[Regional inequalities in access to hospital birth in the state of Rio de Janeiro, Brazil: travel networks, distance, and time (2010-2019)]. / Desigualdades regionais no acesso ao parto hospitalar no Estado do Rio de Janeiro, Brasil: redes de deslocamento, distância e tempo (2010-2019).

Difficult access to birth care services is associated with infant and neonatal mortality and maternal morbidity and mortality. In this study, data from the Brazilian Unified National Health System (SUS) were used to map the evolution of geographic accessibility to hospital birth of usual risk in the state of Rio de Janeiro, Brazil, corresponding to 418,243 admissions in 2010-2011 and 2018-2019. Travel flows, distances traveled, and intermunicipal travel time between the pregnant women's municipality and hospital location were estimated. An increase from 15.9% to 21.5% was observed in the number of pregnant women who needed to travel. The distance traveled increased from 24.6 to 26km, and the travel time from 76.4 to 96.1 minutes, with high variation between Health Regions (HR). Pregnant women living in HR Central-South traveled more frequently (37.4-48.9%), and those living in the HRs Baía da Ilha Grande and Northwest traveled the largest distances (90.9-132.1km) and took more time to get to the hospital in 2018-2019 (96-137 minutes). The identification of municipalities that received pregnant women from many other municipalities and municipalities that treated a higher number of pregnant women (hubs and attraction poles, respectively) reflected the unavailability and disparities in access to services. Regional inequalities and reduced accessibility highlight the need to adapt supply to demand and review the distribution of birth care services in the state of Rio de Janeiro. This study contributes to research and planning on access to maternal and child health services and can be used as a reference study for other states in the country.

A dificuldade de acesso aos serviços de atenção ao parto está associada à mortalidade infantil e neonatal e à morbimortalidade materna. Neste estudo, dados do Sistema Único de Saúde (SUS) foram utilizados para mapear a evolução da acessibilidade geográfica ao parto hospitalar de risco habitual no Estado do Rio de Janeiro, Brasil, correspondentes a 418.243 internações nos biênios 2010-2011 e 2018-2019. Foram estimados os fluxos de deslocamento, as distâncias percorridas e o tempo de deslocamento intermunicipal entre o município de residência e de internação das gestantes. Houve um crescimento de 15,9% para 21,5% na proporção de gestantes que precisaram se deslocar. A distância percorrida aumentou de 24,6 para 26km, e o tempo de deslocamento de 76,4 para 96,1 minutos, com grande variação entre as Regiões de Saúde (RS). As gestantes residentes na RS Centro Sul se deslocaram mais frequentemente (37,4-48,9%), e as residentes nas RS Baía da Ilha Grande e Noroeste percorreram as maiores distâncias (90,9-132,1km) e levaram mais tempo para chegar ao hospital no último biênio (96-137 minutos). A identificação dos municípios que receberam gestantes de muitos outros municípios e daqueles que atenderam maior volume de gestantes (núcleos e polos de atração, respectivamente) refletiu a indisponibilidade e as disparidades no acesso aos serviços. As desigualdades regionais e a redução da acessibilidade alertam para a necessidade de adequar a oferta à demanda e de revisar a distribuição dos serviços de atenção ao parto no Rio de Janeiro. O estudo contribui para as pesquisas e o planejamento sobre o acesso a serviços de saúde materno-infantil, além de servir como referência para outros estados do país.

