Typing of Treponema pallidum in a Brazilian sample and follow-up of treatment using molecular assays.

Syphilis remains a significant public health concern, with serological assays being the primary method for diagnosis. However, molecular techniques have proven to be reliable tools for the diagnosis and understanding of the transmission dynamics of Treponema pallidum infection. This study aimed to evaluate the efficacy of syphilis treatment using molecular assays, perform Enhanced Centers for Disease Control and Prevention (ECDC) typing, and analyze resistance (macrolide and doxycycline) in the T. pallidum isolate. PCR assay amplified treponemal DNA only from the lesion sample, whereas qPCR was able to amplify DNA in both lesion and blood samples before treatment. Throughout the treatment follow-up, qPCR effectively did not identify treponemal DNA in the blood for up to one to two weeks after treatment. ECDC typing revealed the genotype 14 e/g in the Brazilian T. pallidum isolate, and the presence of the A2058G mutation in 23 S rRNA gene, indicating macrolide resistance. Although, the G1058C mutation in 16 S rRNA gene was not detected. Notably, qPCR demonstrated its potential for diagnosing T. pallidum in blood samples, even when the treponemal DNA levels were low, enabling more accurate and sensitive diagnosis and guiding better syphilis therapy. In addition, to the best of our knowledge, this study represents the first identification of subtype 14 e/g and azithromycin resistance in a Brazilian T. pallidum isolate.

Molecular characterization of Treponema pallidum isolates from Brazil.

Syphilis remains a public health concern in Brazil, and the data on the characterization and resistance of Treponema pallidum in Brazil is limited. The present study aimed to detect Treponema DNA in the lesions and blood samples obtained from individuals diagnosed with syphilis. The Brazilian isolates were submitted to the Enhanced Centers for Disease Control and Prevention (ECDC) scheme and also analyzed for resistance gene. Treponemal DNA from 18 lesions and 18 blood specimens were submitted for amplification using Polymerase Chain Reaction (PCR) and Polymerase Chain Reaction in Real Time (RT-PCR). Eight samples from lesions and eight from blood were positive in the RT-PCR analysis. Eight lesions and three blood samples were positive using PCR. Two samples exhibited azithromycin resistance. The Brazilian isolate types 14d/g, 14 d/c, 15d/c, and 15d/e were identified using the ECDC scheme. The three subtypes 14d/c, 15d/c, and 15d/e have been identified in Brazil for the first time.

Immune Response to an Inactivated Vaccine of SARS-CoV-2 (CoronaVac) in an Indigenous Brazilian Population: A Cohort Study.

INTRODUCTION: Although the adaptive immune responses to the CoronaVac vaccine are known, their dynamics in indigenous communities remain unclear. In this study, we assessed the humoral and cellular immune responses to CoronaVac (Sinovac Biotech Life Sciences, 2021 NCT05225285, Beijing, China), in immunized Brazilian indigenous individuals. METHODS: We conducted a prospective cohort study on indigenous Brazilian people between February 2021 and June 2021. Analyses of immune responses were carried out before (T1) and after a vaccination schedule was completed (T2). Demographic data were collected using a questionnaire. RESULTS: We initially included 328 patients; among them, 120 (36.6%) had no SARS-CoV-2 antibodies. Peripheral blood mononuclear cells (PBMCs) were collected from 106 patients during follow-up visits, of which 91 samples were analyzed by immunophenotyping assay to detect SARS-CoV-2-specific memory T-cell response. Post-vaccination, the levels of memory B-cells and Natural Killer T-lymphocytes increased. Bororó village residents, females, and Terena ethnic group members had higher levels of anti-spike IgG antibodies post-vaccination, whereas alcohol and tobacco users had lower concentrations. CONCLUSIONS: To our best knowledge, this was the first comprehensive assessment of antibody and T-cell responses against CoronaVac vaccination in indigenous patients. Our findings showed that antibody response and T-cell immunity against SARS-CoV-2 were present in most patients following the vaccination schedule.

