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1.
PLoS One ; 19(9): e0296201, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39325811

RESUMEN

Pre-exposure prophylaxis (PrEP) is an effective HIV prevention strategy that consists in the use of antiretroviral drugs by seronegative people at risk of HIV. Negative perceptions, inadequate understanding, and access barriers have been associated with decreased medication adherence. Manaus is the largest city in the Brazilian Amazon, where the incidence of HIV/AIDS is high, and the rates of adherence to the antiretroviral treatment for HIV and PrEP are low. In this qualitative study among PrEP users, mostly MSM, we explored perceptions, knowledge, and access barriers. We conducted 21 in-depth interviews with an intentionally sampled group of participants who had used PrEP at least once in their lifetime, selected through the snowball technique, between April and July 2022. A thematic analysis was conducted with a predominantly inductive approach. We highlight three relevant themes: (i) access to information about PrEP and its influences on users, (ii) access, monitoring, and barriers encountered, and (iii) facilitators for PrEP adherence and sexual behaviors. One of the negative perceptions identified in the study involves a misunderstanding of the association between PrEP users and the HIV/AIDS status. Participants revealed that some non-PrEP users suspect that individuals claiming PrEP usage are concealing an HIV-positive status to engage in unprotected sex. Lack of information by health professionals regarding HIV prevention methods poses significant barriers to PrEP access and adherence. Participants emphasized social media's crucial role in PrEP awareness. The results suggest a need to increase digital outreach regarding PrEP, decentralize PrEP services, and provide comprehensive healthcare training to improve the effectiveness of the preventive measure.


Asunto(s)
Infecciones por VIH , Conocimientos, Actitudes y Práctica en Salud , Homosexualidad Masculina , Profilaxis Pre-Exposición , Investigación Cualitativa , Humanos , Masculino , Brasil , Adulto , Homosexualidad Masculina/psicología , Infecciones por VIH/prevención & control , Persona de Mediana Edad , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/administración & dosificación , Accesibilidad a los Servicios de Salud , Adulto Joven , Cumplimiento de la Medicación/psicología , Síndrome de Inmunodeficiencia Adquirida/prevención & control , Conducta Sexual/psicología , Percepción
2.
DST j. bras. doenças sex. transm ; 36: e24361499, 15 fev. 2024. ilus, tab
Artículo en Inglés | LILACS | ID: biblio-1570776

RESUMEN

Introduction: Women living with HIV/AIDS have a higher frequency of anogenital neoplasms resulting from human papillomavirus (HPV) infection. The World Health Organization recommends that cervical cancer screening uses molecular tests that amplify viral genetic material, such as HPV-DNA. In addition to collection by health professionals, self-collection of vaginal samples is a useful tool for expanding access to testing. Objective: To describe the results of the pilot study that evaluated the acceptability of self-collection of vaginal samples and the applicability of offering HPV-DNA tests with self-collection of vaginal samples for women living with HIV/AIDS in Brazil. Methods: Descriptive cross-sectional study involving women living with HIV/AIDS treated in eight HIV-specialty healthcare facilities distributed in all regions of the country from May 2021 to May 2022 and a central laboratory. Vaginal self-collection was offered, and participants were interviewed about sociodemographic data and impressions of self-collection. Results: In total, 1,919 women living with HIV/AIDS with an average age of 45 years participated in the study. Some type of HPV was detected in 66% (1,267) of cases. The majority (71.9%) said they preferred self-collection to sample collection by health care professionals. Only 53.8% of participants underwent cytology at the appropriate frequency, as recommended by the protocol. Conclusion: The results may support the implementation of molecular biology tests to detect HPV in women living with HIV/AIDS, including the possibility of vaginal self-collection, promoting increased access to cervical cancer screening. (AU)


Introdução: Mulheres vivendo com HIV/AIDS possuem maior frequência de neoplasias anogenitais decorrentes da infecção pelo papilomavírus humano (HPV). A Organização Mundial da Saúde recomenda que o rastreio de câncer do colo do útero seja utilizado por testes moleculares que amplificam o material genético viral, como o HPV-DNA. Além da coleta por profissionais da saúde, a autocoleta de amostras vaginais consiste em uma ferramenta útil para ampliação do acesso à testagem. Objetivo: Descrever os resultados do estudo piloto que avaliou a aceitabilidade da autocoleta de amostra vaginal e aplicabilidade da oferta de testes HPV-DNA com autocoleta de amostras vaginais para mulheres vivendo com HIV/AIDS no Brasil. Métodos: Estudo transversal descritivo envolvendo mulheres vivendo com HIV/AIDS atendidas em oito serviços ambulatoriais distribuídos em todas as regiões do país no período de maio/2021 a maio/2022 e um laboratório central. Realizou-se a oferta de autocoleta vaginal e uma entrevista com as participantes sobre dados sociodemográficos e impressões da autocoleta. Resultados: No total, 1.919 mulheres vivendo com HIV/AIDS com média de 45 anos participaram do estudo. Houve detecção de algum tipo de HPV em 66% (1.267) dos casos. A maioria (71,9%) afirmou preferir a autocoleta à coleta de amostras por profissionais da saúde. Apenas 53,8% das participantes realizaram citologia na periodicidade adequada, conforme recomendação do protocolo. Conclusão:Os resultados poderão apoiar a implementação dos testes de biologia molecular para detecção de HPV em mulheres vivendo com HIV/AIDS, incluindo a possibilidade de autocoleta vaginal, promovendo a ampliação do acesso ao rastreamento de câncer do colo do útero. (AU)