La dificultad para acceder a los servicios de atención al parto está asociada con la mortalidad infantil y neonatal, y con la morbimortalidad materna. En este estudio, se utilizaron datos del Sistema Único de Salud (SUS) para mapear la evolución de la accesibilidad geográfica al parto hospitalario de riesgo habitual en el estado de Río de Janeiro, Brasil, correspondiente a 418.243 hospitalizaciones en los bienios 2010-2011 y 2018-2019. Se estimaron los flujos de desplazamiento, las distancias recorridas y el tiempo de desplazamiento intermunicipal entre el municipio de residencia y la hospitalización de las mujeres embarazadas. Hubo un aumento del 15,9% al 21,5% en la proporción de mujeres embarazadas que necesitaron desplazarse. La distancia recorrida aumentó de 24,6 a 26km y el tiempo de desplazamiento de 76,4 a 96,1 minutos, con gran variación entre las Regiones de Salud (RS). Las mujeres embarazadas residentes en la RS Centro Sul se desplazaron con mayor frecuencia (37,4-48,9%), y las residentes en las RS Baía da Ilha Grande y Noroeste recorrieron las mayores distancias (90,9-132,1km) y tardaron más en llegar al hospital en el últimos bienio (96-137 minutos). La identificación de los municipios que recibieron mujeres embarazadas de muchos otros municipios y de aquellos que atendieron a un mayor volumen de mujeres embarazadas (núcleos y polos de atracción, respectivamente) reflejó la indisponibilidad y las disparidades en el acceso a los servicios. Las desigualdades regionales y la reducida accesibilidad alertan sobre la necesidad de adaptar la oferta a la demanda, y de revisar la distribución de los servicios de atención al parto en el estado de Rio de Janeiro. El estudio contribuye a las investigaciones y a la planificación sobre el acceso a los servicios de salud materno-infantil, y puede servir como referencia para otros estados del país.

Desigualdades regionais no acesso ao parto hospitalar no Estado do Rio de Janeiro, Brasil: redes de deslocamento, distância e tempo (2010-2019) / Regional inequalities in access to hospital birth in the state of Rio de Janeiro, Brazil: travel networks, distance, and time (2010-2019) / Desigualdades regionales en el acceso al parto hospitalario en el estado de Río de Janeiro, Brasil: redes de desplazamiento, distancia y tiempo (2010-2019)

Resumo: A dificuldade de acesso aos serviços de atenção ao parto está associada à mortalidade infantil e neonatal e à morbimortalidade materna. Neste estudo, dados do Sistema Único de Saúde (SUS) foram utilizados para mapear a evolução da acessibilidade geográfica ao parto hospitalar de risco habitual no Estado do Rio de Janeiro, Brasil, correspondentes a 418.243 internações nos biênios 2010-2011 e 2018-2019. Foram estimados os fluxos de deslocamento, as distâncias percorridas e o tempo de deslocamento intermunicipal entre o município de residência e de internação das gestantes. Houve um crescimento de 15,9% para 21,5% na proporção de gestantes que precisaram se deslocar. A distância percorrida aumentou de 24,6 para 26km, e o tempo de deslocamento de 76,4 para 96,1 minutos, com grande variação entre as Regiões de Saúde (RS). As gestantes residentes na RS Centro Sul se deslocaram mais frequentemente (37,4-48,9%), e as residentes nas RS Baía da Ilha Grande e Noroeste percorreram as maiores distâncias (90,9-132,1km) e levaram mais tempo para chegar ao hospital no último biênio (96-137 minutos). A identificação dos municípios que receberam gestantes de muitos outros municípios e daqueles que atenderam maior volume de gestantes (núcleos e polos de atração, respectivamente) refletiu a indisponibilidade e as disparidades no acesso aos serviços. As desigualdades regionais e a redução da acessibilidade alertam para a necessidade de adequar a oferta à demanda e de revisar a distribuição dos serviços de atenção ao parto no Rio de Janeiro. O estudo contribui para as pesquisas e o planejamento sobre o acesso a serviços de saúde materno-infantil, além de servir como referência para outros estados do país.

Abstract: Difficult access to birth care services is associated with infant and neonatal mortality and maternal morbidity and mortality. In this study, data from the Brazilian Unified National Health System (SUS) were used to map the evolution of geographic accessibility to hospital birth of usual risk in the state of Rio de Janeiro, Brazil, corresponding to 418,243 admissions in 2010-2011 and 2018-2019. Travel flows, distances traveled, and intermunicipal travel time between the pregnant women's municipality and hospital location were estimated. An increase from 15.9% to 21.5% was observed in the number of pregnant women who needed to travel. The distance traveled increased from 24.6 to 26km, and the travel time from 76.4 to 96.1 minutes, with high variation between Health Regions (HR). Pregnant women living in HR Central-South traveled more frequently (37.4-48.9%), and those living in the HRs Baía da Ilha Grande and Northwest traveled the largest distances (90.9-132.1km) and took more time to get to the hospital in 2018-2019 (96-137 minutes). The identification of municipalities that received pregnant women from many other municipalities and municipalities that treated a higher number of pregnant women (hubs and attraction poles, respectively) reflected the unavailability and disparities in access to services. Regional inequalities and reduced accessibility highlight the need to adapt supply to demand and review the distribution of birth care services in the state of Rio de Janeiro. This study contributes to research and planning on access to maternal and child health services and can be used as a reference study for other states in the country.

