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Defining cases of Zika virus (ZIKV) infection is a critical challenge for epidemiological research. Due to ZIKV’s overlapping clinical features and potential immunologic cross-reactivity with other flaviviruses and the current lack of an optimal ZIKV-specific diagnostic assay, varying approaches for identifying ZIKV infections have been employed to date. This paper presents the laboratory results and diagnostic criteria developed by the Microcephaly Epidemic Research Group for defining cases of maternal ZIKV infection in a cohort of pregnant women with rash (N = 694) recruited during the declining 2015–2017 epidemic in northeast Brazil. For this investigation, we tested maternal sera for ZIKV by quantitative reverse transcription polymerase chain reaction (qRT-PCR), Immunoglobulin (Ig) M and IgG3 enzyme-linked immunosorbent assays (ELISAs), and Plaque Reduction Neutralization Test (PRNT50). Overall, 23.8% of participants tested positive by qRT-PCR during pregnancy (range of detection: 0–72 days after rash onset). However, the inter-assay concordance was lower than expected. Among women with qRT-PCR-confirmed ZIKV and further testing, only 10.1% had positive IgM tests within 90 days of rash, and only 48.5% had ZIKV-specific PRNT50 titers ≥20 within 1 year of rash. Given the complexity of these data, we convened a panel of experts to propose an algorithm for identifying ZIKV infections in pregnancy based on all available lines of evidence. When the diagnostic algorithm was applied to the cohort, 26.9% of participants were classified as having robust evidence of a ZIKV infection during pregnancy, 4.0% as having moderate evidence, 13.3% as having limited evidence of a ZIKV infection but with uncertain timing, and 19.5% as having evidence of an unspecified flavivirus infection before or during pregnancy. Our findings suggest that integrating longitudinal data from nucleic acid and serologic testing may enhance diagnostic sensitivity and underscore the need for an on-going dialogue regarding the optimization of strategies for defining cases of ZIKV in research. [ABSTRACT FROM AUTHOR]

Saturnalia tupiniquim is a sauropodomorph dinosaur from the Late Triassic (Carnian–c. 233 Ma) Santa Maria Formation of Brazil. Due to its phylogenetic position and age, it is important for studies focusing on the early evolution of both dinosaurs and sauropodomorphs. The osteology of Saturnalia has been described in a series of papers, but its cranial anatomy remains mostly unknown. Here, we describe the skull bones of one of its paratypes (only in the type-series to possess such remains) based on CT Scan data. The newly described elements allowed estimating the cranial length of Saturnalia and provide additional support for the presence of a reduced skull (i.e. two thirds of the femoral length) in this taxon, as typical of later sauropodomorphs. Skull reduction in Saturnalia could be related to an increased efficiency for predatory feeding behaviour, allowing fast movements of the head in order to secure small and elusive prey, a hypothesis also supported by data from its tooth and brain morphology. A principal co-ordinates analysis of the sauropodomorph jaw feeding apparatus shows marked shifts in morphospace occupation in different stages of the first 30 million years of their evolutionary history. One of these shifts is observed between non-plateosaurian and plateosaurian sauropodomorphs, suggesting that, despite also having an omnivorous diet, the feeding behaviour of some early Carnian sauropodomorphs, such as Saturnalia, was markedly different from that of later Triassic taxa. A second shift, between Late Triassic and Early Jurassic taxa, is congruent with a floral turnover hypothesis across the Triassic-Jurassic boundary. [ABSTRACT FROM AUTHOR]

