ABSTRACT
BACKGROUND: A single-dose dengue vaccine that protects individuals across a wide age range and regardless of dengue serostatus is an unmet need. We assessed the safety and efficacy of the live, attenuated, tetravalent Butantan-dengue vaccine (Butantan-DV) in adults, adolescents, and children. We previously reported the primary and secondary efficacy and safety endpoints in the initial 2 years of follow-up. Here we report the results through an extended follow-up period, with an average of 3·7 years of follow-up. METHODS: In this double-blind, randomised, placebo-controlled, phase 3, multicentre trial in Brazil, healthy participants (aged 2-59 years) who had not previously received a dengue vaccine were enrolled and randomly assigned 2:1 (stratified by age 18-59 years, 7-17 years, and 2-6 years) using a central electronic randomisation system to receive 0·5 mL of Butantan-DV (containing approximately 103 plaque-forming units of each of the four vaccine virus strains) or placebo, administered subcutaneously. Syringes containing vaccine or placebo were prepared by an unmasked trial pharmacist who was not involved in any subsequent participant assessments; other site staff and the participants remained unaware of the group allocations. Vaccine efficacy was calculated with the accrual of virologically confirmed dengue (VCD) cases (by RT-PCR) at least 28 days after vaccination up until the cutoff (at least 2 years of follow-up from the last participant enrolled). The primary endpoint was vaccine efficacy against VCD after day 28 by any dengue virus (DENV) serotype regardless of dengue serostatus at baseline in the per-protocol population. The primary and secondary safety endpoints up until day 21 were previously reported; secondary safety endpoints include the frequency of unsolicited vaccine-related adverse events after day 22. Safety analyses were done on all participants as treated. This trial is registered with ClinicalTrials.gov (NCT02406729) and is ongoing. FINDINGS: Of 16â363 participants assessed for eligibility, 16â235 were randomly assigned between Feb 22, 2016, and July 5, 2019, and received single-dose Butantan-DV (10â259 participants) or placebo (5976 participants). 16â162 participants (Butantan-DV n=10â215; placebo n=5947) were included in the per-protocol population and 16â235 (Butantan-DV n=10â259; placebo n=5976) in the safety population. At the data cutoff (July 13, 2021), participants had 2-5 years of follow-up (mean 3·7 years [SD 1·0], median 4·0 years [IQR 3·2-4·5]). 356 VCD cases were captured through the follow-up (128 in the vaccine group and 228 in the placebo group). Vaccine efficacy against VCD caused by any DENV serotype was 67·3% (95% CI 59·4-73·9); cases caused by DENV-3 or DENV-4 were not observed. The proportions of participants who had serious adverse events were similar between treatment groups (637 [6·2%] in the vaccine group and 395 [6·6%] in the placebo group) up until the cutoff. INTERPRETATION: A single dose of Butantan-DV was generally well tolerated and efficacious against symptomatic VCD (caused by DENV-1 and DENV-2) for a mean of 3·7 years. These findings support the continued development of Butantan-DV to prevent dengue disease in children, adolescents, and adults regardless of dengue serostatus. FUNDING: Instituto Butantan and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.
ABSTRACT
Forest edges, where humans, mosquitoes, and wildlife interact, may serve as a nexus for zoonotic arbovirus exchange. Although often treated as uniform interfaces, the landscape context of edge habitats can greatly impact ecological interactions. Here, we investigated how the landscape context of forest edges shapes mosquito community structure in an Amazon rainforest reserve near the city of Manaus, Brazil, using hand-nets to sample mosquitoes at three distinct forest edge types. Sampling sites were situated at edges bordering urban land cover, rural land cover, and natural treefall gaps, while sites in continuous forest served as controls. Community composition differed substantially among edge types, with rural edges supporting the highest species diversity. Rural edges also provided suitable habitat for forest specialists, including key sylvatic vectors, of which Haemagogus janthinomys was the most abundant species sampled overall. Our findings emphasize the importance of landscape context in assessing pathogen emergence risk at forest edges.