Asunto(s)
Humanos , Femenino , Pruebas Serológicas , Seropositividad para VIH , Sobrevivientes de VIH a Largo Plazo , Calidad de la Atención de Salud , Neoplasias del Cuello Uterino , Tamizaje Masivo , Papillomaviridae
3.
Rev Soc Bras Med Trop ; 56: e02772023, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37820103

RESUMEN

BACKGROUND: Women living with human immunodeficiency virus (HIV) (WLWH) are more likely to be infected with the oncogenic human papillomavirus (HPV). We assessed the prevalence of high-risk (HR) (16/18/31/33/35/39/45/51/52/56/58/59/68/73/82), probable high-risk (pHR) (26/53/66), and low-risk (LR) (6/11/40/42/43/44/54/61/70) HPV types and their associated risk factors. METHODS: This cross-sectional study of WLWH aged 18-64 years included one laboratory and eight HIV-specialty healthcare facilities in the pilot network. Descriptive statistics were used to assess sociodemographic and behavioral characteristics. Adjusted analyses were conducted to evaluate risk factors associated with HR and/or pHR HPV infection in WLWH. RESULTS: From May/2021 to May/2022, 1,914 (92.5%) WLWH participated in the pilot study and had valid HPV-DNA results of self-collected vaginal samples. The median age of the participants was 45 years, 60.1% had ≥ 9 years of schooling, 80.5% were ≤ 18 years at first sexual intercourse, and 51.7% had > 4 sexual partners throughout life. The prevalence of any HPV type, HR HPV, pHR HPV, and LR HPV was 65.8%, 49.6%, 16.7%, and 40.0%, respectively. Age was inversely associated with pHR and/or HR-HPV (p < 0.001), and education level was inversely associated with HR-HPV (p = 0.003) types. Any HR or pHR was associated with being single (p = 0.029) and exchanging sex for drugs (p = 0.037). CONCLUSIONS: The prevalence of HPV, especially HR HPV, among WLWH is high in Brazil, highlighting the need for HPV screening in this population. Self-collection of vaginal samples is an important strategy for increasing testing access.


Asunto(s)
Infecciones por VIH , Infecciones por Papillomavirus , Humanos , Femenino , Persona de Mediana Edad , VIH/genética , Infecciones por VIH/complicaciones , Brasil/epidemiología , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/complicaciones , Prevalencia , Estudios Transversales , Salud Pública , Proyectos Piloto , Factores de Riesgo , ADN/uso terapéutico , Virus del Papiloma Humano , Papillomaviridae/genética , Genotipo
4.
Viruses ; 15(4)2023 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-37112998

RESUMEN

Numerous studies have focused on inflammation-related markers to understand COVID-19. In this study, we performed a comparative analysis of spike (S) and nucleocapsid (N) protein-specific IgA, total IgG and IgG subclass response in COVID-19 patients and compared this to their disease outcome. We observed that the SARS-CoV-2 infection elicits a robust IgA and IgG response against the N-terminal (N1) and C-terminal (N3) region of the N protein, whereas we failed to detect IgA antibodies and observed a weak IgG response against the disordered linker region (N2) in COVID-19 patients. N and S protein-specific IgG1, IgG2 and IgG3 response was significantly elevated in hospitalized patients with severe disease compared to outpatients with non-severe disease. IgA and total IgG antibody reactivity gradually increased after the first week of symptoms. Magnitude of RBD-ACE2 blocking antibodies identified in a competitive assay and neutralizing antibodies detected by PRNT assay correlated with disease severity. Generally, the IgA and total IgG response between the discharged and deceased COVID-19 patients was similar. However, significant differences in the ratio of IgG subclass antibodies were observed between discharged and deceased patients, especially towards the disordered linker region of the N protein. Overall, SARS-CoV-2 infection is linked to an elevated blood antibody response in severe patients compared to non-severe patients. Monitoring of antigen-specific serological response could be an important tool to accompany disease progression and improve outcomes.