Marine environments are visual domains restricted regarding light characteristics. Overall, blue monochromatic spectrum prevails in offshore areas especially below 15m depth, since long wavelengths are quickly attenuated. Light intensity is even more constrained in coastal waters, particularly those of tropical estuaries and bays, because further scattering through dissolved and suspended materials. Biofluorescence, which is the ability of organisms to absorb light and reflect it in a different wavelength, has been reported for many marine fish. In this paper, biofluorescence was recorded for the first time for the longsnout seahorse Hippocampus reidi, under natural conditions at Ilha Grande bay, Brazil, and both adult, juvenile and fry individuals kept in captivity. Although displaying the same colour emissions, seahorses differed in relation to body lighting, colour patterns, and age wherein fluorescence occurs. Newborn seahorses exhibit green biofluorescence only in the eyes and stomach. Further experiments are necessary to address whether H. reidi can change the patterns of biofluorescence emission for sensorial and social purposes. [ABSTRACT FROM AUTHOR]

Primary health care has been recognized as a critical strategy for improving population health in developing countries. This paper investigates the effect of primary care physicians on the infant mortality rate in Brazil using a dynamic panel data approach. This method accounts for the endogeneity problem and the persistence of infant mortality over time. The empirical analysis uses an eight-year panel of municipalities between 2005 and 2012. The results indicate that primary care physician supply contributed to the decline of infant mortality in Brazil. An increase of one primary care physician per 10,000 population was associated with 7.08 fewer infant deaths per 10,000 live births. This suggests that, in addition to other determinants, primary care physicians can play an important role in accounting for the reduction of infant mortality rates. [ABSTRACT FROM AUTHOR]

The ability of high school students to know endangered species can vary among species (e.g., large body size can influence people’s interest) or among municipalities (e.g., more contact with biodiversity can influence people’s interest). Thus, in the present paper, we evaluated high school students’ knowledge about the endangered and non-endangered mammalian species of the Brazilian Cerrado. We tested whether the recognition of the endangered and non-endangered species varied in a cross-species analysis (twelve total species) according to species characteristics, such as body size, popularity, endangered status and the length of time of inclusion on the endangered species list. Moreover, we tested whether the recognition of the endangered mammal species varied between municipalities (spatial analysis). We interviewed 366 students in their first year of high school in 21 schools (one in each municipality). Our results indicated that the proportion of correctly identified endangered species varied according to species (cross-species). The endangered species that were most often correctly identified were Myrmecophaga tridactyla (known by its popular name, Tamanduá-bandeira, in Brazil), Priodontes maximus (Tatu canastra) and Panthera onca (onça-pintada), with more than 80% correct answers. Thus, students tended to recognize the more popular species and the endangered species more than the non-endangered species. The analysis of student knowledge according to municipality demonstrated that the students’ ability to recognize endangered species followed a spatial pattern. Finally, the cross-species and spatial variation patterns detected in the present study indicated the importance of formal education in increasing high school students’ knowledge about endangered species and suggested that education should also promote less well-known species, species with smaller body sizes, and other groups of vertebrates and invertebrates and consider local and regional biodiversity whenever possible. [ABSTRACT FROM AUTHOR]