ABSTRACT
Background: The coronavirus disease-2019 (COVID-19) pulmonary rehabilitation (PR) seems to be a better choice to improve physical and functional capacity after acute infection. However, there is a lack of evidence regarding the effects of different strategies to optimize post-acute phase rehabilitation and reduce long COVID-19 physical deteriorations. Objective: To compare the use of a noninvasive ventilation (NIV) plus aerobic exercise strategy during PR program with to a standard PR (without NIV) on physical capacity and quality of life outcomes in post-COVID-19. Methods: Double-blinded randomized controlled clinical trial. A total of 100 individuals discharged from hospital in a post-acute phase of severe COVID-19 will be randomized into two groups: PR + NIV (Group 1) and PR (Group 2). Inclusion criteria include participants who present symptomatic dyspnea II and III by the modified Medical Research Council, aged 18 years or older. Both groups will receive aerobic and resistance exercise, and inspiratory muscle training. However, group 1 will perform aerobic training with bilevel NIV. Cardiopulmonary exercise test will assess the O2 peak uptake, 6-minute walk test will assess the walking distance and short-form 36 will assess the quality of life before and after 8 weeks (after 24 PR sessions). Moreover, patients will be contacted by telephone every 3 months for one year to record possible adverse events, hospitalizations, and death. All data will be registered in RedCap, and analyses will be performed in the STATA v13 software. Clinical Trial Registration: RBR-3t9pkzt.
ABSTRACT
Glucose-6 phosphate dehydrogenase deficiency (G6PDd) was suggested as a risk factor for severe disease in patients with COVID-19. We evaluated clinical outcomes and glucose-6 phosphate dehydrogenase (G6PD) activity during and after illness in patients with COVID-19. This prospective cohort study included adult participants (≥ 18 years old) who had clinical and/or radiological COVID-19 findings or positive reverse transcription-polymerase chain reaction results. Epidemiological and clinical data were extracted from electronic medical records. Glucose-6 phosphate dehydrogenase activity was measured using SD Biosensor STANDARD G6PD® equipment on admission and 1 year after discharge. Samples were genotyped for the three most common single nucleotide polymorphisms for G6PDd in the Brazilian Amazon. Seven hundred fifty-three patients were included, of whom 123 (16.3%) were G6PD deficient. There was no difference between groups regarding the risks of hospitalization (P = 0.740) or invasive mechanical ventilation (P = 0.31), but the risk of death was greater in patients with normal G6PD levels (P = 0.022). Only 29 of 116 participants (25%) carried the African G6PDd genotype. Of 30 participants tested as G6PD deficient during disease, only 11 (36.7%) results agreed 1 year after discharge. In conclusion, this study does not demonstrate an association of G6PDd with severity of COVID-19. Limitations of the test for detecting enzyme levels during COVID-19 illness were demonstrated by genotyping and retesting after the disease period. Care must be taken when screening for G6PDd in patients with acute COVID-19.
Subject(s)
COVID-19 , Glucosephosphate Dehydrogenase Deficiency , Glucosephosphate Dehydrogenase , SARS-CoV-2 , Adult , Aged , Female , Humans , Male , Middle Aged , Brazil/epidemiology , COVID-19/epidemiology , Genotype , Glucosephosphate Dehydrogenase/genetics , Glucosephosphate Dehydrogenase/metabolism , Glucosephosphate Dehydrogenase Deficiency/epidemiology , Glucosephosphate Dehydrogenase Deficiency/genetics , Hospitalization , Polymorphism, Single Nucleotide , Prospective Studies , Risk Factors , SARS-CoV-2/geneticsABSTRACT
BACKGROUND: The effectiveness of BCG vaccine for adult pulmonary tuberculosis remains uncertain. In this study, we aimed to evaluate the effect of vaccination with BCG-Denmark to prevent initial and sustained interferon-γ release assay conversion in Brazilian health-care workers. METHODS: This substudy is a nested randomised controlled trial embedded within the BRACE trial (NCT04327206). Specifically, this substudy enrolled Brazilian health-care workers (aged ≥18 years) from three sites in Brazil (Manaus, Campo Grande, and Rio de Janeiro) irrespective of previously receiving BCG vaccination. Participants were excluded if they had contraindications to BCG vaccination, more than 1 month of treatment with specific tuberculosis treatment drugs, previous adverse reactions to BCG, recent BCG vaccination, or non-compliance with assigned interventions. Those eligible were randomly assigned (1:1) to either the BCG group (0·1 mL