Asunto(s)
COVID-19 , Humanos , SARS-CoV-2 , Anticuerpos Antivirales , Inmunoglobulina G , Inmunoglobulina A , Inmunoglobulina M , Glicoproteína de la Espiga del Coronavirus
5.
PLoS Negl Trop Dis ; 17(4): e0011296, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37099599

RESUMEN

Risk of spillover and spillback of mosquito-borne viruses in the neotropics, including yellow fever, dengue, Zika (Flaviviridae: Flavivirus), chikungunya, and Mayaro (Togaviridae: Alphavirus) viruses, is highest at ecotones where humans, monkeys, and mosquitoes coexist. With a view to identifying potential bridge vectors, we investigated changes in mosquito community composition and environmental variables at ground level at distances of 0, 500, 1000, and 2000 m from the edge of a rainforest reserve bordering the city of Manaus in the central Brazilian Amazon. During two rainy seasons in 2019 and 2020, we sampled 9,467 mosquitoes at 244 unique sites using BG-Sentinel traps, hand-nets, and Prokopack aspirators. Species richness and diversity were generally higher at 0 m and 500 m than at 1000 m and 2000 m, while mosquito community composition changed considerably between the forest edge and 500 m before stabilizing by 1000 m. Shifts in environmental variables mainly occurred between the edge and 500 m, and the occurrence of key taxa (Aedes albopictus, Ae. scapularis, Limatus durhamii, Psorophora amazonica, Haemagogus, and Sabethes) was associated with one or more of these variables. Sites where Ae. aegypti and Ae. albopictus were detected had significantly higher surrounding mean NDBI (Normalized Difference Built-up Index) values than sites where they were not detected, while the opposite was true for Sabethes mosquitoes. Our findings suggest that major changes in mosquito communities and environmental variables occur within 500 m of the forest edge, where there is high risk for contact with both urban and sylvatic vectors. By 1000 m, conditions stabilize, species diversity decreases, and forest mosquitoes predominate. Environmental variables associated with the occurrence of key taxa may be leveraged to characterize suitable habitat and refine risk models for pathogen spillover and spillback.


Asunto(s)
Aedes , Flavivirus , Infección por el Virus Zika , Virus Zika , Humanos , Animales , Brasil , Mosquitos Vectores , Bosques , Ecosistema
6.
Rev. Soc. Bras. Med. Trop ; Rev. Soc. Bras. Med. Trop;56: e0277, 2023. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1514851

RESUMEN

ABSTRACT Background: Women living with human immunodeficiency virus (HIV) (WLWH) are more likely to be infected with the oncogenic human papillomavirus (HPV). We assessed the prevalence of high-risk (HR) (16/18/31/33/35/39/45/51/52/56/58/59/68/73/82), probable high-risk (pHR) (26/53/66), and low-risk (LR) (6/11/40/42/43/44/54/61/70) HPV types and their associated risk factors. Methods: This cross-sectional study of WLWH aged 18-64 years included one laboratory and eight HIV-specialty healthcare facilities in the pilot network. Descriptive statistics were used to assess sociodemographic and behavioral characteristics. Adjusted analyses were conducted to evaluate risk factors associated with HR and/or pHR HPV infection in WLWH. Results: From May/2021 to May/2022, 1,914 (92.5%) WLWH participated in the pilot study and had valid HPV-DNA results of self-collected vaginal samples. The median age of the participants was 45 years, 60.1% had ≥ 9 years of schooling, 80.5% were ≤ 18 years at first sexual intercourse, and 51.7% had > 4 sexual partners throughout life. The prevalence of any HPV type, HR HPV, pHR HPV, and LR HPV was 65.8%, 49.6%, 16.7%, and 40.0%, respectively. Age was inversely associated with pHR and/or HR-HPV (p < 0.001), and education level was inversely associated with HR-HPV (p = 0.003) types. Any HR or pHR was associated with being single (p = 0.029) and exchanging sex for drugs (p = 0.037). Conclusions: The prevalence of HPV, especially HR HPV, among WLWH is high in Brazil, highlighting the need for HPV screening in this population. Self-collection of vaginal samples is an important strategy for increasing testing access.