Resumen: La dificultad para acceder a los servicios de atención al parto está asociada con la mortalidad infantil y neonatal, y con la morbimortalidad materna. En este estudio, se utilizaron datos del Sistema Único de Salud (SUS) para mapear la evolución de la accesibilidad geográfica al parto hospitalario de riesgo habitual en el estado de Río de Janeiro, Brasil, correspondiente a 418.243 hospitalizaciones en los bienios 2010-2011 y 2018-2019. Se estimaron los flujos de desplazamiento, las distancias recorridas y el tiempo de desplazamiento intermunicipal entre el municipio de residencia y la hospitalización de las mujeres embarazadas. Hubo un aumento del 15,9% al 21,5% en la proporción de mujeres embarazadas que necesitaron desplazarse. La distancia recorrida aumentó de 24,6 a 26km y el tiempo de desplazamiento de 76,4 a 96,1 minutos, con gran variación entre las Regiones de Salud (RS). Las mujeres embarazadas residentes en la RS Centro Sul se desplazaron con mayor frecuencia (37,4-48,9%), y las residentes en las RS Baía da Ilha Grande y Noroeste recorrieron las mayores distancias (90,9-132,1km) y tardaron más en llegar al hospital en el últimos bienio (96-137 minutos). La identificación de los municipios que recibieron mujeres embarazadas de muchos otros municipios y de aquellos que atendieron a un mayor volumen de mujeres embarazadas (núcleos y polos de atracción, respectivamente) reflejó la indisponibilidad y las disparidades en el acceso a los servicios. Las desigualdades regionales y la reducida accesibilidad alertan sobre la necesidad de adaptar la oferta a la demanda, y de revisar la distribución de los servicios de atención al parto en el estado de Rio de Janeiro. El estudio contribuye a las investigaciones y a la planificación sobre el acceso a los servicios de salud materno-infantil, y puede servir como referencia para otros estados del país.

Leadership and international collaboration on COVID-19 research: reducing the North-South divide?

The COVID-19 pandemic triggered unprecedented scientific efforts worldwide and launched several initiatives to promote international cooperation. Because international scientific collaborations between high-income countries (HICs) and low- and middle-income countries (LMICs) are not always balanced, analyzing research leadership helps to understand the global dynamics of knowledge production during COVID-19. In this study, we focused on HIC-LMIC collaborations on COVID-19 research in 469,937 scientific publications during the first 2 years of the pandemic (2020-2021). Co-authorship and authors' affiliation were used to identify international collaborations, according to country income level. The leadership analysis considered the countries of the first and last authors of publications. The results show that (i) most publications with international collaborations (49.3%) involved researchers from HICs and LMICs; (ii) collaborative research between HICs and LMICs addressed relevant public health needs; (iii) HIC-LMIC collaborations were primarily led by researchers from the United States, China, the United Kingdom, and India; (iv) most HIC-LMIC publications (44%) had shared leadership, with research interests linked to national expertise and global interests. This study contributes to the analysis of research collaborations on COVID-19 and sheds light on North-South relations in the production and dissemination of scientific knowledge.

Geographic accessibility to cancer treatment in Brazil: A network analysis.