intradermal injection of BCG-Denmark [Danish strain 1331; AJ Vaccines, Copenhagen]) or the placebo group (intradermal injection of 0·9% saline) using a web-based randomisation process in variable-length blocks (2, 4, or 6), and were stratified based on the study site, age (<40, ≥40 to <60, ≥60 years), and comorbidity presence (diabetes, chronic respiratory disease, cardiac condition, hypertension). Sealed syringes were used to prevent inadvertent disclosure of group assignments. The QuantiFERON-TB Gold (QFT) Plus test (Qiagen; Hilden, Germany) was used for baseline and 12-month tuberculosis infection assessments. The primary efficacy outcome was QFT Plus conversion (≥0·35 IU/mL) by 12 months following vaccination in participants who had a negative baseline result (<0·35 IU/mL). FINDINGS: Between Oct 7, 2020, and April 12, 2021, 1985 (77·3%) of 2568 participants were eligible for QFT Plus assessment at 12 months and were included in this substudy; 996 (50·2%) of 1985 were in the BCG group and 989 (49·8%) were in the placebo group. Overall, 1475 (74·3%) of 1985 participants were women and 510 (25·7%) were men, and the median age was 39 years (IQR 32-47). During the first 12 months, QFT Plus conversion occurred in 66 (3·3%) of 1985 participants, with no significant differences by study site (p=0·897). Specifically, 34 (3·4%) of 996 participants had initial QFT conversion in the BCG group compared with 32 (3·2%) of 989 in the placebo group (risk ratio 1·09 [95% CI 0·67-1·77]; p=0·791). INTERPRETATION: BCG-Denmark vaccination did not reduce initial QFT Plus conversion risk in Brazilian health-care workers. This finding underscores the need to better understand tuberculosis prevention in populations at high risk. FUNDING: Bill & Melinda Gates Foundation, the Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the United Health Group Foundation, Epworth Healthcare, and individual donors. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.
Subject(s)
BCG Vaccine , Health Personnel , Humans , BCG Vaccine/administration & dosage , BCG Vaccine/immunology , Male , Adult , Female , Brazil , Middle Aged , Vaccination , Mycobacterium tuberculosis/immunology , Tuberculosis, Pulmonary/prevention & control , Interferon-gamma Release Tests , Young AdultABSTRACT
BACKGROUND: Butantan-Dengue Vaccine (Butantan-DV) is an investigational, single-dose, live, attenuated, tetravalent vaccine against dengue disease, but data on its overall efficacy are needed. METHODS: In an ongoing phase 3, double-blind trial in Brazil, we randomly assigned participants to receive Butantan-DV or placebo, with stratification according to age (2 to 6 years, 7 to 17 years, and 18 to 59 years); 5 years of follow-up is planned. The objectives of the trial were to evaluate overall vaccine efficacy against symptomatic, virologically confirmed dengue of any serotype occurring more than 28 days after vaccination (the primary efficacy end point), regardless of serostatus at baseline, and to describe safety up to day 21 (the primary safety end point). Here, vaccine efficacy was assessed on the basis of 2 years of follow-up for each participant, and safety as solicited vaccine-related adverse events reported up to day 21 after injection. Key secondary objectives were to assess vaccine efficacy among participants according to dengue serostatus at baseline and according to the dengue viral serotype; efficacy according to age was also assessed. RESULTS: Over a 3-year enrollment period, 16,235 participants received either Butantan-DV (10,259 participants) or placebo (5976 participants). The overall 2-year vaccine efficacy was 79.6% (95% confidence interval [CI], 70.0 to 86.3) - 73.6% (95% CI, 57.6 to 83.7) among participants with no evidence of previous dengue exposure and 89.2% (95% CI, 77.6 to 95.6) among those with a history of exposure. Vaccine efficacy was 80.1% (95% CI, 66.0 to 88.4) among participants 2 to 6 years of age, 77.8% (95% CI, 55.6 to 89.6) among those 7 to 17 years of age, and 90.0% (95% CI, 68.2 to 97.5) among those 18 to 59 years of age. Efficacy against DENV-1 was 89.5% (95% CI, 78.7 to 95.0) and against DENV-2 was 69.6% (95% CI, 50.8 to 81.5). DENV-3 and DENV-4 were not detected during the follow-up period. Solicited systemic vaccine- or placebo-related adverse events within 21 days after injection were more common with Butantan-DV than with placebo (58.3% of participants, vs. 45.6%). CONCLUSIONS: A single dose of Butantan-DV prevented symptomatic DENV-1 and DENV-2, regardless of dengue serostatus at baseline, through 2 years of follow-up. (Funded by Instituto Butantan and others; DEN-03-IB ClinicalTrials.gov number, NCT02406729, and WHO ICTRP number, U1111-1168-8679.).