7.
Braz. J. Pharm. Sci. (Online) ; 59: e23169, 2023. tab
Artículo en Inglés | LILACS | ID: biblio-1520313

RESUMEN

Abstract Genetic variability in the host metabolism of antimalarial drugs influenced by the polymorphisms of cytochrome P450 (CYP) could lead to significant changes in antimalarial treatment response. However, little is known about the frequency of alleles CYP2B6, CYP2C8, and CYP2D6 in an Amazonian population, especially with vivax malaria. Therefore, this study aimed to determine the frequency of CYP alleles CYP2B6*6, CYP2C8*3, and CYP2D6*4 in patients with vivax malaria. The study included 231 patients with vivax malaria treated at a health care reference in Manaus, northern Brazil. A sample of peripheral blood from each subject was collected to perform DNA extraction and genotypic analysis. Genotyping of polymorphisms was performed by allelic discrimination using Real-time polymerase chain reaction. The CYP2D6*4 allele was the most prevalent among patients who developed severe malaria. The frequencies of the CYP2B6*6 and CYP2D6*4 were not different between the severe and uncomplicated malaria. There was a significant association between heterozygous CYP2D6*4 and severe cases of malaria. The results are in agreement with other reports described in the literature for different populations. Future studies are needed to understand the clinical implications of the polymorphisms in patients with vivax malaria.


Asunto(s)
Humanos , Masculino , Femenino , Pacientes/clasificación , Polimorfismo Genético , Malaria Vivax/patología , Ecosistema Amazónico , Citocromo P-450 CYP2D6/efectos adversos , Alelos , Citocromo P-450 CYP2B6/efectos adversos , Citocromo P-450 CYP2C8/efectos adversos , Antimaláricos/administración & dosificación
8.
Rev Lat Am Enfermagem ; 30: e3591, 2022.
Artículo en Portugués, Inglés, Español | MEDLINE | ID: mdl-35830126

RESUMEN

OBJECTIVE: to describe the technical-assistance arrangements developed within the scope of work management in the COVID-19 pandemic care network, from the managers' perspective. METHOD: a qualitative research study, of the incorporated single case type, conducted with 23 managers of a Health Care Network. The analysis was applied in two thematic coding cycles, with the aid of the ATLAS.ti software. RESULTS: the arrangements were analyzed in categories related to health care; management; incorporation of technologies; implementation of a field hospital; and retrospective analysis of the experiences as a whole. There was emphasis on the implementation of care flows, virtual health bulletins, Telemonitoring, chatbots, use of applications, and implementation of field hospitals and of basic urgency services within the scope of the Basic Health Units. Hyperjudicialization in the system was identified; as well as weaknesses in information management, intersectoriality and technical-political leadership at the national level; the role of nurses in management positions and for coping with the pandemic. CONCLUSION: despite the health services' unpreparedness to face the pandemic, the actors' resilience promoted dynamism and technical-assistance arrangements in the context of management and humanized care. The study has a potential to contribute to the qualification of the public policy management and development practices.


Asunto(s)
COVID-19 , Adaptación Psicológica , Humanos , Liderazgo , Pandemias , Investigación Cualitativa , Estudios Retrospectivos
9.
Rev. latinoam. enferm. (Online) ; 30: e3591, 2022. tab, graf
Artículo en Portugués | LILACS, BDENF - Enfermería | ID: biblio-1389137

RESUMEN

Resumo Objetivo: descrever os arranjos tecnoassistenciais desenvolvidos no âmbito da gestão do trabalho na rede de atenção à pandemia de COVID-19, na perspectiva de gestores. Método: pesquisa qualitativa, do tipo caso único incorporado, com 23 gestores de uma Rede de Atenção à Saúde. Análise aplicada em dois ciclos de codificação temática, com o auxílio do software ATLAS.ti. Resultados: os arranjos foram analisados em categorias vinculadas à: atenção à saúde; gestão; incorporação de tecnologias; implantação de hospital de campanha; e análise retrospectiva das experiências como um todo. Houve destaque para a implantação de fluxo de atendimentos, boletins de saúde virtuais, telemonitoramento, chatbots, uso de aplicativos, implantação de hospitais de campanha e da urgência básica no âmbito de Unidades Básicas de Saúde. Identificou-se a hiperjudicialização no sistema; fragilidades na gestão das informações, intersetorialidade e condução técnico-política em âmbito nacional; o protagonismo dos enfermeiros em cargos de gestão e para o enfrentamento da pandemia. Conclusão: apesar do despreparo dos serviços de saúde para o enfrentamento da pandemia, a resiliência dos atores promoveu dinamicidade e arranjos tecnoassistenciais no âmbito da gestão e do cuidado humanizado. O estudo tem potencial contribuição para qualificação das práticas de gestão e desenvolvimento de políticas públicas.