Antifungal activity of Caryocar brasiliense camb. Alone or along with antifungal agents against multidrug-resistant Candida auris.

ETHNOPHARMACOLOGICAL RELEVANCE: Candida auris poses a severe global health threat, with many strains resistant to antifungal treatments, complicating therapy. Exploring natural compounds alongside conventional drugs offers promising therapeutic avenues. The antifungal potential of the ethanolic extract from Caryocar brasiliense (Cb-EE), a plant native to the Brazilian cerrado and renowned for its medicinal properties, was investigated against C. auris. AIM OF THE STUDY: The study examined the chemical composition, antifungal activity, mechanisms of action, and in vivo effects of Cb-EE. MATERIALS AND METHODS: Leaves of C. brasiliense were processed to extract ethanolic extract, which was evaluated for phenolic compounds, flavonoids, and tannins. The antifungal capacity was determined through broth microdilution and checkerboard methods, assessing interaction with conventional antifungals. RESULTS: Cb-EE demonstrated fungistatic activity against various Candida species and Cryptococcus neoformans. Synergy with fluconazole and additive effects with other drugs were observed. Cb-EE inhibited C. auris growth, with the combination of fluconazole extending inhibition. Mechanistic studies revealed interference with fungal membranes, confirmed by sorbitol protection assays, cellular permeability tests, and scanning electron microscopy (SEM). Hemocompatibility and in vivo toxicity tests on Tenebrio molitor showed safety. CONCLUSION: Cb-EE, alone or in combination with fluconazole, effectively treated C. auris infections in vitro and in vivo, suggesting its prospective role as an antifungal agent against this emerging pathogen.

Synergistic interaction of polymyxin B with carvacrol: antimicrobial strategy against polymyxin-resistant Klebsiella pneumoniae.

Objective: The antimicrobial activities of the synergistic combination of carvacrol and polymyxin B against polymyxin-resistant Klebsiella pneumoniae were evaluated. Methods: The methods employed checkerboard assays to investigate synergism, biofilm inhibition assessment and membrane integrity assay. In addition, the study included in vivo evaluation using a mouse infection model. Results: The checkerboard method evaluated 48 combinations, with 23 indicating synergistic action. Among these, carvacrol 10 mg/kg plus polymyxin B 2 mg/kg exhibited in vivo antimicrobial activity in a mouse model of infection, resulting in increased survival and a significant decrease in bacterial load in the blood. Conclusion: Polymyxin in synergy with carvacrol represents a promising alternative to be explored in the development of new antimicrobials.

In this study, we wanted to find a new way to fight a bacteria called Klebsiella pneumoniae, which is not easily killed by medication. We mixed two drugs, carvacrol and polymyxin B, to see if they would work together to fight the bacteria. We found that the mixed treatment helped to kill the bacteria. We also tried this mixed treatment in sick mice, and they got better. Our study shows that this mixed treatment might be a new way to fight bacteria that are hard to kill with regular drugs. Next, we hope to learn more about how it works.

Impact of COVID-19 pandemic in the Brazilian maternal mortality ratio: A comparative analysis of Neural Networks Autoregression, Holt-Winters exponential smoothing, and Autoregressive Integrated Moving Average models.