Background: Geographic accessibility to healthcare services is a fundamental component in achieving universal health coverage, the central commitment of the Brazilian Unified Health System (SUS). For cancer patients, poor accessibility has been associated with inadequate treatment, worse prognosis, and poorer quality of life. Methods: We explored nationwide healthcare data from the SUS health information systems, and mapped the geographic accessibility to cancer treatment in two time-frames: 2009-2010 and 2017-2018. We applied social network analysis (SNA) to estimate the commuting route, flow, and distances travelled by cancer patients to undergo surgical, radiotherapy, and chemotherapy treatment. Findings: A total of 12,751,728 treatment procedures were analyzed. Overall, more than half of the patients (49·2 to 60·7%) needed to travel beyond their municipality of residence for treatment, a fact that did not change over time. Marked regional differences were observed, as patients living in the northern and midwestern regions of the country had to travel longer distances (weighted average of 296 to 870 km). Cancer care hubs and attraction poles were mostly identified in the southeast and northeast regions, with Barretos being the main hub for all types of treatment throughout time. Interpretation: Important regional disparities in the accessibility to cancer treatment in Brazil were revealed, suggesting the need to review the distribution of specialized care in the country. The data presented here contribute to ongoing research on improving access to cancer care and can provide reference to other countries, offering relevant data for oncological and healthcare service evaluation, monitoring, and strategic planning. Funding: This work was funded by the Oswaldo Cruz Foundation - Fiocruz (Inova - no. 8451635123 to BPF) and the National Council for Scientific and Technological Development - CNPq (no. 407060/2018-9 to BPF); Coordination for the Improvement of Higher Education Personnel - CAPES (scholarship to PCA, Finance Code 001); and Instituto Nacional de Ciência e Tecnologia de Inovação em Doenças de Populações Negligenciadas (INCT-IDPN). Resumo: A acessibilidade geográfica aos serviços de saúde é um componente fundamental para o alcance da cobertura universal de saúde, compromisso central do Sistema Único de Saúde (SUS). Para pacientes com câncer, a baixa acessibilidade aos serviços especializados tem sido associada ao tratamento inadequado, piora no prognóstico e na qualidade de vida.Neste estudo, dados de saúde dos sistemas de informação em saúde do SUS foram utilizados para mapear a acessibilidade geográfica ao tratamento do câncer em dois períodos: 2009-2010 e 2017-2018. Aplicamos a análise de redes sociais (ARS) para estimar os fluxos de deslocamento e as distâncias percorridas por pacientes com câncer para receberem tratamento cirúrgico, radioterápico e quimioterápico.Um total de 12.751.728 procedimentos de tratamento foram analisados. Em geral, mais da metade dos pacientes (49,2 a 60,7%) precisaram se deslocar de seus municípios de residência para receber tratamento, fato que não mudou comparando os dois períodos de tempo analisados. Foram observadas importantes diferenças regionais no acesso. Pacientes residentes das regiões norte e centro-oeste do país tiveram que percorrer maiores distâncias para alcançar os serviços (média ponderada = 296 a 870 km). A maioria dos hubs e polos de atração para atendimento oncológico foram identificados nas regiões Sudeste e Nordeste, sendo o município de Barretos o principal hub para todos os tipos de tratamento ao longo do tempo.As disparidades de acessibilidade para o tratamento de câncer, alertam para a necessidade de revisar a distribuição dos serviços de atenção especializada no país. A metodologia e os resultados apresentados neste estudo contribuem para as pesquisas sobre a melhoria do acesso ao tratamento do câncer e podem servir como referência para outros países, oferecendo dados relevantes para avaliação, monitoramento e planejamento estratégico de serviços oncológicos e de saúde em geral.

Neglected tropical diseases in Brazil: lack of correlation between disease burden, research funding and output.

OBJECTIVES: To assess the correlation between the burden of seven priority neglected tropical diseases (NTDs) included in the Brazilian National Agenda of Priorities in Health Research - tuberculosis, Chagas disease, leprosy, malaria, leishmaniasis, dengue and schistosomiasis - and their respective research funding and output. METHODS: This retrospective review obtained data on disease burden from the Global Burden of Disease Study and funding data from open access sources. Publications were retrieved from Scopus and SciELO, and characterised according to the type of research conducted. Correlation between funding, research output and burden was assessed by comparing the 'expected' and 'observed' values for funding and publications relative to the proportional burden for each disease. RESULTS: There was an emphasis in basic biomedical research (average 30% of publications) and a shortage of health policy and systems (average 7%) and social sciences research (average 3%). Research output and funding were poorly correlated with disease burden. Tuberculosis, Chagas disease and schistosomiasis accounted for more than 75% of total NTD-related DALYs, but accounted for only 34% of publications. Leprosy, leishmaniasis and malaria, together, received 49% of NTD-related funding despite being responsible for only 9% of DALYs. CONCLUSIONS: The analysis evidenced a lack of correlation between disease burden, research output and government funding for priority NTDs in Brazil. Our findings highlight the importance of monitoring health needs, research investments and outputs to inform policy and optimise the uptake of evidence for action, particularly in developing countries, where resources are scarce and the research capacity is limited. The results contribute to health policy by highlighting the need for improving coordination of scientific activities and public health needs for effective impact.