Abstract Objective: to describe the technical-assistance arrangements developed within the scope of work management in the COVID-19 pandemic care network, from the managers' perspective. Method: a qualitative research study, of the incorporated single case type, conducted with 23 managers of a Health Care Network. The analysis was applied in two thematic coding cycles, with the aid of the ATLAS.ti software. Results: the arrangements were analyzed in categories related to health care; management; incorporation of technologies; implementation of a field hospital; and retrospective analysis of the experiences as a whole. There was emphasis on the implementation of care flows, virtual health bulletins, Telemonitoring, chatbots, use of applications, and implementation of field hospitals and of basic urgency services within the scope of the Basic Health Units. Hyperjudicialization in the system was identified; as well as weaknesses in information management, intersectoriality and technical-political leadership at the national level; the role of nurses in management positions and for coping with the pandemic. Conclusion: despite the health services' unpreparedness to face the pandemic, the actors' resilience promoted dynamism and technical-assistance arrangements in the context of management and humanized care. The study has a potential to contribute to the qualification of the public policy management and development practices.


Resumen Objetivo: describir los preparativos tecnoasistenciales que se desarrollaron en el ámbito de la gestión del trabajo en la red de atención de la pandemia de COVID-19, desde la perspectiva de los gestores. Método: investigación cualitativa, del tipo caso único incorporado, con 23 gestores de una Red de Atención de Salud. Análisis aplicado en dos ciclos de codificación temática, con ayuda del software ATLAS.ti. Resultados: los preparativos fueron analizados en categorías relacionadas con: la atención de la salud; la administración; la incorporación de tecnologías; la implementación de un hospital de campaña; y el análisis retrospectivo de las experiencias en general. Se destacaron la implementación del flujo de atención, los boletines virtuales de salud, el telemonitoreo, los chatbots, el uso de aplicaciones, la implementación de hospitales de campaña y emergencias básicas en el ámbito de las Unidades Básicas de Salud. Se identificaron la hiperjudicialización en el sistema; las debilidades en la gestión de la información, la intersectorialidad y conducción técnico-política a nivel nacional; el protagonismo de los enfermeros en cargos de gestión y para hacer frente a la pandemia. Conclusión: a pesar de la falta de preparación de los servicios de salud para enfrentar la pandemia, la resiliencia de los actores promovió el dinamismo y los preparativos tecnoasistenciales en el ámbito de la gestión y de la atención humanizada. El estudio tiene una contribución potencial para la calificación de las prácticas de gestión y el desarrollo de políticas públicas.


Asunto(s)
Humanos , Adaptación Psicológica , Estudios Retrospectivos , Gestión en Salud , COVID-19 , Liderazgo
10.
PLoS Negl Trop Dis ; 15(11): e0009839, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34727099

RESUMEN

Dengue virus (DENV) and Zika virus (ZIKV) belong to the same viral family, the Flaviviridae. They cause recurring threats to the public health systems of tropical countries such as Brazil. The primary Brazilian vector of both viruses is the mosquito Aedes aegypti. After the mosquito ingests a blood meal from an infected person, the viruses infect and replicate in the midgut, disseminate to secondary tissues and reach the salivary gland (SG), where they are ready to be transmitted to a vertebrate host. It is thought that the intrinsic discrepancies among mosquitoes could affect their ability to deal with viral infections. This study confirms that the DENV and ZIKV infection patterns of nine Ae. aegypti field populations found in geographically separate health districts of an endemic Brazilian city vary. We analyzed the infection rate, disseminated infection, vector competence, and viral load through quantitative PCR. Mosquitoes were challenged using the membrane-feeding assay technique and were tested seven and fourteen days post-infection (early and late infection phases, respectively). The infection responses varied among the Ae. aegypti populations for both flaviviruses in the two infection phases. There was no similarity between DENV and ZIKV vector competencies or viral loads. According to the results of our study, the risk of viral transmission overtime after infection either increases or remains unaltered in ZIKV infected vectors. However, the risk may increase, decrease, or remain unaltered in DENV-infected vectors depending on the mosquito population. For both flaviviruses, the viral load persisted in the body even until the late infection phase. In contrast to DENV, the ZIKV accumulated in the SG over time in all the mosquito populations. These findings are novel and may help direct the development of control strategies to fight dengue and Zika outbreaks in endemic regions, and provide a warning about the importance of understanding mosquito responses to arboviral infections.


Asunto(s)
Aedes/virología , Mosquitos Vectores/virología , Virus Zika/aislamiento & purificación , Aedes/fisiología , Animales , Brasil/epidemiología , Enfermedades Endémicas , Femenino , Humanos , Masculino , Mosquitos Vectores/fisiología , Glándulas Salivales/virología , Carga Viral , Virus Zika/genética , Virus Zika/fisiología , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/transmisión , Infección por el Virus Zika/virología
11.
Mem Inst Oswaldo Cruz ; 116: e200584, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34076074

RESUMEN

In the present study, we investigated the genetic diversity of Plasmodium vivax metacaspase 1 (PvMCA1) catalytic domain in two municipalities of the main malaria hotspot in Brazil, i.e., the Juruá Valley, and observed complete sequence identity among all P. vivax field isolates and the Sal-1 reference strain. Analysis of PvMCA1 catalytic domain in different P. vivax genomic sequences publicly available also revealed a high degree of conservation worldwide, with very few amino acid substitutions that were not related to putative histidine and cysteine catalytic residues, whose involvement with the active site of protease was herein predicted by molecular modeling. The genetic conservation presented by PvMCA1 may contribute to its eligibility as a druggable target candidate in vivax malaria.