BACKGROUND AND OBJECTIVES: The acute respiratory infection caused by severe acute respiratory syndrome coronavirus disease (COVID-19) has resulted in increased mortality among pregnant, puerperal, and neonates. Brazil has the highest number of maternal deaths and a distressing fatality rate of 7.2%, more than double the country's current mortality rate of 2.8%. This study investigates the impact of the COVID-19 pandemic on the Brazilian Maternal Mortality Ratio (BMMR) and forecasts the BMMR up to 2025. METHODS: To assess the impact of the COVID-19 pandemic on the BMMR, we employed Holt-Winters, Autoregressive Integrated Moving Average (ARIMA), and Neural Networks Autoregression (NNA). We utilized a retrospective time series spanning twenty-five years (1996-2021) to forecast the BMMR under both a COVID-19 pandemic scenario and a controlled COVID-19 scenario. RESULTS: Brazil consistently exhibited high maternal mortality values (mean BMMR [1996-2019] = 57.99 ±6.34/100,000 live births) according to World Health Organization criteria. The country experienced its highest mortality peak in the historical BMMR series in the second quarter of 2021 (197.75/100,000 live births), representing a more than 200% increase compared to the previous period. Holt-Winter and ARIMA models demonstrated better agreement with prediction results beyond the sample data, although NNA provided a better fit to previous data. CONCLUSIONS: Our study revealed an increase in BMMR and its temporal correlation with COVID-19 incidence. Additionally, it showed that Holt-Winter and ARIMA models can be employed for BMMR forecasting with lower errors. This information can assist governments and public health agencies in making timely and informed decisions.

Seroprevalence Of SARS-COV-2 infection in asymptomatic indigenous from the largest Brazilian periurban area.

This study assessed the seroprevalence of SARS-CoV-2 in 496 asymptomatic individuals from Mato Grosso do Sul, located in Dourados, the largest periurban indigenous area in Brazil, from January 25 to February 4, 2021. The volunteers participated before receiving their first dose of the CoronaVac inactivated vaccine. For screening, blood samples were collected and analyzed using SARS-CoV-2 rapid tests and the enzyme-linked immunosorbent assay (ELISA). We observed varying trends in total anti-SARS-CoV-2 antibodies across different variables. Seropositivity among the participants tested was 63.70% (316/496) using the rapid test and 52.82% (262/496) were positive using the ELISA method. The majority of participants identified with the Guarani-Kaiowá ethnic group, with 66.15% (217/328), and other ethnic groups with 58.84% (193/328). The median age of the subjects was 30.5 years, with 79.57% (261/328) being femaleThis research showed the elevated seroprevalence of SARS-CoV-2 antibodies in asymptomatic Brazilians. The findings indicate a high seropositivity rate among the asymptomatic indigenous population of Midwest Brazil. This underscores the overlooked status of these communities and underscores the need for targeted national initiatives that emphasize the protection of vulnerable ethnic groups in the fight against COVID-19.

Genomic characterization of SARS-CoV-2 from an indigenous reserve in Mato Grosso do Sul, Brazil.

Background: The COVID-19 pandemic had a major impact on indigenous populations. Understanding the viral dynamics within this population is essential to create targeted protection measures. Methods: A total of 204 SARS-CoV-2 positive samples collected between May 2020 and November 2021 from an indigenous area in Mato Grosso do Sul (MS), Midwestern Brazil, were screened. Samples were submitted to whole genome sequencing using the Nanopore sequencing platform. Clinical, demographic, and phylogenetic data were analyzed. Results: We found the co-circulation of six main SARS-CoV-2 lineages in the indigenous population, with the Zeta lineage being the most prevalent (27.66%), followed by B.1.1 (an ancestral strain) (20.21%), Gamma (14.36%) and Delta (13.83%). Other lineages represent 45.74% of the total. Our phylogenetic reconstruction indicates that multiple introduction events of different SARS-CoV-2 lineages occurred in the indigenous villages in MS. The estimated indigenous population mortality rate was 1.47%. Regarding the ethnicity of our cohort, 64.82% belong to the Guarani ethnicity, while 33.16% belong to the Terena ethnicity, with a slightly higher prevalence of males (53.43%) among females. Other ethnicities represent 2.01%. We also observed that almost all patients (89.55%) presented signs and symptoms related to COVID-19, being the most prevalent cough, fever, sore throat, and headache. Discussion: Our results revealed that multiple independent SARS-CoV-2 introduction events had occurred through time, probably due to indigenous mobility, since the villages studied here are close to urban areas in MS. The mortality rate was slightly below of the estimation for the state in the period studied, which we believe could be related to the small number of samples evaluated, the underreporting of cases and deaths among this population, and the inconsistency of secondary data available for this study. Conclusion: In this study, we showed the circulation of multiple SARS-CoV-2 variants in this population, which should be isolated and protected as they belong to the most fragile group due to their socioeconomic and cultural disparities. We reinforce the need for constant genomic surveillance to monitor and prevent the spread of new emerging viruses and to better understand the viral dynamics in these populations, making it possible to direct specific actions.