Subject(s)
Dengue Vaccines , Dengue Virus , Dengue , Vaccines, Attenuated , Adult , Child , Child, Preschool , Humans , Antibodies, Viral , Dengue/prevention & control , Dengue Vaccines/adverse effects , Dengue Vaccines/therapeutic use , Dengue Virus/immunology , Double-Blind Method , Vaccination , Vaccines , Vaccines, Attenuated/adverse effects , Vaccines, Attenuated/therapeutic use , Brazil , Vaccine Efficacy , Adolescent , Young Adult , Middle Aged , Follow-Up StudiesABSTRACT
Malaria is a severe public health problem in several developing tropical and subtropical countries. Anopheles aquasalis is the primary coastal malaria vector in Central and South America and the Caribbean Islands, and it has the peculiar feature of living in water with large changes in salinity. Recent research has recognised An. aquasalis as an important model for studying the interactions of murine and human Plasmodium parasites. This study presents the complete genome of An. aquasalis and offers insights into its evolution and physiology. The genome is similar in size and gene content to other Neotropical anophelines, with 162 Mb and 12,446 protein-coding genes. There are 1387 single-copy orthologs at the Diptera level (eg. An. gambiae, An. darlingi and Drosophila melanogaster). An. aquasalis diverged from An. darlingi, the primary malaria vector in inland South America, nearly 20 million years ago. Proteins related to ion transport and metabolism belong to the most abundant gene families with 660 genes. We identified gene families relevant to osmosis control (e.g., aquaporins, vacuolar-ATPases, Na+/K+-ATPases, and carbonic anhydrases). Evolutionary analysis suggests that all osmotic regulation genes are under strong purifying selection. We also observed low copy number variation in insecticide resistance and immunity-related genes for all known classical pathways. The data provided by this study offers candidate genes for further studies of parasite-vector interactions and for studies on how anophelines of brackish water deal with the high fluctuation in water salinity. We also established data and insights supporting An. aquasalis as an emerging Neotropical malaria vector model for genetic and molecular studies.
Subject(s)
Anopheles , Malaria , Humans , Animals , Mice , Malaria/parasitology , Anopheles/genetics , Anopheles/parasitology , DNA Copy Number Variations/genetics , Drosophila melanogaster , Mosquito Vectors/genetics , Water , Adenosine Triphosphatases/geneticsABSTRACT
BACKGROUND: Plasmodium vivax is the main species responsible for human malaria in Brazil, and one of its manifestations is splenic malaria, though there are still challenges in its diagnosis. The present study aimed to standardize Plasmodium sp. DNA extraction from histological slices of spleen and diagnosis using real-time qPCR. METHODS: This study performed a microtomy of a paraffin-embedded spleen as a positive control for P. vivax from a patient who had been previously diagnosed with the parasite. The sample was deparaffinized with xylol and ethanol, then DNA extraction was performed with two commercial kits. qPCR was carried out with the Taqman system for detection of Plasmodium sp. and was made species-specific using PvmtCOX1 gene. From 2015 to 2019, 200 spleen samples were obtained from trauma patients subjected to splenectomy in Manaus, Amazonas. All the samples were tested for cell-free human DNA (cfDNA). RESULTS: The deparaffinization and the Plasmodium vivax DNA extraction method was successfully standardized, and the control sample was positive for P. vivax. Of the 200 samples, all qPCRs were negative, but they were positive for human PCR. CONCLUSION: Paraffinization is practical and efficient for the preservation of samples, but the formation of bonds between proteins and DNA makes extraction difficult. Despite this, in this study, it was possible to standardize a method of DNA extraction for detecting P. vivax.