Asunto(s)
Malaria Vivax , Plasmodium vivax , Brasil , Dominio Catalítico , Variación Genética/genética , Humanos , Plasmodium vivax/genética , Proteínas Protozoarias/genética
12.
ACS Infect Dis ; 7(4): 759-776, 2021 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-33689276

RESUMEN

Antimalarial drugs with novel modes of action and wide therapeutic potential are needed to pave the way for malaria eradication. Violacein is a natural compound known for its biological activity against cancer cells and several pathogens, including the malaria parasite, Plasmodium falciparum (Pf). Herein, using chemical genomic profiling (CGP), we found that violacein affects protein homeostasis. Mechanistically, violacein binds Pf chaperones, PfHsp90 and PfHsp70-1, compromising the latter's ATPase and chaperone activities. Additionally, violacein-treated parasites exhibited increased protein unfolding and proteasomal degradation. The uncoupling of the parasite stress response reflects the multistage growth inhibitory effect promoted by violacein. Despite evidence of proteotoxic stress, violacein did not inhibit global protein synthesis via UPR activation-a process that is highly dependent on chaperones, in agreement with the notion of a violacein-induced proteostasis collapse. Our data highlight the importance of a functioning chaperone-proteasome system for parasite development and differentiation. Thus, a violacein-like small molecule might provide a good scaffold for development of a novel probe for examining the molecular chaperone network and/or antiplasmodial drug design.


Asunto(s)
Antimaláricos , Antimaláricos/farmacología , Indoles/farmacología , Chaperonas Moleculares , Plasmodium falciparum
13.
Mem Inst Oswaldo Cruz ; 116: e200513, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33566952

RESUMEN

BACKGROUND: Different strategies for improvement of malaria control and elimination are based on the blockage of malaria parasite transmission to the mosquito vector. These strategies include the drugs that target the plasmodial sexual stages in humans and the early developmental stages inside mosquitoes. OBJECTIVES: Here we tested Malaria Box compounds in order to evaluate their activity against male and female gametocytes in Plasmodium berghei, mosquito infection in P. vivax and ookinete formation in both species. METHODS/FINDINGS: The membrane feeding assay and the development of ookinetes by a 24 h ex vivo culture and the ookinete yield per 1000 erythrocytes were used to test transmission-blocking potential of the Malaria Box compounds in P. vivax. For P. berghei we used flow cytometry to evaluate male and female gametocyte time course and fluorescence microscopy to check the ookinete development. The two species used in this study showed similar results concerning the compounds' activity against gametocytes and ookinetes, which were different from those in P. falciparum. In addition, from the eight Malaria Box compounds tested in both species, compounds MMV665830, MMV665878 and MMV665941 were selected as a hit compounds due the high inhibition observed. CONCLUSION: Our results showed that P. berghei is suitable as an initial screening system to test compounds against P. vivax.


Asunto(s)
Malaria Vivax/prevención & control , Mosquitos Vectores/parasitología , Plasmodium berghei/efectos de los fármacos , Plasmodium vivax/efectos de los fármacos , Animales , Malaria Vivax/tratamiento farmacológico , Malaria Vivax/transmisión
14.
Mem. Inst. Oswaldo Cruz ; 116: e200584, 2021. graf
Artículo en Inglés | LILACS | ID: biblio-1250360

RESUMEN

In the present study, we investigated the genetic diversity of Plasmodium vivax metacaspase 1 (PvMCA1) catalytic domain in two municipalities of the main malaria hotspot in Brazil, i.e., the Juruá Valley, and observed complete sequence identity among all P. vivax field isolates and the Sal-1 reference strain. Analysis of PvMCA1 catalytic domain in different P. vivax genomic sequences publicly available also revealed a high degree of conservation worldwide, with very few amino acid substitutions that were not related to putative histidine and cysteine catalytic residues, whose involvement with the active site of protease was herein predicted by molecular modeling. The genetic conservation presented by PvMCA1 may contribute to its eligibility as a druggable target candidate in vivax malaria.