Determining reference ranges for immunological cells of healthy indigenous individuals from a region in Brazil.

Morais et al. conducted a pioneering study with Brazilian indigenous populations to determine reference values for immunologic cells from healthy adult individuals. The main findings included a higher relative median for T lymphocyte subsets in females than males, and T CD3+, T CD4+, and T CD8+ relative values were statistically different when compared with Brazilian populations from other Brazilian regions. The relative medians of CD3+, CD4+, and CD8+ T cells were significantly higher in women than in men in a healthy indigenous population. Demographic and ethnic diversity of the Brazilian population can be associated with quantitative modifications in the immunologic cells of healthy individuals. OBJECTIVE: The establishment of reference values for a subset of leukocytes is common in clinical practice, and ethnic variations are strongly associated with disease development. In Brazil, indigenous people are vulnerable to infections, and few studies have described the health and disease conditions of this population. This study aimed to provide reference values for immunological cell subsets in indigenous Brazilians living in the state of Mato Grosso do Sul. METHODS: Flow cytometry and 4-color combinations of monoclonal antibodies were used to characterize cells. A total of 115 healthy adults, mostly females (72%), were included in the study. The results are presented as mean and median (2.5%-97.5% percentiles) for T and B lymphocytes, CD4+ T cells, CD8+ T cells, Natural Killer cells, monocytes, and dendritic cells, providing an average immunological profile for the population in question. RESULTS: The relative medians of CD3+, CD4+, and CD8+ T cells were significantly higher in women than in men in a healthy indigenous population. CONCLUSION: To our knowledge, cell reference data from indigenous Brazilians are unknown in the literature. The immune cell results presented in this pioneering study will contribute to the clinical and laboratory evaluation of the Brazilian indigenous population, especially given the important differences when compared with other Brazilian ethnic groups.

How Did COVID-19 Impact the Antimicrobial Consumption and Bacterial Resistance Profiles in Brazil?

The indiscriminate use of antibiotics has favored the selective pressure of multidrug resistance among microorganisms. This research evaluated the pattern of antibiotic prescriptions among the Brazilian population between January 2018 and December 2021. Additionally, the study sought to analyze the incidence rates of central line-associated bloodstream infection (CLABSI) and examine the profiles of antibiotic resistance. We assessed the hospital and community antimicrobial consumption from the National Health Surveillance Agency Database and correlated it to microorganisms. The consumption of antimicrobials in the hospital environment increased by 26% in 2021, highlighting polymyxin B, which increased by 204%. In 2021, 244,266 cases of CLABSI were reported, indicating a nosocomial infection rate of 7.9%. The rate of resistance to polymyxin B was higher in Pseudomonas aeruginosa (1400%) and Klebsiella pneumoniae (514%). Azithromycin emerged as the predominant antibiotic utilized within the community setting, accounting for 24% of the overall consumption. Pearson's correlation analysis revealed a significant and positive correlation (r = 0.71) between the elevated usage of azithromycin and the incidence of COVID-19. Our results indicate an increase in antimicrobial consumption during the COVID-19 pandemic and reinforce the fact that the misuse of antimicrobials may lead to an expansion in antimicrobial resistance.

Synergy between amikacin and Protium heptaphyllum essential oil against polymyxin resistance Klebsiella pneumoniae.

