High seroprevalence of Leishmania infantum is linked to immune activation in people with HIV: a two-stage cross-sectional study in Bahia, Brazil.

Visceral leishmaniasis is an opportunistic disease in HIV-1 infected individuals, unrecognized as a determining factor for AIDS diagnosis. The growing geographical overlap of HIV-1 and Leishmania infections is an emerging challenge worldwide, as co-infection increases morbidity and mortality for both infections. Here, we determined the prevalence of people living with HIV (PWH) with a previous or ongoing infection by Leishmania infantum and investigated the virological and immunological factors associated with co-infection. We adopted a two-stage cross-sectional cohort (CSC) design (CSC-I, n = 5,346 and CSC-II, n = 317) of treatment-naïve HIV-1-infected individuals in Bahia, Brazil. In CSC-I, samples collected between 1998 and 2013 were used for serological screening for leishmaniasis by an in-house Enzyme-Linked Immunosorbent Assay (ELISA) with SLA (Soluble Leishmania infantum Antigen), resulting in a prevalence of previous or ongoing infection of 16.27%. Next, 317 PWH were prospectively recruited from July 2014 to December 2015 with the collection of sociodemographic and clinical data. Serological validation by two different immunoassays confirmed a prevalence of 15.46 and 8.20% by anti-SLA, and anti-HSP70 serology, respectively, whereas 4.73% were double-positive (DP). Stratification of these 317 individuals in DP and double-negative (DN) revealed a significant reduction of CD4+ counts and CD4+/CD8+ ratios and a tendency of increased viral load in the DP group, as compared to DN. No statistical differences in HIV-1 subtype distribution were observed between the two groups. However, we found a significant increase of CXCL10 (p = 0.0076) and a tendency of increased CXCL9 (p = 0.061) in individuals with DP serology, demonstrating intensified immune activation in this group. These findings were corroborated at the transcriptome level in independent Leishmania- and HIV-1-infected cohorts (Swiss HIV Cohort and Piaui Northeast Brazil Cohort), indicating that CXCL10 transcripts are shared by the IFN-dominated immune activation gene signatures of both pathogens and positively correlated to viral load in untreated PWH. This study demonstrated a high prevalence of PWH with L. infantum seropositivity in Bahia, Brazil, linked to IFN-mediated immune activation and a significant decrease in CD4+ levels. Our results highlight the urgent need to increase awareness and define public health strategies for the management and prevention of HIV-1 and L. infantum co-infection.

Efficacy of Brazilian green propolis (EPP-AF®) as an adjunct treatment for hospitalized COVID-19 patients: A randomized, controlled clinical trial.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promotes challenging immune and inflammatory phenomena. Though various therapeutic possibilities have been tested against coronavirus disease 2019 (COVID-19), the most adequate treatment has not yet been established. Propolis is a natural product with considerable evidence of immunoregulatory and anti-inflammatory activities, and experimental data point to potential against viral targets. We hypothesized that propolis can reduce the negative effects of COVID-19. METHODS: In a randomized, controlled, open-label, single-center trial, hospitalized adult COVID-19 patients were treated with a standardized green propolis extract (EPP-AF®ï¸) as an adjunct therapy. Patients were allocated to receive standard care plus an oral dose of 400 mg or 800 mg/day of green propolis for seven days, or standard care alone. Standard care included all necessary interventions, as determined by the attending physician. The primary end point was the time to clinical improvement, defined as the length of hospital stay or oxygen therapy dependency duration. Secondary outcomes included acute kidney injury and need for intensive care or vasoactive drugs. Patients were followed for 28 days after admission. RESULTS: We enrolled 124 patients; 40 were assigned to EPP-AF®ï¸ 400 mg/day, 42 to EPP-AF®ï¸ 800 mg/day, and 42 to the control group. The length of hospital stay post-intervention was shorter in both propolis groups than in the control group; lower dose, median 7 days versus 12 days (95% confidence interval [CI] -6.23 to -0.07; p = 0.049) and higher dose, median 6 days versus 12 days (95% CI -7.00 to -1.09; p = 0.009). Propolis did not significantly affect the need for oxygen supplementation. In the high dose propolis group, there was a lower rate of acute kidney injury than in the controls (4.8 vs 23.8%), (odds ratio [OR] 0.18; 95% CI 0.03-0.84; p = 0.048). No patient had propolis treatment discontinued due to adverse events. CONCLUSIONS: Addition of propolis to the standard care procedures resulted in clinical benefits for the hospitalized COVID-19 patients, especially evidenced by a reduction in the length of hospital stay. Consequently, we conclude that propolis can reduce the impact of COVID-19.