Background: Measures to ensure research integrity have been widely discussed due to the social, economic and scientific impact of research integrity. In the past few years, financial support for health research in emerging countries has steadily increased, resulting in a growing number of scientific publications. These achievements, however, have been accompanied by a rise in retracted publications followed by concerns about the quality and reliability of such publications. Objective: This systematic review aimed to investigate the profile of medical and life sciences research retractions from authors affiliated with Brazilian academic institutions. The chronological trend between publication and retraction date, reasons for the retraction, citation of the article after the retraction, study design, and the number of retracted publications by author and affiliation were assessed. Additionally, the quality, availability and accessibility of data regarding retracted papers from the publishers are described. Methods: Two independent reviewers searched for articles that had been retracted since 2004 via PubMed, Web of Science, Biblioteca Virtual em Saúde (BVS) and Google Scholar databases. Indexed keywords from Medical Subject Headings (MeSH) and Descritores em Ciências da Saúde (DeCS) in Portuguese, English or Spanish were used. Data were also collected from the Retraction Watch website (). This study was registered with the PROSPERO systematic review database (CRD42017071647). Results: A final sample of 65 articles was retrieved from 55 different journals with reported impact factors ranging from 0 to 32.86, with a median value of 4.40 and a mean of 4.69. The types of documents found were erratum (1), retracted articles (3), retracted articles with a retraction notice (5), retraction notices with erratum (3), and retraction notices (45). The assessment of the Retraction Watch website added 8 articles that were not identified by the search strategy using the bibliographic databases. The retracted publications covered a wide range of study designs. Experimental studies (40) and literature reviews (15) accounted for 84.6% of the retracted articles. Within the field of health and life sciences, medical science was the field with the largest number of retractions (34), followed by biological sciences (17). Some articles were retracted for at least two distinct reasons (13). Among the retrieved articles, plagiarism was the main reason for retraction (60%). Missing data were found in 57% of the retraction notices, which was a limitation to this review. In addition, 63% of the articles were cited after their retraction. Conclusion: Publications are not retracted solely for research misconduct but also for honest error. Nevertheless, considering authors affiliated with Brazilian institutions, this review concluded that most of the retracted health and life sciences publications were retracted due to research misconduct. Because the number of publications is the most valued indicator of scientific productivity for funding and career progression purposes, a systematic effort from the national research councils, funding agencies, universities and scientific journals is needed to avoid an escalating trend of research misconduct. More investigations are needed to comprehend the underlying factors of research misconduct and its increasing manifestation. [ABSTRACT FROM AUTHOR]

During the last years, the new science of cities has been established as a fertile quantitative approach to systematically understand the urban phenomena. One of its main pillars is the proposition that urban systems display universal scaling behavior regarding socioeconomic, infrastructural and individual basic services variables. This paper discusses the extension of the universality proposition by testing it against a broad range of urban metrics in a developing country urban system. We present an exploration of the scaling exponents for over 60 variables for the Brazilian urban system. Estimating those exponents is challenging from the technical point of view because the Brazilian municipalities’ definition follows local political criteria and does not regard characteristics of the landscape, density, and basic utilities. As Brazilian municipalities can deviate significantly from urban settlements, urban-like municipalities were selected based on a systematic density cut-off procedure and the scaling exponents were estimated for this new subset of municipalities. To validate our findings we compared the results for overlaying variables with other studies based on alternative methods. It was found that the analyzed socioeconomic variables follow a superlinear scaling relationship with the population size, and most of the infrastructure and individual basic services variables follow expected sublinear and linear scaling, respectively. However, some infrastructural and individual basic services variables deviated from their expected regimes, challenging the universality hypothesis of urban scaling. We propose that these deviations are a product of top-down decisions/policies. Our analysis spreads over a time-range of 10 years, what is not enough to draw conclusive observations, nevertheless we found hints that the scaling exponent of these variables are evolving towards the expected scaling regime, indicating that the deviations might be temporally constrained and that the urban systems might eventually reach the expected scaling regime. [ABSTRACT FROM AUTHOR]

In recent decades, we have observed an intensification of science, technology and innovation activities in Brazil. The increase in production of scientific papers indexed in international databases, however, has not been accompanied by an equivalent increase in the impact of publications. This paper presents a methodology for analyzing production and the impact of certain research areas in Brazil related to two aspects: the origin of the journals (national or foreign) and international collaboration. These two variables were selected for being of particular importance in understanding the context of scientific production and communication in countries with emerging economies. The sample consisted of papers written by Brazilian researchers in 19 subfields of knowledge published from 2002 to 2011, totaling 85,082 papers. To calculate the impact, we adopted a normalized indicator called the relative subfield citedness (Rw) using a window of 5 years to obtain measurements evaluated in 2 different years: 2007 and 2012. The data on papers and citations were collected from the Web of Science database. From the results, we note that most of the subfields have presented, from one quinquennium to another, improved performance in the world production rankings. Regarding publication in national and foreign journals, we observed a trend in the distribution maintenance of production of the subfields based on the origin of the journal. Specifically, for impact, we identified a lower Rw pattern for Brazilian papers when they were published in national journals in all subfields. When Brazilian products are published in foreign journals, we observed a higher impact for those papers, even surpassing the average global impact in some subfields. For international collaboration, we analyzed the percentage of participation of foreign researchers and the connection between collaboration and the impact of papers, especially emphasizing the distinction of hyperauthorship papers in terms of production and impact. [ABSTRACT FROM AUTHOR]