AIMS: We investigated the chemical composition and the in vitro and in vivo antibacterial effects of Protium heptaphyllum essential oil (PHEO) alone and in combination with antibiotics against polymyxin-resistant Klebsiella pneumoniae isolates. METHODS AND RESULTS: Hydrodistillation was used to obtain PHEO, and gas chromatography coupled with mass spectrometry revealed α-pinene, δ-3-carene, and ß-pinene as major components present in PHEO. Minimum inhibitory concentration was determined using the broth microdilution technique and ranged from 256 to 512 µg ml-1. The checkerboard method showed synergy with the combination of PHEO and amikacin (AMK) against the polymyxin-resistant K. pneumoniae isolates. In 8 of the 10 isolates tested, the fractional inhibitory concentration indexes (FICIs) ranged from 0.06 to 0.5, while in the remaining two isolates, the combination exerted an additive effect (FICI of 0.6 and 1.0), resulting in AMK dose reduce of range 2- to 16-fold, in the presence of PHEO. Analysis using zero interaction potency revealed high synergy score (63.9). In the in vivo assay, the survival of Caenorhabditis elegans was significantly improved in the presence of PHEO (1 µg ml-1) + AMK (µg ml-1) combination as compared to 32 µg ml-1 AMK alone. Furthermore, PHEO concentrations of 256 and 512 µg ml-1 were found to be non-toxic on the experimental model. CONCLUSION: To our knowledge, this is the first report of such type of synergism demonstrating an antimicrobial effect against polymyxin-resistant K. pneumoniae isolates.

Prevalence of HIV-1 infection and associated characteristics in a Brazilian indigenous population: a cross-sectional study.

Background: Despite significant progress in the areas of prevention, diagnosis, and treatment, HIV continues to result in a substantial number of fatalities on a global scale each year. Gaining insights from epidemiological data can prove instrumental in the development of health promotion strategies, particularly within vulnerable populations, such as indigenous groups. Consequently, our study aimed to investigate the prevalence of HIV infection within the indigenous population residing in the second-largest region of Brazil. Additionally, we sought to explore the subtypes of HIV-1 and detect any drug-resistance mutations present within this population. Methods: In this cross-sectional study, we aimed to evaluate the prevalence of HIV-1 infection and explore its associated characteristics within the indigenous population residing in the villages of Jaguapiru and Bororó, located in the Dourados area of Mato Grosso do Sul (MS), Brazil. Blood samples were collected for rapid HIV screening, serological tests, nucleic acid amplification, and HIV subtyping. Additionally, the HIV-1 viral load and CD4+ T lymphocyte count of the people living with HIV (PLHIV) were assessed at the time of recruitment and 24 weeks later. Findings: Out of the 2190 invited individuals, 1927 (88%) were included in this study. The average age of the participants was 34.2 (±13.8) years, with a majority of 74% being female. Moreover, 68.44% of the participants identified themselves as belonging to the Guarani-Kaiowa ethnic group. HIV seroprevalence was 0.93% (18/1927), and 73.22% (1411/1927) were unaware of their serological status. The prevalence of HIV-1 was higher in single indigenous people [10/617 (1.62%)], who received government benefits [14/1021 (1.37%)], had less than five years of formal education [11/685 (1.61%)], had sexual intercourse with users of injectable drugs [2/21 (9.52%)], with history of sexually transmitted infections (STIs) [10/62 (16.2%)] and incarceration [3/62 (4.84%)]. Of 18 positive samples, 44.4% (8/18) were successfully amplified, and HIV-1 subtype C was prevalent. Furthermore, we identified HIV-1 drug resistance mutations in four patients, specifically from the classes of Protease Inhibitor, Nucleoside Reverse Transcriptase Inhibitor, and Non-Nucleoside Reverse Transcriptase Inhibitor. Notably, three of these patients exhibited a high viral load even after 24 weeks of undergoing antiretroviral therapy. Out of the 18 PLHIV, 66.66% (12/18) had a viral load below 1000 copies/mL, while 50% (9/18) had a CD4+ T lymphocytes count greater than 350 cells/mL after 24 weeks of treatment. Interpretation: Despite the concerted efforts to control HIV infection, the prevalence observed in the indigenous population under study surpassed that reported in other Brazilian indigenous groups. This disparity highlights the disproportionate impact of the disease on this particular group. The detection of drug-resistance mutations further emphasizes the critical need to expand diagnostic coverage, closely monitor treatment strategies, and maintain ongoing molecular surveillance. These measures are imperative for enhancing HIV management within this vulnerable population. Funding: This study was partially funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do Sul (FUNDECT), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Secretaria do Estado de Saúde (SES) of Governo do Estado de Mato Grosso do Sul, and Universidade Federal da Grande Dourados (UFGD).