OBJECTIFS: Evaluer la corrélation entre la charge de sept maladies tropicales négligées (MTN) prioritaires incluses dans le programme national brésilien des priorités en matière de recherche en santé - tuberculose, maladie de Chagas, lèpre, paludisme, leishmaniose, dengue et schistosomiase - et leurs financements de recherche respectifs et les résultats. MÉTHODES: Cette revue rétrospective a obtenu des données sur la charge de morbidité de l'étude sur la Charge Globale des Maladies et des données de financement provenant de sources en accès publique. Les publications ont été extraites de Scopus et SciELO et caractérisées selon le type de recherche menée. La corrélation entre le financement, les résultats de la recherche et la charge a été évaluée en comparant les valeurs "attendues" et "observées" pour le financement et les publications par rapport à la charge proportionnel de chaque maladie. RÉSULTATS: L'accent a été mis sur la recherche biomédicale fondamentale (en moyenne 30% des publications) et une pénurie de politiques et de systèmes de santé (en moyenne 7%) et de recherche en sciences sociales (en moyenne 3%). Les résultats et le financement de la recherche étaient mal associés à la charge de morbidité. La tuberculose, la maladie de Chagas et la schistosomiase représentaient plus de 75% du total des EVCI, mais ne représentaient que 34% des publications. La lèpre, la leishmaniose et le paludisme, ensemble, ont reçu 49% des financements liés aux MTN alors qu'ils n'étaient responsables que de 9% des EVCI. CONCLUSIONS: L'analyse a mis en évidence une absence de corrélation entre la charge de morbidité, le résultat de la recherche et le financement de la plupart des MTN. Nos résultats soulignent l'importance du suivi des besoins en matière de santé, des investissements dans la recherche et des résultats pour éclairer les politiques et optimiser l'utilisation des données pour l'action, en particulier dans les pays en développement, où les ressources sont rares et la capacité de recherche est limitée. Les résultats contribuent à la politique de santé en soulignant la nécessité d'améliorer la coordination et la planification stratégique des activités scientifiques pour un impact efficace.

Bibliometric assessment and key messages of sporotrichosis research (1945-2018).

Background: Sporotrichosis has recently emerged as an important mycosis worldwide, with diverse transmission and epidemiologic profiles. For instance, in Brazil most cases are related to zoonotic transmission from naturally infected cats, and the majority of cases in China are due to external injury with environmental materials. Publications on sporotrichosis and on its etiologic agent may guide the direction of the research in this field. It can also define priorities for future studies. Methods: In this study, we evaluated the trends of global research in Sporothrix and sporotrichosis, based on publications records retrieved from Scopus and Web of Science databases for the period of 1945 to 2018. The overall productivity in the field, its geographical and temporal distribution, research themes, co-authorship networks, funding sources, and if audience and research findings are addressed in the abstracts. Results: A total of 4,007 unique publications involving 99 countries were retrieved, most of them published after 2000. Authors based on institutions from the United States of America and Brazil accounted for 57.4% of the publications. Brazil was the leading country in terms of research collaboration and networking, with co-authorship with 45 countries. The thematic mapping revealed a temporal shift from clinical to applied research. Despite the large number of countries publishing in this field, most of funded studies came from Brazil, Mexico, China, South Africa, or the United States of America. The analysis of content identified few specific public health recommendations for prevention, case-management, or research. Moreover, most papers do not have a clearly defined intended audience. Conclusion: As the research in this field is emerging in several countries, with the generation of a large amount of data, it is necessary that scientists strengthen efforts to translate the research results into practice to curb this neglected infection.

South-south collaboration on HIV/AIDS prevention and treatment research: when birds of a feather rarely flock together.