Obligate river dolphins occur only in the rivers of Asia and South America, where they are increasingly subject to damaging pressures such as habitat degradation, food competition and entanglement in fishing gear as human populations expand. The Amazon basin hosts two, very different, dolphins—the boto or Amazon river dolphin (Inia geoffrensis) and the smaller tucuxi (Sotalia fluviatilis). Both species have wide geographical ranges and were once considered to be relatively abundant. Their IUCN Red List conservation status of Data Deficient (DD), due to limited information on threats, ecology, population numbers and trends, did not initially cause alarm. However, the development of dolphin hunting to provide fish bait at around the beginning of this millennium broadly coincided with the onset of a widespread perception that numbers of both species were in decline. Consequently, the need for population trend data to inform conservation advice and measures became urgent. This paper presents a 22-year time series of standardised surveys for both dolphins within the Mamirauá Reserve, Amazonas State, Brazil. Analysis of these data show that both species are in steep decline, with their populations halving every 10 years (botos) and 9 years (tucuxis) at current rates. These results are consistent with published, independent information on survival rates of botos in this area, which demonstrated a substantial drop in annual survival, commencing at around the year 2000. Mamirauá is a protected area, and is subject to fewer environmental pressures than elsewhere in the region, so there is no reason to suspect that the decline in dolphins within the Reserve is more pronounced than outside it. If South America's freshwater cetaceans are to avoid following their Asian counterparts on the path to a perilous conservation status, effective conservation measures are required immediately. Enforcement of existing fishery laws would greatly assist in achieving this. [ABSTRACT FROM AUTHOR]

Background: Aedes aegypti, vector of dengue, chikungunya and Zika viruses, is found at high densities in tropical urban areas. The dissemination of this vector is partially the consequence of failures in current vector control methods, still mainly relying upon insecticides. In the State of São Paulo (SP), Brazil, public health managers employed pyrethroids against Ae. aegypti adults from 1989 to 2000, when a robust insecticide resistance monitoring system detected resistance to pyrethroids in several Ae. aegypti populations. However, pyrethroids are also the preferred compounds engaged in household applications due to their rapid knockdown effect, lower toxicity to mammals and less irritating smell. Methodology/Principal findings: We evaluated pyrethroid resistance in Ae. aegypti populations over the course of a decade, from 2004 to 2015, after interruption of pyrethroid public applications in SP. Qualitative bioassays with papers impregnated with a deltamethrin diagnostic dose (DD) performed with insects from seven SP municipalities and evaluated yearly from 2006 to 2014, detected resistance in most of the cases. Quantitative bioassays were also carried out with four populations in 2011, suggesting a positive correlation between resistance level and survivorship in the DD bioassays. Biochemical tests conducted with seven insect populations in 2006 and 2015, detected increasing metabolic alterations of all major classes of detoxifying enzymes, mostly of mixed function oxidases. Genotyping of the voltage-gated sodium channel (AaNaV, the pyrethroid target-site) with a TaqMan real time PCR based technique was performed from 2004 to 2014 in all seven localities. The two kdr mutations, Val1016Ile and Phe1534Cys, known to be spread throughout Brazil, were always present with a severe decrease of the susceptible allele over time. Conclusions/Significance: These results are discussed in the context of public and domestic insecticide use, the necessity of implementation of a strong integrated vector control strategy and the conceptual misunderstanding between 'vector control' and 'chemical control of vectors'. [ABSTRACT FROM AUTHOR]