Antimicrobial activity of cinnamaldehyde against multidrug-resistant Klebsiella pneumoniae: an in vitro and in vivo study.

The emergence and spread of multidrug-resistant (MDR) Klebsiella pneumoniae strains have increased worldwide, posing a significant health threat by limiting the therapeutic options. This study aimed to investigate the antimicrobial potential of cinnamaldehyde against MDR-K. pneumoniae strains in vitro and in vivo assays. The presence of resistant genes in MDR- K. pneumoniae strains were evaluated by Polymerase Chain Reaction (PCR) and DNA sequencing. Carbapenem-resistant K. pneumoniae strains show the blaKPC-2 gene, while polymyxin-resistant K. pneumoniae presented blaKPC-2 and alterations in the mgrB gene. Cinnamaldehyde exhibited an inhibitory effect against all MDR- K. pneumoniae evaluated. An infected mice model was used to determine the in vivo effects against two K. pneumoniae strains, one carbapenem-resistant and another polymyxin-resistant. After 24 h of cinnamaldehyde treatment, the bacterial load in blood and peritoneal fluids decreased. Cinnamaldehyde showed potential effectiveness as an antibacterial agent by inhibiting the growth of MDR-K. pneumoniae strains.

Multidrug-resistant gram-negative bacteria in patients with COVID-19: An epidemiological and clinical study.

Epidemiological data regarding the incidence of secondary multidrug-resistant (MDR) Gram-negative infection in patients with coronavirus disease (COVID-19) in Brazil are still ambiguous. Thus, a case-control study was designed to determine factors associated with the acquisition of MDR Gram-negative bacteria (GNB) in patients with and without COVID-19 and describe the mortality rates and clinical features associated with unfavorable outcomes. In total, we assessed 280 patients admitted to Brazilian intensive care units from March/2020 to December/2021. During the study, 926 GNB were isolated. Out of those, 504 were MDR-GNB, representing 54.4% of the resistance rate. In addition, out of 871 patients positive for COVID-19, 73 had secondary MDR-GNB infection, which represented 8.38% of documented community-acquired GNB-MDR infections. The factors associated with patients COVID-19-MDR-GNB infections were obesity, heart failure, use of mechanical ventilation, urinary catheter, and previous use of ß-lactams. Several factors associated with mortality were identified among patients with COVID-19 infected with MDR-GNB, including the use of a urinary catheter; renal failure; and the origin of bacterial cultures such as tracheal secretion, exposure to carbapenem antibiotics, and polymyxin. Mortality was significantly higher in patients with COVID-19-MDR-GNB (68.6%) compared to control groups, where COVID-19 was 35.7%, MDR-GNB was 50%, and GNB was 21.4%. Our findings demonstrate that MDR-GNB infection associated with COVID-19 has an expressive impact on increasing the case fatality rate, reinforcing the importance of minimizing the use of invasive devices and prior exposure to antimicrobials to control the bacterial spread in healthcare environments to improve the prognosis among critical patients.

Epidemiological Survey of Human Alphaherpesvirus 2 (HSV-2) Infection in Indigenous People of Dourados Municipality, Central Brazil.

