Detection of HPV DNA in vaginal samples self-collected by women living with HIV treated through the Brazilian public health system: Prevalence and analysis of risk factors

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.

Genetic polymorphisms of CYP2B6*6, CYP2C8*3 and CYP2D6*4 in vivax malaria patients from Brazilian Amazon

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.

Malaria and COVID-19 coinfection in a non-malaria-endemic area in Brazil

ABSTRACT Differential diagnosis of coronavirus disease 2019 (COVID-19) from other febrile diseases is one of several challenges imposed by the pandemic. We present a case of severe malaria and COVID-19 coinfection in a non-malaria-endemic region. A 44-year-old female with malaise, fever, hypotension, jaundice, and enlarged liver and spleen was admitted to the intensive care unit. Reverse transcription-quantitative PCR results for severe acute respiratory syndrome coronavirus 2 were positive. Rapid tests, microscopy, and quantitative PCR were positive for Plasmodium vivax. Cytokine storm profiles were identified. We could not determine whether the severe vivax malaria in our patient was triggered by COVID-19 coinfection.

Searching for new antifungals for the treatment of cryptococcosis

ABSTRACT There is a consensus that the antifungal repertoire for the treatment of cryptococcal infections is limited. Standard treatment involves the administration of an antifungal drug derived from natural sources (i.e., amphotericin B) and two other drugs developed synthetically (i.e., flucytosine and fluconazole). Despite treatment, the mortality rates associated with fungal cryptococcosis are high. Amphotericin B and flucytosine are toxic, require intravenous administration, and are usually unavailable in low-income countries because of their high cost. However, fluconazole is cost-effective, widely available, and harmless with regard to its side effects. However, fluconazole is a fungistatic agent that has contributed considerably to the increase in fungal resistance and frequent relapses in patients with cryptococcal meningitis. Therefore, there is an unquestionable need to identify new alternatives or adjuvants to conventional drugs for the treatment of cryptococcosis. A potential antifungal agent should be able to kill cryptococci and "bypass" the virulence mechanism of the yeast. Furthermore, it should have fungicidal action, low toxicity, high selectivity, easily penetrate the central nervous system, and widely available. In this review, we describe cryptococcosis, its conventional therapy, and failures arising from the use of drugs traditionally considered to be the reference standard. Additionally, we present the approaches used for the discovery of new drugs to counteract cryptococcosis, ranging from the conventional screening of natural products to the inclusion of structural modifications to optimize anticryptococcal activity, as well as drug repositioning and combined therapies.

Arranjos tecnoassistenciais no enfrentamento da pandemia da COVID-19 na perspectiva de gestores / Technical-assistance arrangements in coping with the COVID-19 pandemic from the managers' perspective / Preparativos tecnoasistenciales para enfrentar la pandemia de COVID-19 desde la perspectiva de los gestores

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.

Pathological findings and morphologic correlation of the lungs of autopsied patients with SARS-CoV-2 infection in the Brazilian Amazon using transmission electron microscopy

Abstract INTRODUCTION: Electron microscopy (EM) is a rapid and effective tool that can be used to create images of a whole spectrum of virus-host interactions and, as such, has long been used in the discovery and description of viral mechanisms. METHODS: Electron microscopy was used to evaluate the pulmonary pathologies of postmortem lung sections from three patients who died from infection with SARS-associated coronavirus 2 (SARS-CoV-2), a new member of the Coronaviridae family. RESULTS: Diffuse alveolar damage (DAD) was predominant in all three patients. The early exudative stage was characterized principally by edema and extravasation of red blood cells into the alveolar space with injury to the alveolar epithelial cells; this was followed by detachment, apoptosis, and necrosis of type I and II pneumocytes. The capillaries exhibited congestion, exposure of the basement membrane from denuded endothelial cells, platelet adhesion, fibrin thrombi, and rupture of the capillary walls. The proliferative stage was characterized by pronounced proliferation of type II alveolar pneumocytes and multinucleated giant cells. The cytopathic effect of SARS-CoV-2 was observed both in degenerated type II pneumocytes and freely circulating in the alveoli, with components from virions, macrophages, lymphocytes, and cellular debris. CONCLUSIONS: Viral particles consistent with the characteristics of SARS-CoV-2 were observed mainly in degenerated pneumocytes, in the endothelium, or freely circulating in the alveoli. In the final stage of illness, the alveolar spaces were replaced by fibrosis.