Selection of value chain strategies by development practitioners and value chain participants themselves has been restricted to preset types of upgrading. This paper argues for an extension of the range of strategy solutions to value chains. An empirical application identifies successful strategies for honey value chains in Brazil for 2015–2020. Strategy and performance indicators were selected using the value chain Structure-Conduct-Performance (SCP) framework. Experts’ opinion was elicited in a Delphi for business scenarios, and adaptive conjoint analysis was used to identify strategies for increasing production growth and local value-added. This study identifies important strategies beyond upgrading typologies, and finds that important strategies differ by performance goal and scenario. The value chain SCP allows searching for promising strategies towards performance–the “better deal”–in an integrated way. [ABSTRACT FROM AUTHOR]

Objective: This study analysed clinical and sociodemographic aspects and follow-up for notified cases of tuberculosis (TB) and explored inequalities in incidence rates and outcome by colour or race and the geographic macro-regions of Brazil. Methods: This paper reports the results of a population-based descriptive epidemiological study of all notified cases of TB in Brazil during the period from 01/01/2008 to 31/12/2011. We analysed sociodemographic and clinical variables according to colour or race (white, black, Asian, mixed, and indigenous) and geographic macro-regions of the country (North, Northeast, Central-West, South, and Southeast). Results: During the study period, the average incidence of TB in Brazil was 36.7 cases per 100,000 inhabitants, with the highest rates occurring in the North and Southeast regions. The analysis of TB notifications by colour or race revealed that the indigenous population presented the highest incidence rates in all macro-regions except the South, where higher rates were reported in black patients. ‘Cured’ was the most frequently reported treatment outcome for all skin colour categories. The highest cure rate occurred among the indigenous population (76.8%), while the lowest cure rate occurred among the black population (70.7%). Rates of treatment default were highest among blacks (10.5%) and lowest among the indigenous population (6.9%). However, the fatality rate was similar across race categories, varying between 2.8% and 3.8% for whites and the indigenous population, respectively. The lowest cure rates were observed when follow-up was inadequate (58.3%), and the highest was observed when the follow-up was classified as excellent (96.8%). Conclusions: This study revealed that—apart from the heterogeneous distribution of TB among the Brazilian macro-regions—ethnic-racial inequalities exist in terms of clinical-epidemiological characteristics and incidence rates as well as follow-up for cases undergoing treatment. The highest rates of TB occurred among the indigenous people. [ABSTRACT FROM AUTHOR]

Background: Cesarean delivery rates continue to increase worldwide and reached 57% in Brazil in 2014. Although the safety of this surgery has improved in the last decades, this trend is a concern because it carries potential risks to women’s health and may be a modifiable risk factor of maternal mortality. This paper aims to investigate the risk of postpartum maternal death directly associated with cesarean delivery in comparison to vaginal delivery in Brazil. Methods: This was a population-based case—control study performed in eight Brazilian states. To control for indication bias, deaths due to antenatal morbidity were excluded. We included 73 cases of postpartum maternal deaths from 2009–2012. Controls were selected from the Birth in Brazil Study, a 2011 nationwide survey including 9,221 postpartum women. We examined the association of cesarean section and postpartum maternal death by multivariate logistic regression, adjusting for confounders. Results: After controlling for indication bias and confounders, the risk of postpartum maternal death was almost three-fold higher with cesarean than vaginal delivery (OR 2.87, 95% CI 1.63–5.06), mainly due to deaths from postpartum hemorrhage and complications of anesthesia. Conclusion: Cesarean delivery is an independent risk factor of postpartum maternal death. Clinicians and patients should consider this fact in balancing the benefits and risks of the procedure. [ABSTRACT FROM AUTHOR]