Sexually transmitted Human alphaherpesvirus 2 (HSV-2) causes genital ulcers, especially among sexually active adolescents and adults. We estimated the exact prevalence of anti-HSV-2 antibodies and correlated it with the demographic and behavioral aspects of the Indigenous population of the Jaguapirú and Bororó villages (Dourados, Mato Grosso do Sul (MS), Brazil). In total, 1360 individuals (>18 years old) were administered serologic tests. The prevalence of anti-HSV-2 IgM was 12.9%, that of anti-HSV-2 IgG was 57.2%, and 8.5% cases tested positive for both HSV-2 IgM and IgG. The prevalence of anti-HSV-2 antibodies was higher in females (59.5%) compared to males (49%), with an OR of 0.64 (0.49-0.83). Anti-HSV-2 antibodies were found in 14.2%, 12.3%, 15.4%, and 14.5% of participants with urinary problems, genital wounds, genital warts, and urethral discharge, respectively. In summary, the seroprevalence of HSV-2 in the Indigenous population was five times higher than that reported in the general adult Brazilian population. Educational level, income level, smoking, condom use, incarceration, illicit drug abuse, the sharing of used needles and syringes without adequate disinfection, homosexual relationships, prostitution, the sexual practices among drug users, and avoidance of contraceptive methods could contribute to the facilitation of HSV-2 transmission in the Indigenous population. Our results may help develop culturally appropriate intervention programs that eliminate health-access barriers and improve the implementation of public health policies aimed at promoting information regarding and preventing, treating, and controlling HSV-2 infection in Brazilian Indigenous populations.

Evaluation of the Synthetic Multifunctional Peptide Hp-MAP3 Derivative of Temporin-PTa.

In recent years, antimicrobial peptides isolated from amphibian toxins have gained attention as new multifunctional drugs interacting with different molecular targets. We aimed to rationally design a new peptide from temporin-PTa. Hp-MAP3 (NH2-LLKKVLALLKKVL-COOH), net charge (+4), hydrophobicity (0.69), the content of hydrophobic residues (69%), and hydrophobic moment (0.73). For the construction of the analog peptide, the physicochemical characteristics were reorganized into hydrophilic and hydrophobic residues with the addition of lysines and leucines. The minimum inhibitory concentration was 2.7 to 43 µM against the growth of Gram-negative and positive bacteria, and the potential for biofilm eradication was 173.2 µM. Within 20 min, the peptide Hp-MAP3 (10.8 µM) prompted 100% of the damage to E. coli cells. At 43.3 µM, eliminated 100% of S. aureus within 5 min. The effects against yeast species of the Candida genus ranged from 5.4 to 86.6 µM. Hp-MAP3 presents cytotoxic activity against tumor HeLa at a concentration of 21.6 µM with an IC50 of 10.4 µM. Furthermore, the peptide showed hemolytic activity against murine erythrocytes. Structural studies carried out by circular dichroism showed that Hp-MAP3, while in the presence of 50% trifluoroethanol or SDS, an α-helix secondary structure. Finally, Amphipathic Hp-MAP3 building an important model for the design of new multifunctional molecules.

Antimicrobial peptides against polymyxin-resistant Klebsiella pneumoniae: a patent review.

The spread of polymyxin-resistant Klebsiella pneumoniae strains represents an emerging health challenge, limiting treatment options for the patients. Thus, the development of new antimicrobials is an urgent requirement. Antimicrobial peptides (AMPs) are a large class of compounds that are part of innate immune response; these peptides are promising compounds in the field of antimicrobial resistance and are present in all organisms. The present review evaluated patents on antimicrobial peptides tested against polymyxin-resistant K. pneumoniae, available on Espacenet as of September 2022. A total of 1313 patents were examined and 1197 excluded as they were out of focus for this review; 104 patents of peptides tested against K. pneumoniae were included; of which only 14 were tested against polymyxin-resistant K. pneumoniae strains. The results indicated that all AMPs evaluated were in the experimental or pre-clinical phase; the clinical phase is pending. Furthermore, a few peptides were tested effectively against polymyxin-resistant K. pneumoniae. Although, the research and patent filing alone are not enough to develop a suitable antimicrobial therapy, they can represent good starting point upon which to develop new antimicrobials. More investment is required to push these pharmaceuticals through the stages of development to introduce them into the market.