Plasmodium vivax metacaspase 1 (PvMCA1) catalytic domain is conserved in field isolates from Brazilian Amazon

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.

Transmission-blocking compound candidates against Plasmodium vivax using P. berghei as an initial screening

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.

Bee sting envenomation severe cases in Manaus, Brazilian Amazon: clinical characteristics and immune markers of case reports

Abstract Bee venom is a natural toxin composed of several peptides. Massive envenoming causes severe local and systemic reactions. We report two cases of severe bee envenomation, of which one was fatal. We also describe clinical characteristics and immune markers. Both victims suffered from respiratory distress, renal failure, rhabdomyolysis, and shock. They required invasive mechanical ventilation, vasoactive drugs, and renal replacement therapy. Moreover, serum levels of chemokines, cytokines, and cell-free circulating nucleic acids demonstrated an intense inflammatory process. Massive envenoming produced systemic injury in the victims, with an uncontrolled inflammatory response, and a more significant chemotactic response in the fatal case.

Chronic use of hydroxychloroquine did not protect against COVID-19 in a large cohort of patients with rheumatic diseases in Brazil

Abstract Background: There is a lack of information on the role of chronic use of hydroxychloroquine during the SARS-CoV-2 outbreak. Our aim was to compare the occurrence of COVID-19 between rheumatic disease patients on hydroxychloroquine with individuals from the same household not taking the drug during the first 8 weeks of community viral transmission in Brazil. Methods: This baseline cross-sectional analysis is part of a 24-week observational multi-center study involving 22 Brazilian academic outpatient centers. All information regarding COVID-19 symptoms, epidemiological, clinical, and demographic data were recorded on a specific web-based platform using telephone calls from physicians and medical students. COVID-19 was defined according to the Brazilian Ministry of Health (BMH) criteria. Mann-Whitney, Chi-square and Exact Fisher tests were used for statistical analysis and two binary Final Logistic Regression Model by Wald test were developed using a backward-stepwise method for the presence of COVID-19. Results: From March 29th to May 17st, 2020, a total of 10,443 participants were enrolled, including 5166 (53.9%) rheumatic disease patients, of whom 82.5% had systemic erythematosus lupus, 7.8% rheumatoid arthritis, 3.7% Sjögren's syndrome and 0.8% systemic sclerosis. In total, 1822 (19.1%) participants reported flu symptoms within the 30 days prior to enrollment, of which 3.1% fulfilled the BMH criteria, but with no significant difference between rheumatic disease patients (4.03%) and controls (3.25%). After adjustments for multiple confounders, the main risk factor significantly associated with a COVID-19 diagnosis was lung disease (OR 1.63; 95% CI 1.03-2.58); and for rheumatic disease patients were diagnosis of systemic sclerosis (OR 2.8; 95% CI 1.19-6.63) and glucocorticoids above 10 mg/ day (OR 2.05; 95% CI 1.31-3.19). In addition, a recent influenza vaccination had a protective effect (OR 0.674; 95% CI 0.46-0.98). Conclusion: Patients with rheumatic disease on hydroxychloroquine presented a similar occurrence of COVID-19 to household cohabitants, suggesting a lack of any protective role against SARS-CoV-2 infection. Trial registration Brazilian Registry of Clinical Trials (ReBEC; RBR - 9KTWX6).