Isolation of blaNDM-producing Enterobacteriaceae in a public hospital in Salvador, Bahia, Brazil

ABSTRACT Carbapenemases have great importance in the global epidemiological scenario since infections with carbapenemase-producing bacteria are associated with high mortality, especially in hospitalized patients in intensive care units. This study describes two microorganisms producers of the New Delhi Metallo-b-lactamase, Klebsiella pneumoniae and Citrobacter freundii, from two patients admitted to a public hospital in Salvador, Bahia. These are the first clinical cases of New Delhi Metallo-b-lactamase described in microorganisms in the north and northeast Brazil. The isolates were characterized by antimicrobial susceptibility test, with resistance to all β-lactams including carbapenems, negative Modified Hodge Test and the synergy test with Ethylenediaminetetraacetic acid, Phenylboronic Acid and Cloxacillin was positive only with Ethylenediaminetetraacetic acid (difference of >5 mm in the inhibition zone between the disk without and with the inhibitor). Analysis by multiplex PCR for blaIMP, blaVIM, blaNDM, blaKPC and blaOXA-48 enzymes confirmed the presence of blaNDM gene. This report of two different New Delhi Metallo-b-lactamase-producing microorganisms in a different region of Brazil confirms the risk of spreading resistance genes between different species and emphasizes the need for prevention and control of infections caused by these pathogens, which have limited treatment options and have been linked to high mortality rates.

Isolation of blaNDM-producing Enterobacteriaceae in a public hospital in Salvador, Bahia, Brazil.

Carbapenemases have great importance in the global epidemiological scenario since infections with carbapenemase-producing bacteria are associated with high mortality, especially in hospitalized patients in intensive care units. This study describes two microorganisms producers of the New Delhi Metallo-b-lactamase, Klebsiella pneumoniae and Citrobacter freundii, from two patients admitted to a public hospital in Salvador, Bahia. These are the first clinical cases of New Delhi Metallo-b-lactamase described in microorganisms in the north and northeast Brazil. The isolates were characterized by antimicrobial susceptibility test, with resistance to all ß-lactams including carbapenems, negative Modified Hodge Test and the synergy test with Ethylenediaminetetraacetic acid, Phenylboronic Acid and Cloxacillin was positive only with Ethylenediaminetetraacetic acid (difference of >5mm in the inhibition zone between the disk without and with the inhibitor). Analysis by multiplex PCR for blaIMP, blaVIM, blaNDM, blaKPC and blaOXA-48 enzymes confirmed the presence of blaNDM gene. This report of two different New Delhi Metallo-b-lactamase-producing microorganisms in a different region of Brazil confirms the risk of spreading resistance genes between different species and emphasizes the need for prevention and control of infections caused by these pathogens, which have limited treatment options and have been linked to high mortality rates.

Direct identification from positive blood broth culture by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS)

ABSTRACT Bloodstream infections (BSIs) are among the most concerning bacterial infections. They are one of the leading causes of morbidity and mortality, and occur in 30-70% of critical care patients. The prompt identification of the causative microorganism can help choosing the appropriate antimicrobial therapy that will lead to better clinical outcomes. Blood culture is one of the most relevant tests for microbiological diagnosis of bacterial infections. The introduction of the MALDI-TOF microbiological diagnosis significantly decreased the time of identifying microorganisms. However, it depends on the growth on solid culture medium. In this study, 538 bottles of positive blood cultures were evaluated to test the accuracy of an in house modified protocol. The study sample consisted of 198 Gram-negative and 350 Gram-positive bacteria. In all, 460 (83.94%) species were identified based on the direct plate findings. The protocol allowed the identification of 185/198 (93.43%) of the Gram-negative bacteria, including aerobes, anaerobes, and non-fermenters, and 275/350 (78.85%) of the Gram-positive bacteria. The proposed method has the potential to provide accurate results in comparison to the traditional method with the potential to reduce the turnaround time for the results and optimize antimicrobial therapy in BSI.

Direct identification from positive blood broth culture by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS).

Bloodstream infections (BSIs) are among the most concerning bacterial infections. They are one of the leading causes of morbidity and mortality, and occur in 30-70% of critical care patients. The prompt identification of the causative microorganism can help choosing the appropriate antimicrobial therapy that will lead to better clinical outcomes. Blood culture is one of the most relevant tests for microbiological diagnosis of bacterial infections. The introduction of the MALDI-TOF microbiological diagnosis significantly decreased the time of identifying microorganisms. However, it depends on the growth on solid culture medium. In this study, 538 bottles of positive blood cultures were evaluated to test the accuracy of an in house modified protocol. The study sample consisted of 198 Gram-negative and 350 Gram-positive bacteria. In all, 460 (83.94%) species were identified based on the direct plate findings. The protocol allowed the identification of 185/198 (93.43%) of the Gram-negative bacteria, including aerobes, anaerobes, and non-fermenters, and 275/350 (78.85%) of the Gram-positive bacteria. The proposed method has the potential to provide accurate results in comparison to the traditional method with the potential to reduce the turnaround time for the results and optimize antimicrobial therapy in BSI.