Asunto(s)
Humanos , Plasmodium vivax/genética , Malaria Vivax , Variación Genética/genética , Brasil , Proteínas Protozoarias/genética , Dominio Catalítico
15.
Mem. Inst. Oswaldo Cruz ; 116: e200513, 2021. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1154879

RESUMEN

BACKGROUND Different strategies for improvement of malaria control and elimination are based on the blockage of malaria parasite transmission to the mosquito vector. These strategies include the drugs that target the plasmodial sexual stages in humans and the early developmental stages inside mosquitoes. OBJECTIVES Here we tested Malaria Box compounds in order to evaluate their activity against male and female gametocytes in Plasmodium berghei, mosquito infection in P. vivax and ookinete formation in both species. METHODS/FINDINGS The membrane feeding assay and the development of ookinetes by a 24 h ex vivo culture and the ookinete yield per 1000 erythrocytes were used to test transmission-blocking potential of the Malaria Box compounds in P. vivax. For P. berghei we used flow cytometry to evaluate male and female gametocyte time course and fluorescence microscopy to check the ookinete development. The two species used in this study showed similar results concerning the compounds' activity against gametocytes and ookinetes, which were different from those in P. falciparum. In addition, from the eight Malaria Box compounds tested in both species, compounds MMV665830, MMV665878 and MMV665941 were selected as a hit compounds due the high inhibition observed. CONCLUSION Our results showed that P. berghei is suitable as an initial screening system to test compounds against P. vivax.


Asunto(s)
Animales , Plasmodium berghei/efectos de los fármacos , Plasmodium vivax/efectos de los fármacos , Malaria Vivax/prevención & control , Mosquitos Vectores/parasitología , Malaria Vivax/tratamiento farmacológico , Malaria Vivax/transmisión
16.
Rev Soc Bras Med Trop ; 53: e20190564, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32935775

RESUMEN

INTRODUCTION: Cardiovascular diseases (CDVs) have become increasingly important for progressively older people living with HIV (PLHIV). Identification of gaps requiring improvement in the care cascade for hypertension, a primary risk factor for CVDs, is of utmost importance. This study analyzed the prevalence of hypertensive status and described the care cascade for hypertension screening, diagnosis, treatment, treatment adherence, and management in PLHIV. METHODS: This cross-sectional study included 298 PLHIV (age >40 years) who visited a referral center in the western Brazilian Amazon. Data were collected through a structured questionnaire interview and medical examinations. Thus, information regarding sociodemographic and clinical aspects, blood pressure, weight, height, body mass index, and laboratory profile was obtained. Descriptive and analytical statistics were performed, and results were considered significant ifp <0.05. RESULTS: In total, 132 (44.3%) participants reported that their blood pressure was never measured. The prevalence of hypertension was found to be 35.9% (107/298). Of these 107 participants, only 36 (33.6%) had prior knowledge of their hypertensive status, and 19 of 36 (52.7%) participants had visited a physician or cardiologist to seek treatment. Adherence to the BP-lowering treatment was noted in 11 (10.2%) participants. CONCLUSIONS: An increased prevalence of hypertension was found, and most of the hypertensive participants were unaware of their hypertensive status. In addition, blood pressure control was poor in the study population. This indicated that public health professionals did not sufficiently consider the full spectrum of healthcare and disease management for PLHIV.


Asunto(s)
Infecciones por VIH , Hipertensión , Brasil , Estudios Transversales , Femenino , Infecciones por VIH/complicaciones , Humanos , Hipertensión/complicaciones , Hipertensión/epidemiología , Masculino , Prevalencia , Factores de Riesgo
17.
Arq Bras Cardiol ; 114(5): 805-816, 2020 05 11.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-32401847

RESUMEN

In face of the pandemic of the novel coronavirus disease 2019 (COVID-19), the management of patients with cardiovascular risk factors and/or disease is challenging. The cardiovascular complications evidenced in patients with COVID-19 derive from several mechanisms, ranging from direct viral injury to complications secondary to the inflammatory and thrombotic responses to the infection. The proper care of patients with COVID-19 requires special attention to the cardiovascular system aimed at better outcomes.


Frente à pandemia da doença causada pelo novo coronavírus (COVID-19), o manejo do paciente com fator de risco e/ou doença cardiovascular é desafiador nos dias de hoje. As complicações cardiovasculares evidenciadas nos pacientes com COVID-19 resultam de vários mecanismos, que vão desde lesão direta pelo vírus até complicações secundárias à resposta inflamatória e trombótica desencadeada pela infecção. O cuidado adequado do paciente com COVID-19 exige atenção ao sistema cardiovascular em busca de melhores desfechos.


