptoms that distinguished patients with Chikungunya infection from those with dengue infection or malaria. Co-infections between malaria and Chikungunya, malaria and dengue fever as well as Chikungunya and dengue were detected. Most patients with Chikungunya and dengue infections were treated with antibacterials. Furthermore, our results revealed that 5(5.2%) of patients had influenza virus while 5(12.8%) had rotavirus and 2(5.1%) had adenovirus.

Conclusion

Our results suggest that even though viral diseases are a major public health concern, they are not given due recognition as a cause of fever in febrile patients. Emphasis on laboratory diagnostic tests for proper diagnosis and management of febrile patients is recommended.  相似文献   

18.
BackgroundTo evaluate the results of elective isolated surgical aortic valve replacement (SAVR) on quality of life (QoL) in patients > 75 years.Methods138 patients operated between January 2008 and December 2011 were included. The EuroQOL questionnaire (EQ-5D, EQ-VAS) was completed preoperatively, and 1- and 2-years postoperatively. The logistic EuroSCORE was used for risk stratification, the Corpus Christi Heart project criteria to assess physical activity.ResultsMean age was 79.5 ± 2.8 years, mean risk 9.7 ± 5.4, hospital mortality 2.8 %. For 115 patients (83.3 %) the preoperative QoL information was complete. Fifty patients were classified as sedentary. In the first postoperative year 13 patients died, mostly sedentary patients (p = 0.046) with a low EQ-5D (p = 0.017). There was no QoL information on 32 survivors, mostly sedentary patients (p = 0.001). The 70 patients with QoL information showed an increased QoL (NS). Two years postoperatively, 16 patients died, significantly more sedentary patients (p = 0.015) with a low EQ-5D (p = 0.006). For 42 survivors, there was no QoL information; these were mostly sedentary patients (p = 0.021). The 57 patients with 2-year QoL information had an increased EQ-5D (NS) and EQ-VAS (p = 0.024).ConclusionsQoL increases after SAVR. However, the patients lost to follow-up were mostly sedentary or had a low preoperative QoL, which can lead to biased results.  相似文献   

19.
The total radical-trapping antioxidative capacity (TRAC) of plasma was evaluated in samples from patients suffering from various inflammatory and autoimmune rheumatic diseases (n=104) and correlated with the phorbol ester-stimulated chemiluminescence (CL) of neutrophils and monocytes in unseparated blood. Plasma and blood samples from age- and sex-matched healthy volunteers (n=25) and from patients with non-rheumatic internal diseases (n=31) served as controls.

A 2 to 10 fold increase in whole blood chemiluminescence was found in rheumatic patients, which paralleled 50–80% decreased levels of plasma TRAC-values. While significant correlations between CL and TRAC were determined for patients with inflammatory arthritic diseases no correlations were found with patients suffering from connective tissue diseases. Prednisolone treatment of individual patients increased plasma TRAC-values substantially and decreased elevated levels of phagocytic CL generation to that of healthy controls.

The main potential application of the assays described here is for the convenient assessment of disease activity and progression in individual patients with rheumatic diseases.  相似文献   

20.
BackgroundChikungunya fever (CHIKF) is a serious public health problem with a high rate of infection and chronic disabling manifestations that has affected more than 2 million people worldwide since 2005. In spite of this, epidemiological data on vulnerable groups such as Indigenous people are scarce, making it difficult to implement public policies in order to prevent this disease and assist these populations.ObjectiveTo describe the serological and epidemiological profile of chikungunya virus (CHIKV) in two Indigenous populations in Northeast Brazil, as well as in an urbanized control community, and to explore associations between CHIKV and anthropometric variables in these populations.Methodology/Principal findingsThis is a cross-sectional ancillary study of the Project of Atherosclerosis among Indigenous Populations (PAI) that included people 30 to 70 years old, recruited from two Indigenous tribes (the less urbanized Fulni-ô and the more urbanized Truká people) and an urbanized non-Indigenous control group from the same area. Subjects underwent clinical evaluation and were tested for anti-CHIKV IgG by enzyme-linked immunosorbent assay. Serological profile was described according to ethnicity, sex, and age. The study population included 433 individuals distributed as follows: 109 (25·2%) Truká, 272 (62·8%) Fulni-ô, and 52 (12%) from the non-Indigenous urbanized control group. Overall prevalence of CHIKV IgG in the study sample was 49.9% (216; 95% CI: 45·1–54·7). When the sample was stratified, positive CHIKV IgG was distributed as follows: no individuals in the Truká group, 78·3% (213/272; 95% CI: 72·9–83·1) in the Fulni-ô group, and 5.8% (3/52; 95% CI: 1.21–16) in the control group.Conclusions/SignificancePositive tests for CHIKV showed a very high prevalence in a traditional Indigenous population, in contrast to the absence of anti-CHIKV serology in the Truká people, who are more urbanized with respect to physical landscape, socio-cultural, and historical aspects, as well as a low prevalence in the non-Indigenous control group, although all groups are located in the same area.  相似文献   

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