Subject(s)
Malaria, Vivax , Malaria , Humans , Spleen , Malaria/diagnosis , Malaria, Vivax/diagnosis , Malaria, Vivax/parasitology , Plasmodium vivax/genetics , DNA , Reference Standards , Plasmodium falciparum/geneticsABSTRACT
Background: The novel coronavirus disease 2019 (COVID-19) presents with complex pathophysiological effects in various organ systems. Following the COVID-19, there are shifts in biomarker and cytokine equilibrium associated with altered physiological processes arising from viral damage or aggressive immunological response. We hypothesized that high daily dose methylprednisolone improved the injury biomarkers and serum cytokine profiles in COVID-19 patients. Methods: Injury biomarker and cytokine analysis was performed on 50 SARS-Cov-2 negative controls and 101 hospitalized severe COVID-19 patients: 49 methylprednisolone-treated (MP group) and 52 placebo-treated serum samples. Samples from the treated groups collected on days D1 (pre-treatment) all the groups, D7 (2 days after ending therapy) and D14 were analyzed. Luminex assay quantified the biomarkers HMGB1, FABP3, myoglobin, troponin I and NTproBNP. Immune mediators (CXCL8, CCL2, CXCL9, CXCL10, TNF, IFN-γ, IL-17A, IL-12p70, IL-10, IL-6, IL-4, IL-2, and IL-1ß) were quantified using cytometric bead array. Results: At pretreatment, the two treatment groups were comparable demographically. At pre-treatment (D1), injury biomarkers (HMGB1, TnI, myoglobin and FABP3) were distinctly elevated. At D7, HMGB1 was significantly higher in the MP group (p=0.0448) compared to the placebo group, while HMGB1 in the placebo group diminished significantly by D14 (p=0.0115). Compared to healthy control samples, several immune mediators (IL-17A, IL-6, IL-10, MIG, MCP-1, and IP-10) were considerably elevated at baseline (all p≤0.05). At D7, MIG and IP-10 of the MP-group were significantly lower than in the placebo-group (p=0.0431, p=0.0069, respectively). Longitudinally, IL-2 (MP-group) and IL-17A (placebo-group) had increased significantly by D14. In placebo group, IL-2 and IL-17A continuously increased, as IL-12p70, IL-10 and IP-10 steadily decreased during follow-up. The MP treated group had IL-2, IFN-γ, IL-17A and IL-12p70 progressively increase while IL-1ß and IL-10 gradually decreased towards D14. Moderate to strong positive correlations between chemokines and cytokines were observed on D7 and D14. Conclusion: These findings suggest MP treatment could ameliorate levels of myoglobin and FABP3, but appeared to have no impact on HMGB1, TnI and NTproBNP. In addition, methylprednisolone relieves the COVID-19 induced inflammatory response by diminishing MIG and IP-10 levels. Overall, corticosteroid (methylprednisolone) use in COVID-19 management influences the immunological molecule and injury biomarker profile in COVID-19 patients.
Subject(s)
COVID-19 , HMGB1 Protein , Humans , Cytokines , Interleukin-10 , Interleukin-17 , Methylprednisolone/therapeutic use , Chemokine CXCL10 , Interleukin-2 , Interleukin-6 , Myoglobin , SARS-CoV-2 , Interleukin-12ABSTRACT
Anophelines are vectors of malaria, the deadliest disease worldwide transmitted by mosquitoes. The availability of genomic data from various Anopheles species allowed evolutionary comparisons of the immune response genes in search of alternative vector control of the malarial parasites. Now, with the Anopheles aquasalis genome, it was possible to obtain more information about the evolution of the immune response genes. Anopheles aquasalis has 278 immune genes in 24 families or groups. Comparatively, the American anophelines possess fewer genes than Anopheles gambiae s. s., the most dangerous African vector. The most remarkable differences were found in the pathogen recognition and modulation families like FREPs, CLIP and C-type lectins. Even so, genes related to the modulation of the expression of effectors in response to pathogens and gene families that control the production of reactive oxygen species were more conserved. Overall, the results show a variable pattern of evolution in the immune response genes in the anopheline species. Environmental factors, such as exposure to different pathogens and differences in the microbiota composition, could shape the expression of this group of genes. The results presented here will contribute to a better knowledge of the Neotropical vector and open opportunities for malaria control in the endemic-affected areas of the New World.