BACKGROUND: South-south collaboration on health and development research is a critical mechanism for social and economic progress. It allows sharing and replicating experiences to find a "southern solution" to meet shared health challenges, such as access to adequate HIV/AIDS prevention and treatment. This study aimed to generate evidence on the dynamics of south-south collaboration in HIV/AIDS research, which could ultimately inform stakeholders on the progress and nature of collaboration towards increased research capacities in low- and middle-income countries (LMIC). METHODS: Bibliometric and social network analysis methods were used to assess the 10-year (2006-2015) scientific contribution of LMIC, through the analysis of scientific publications on HIV/AIDS prevention and/or treatment. Five dimensions oriented the study: knowledge production, co-authorship analysis, research themes mapping, research types classification and funding sources. RESULTS: Publications involving LMIC have substantially increased overtime, despite small expression of south-south collaboration. Research themes mapping revealed that publication focus varied according to collaborating countries' income categories, from diagnosis, opportunistic infections and laboratory-based research (LMIC single or LMIC-LMIC) to human behavior and healthcare, drug therapy and mother to child transmission (LMIC-HIC). The analysis of research types showed that south-south collaborations frequently targeted social sciences issues. Funding agencies acknowledged in south-south collaboration also showed diverse focus: LMIC-based funders tended to support basic biomedical research whereas international/HIC-based funders seem to cover predominantly social sciences-oriented research. CONCLUSIONS: Although the global environment has fostered an increasing participation of LMIC in collaborative learning models, south-south collaboration on HIV/AIDS prevention and/or treatment research seemed to be lower than expected, stressing the need for strategies to foster these partnerships. The evidence presented in this study can be used to strengthen a knowledge platform to inform future policy, planning and funding decisions, contributing to the development of enhanced collaboration and a priority research agenda for LMICs.

Compositional and immunobiological analyses of extracellular vesicles released by Candida albicans.

The release of extracellular vesicles (EV) by fungal organisms is considered an alternative transport mechanism to trans-cell wall passage of macromolecules. Previous studies have revealed the presence of EV in culture supernatants from fungal pathogens, such as Cryptococcus neoformans, Histoplasma capsulatum, Paracoccidioides brasiliensis, Sporothrix schenckii, Malassezia sympodialis and Candida albicans. Here we investigated the size, composition, kinetics of internalization by bone marrow-derived murine macrophages (MO) and dendritic cells (DC), and the immunomodulatory activity of C. albicans EV. We also evaluated the impact of EV on fungal virulence using the Galleria mellonella larvae model. By transmission electron microscopy and dynamic light scattering, we identified two populations ranging from 50 to 100 nm and 350 to 850 nm. Two predominant seroreactive proteins (27 kDa and 37 kDa) and a group of polydispersed mannoproteins were observed in EV by immunoblotting analysis. Proteomic analysis of C. albicans EV revealed proteins related to pathogenesis, cell organization, carbohydrate and lipid metabolism, response to stress, and several other functions. The major lipids detected by thin-layer chromatography were ergosterol, lanosterol and glucosylceramide. Short exposure of MO to EV resulted in internalization of these vesicles and production of nitric oxide, interleukin (IL)-12, transforming growth factor-beta (TGF-ß) and IL-10. Similarly, EV-treated DC produced IL-12p40, IL-10 and tumour necrosis factor-alpha. In addition, EV treatment induced the up-regulation of CD86 and major histocompatibility complex class-II (MHC-II). Inoculation of G. mellonella larvae with EV followed by challenge with C. albicans reduced the number of recovered viable yeasts in comparison with infected larvae control. Taken together, our results demonstrate that C. albicans EV were immunologically active and could potentially interfere with the host responses in the setting of invasive candidiasis.

Vesicular transport in Histoplasma capsulatum: an effective mechanism for trans-cell wall transfer of proteins and lipids in ascomycetes.