Asunto(s)
Betacoronavirus , Enfermedades Cardiovasculares/virología , Infecciones por Coronavirus/complicaciones , Personal de Salud , Neumonía Viral/complicaciones , COVID-19 , Reanimación Cardiopulmonar/normas , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/terapia , Fenómenos Fisiológicos Cardiovasculares , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/terapia , Personal de Salud/normas , Corazón/fisiopatología , Humanos , Pandemias , Atención al Paciente/normas , Neumonía Viral/diagnóstico , Neumonía Viral/terapia , Guías de Práctica Clínica como Asunto , Factores de Riesgo , SARS-CoV-2 , Disfunción Ventricular/etiología
18.
Arq. bras. cardiol ; Arq. bras. cardiol;114(5): 805-816, maio 2020. tab, graf
Artículo en Portugués | Sec. Est. Saúde SP, LILACS | ID: biblio-1131225

RESUMEN

Resumo Frente à pandemia da doença causada pelo novo coronavírus (COVID-19), o manejo do paciente com fator de risco e/ou doença cardiovascular é desafiador nos dias de hoje. As complicações cardiovasculares evidenciadas nos pacientes com COVID-19 resultam de vários mecanismos, que vão desde lesão direta pelo vírus até complicações secundárias à resposta inflamatória e trombótica desencadeada pela infecção. O cuidado adequado do paciente com COVID-19 exige atenção ao sistema cardiovascular em busca de melhores desfechos.


Abstract In face of the pandemic of the novel coronavirus disease 2019 (COVID-19), the management of patients with cardiovascular risk factors and/or disease is challenging. The cardiovascular complications evidenced in patients with COVID-19 derive from several mechanisms, ranging from direct viral injury to complications secondary to the inflammatory and thrombotic responses to the infection. The proper care of patients with COVID-19 requires special attention to the cardiovascular system aimed at better outcomes.


Asunto(s)
Humanos , Neumonía Viral/complicaciones , Enfermedades Cardiovasculares/virología , Personal de Salud/normas , Infecciones por Coronavirus/complicaciones , Betacoronavirus , Neumonía Viral/diagnóstico , Neumonía Viral/terapia , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/terapia , Fenómenos Fisiológicos Cardiovasculares , Factores de Riesgo , Reanimación Cardiopulmonar/normas , Guías de Práctica Clínica como Asunto , Infecciones por Coronavirus , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/terapia , Disfunción Ventricular/etiología , Pandemias , Atención al Paciente/normas , Corazón/fisiopatología
20.
Acta Trop ; 206: 105441, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32173316

RESUMEN

Mosquito-borne Zika virus (ZIKV) was recently introduced into the Americas and now has the potential to spill back into a sylvatic cycle in the region, likely involving non-human primates and Aedes, Haemagogus, and Sabethes species mosquitoes. We investigated potential routes of mosquito-borne virus exchange between urban and sylvatic transmission cycles by characterizing mosquito communities in three urban forest parks that receive heavy traffic from both humans and monkeys in Manaus, Brazil. Parks were stratified by both distance from the urban-forest edge (0, 50, 100, and 500 m) and relative Normalized Difference Vegetation Index (NDVI) (low, medium, or high), and mosquitoes were sampled at randomly selected sites within each stratum using BG-Sentinel traps. Additionally, temperature, relative humidity, and other environmental data were collected at each site. A total of 1,172 mosquitoes were collected from 184 sites sampled in 2018, of which 98 sites were resampled in 2019. Using park as the unit of replication (i.e. 3 replicates per sampling stratum), a two-way ANOVA showed no effect of distance or NDVI on the mean number of identified species (P > 0.05 for both comparisons) or on species diversity as measured by the Shannon-Wiener diversity index (P > 0.10 for both comparisons). However, the Morisita overlap index revealed that mosquito communities changed substantially with increasing distance from edge, with communities at 0 m and 500 m being quite distinct. Aedes albopictus and Ae. aegypti penetrated at least 100 m into the forest, while forest specialists including Haemagogus janthinomys, Sabethes glaucodaemon, and Sa. tridentatus were detected in low numbers within 100 m from the forest edge. Trichoprosopon digitatum and Psorophora amazonica were among the most abundant species collected, and both showed distributions extending from the forest edge to its interior. Our results show overlapping distributions of urban and forest mosquitoes at park edges, which highlights the risk of arbovirus exchange via multiple bridge vectors in Brazilian urban forest parks. These parks may also provide refugia for both Ae. albopictus and Ae. aegypti from mosquito control programs.


Asunto(s)
Culicidae , Bosques , Mosquitos Vectores , Infección por el Virus Zika/transmisión , Animales , Brasil , Culicidae/virología , Demografía , Humanos , Control de Mosquitos , Mosquitos Vectores/virología , Parques Recreativos , Virus Zika/aislamiento & purificación
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