Subject(s)
Anopheles , Malaria , Animals , Anopheles/genetics , Mosquito Vectors/genetics , South America , West IndiesABSTRACT
The present study aimed to know and analyze the repercussions and legacy of the COVID-19 pandemic for the Unified Health System from the perspective of health managers working in Manaus, a city considered the epicenter of the pandemic in Brazil. This qualitative research was designed as the study of a single incorporated case and conducted with 23 Health Care Network managers. The analysis was applied in two thematic coding cycles (values and focused coding methods), with the aid of the ATLAS.ti software. The categories we analyzed covered the lessons learned within the scope of the work process, change in stance, and human values, as well as the coping strategies adopted by individual or team initiatives or by the incorporation of innovations in practices. This study highlighted the importance of strengthening primary health care; of promoting team spirit in the service and establishing partnerships with public and private institutions, of being integrated with the training in complex situations, and of reflecting on human values and appreciation of life. Coping with the pandemic promoted an in-depth reflection about the functioning of the Unified Health System and the individual ways of being.
Subject(s)
COVID-19 , Humans , Pandemics , Brazil/epidemiology , Qualitative ResearchABSTRACT
BACKGROUND: Zika virus infection is commonly described as a mild and self-limiting illness. However, cardiac complications were associated with acute Zika virus infection. CASE PRESENTATION: A 46-year-old woman without previous comorbidities with a 1-day history of symptoms tested positive for ZIKV by real time reverse transcriptase polymerase chain reaction (rRT-PCR). She was admitted two days after with clinical worsening, cardiac enzymes elevated, and cardiac imaging findings, and the diagnosis of myopericarditis was made. The patient was treated and presented significant clinical improvement after one year. CONCLUSIONS: Cardiac complication following ZIKV infection appears to be infrequent. Here, we report a rare case of viral myopericarditis caused by ZIKV infection.
Subject(s)
Zika Virus Infection , Zika Virus , Female , Humans , Middle Aged , Real-Time Polymerase Chain Reaction , Zika Virus/genetics , Zika Virus Infection/complications , Zika Virus Infection/diagnosisABSTRACT
The severity, disabilities, and lethality caused by the coronavirus 2019 (COVID-19) disease have dumbfounded the entire world on an unprecedented scale. The multifactorial aspect of the infection has generated interest in understanding the clinical history of COVID-19, particularly the classification of severity and early prediction on prognosis. Metabolomics is a powerful tool for identifying metabolite signatures when profiling parasitic, metabolic, and microbial diseases. This study undertook a metabolomic approach to identify potential metabolic signatures to discriminate severe COVID-19 from non-severe COVID-19. The secondary aim was to determine whether the clinical and laboratory data from the severe and non-severe COVID-19 patients were compatible with the metabolomic findings. Metabolomic analysis of samples revealed that 43 metabolites from 9 classes indicated COVID-19 severity: 29 metabolites for non-severe and 14 metabolites for severe disease. The metabolites from porphyrin and purine pathways were significantly elevated in the severe disease group, suggesting that they could be potential prognostic biomarkers. Elevated levels of the cholesteryl ester CE (18:3) in non-severe patients matched the significantly different blood cholesterol components (total cholesterol and HDL, both p < 0.001) that were detected. Pathway analysis identified 8 metabolomic pathways associated with the 43 discriminating metabolites. Metabolomic pathway analysis revealed that COVID-19 affected glycerophospholipid and porphyrin metabolism but significantly affected the glycerophospholipid and linoleic acid metabolism pathways (p = 0.025 and p = 0.035, respectively). Our results indicate that these metabolomics-based markers could have prognostic and diagnostic potential when managing and understanding the evolution of COVID-19.
ABSTRACT
Parasitic agents have been known to cause human disease since ancient times and are endemic in tropical and subtropical regions. Complications of parasitic diseases, including kidney involvement, are associated with worse outcomes. Chagas disease, filariasis, leishmaniasis, malaria and schistosomiasis are important parasitic diseases that can damage the kidney. These diseases affect millions of people worldwide, primarily in Africa, Asia and Latin America, and kidney involvement is associated with increased mortality. The most common kidney complications of parasitic diseases are acute kidney injury, glomerulonephritis and tubular dysfunction. The mechanisms that underlie parasitic disease-associated kidney injury include direct parasite damage; immunological phenomena, including immune complex deposition and inflammation; and systemic manifestations such as haemolysis, haemorrhage and rhabdomyolysis. In addition, use of nephrotoxic drugs to treat parasitic infections is associated with acute kidney injury. Early diagnosis of kidney involvement and adequate management is crucial to prevent progression of kidney disease and optimize patient recovery.