Vesicular secretion of macromolecules has recently been described in the basidiomycete Cryptococcus neoformans, raising the question as to whether ascomycetes similarly utilize vesicles for transport. In the present study, we examine whether the clinically important ascomycete Histoplasma capsulatum produce vesicles and utilized these structures to secrete macromolecules. Transmission electron microscopy (TEM) shows transcellular secretion of vesicles by yeast cells. Proteomic and lipidomic analyses of vesicles isolated from culture supernatants reveal a rich collection of macromolecules involved in diverse processes, including metabolism, cell recycling, signalling and virulence. The results demonstrate that H. capsulatum can utilize a trans-cell wall vesicular transport secretory mechanism to promote virulence. Additionally, TEM of supernatants collected from Candida albicans, Candida parapsilosis, Sporothrix schenckii and Saccharomyces cerevisiae documents that vesicles are similarly produced by additional ascomycetes. The vesicles from H. capsulatum react with immune serum from patients with histoplasmosis, providing an association of the vesicular products with pathogenesis. The findings support the proposal that vesicular secretion is a general mechanism in fungi for the transport of macromolecules related to virulence and that this process could be a target for novel therapeutics.

Vesículas de transporte de proteínas e lipídeos em histoplasma capsulatum e outros ascomicetos / Transport vesicle proteins and lipids in histoplasma capsulatum and other ascomycetes

Secreção vesicular de macromoléculas foi demonstrada recentemente em Cryptococcus neoformans levantando a hipótese da possibilidade desse mecanismo de transporte vesicular ocorrer também em ascomicetos. Neste trabalho, analisamos se o fungo Histoplasma capsulatum e outros ascomicetos com importância clínica produzem vesículas e utilizam essas estruturas na secreção de macromoléculas. Microscopia eletrônica de transmissão (MET) evidenciou secreção trans-celular de vesículas na fase leveduriforme. Análises proteômicas e de lipídeos revelaram uma gama de macromoléculas envolvidas em diversos processos celulares, como por exemplo: metabolismo, sinalização e virulência. Os resultados demonstraram que H. capsulatum utiliza-se de um transporte secretório celular vesicular trans-membrana para promover virulência...

MET de sobrenadantes de cultura de Candida albicans, Candida parapsilosis, Sporothrix schenckii, e Saccharomyces cerevisiae evidenciaram a presença de vesículas, confirmando a hipótese de que os ascomicetos similarmente produzem vesículas. Anticorpos presentes em pool de soros de pacientes com histoplasmose, reagiram com moléculas presentes nas vesículas isoladas, ressaltando a possível associação dos produtos vesiculares no processo de patogênese. Nossos resultados corroboram a proposta de que a secreção vesicular é um mecanismo comum em fungos para o transporte de macromoléculas relacionadas à virulência, sendo este um promissor alvo em novas linhas terapêuticas...

ELISA for early diagnosis of histoplasmosis.

An ELISA was developed and evaluated as a method for detecting antibodies against glycosylated and deglycosylated histoplasmin (HMIN). Sera from patients with histoplasmosis, paracoccidioidomycosis, sporotrichosis, coccidioidomycosis, aspergillosis, cryptococcosis and healthy donors were tested by ELISA against purified, deglycosylated histoplasmin (ptHMIN) and compared with purified, native (i.e. glycosylated) histoplasmin (pHMIN). Although cross-reactivity was not abolished when ptHMIN was used in the test, it was reduced (pHMIN ELISA 93 % versus ptHMIN ELISA 96 %). However, there were statistically significant differences between the sensitivities of these two methods for the detection of antibodies (pHMIN ELISA 57 % versus ptHMIN ELISA 92 %; P < 0.001) and between the efficiency of the methods (pHMIN ELISA 83 % versus ptHMIN ELISA 95 %; P < 0.001). These parameters compare better than previously published data relating to the use of treated HMIN in diagnostic ELISAs. Some of the reactivities of serum samples were compared by immunoblotting using deglycosylated HMIN and by immunodiffusion using the crude antigen. The results demonstrated that cross-reactions with heterologous sera in both ELISAs could also be observed in immunoblotting and arose from shared protein epitopes. These data suggest that ELISA using deglycosylated HMIN is a very sensitive diagnostic method and, by using commercially available antigen, it can be easily standardized and performed faster than previous Western blot-based tests using the same antigen. It provides a useful adjunct to existing methods of diagnosis that could be applied even in situations where laboratory facilities were relatively limited.