Severe tissue complications in patients of Bothrops snakebite at a tertiary health unit in the Brazilian Amazon: clinical characteristics and associated factors

Abstract INTRODUCTION: Snakebites in the Brazilian Amazon are caused mostly by snakes from the Bothrops genus and envenomated patients may suffer from tissue complications. METHODS: This study aimed to identify risk factors for severe tissue complications (STC) in patients with Bothrops snakebite in the Amazonas state, Brazil. RESULTS: Snakebites that were classified as severe and affected female patients with comorbidities presented greater risks of developing STCs. In addition, hospitalizations of patients with STC exceeded 5 days. CONCLUSIONS: Clinical and epidemiological characteristics can prove essential for assessing the evolution of STC and clinical prognosis of patients with Bothrops snakebites.

O Coração e a COVID-19: O que o Cardiologista Precisa Saber / The Heart and COVID-19: What Cardiologists Need to Know

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.

Zika virus RNA excretion in sweat with concomitant detection in other body fluid specimens

We evaluated sweat, blood and urine specimens obtained from an ongoing cohort study in Brazil. Samples were collected at pre-established intervals after the initial rash presentation and tested for Zika virus (ZIKV) RNA presence by real-time reverse transcriptase polymerase chain reaction (rRT-PCR). From 254 participants with confirmed infection, ZIKV RNA was detected in the sweat of 46 individuals (18.1%). Sweat presented a median cycle threshold (Ct) of 34.74 [interquartile range (IQR) 33.44-36.04], comparable to plasma (Ct 35.96 - IQR 33.29-36.69) and higher than urine (Ct 30.78 - IQR 28.72-33.22). Concomitant detection with other specimens was observed in 33 (72%) of 46 participants who had a positive result in sweat. These findings represent an unusual and not yet investigated virus shedding through eccrine glands.

Increased platelet distribution width and reduced IL-2 and IL-12 are associated with thrombocytopenia in Plasmodium vivax malaria

BACKGROUND Thrombocytopenia in malaria involves platelet destruction and consumption; however, the cellular response underlying this phenomenon has still not been elucidated. OBJECTIVE To find associations between platelet indices and unbalanced Th1/Th2/Th17 cytokines as a response to thrombocytopenia in Plasmodium vivax infected (Pv-MAL) patients. METHODS Platelet counts and quantification of Th1/Th2/Th17 cytokine levels were compared in 77 patients with uncomplicated P. vivax malaria and 37 healthy donors from the same area (endemic control group - ENCG). FINDINGS Thrombocytopenia was the main manifestation in 55 patients, but was not associated with parasitaemia. The Pv-MAL patients showed increases in the mean platelet volume (MPV), which may be consistent with larger or megaplatelets. Contrary to the findings regarding the endemic control group, MPV and platelet distribution width (PDW) did not show an inverse correlation, due the increase in the heterogeneity of platelet width. In addition, the Pv-MAL patients presented increased IL-1β and reduced IL-12p70 and IL-2 serum concentrations. Furthermore, the reduction of these cytokines was associated with PDW values. MAIN CONCLUSIONS Our data demonstrate that an increase in MPV and the association between reductions of IL-2 and IL-12 and PDW values may be an immune response to thrombocytopenia in uncomplicated P. vivax malaria.

Increased prevalence of hypertension among people living with HIV: where to begin?

Abstract 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.

Confirmed Invasive Pulmonary Aspergillosis and COVID-19: the value of postmortem findings to support antemortem management

Abstract We present postmortem evidence of invasive pulmonary aspergillosis (IPA) in a patient with severe COVID-19. Autopsies of COVID-19 confirmed cases were performed. The patient died despite antimicrobials, mechanical ventilation, and vasopressor support. Histopathology and peripheral blood galactomannan antigen testing confirmed IPA. Aspergillus penicillioides infection was confirmed by nucleotide sequencing and BLAST analysis. Further reports are needed to assess the occurrence and frequency of IPA in SARS-CoV-2 infections, and how they interact clinically.