Subject(s)
Acute Kidney Injury , Malaria , Parasitic Diseases , Schistosomiasis , Acute Kidney Injury/etiology , Humans , Kidney , Malaria/complications , Malaria/drug therapy , Malaria/epidemiology , Parasitic Diseases/complications , Parasitic Diseases/epidemiology , Schistosomiasis/epidemiologyABSTRACT
Haemagogus (Haemagogus) janthinomys (Dyar, 1921), the major neotropical vector of sylvatic yellow fever virus, is notoriously difficult to maintain in captivity. It has never been reared beyond an F1 generation, and almost no experimental transmission studies have been performed with this species since the 1940s. Herein we describe installment hatching, artificial blood feeding, and forced-mating techniques that enabled us to produce small numbers of F3 generation Hg. janthinomys eggs for the first time. A total of 62.8% (1562/2486) F1 generation eggs hatched during ≤10 four-day cycles of immersion in a bamboo leaf infusion followed by partial drying. Hatching decreased to 20.1% (190/944) in the F2 generation for eggs laid by mosquitoes copulated by forced mating. More than 85% (79/92) female F2 mosquitoes fed on an artificial blood feeding system. While we were unable to maintain a laboratory colony of Hg. janthinomys past the F3 generation, our methods provide a foundation for experimental transmission studies with this species in a laboratory setting, a critical capacity in a region with hyper-endemic transmission of dengue, Zika, and chikungunya viruses, all posing a risk of spillback into a sylvatic cycle.
Subject(s)
Blood Substitutes , Culicidae , Yellow Fever , Zika Virus Infection , Zika Virus , Animals , Female , Mosquito Vectors , Yellow fever virus , BrazilABSTRACT
BACKGROUND: Healthcare workers are susceptible to colonization by multiresistant bacteria, which can increase the risk of outbreaks. METHODS: Samples were collected from the nasopharynx, hands, and lab coats of healthcare workers. The phenotypic identification was carried out using a VITEK®2 rapid test system. PCR tests for the mecA gene and the sequencing of the amplicons were performed. Staphylococcus epidermidis and Staphylococcus aureus phylogenies were reconstructed using the Bayesian inference. RESULTS: A total of 225 healthcare workers participated in this study. Of these, 21.3% were male and 78.7% female. S. epidermidis and S.aureus showed high levels of resistance to penicillin, ampicillin, erythromycin, tetracycline and cefoxitin. The prevalence of methicillin resistant S. aureus was 3.16% and methicillin resistant S. epidermidis was 100%. Multilocus sequence typing identified 23 new S. epidermidis sequence types, and one new allele and sequence type for S. aureus. The frequency of methicillin-resistant S. epidermidis in nursing and hemotherapy technicians as a percentage of the total number of healthcare workers was 5.8-3.1%, while the frequency of methicillin resistant S. aureus in hemotherapy technicians and biomedics, as a percentage of the total number of healthcare workers was 4.2-8.9%%. CONCLUSIONS: The healthcare workers at the city's blood bank, even when taking the necessary care with their hands, body and clothes, harbour methicillin-resistant S. aureus and S. epidermidis sequence types, which, as a potential source of multidrug resistant bacteria, can contribute to nosocomial infections among hematological patients.
Subject(s)
Carrier State/microbiology , Health Personnel/statistics & numerical data , Methicillin-Resistant Staphylococcus aureus/genetics , Adult , Anti-Bacterial Agents , Blood Banks/statistics & numerical data , Brazil/epidemiology , Carrier State/epidemiology , Female , Hand/microbiology , Humans , Male , Methicillin Resistance , Methicillin-Resistant Staphylococcus aureus/classification , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Microbial Sensitivity Tests , Middle Aged , Molecular Epidemiology , Nasopharynx/microbiology , Phylogeny , Staphylococcus epidermidis/classification , Staphylococcus epidermidis/drug effects , Staphylococcus epidermidis/genetics , Staphylococcus epidermidis/isolation & purificationABSTRACT
In the Americas, some mosquito-borne viruses such as Zika, chikungunya, and dengue circulate among humans in urban transmission cycles, while others, including yellow fever and Mayaro, circulate among monkeys in sylvatic cycles. The intersection of humans and wildlife at forest edges creates risk for zoonotic virus exchange. We built a scaffold tower at the edge of a treefall gap in rainforest bordering Manaus, Brazil, to identify vectors that may bridge transmission between humans and monkeys. We vertically sampled diurnally active, anthropophilic mosquitoes using handheld nets at 0, 5, and 9 m and container-breeding mosquitoes in ovitraps at 0, 5, 10, and 15 m. Haemagogus janthinomys and Psorophora amazonica were present in high relative abundance in nets at each height sampled, while anthropophilic species were uncommon in ovitraps. Hg. janthinomys was more abundant at elevated heights than at ground level, while Ps. amazonica abundance was not significantly stratified across heights. The presence of each species increased with increasing 7-day rainfall lagged at 1 week, and at 1 and 4 weeks prior to collection, respectively. In addition, Hg. janthinomys was most frequently collected at 29.9 °C, irrespective of height. These data provide insight into the potential role of each species as bridge vectors.