Deforestation in the Brazilian Amazon has dropped substantially after a peak of over 27 thousand square kilometers in 2004. Starting in 2008, the Brazilian Ministry of the Environment has regularly published blacklists of critical districts with high annual forest loss. Farms in blacklisted districts face additional administrative hurdles to obtain authorization for clearing forests. In this paper we add to the existing literature on evaluating the Brazilian anti-deforestation policies by specifically quantifying the impact of blacklisting on deforestation. We first use spatial matching techniques using a set of covariates that includes official blacklisting criteria to identify control districts. We then explore the effect of blacklisting on change in deforestation in double difference regressions with panel data covering the period from 2002 to 2012. Multiple robustness checks are conducted including an analysis of potential causal mechanisms behind the success of the blacklist. We find that the blacklist has considerably reduced deforestation in the affected districts even after controlling for the potential mechanism effects of field-based enforcement, environmental registration campaigns, and rural credit. [ABSTRACT FROM AUTHOR]

Scientific collaboration has been studied by researchers for decades. Several approaches have been adopted to address the question of how collaboration has evolved in terms of publication output, numbers of coauthors, and multidisciplinary trends. One particular type of collaboration that has received very little attention concerns advisor and advisee relationships. In this paper, we examine this relationship for the researchers who are involved in the area of Exact and Earth Sciences in Brazil and its eight subareas. These pairs are registered in the Lattes Platform that manages the individual curricula vitae of Brazilian researchers. The individual features of these academic researchers and their coauthoring relationships were investigated. We have found evidence that there exists positive correlation between time of advisor–advisee relationship with the advisee’s productivity. Additionally, there has been a gradual decline in advisor–advisee coauthoring over a number of years as measured by the Kulczynski index, which could be interpreted as decline of the dependence. [ABSTRACT FROM AUTHOR]

Rabies is a viral zoonosis affecting mammal species and causes large economic losses. Included among the neglected diseases, it is still insufficiently addressed by governments and the international community, despite formal surveillance and control programs. This study used a dataset of 10,112 rabies diagnoses in animals provided by the Brazilian passive surveillance system from 2001 to 2012. The positivity rate of the tested samples was 26.4%, and a reduction in the total samples sent during the last six years was observed. The kernel density map indicated case concentration in the south region and a decrease in density of rabies cases in the second period studied (2007 to 2012). The directional trend of positive rabies diagnoses remained in the south region, as shown by the standard deviational ellipse. The spatial scan statistic identified three large clusters of positive diagnoses, one in the first period (2001-2006) and two in the second period (2007-2012), indicating an expansion of risk areas. The decrease in rabies cases from 2006 to 2012 does not necessarily reflect lower viral circulation or improvement in actions by epidemiological surveillance; this decrease could indicate a deficiency in epidemiological surveillance during the observation period due to the increase in the silent areas. Surveillance should maintain an increasing or constant number of tests during the years in addition to a reduction in the number of outbreaks of rabies, which would indicate a lower positivity rate. The findings in this study indicate deterioration in the effectiveness of the passive surveillance for rabies. The number of rabies cases, total number of tests performed and positivity rate are good indicators for evaluating passive surveillance. This paper can function as a guide for the assessment and improvement of the actions in passive surveillance of rabies. [ABSTRACT FROM AUTHOR]

The techniques used for diagnosis of canine visceral leishmaniasis (CVL) in Brazil ELISA and IFAT have been extensively questioned because of the accuracy of these tests. A recent change in the diagnosis protocol excluded IFAT and included the Dual-Path Platform (DPP). We evaluated the prevalence and incidence rates of Leishmania spp. before and after the change in the protocol. In addition, based on our results, we propose a new alternative that is less expensive for the screening and confirmation of CVL. Plasma samples were obtained from a serobank from dogs evaluated in a cross-sectional study (1,226 dogs) and in a cohort study of susceptible animals (n = 447), followed for 26 months. Serology testing was performed using ELISA, IFAT, and DPP. The incidence and prevalence of CVL were determined by using the protocol of the Visceral Leishmaniasis Control and Surveillance Program until 2012 (ELISA and IFAT using filter paper) and the protocol used after 2012 (DPP and ELISA using plasma). The prevalence was 6.2% and the incidence was 2.8 per 1,000 dog-months for the protocol used until 2012. For the new diagnosis protocol for CVL resulted in an incidence of 5.4 per 1,000 dog-months and a prevalence of 8.1%. Our results showed that the prevalence and incidence of infection were far greater than suggested by the previously used protocol and that the magnitude of infection in endemic areas has been underestimated. As tests are performed sequentially and euthanasia of dogs is carried out when the serological results are positive in both tests, the sequence does not affect the number of animals to be eliminated by the Control Program. Then we suggest to municipalities with a large demand of exams to use ELISA for screening and DPP for confirmation, since this allows easier performance and reduced cost. [ABSTRACT FROM AUTHOR]