Avaliação da prevalência de resistência transmitida aos antirretrovirais em indivíduos infectados pelo HIV-1 em Salvador- Bahia / Prevalence of transmitted resistance to antiretroviraldrugs in patients infected with HIV-1 in Salvador, Bahia. Luiz Carl

Avaliar a prevalência de resistência transmitida aos antirretrovirais em indivíduos infectados pelo HIV-1 em acompanhamento clínico e laboratorial na cidade de Salvador-Bahia. Estudo descritivo de corte transversal com amostragem de conveniência composto por 121 pacientes infectados pelo HIV-1, com 18 anos de idade ou mais, virgens de tratamento antirretrovial e que fazem coletas de exame para quantificação das Subpopulações Linfocitárias e da carga viral sérica do HIV-1 no Laboratório de Retrovírus do Hospital Universitário Professor Edgard Santos ou no Centro Especializado em Diagnóstico, Assistência e Pesquisa (CEDAP). Os pacientes foram entrevistados para preenchimento de um questionário epidémiologico e consentiram na utilização do excedente de sangue para realização do sequenciamento do gene pol do HIV-1 contendo parte da Transcriptase e da Protease para análise das mutações de resistência aos antirretrovirais e a caracterização genotípica, análise de recombinações e estudo da história evolutiva viral. Entre os 103 pacientes 66% são do sexo masculino, a mediana de idade e do tempo estimado do diagnóstico do HIV-1 são respectivamente de 35 anos e 29 meses. A principal categoria de exposição relatada foi a sexual com 88,3%, seguida por 3% com acidentes com perfurocortantes e 1% uso de drogas intravenosas. A mediana da contagem dos Linfócitos TCD4+ foi de 438 cel/mm3 e de 4,4 log10. Na análise de Mutação de Resistência à Fármacos (DRM) atráves da ferramenta de Calibração da População com Resistência (CPR) observamos uma prevalência global de 6,8%, 3 (2,9%)...

To evaluate the prevalence of transmitted resistance to antiretroviral drugs in patients infected with HIV- 1 assisted in the city of Salvador, Bahia. A descriptive crosssectional study with 121 patients with 18 years of age or older, chronic or recent diagnosis of HIV -1, antirretrovial naïve and make collections for examination and quantification of lymphocyte subpopulations serum viral load of HIV -1 in the Retrovirus Laboratory, Hospital Universitário Professor Edgard Santos or in Centro Especializado em Diagnóstico, Assistência e Pesquisa (CEDAP). Patients were interviewed to fill an epidemiological questionnaire and consented to the use of drawed blood to be sequenced of the transcriptase and protease region of the pol gene of HIV - 1 for analysis of antiretroviral resistance mutations and subtype viral. Of the 121 patients, 104 sequences for phylogenetic analysis and transmitted resistance were obtained, 18 individuals were excluded due quality or amplification problems. Among 103 patients 66% were male, the median age and the estimated time of diagnosis of HIV -1 were respectively 35 and 29 months. The main category of reported exposure was sexual with 88.3%, followed by 3% with Occupational Exposure and 1% use of Intravenous Drugs. The median CD4 + lymphocyte count was 438 cells/mm3 and 4.4 log10. The analysis of Drug Resistance Mutation (DRM) by Calibrating Population Resistance tool (CPR) has a global prevalence of 6.8%, distributed: 2.9%...

Acute HIV infection with rapid progression to AIDS.

Acute HIV infection is rarely recognized as the signs and symptoms are normally unspecific and can persist for days or weeks. The normal HIV course is characterized by a progressive loss of CD4+ cells, which normally leads to severe immunodeficiency after a variable time interval. The mean time from initial infection to development of clinical AIDS is approximately 8-10 years, but it is variable among individuals and depends on a complex interaction between virus and host. Here we describe an extraordinary case of a man who developed Pneumocisits jiroveci pneumonia within one month after sexual exposure to HIV-1, and then presented with 3 consecutive CD4 counts bellow 200 cells/mm³ within 3 months, with no other opportunistic disease. Although antiretroviral therapy (AZT+3TC+ATZ/r) was started, with full adherence of the patient, and genotyping indicating no primary antiretroviral resistance mutations, he required more than six months to have a CD4 restoration to levels above 200 cells/mm³ and 10 months to HIV-RNA to become undetectable.

Acute HIV infection with rapid progression to AIDS

Acute HIV infection is rarely recognized as the signs and symptoms are normally unspecific and can persist for days or weeks. The normal HIV course is characterized by a progressive loss of CD4+ cells, which normally leads to severe immunodeficiency after a variable time interval. The mean time from initial infection to development of clinical AIDS is approximately 8-10 years, but it is variable among individuals and depends on a complex interaction between virus and host. Here we describe an extraordinary case of a man who developed Pneumocisits jiroveci pneumonia within one month after sexual exposure to HIV-1, and then presented with 3 consecutive CD4 counts bellow 200 cells/mm³ within 3 months, with no other opportunistic disease. Although antiretroviral therapy (AZT+3TC+ATZ/r) was started, with full adherence of the patient, and genotyping indicating no primary antiretroviral resistance mutations, he required more than six months to have a CD4 restoration to levels above 200 cells/mm³ and 10 months to HIV-RNA to become undetectable.