Antimicrobial and antibiofilm activities of desloratadine against multidrug-resistant Acinetobacter baumannii.

Aim: The antimicrobial and antibiofilm activities of the antihistamine desloratadine against multidrug-resistant (MDR) Acinetobacter baumannii were evaluated. Results: Desloratadine inhibited 90% bacterial growth at a concentration of 64 µg/ml. The combination of desloratadine with meropenem reduced the MIC by twofold in the planktonic state and increased the antibiofilm activity by eightfold. Survival curves showed that combinations of these drugs were successful in eradicating all bacterial cells within 16 h. Scanning electron microscopy also confirmed a synergistic effect in imparting a harmful effect on the cellular structure of MDR A. baumannii. An in vivo model showed significant protection of up to 83% of Caenorhabditis elegans infected with MDR A. baumannii. Conclusion: Our results indicate that repositioning of desloratadine may be a safe and low-cost alternative as an antimicrobial and antibiofilm agent for the treatment of MDR A. baumannii infections.

Determining reference ranges for immunological cells of healthy indigenous individuals from a region in Brazil

ABSTRACT Objective The establishment of reference values for a subset of leukocytes is common in clinical practice, and ethnic variations are strongly associated with disease development. In Brazil, indigenous people are vulnerable to infections, and few studies have described the health and disease conditions of this population. This study aimed to provide reference values for immunological cell subsets in indigenous Brazilians living in the state of Mato Grosso do Sul. Methods Flow cytometry and 4-color combinations of monoclonal antibodies were used to characterize cells. A total of 115 healthy adults, mostly females (72%), were included in the study. The results are presented as mean and median (2.5%-97.5% percentiles) for T and B lymphocytes, CD4+ T cells, CD8+ T cells, Natural Killer cells, monocytes, and dendritic cells, providing an average immunological profile for the population in question. Results The relative medians of CD3+, CD4+, and CD8+ T cells were significantly higher in women than in men in a healthy indigenous population. Conclusion To our knowledge, cell reference data from indigenous Brazilians are unknown in the literature. The immune cell results presented in this pioneering study will contribute to the clinical and laboratory evaluation of the Brazilian indigenous population, especially given the important differences when compared with other Brazilian ethnic groups.

The first year of the COVID-19 pandemic in an indigenous population in Brazil: an epidemiological study.

This cross-sectional observational study that describes the epidemiological data of the first year of the COVID-19 pandemic in the Mato Grosso do Sul State, aimed to demonstrate the differences between indigenous and non-indigenous populations, characterize confirmed cases of COVID-19 according to risk factors related to ethnicity, comorbidities and their evolution and to verify the challenges in facing the disease in Brazil. SIVEP-Gripe and E-SUS-VE, a nationwide surveillance database in Brazil, from March 2020 to March 2021 in Mato Grosso do Sul state, were used to compare survivors and non-survivors from indigenous and non-indigenous populations and the epidemiological incidence curves of these populations. A total of 176,478, including 5,299 indigenous people, were confirmed. Among the indigenous population, 52.5% (confidence interval [CI] 51.2-53.9) were women, 38% (CI 36.7-39.4) were 20-39 years old, 56.7% were diagnosed by rapid antibody tests, 12.3% (CI 95%:11.5-13.2) had at least one comorbidity, and 5.3% (CI 95%:4.7-5.9) were hospitalized. In the non-indigenous patients, 56.8% were confirmed using RT-PCR, 4.4% (CI 95%:4.3-4.5) had at least one comorbidity, and 8.0% (CI 95%:7.9-8.2) were hospitalized. The majority of non-survivors were ≥60 years old (65.1% indigenous vs. 74.1% non-indigenous). The mortality in indigenous people was more than three times higher (11% vs. 2.9%). Indigenous people had a lower proportion of RT-PCR diagnoses; deaths were more frequent in younger patients and were less likely to be admitted to hospital. Mass vaccination may have controlled the incidence and mortality associated with COVID-19 in this population during the period of increased viral circulation.