Introduction: Progress towards the MDG targets on maternal and child mortality is hindered worldwide by large differentials between poor and rich populations. Using the case of Brazil, we investigate the extent to which policies and interventions seeking to increase the accessibility of health services among the poor have been effective in decreasing neonatal mortality. Methods: With a panel data set for the 4,267 Minimum Comparable Areas (MCA) in Brazil in 1991 and 2000, we use a fixed effect regression model to evaluate the effect of the provision of physicians, nurse professionals, nurse associates and community health workers on neonatal mortality for poor and non-poor areas. We additionally forecasted the neonatal mortality rate in 2005. Results: We find that the provision of health workers is particularly important for neonatal mortality in poor areas. Physicians and especially nurse professionals have been essential in decreasing neonatal mortality: an increase of one nurse professional per 1000 population is associated with a 3.8% reduction in neonatal mortality while an increase of one physician per 1000 population is associated with a 2.3% reduction in neonatal mortality. We also find that nurse associates are less important for neonatal mortality (estimated reduction effect of 1.2% ) and that community health workers are not important particularly among the poor. Differences in the provision of health workers explain a large proportion of neonatal mortality. Discussion: In this paper, we show new evidence to inform decision making on maternal and newborn health. Reductions in neonatal mortality in Brazil have been hampered by the unequal distribution of health workers between poor and non-poor areas. Thus, special attention to a more equitable health system is required to allocate the resources in order to improve the health of poor and ensure equitable access to health services to the entire population. [ABSTRACT FROM AUTHOR]

Background:Factors related to the development of extrapulmonary forms of tuberculosis (EPTB) are still poorly understood, particularly in high-endemic countries like Brazil. The objective of the paper is to determine host and Mycobacterium tuberculosis (MTB) strain-related factors associated with the development of EPTB in Espírito Santo state, Brazil. Methods and Findings:We conducted a retrospective laboratory-based surveillance study of new tuberculosis (TB) cases diagnosed in Espírito Santo state, Brazil between 1998 and 2007. We genotyped 612 isolates of MTB from 606 TB patients using spoligotyping and IS6110-restriction fragment length polymorphism (RFLP) typing and compared sociodemographic and clinical characteristics of patients with pulmonary TB (PTB) and EPTB. Among 606 patients, 464 (77%) had PTB, 79 (13%) had EPTB, 51 (8%) had both, and 12 (2%) had miliary TB. The IS6110 RFLP analysis demonstrated that 250 (41%) isolates belonged to clustered RFLP patterns, 27 (11%) of which were from EPTB. We identified 73 clusters including 35 (48%) composed of 2 isolates each. By spoligotyping, 506 (83%) MTB isolates fell into known patterns and 106 (17%) fell into patterns with no family assignment; 297 (48%) isolates belonged to the Latin-American Mediterranean family. Higher school level (4-7 years OR: 0.16 95% CI 0.34-0.73 and > 8 years of education, OR 0.06 95% CI 0.009-0.50) white ethnicity (OR: 2.54 95% CI 1.03-6.25) and HIV infection (OR: 16.83 95% CI 5.23-54.18) were associated with EPTB. No specific strain lineage or percentage of clustering was associated with EPTB. Conclusions:These results demonstrate that risk factors for EPTB are related more to host than to MTB strain lineage characteristics. [ABSTRACT FROM AUTHOR]