Subject(s)
Arboviruses , Culicidae/virology , Forests , Microclimate , Models, Biological , Mosquito Vectors/virology , Animals , Arboviruses/classification , Arboviruses/isolation & purification , Arboviruses/metabolism , Brazil , Culicidae/physiology , Haplorhini , Mosquito Vectors/physiologyABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent of coronavirus disease 2019 (COVID-19), is responsible for the worst pandemic of the 21st century. Like all human coronaviruses, SARS-CoV-2 originated in a wildlife reservoir, most likely from bats. As SARS-CoV-2 has spread across the globe in humans, it has spilled over to infect a variety of non-human animal species in domestic, farm, and zoo settings. Additionally, a broad range of species, including one neotropical monkey, have proven to be susceptible to experimental infection with SARS-CoV-2. Together, these findings raise the specter of establishment of novel enzootic cycles of SARS-CoV-2. To assess the potential exposure of free-living non-human primates to SARS-CoV-2, we sampled 60 neotropical monkeys living in proximity to Manaus and São José do Rio Preto, two hotspots for COVID-19 in Brazil. Our molecular and serological tests detected no evidence of SAR-CoV-2 infection among these populations. While this result is reassuring, sustained surveillance efforts of wildlife living in close association with human populations is warranted, given the stochastic nature of spillover events and the enormous implications of SARS-CoV-2 spillover for human health.
Subject(s)
COVID-19/epidemiology , Epidemiological Monitoring/veterinary , Primates/virology , Alouatta/virology , Animals , Animals, Wild/virology , Brazil/epidemiology , COVID-19/veterinary , Callicebus/virology , Callithrix/virology , Pandemics , SARS-CoV-2/pathogenicity , Viral Zoonoses/transmissionABSTRACT
Dengue fever and chikungunya are viral diseases that have spread rapidly throughout the world in recent decades. The occurrence of complications is well known, including prerenal acute kidney injury (AKI), which is usually thought to be caused by dehydration and fluid loss. Thrombotic microangiopathy (TMA) is an uncommon aggravation of dengue fever and chikungunya, with only a few cases described in the medical literature. The aim of this study is to present 3 cases of TMA associated with arboviral infection. Three patients with clinical history, laboratory test, and kidney biopsy results compatible with TMA were selected for the study, 2 of whom had a serological diagnosis of dengue fever and 1 of chikungunya. The 3 patients were followed up at the Federal University of Maranhão Hospital's Nephrology Service in 2018. A targeted gene panel sequencing (TGPS) plus multiple to atypical hemolytic uremic syndrome (aHUS) multiplex ligation-dependent probe amplification (MLPA) was performed in 2 of the patients and revealed in the patient 1 a heterozygous pathogenic variant in the gene THBD, as well as heterozygous deletions in CFH, CFHR1, and CFHR3. In the patient 2, there were heterozygous pathogenic variant in the genes CFI and CFB, in addition to heterozygous deletions in the genes CFHR1 and CFHR3. Both received treatment with eculizumab and undergone recovery of renal function. The third patient had TMA not classified as either aHUS or thrombotic thrombocytopenic purpura (TTP); he abandoned the treatment and returned to the service after 2 years for a dialysis emergency. Patients with arboviral infectious disease and changes that suggest TMA should have appropriate support to establish early diagnosis and useful treatment.
Subject(s)
Arbovirus Infections/virology , Arboviruses/isolation & purification , Thrombotic Microangiopathies/virology , Adolescent , Adult , Arbovirus Infections/genetics , Arboviruses/classification , Arboviruses/genetics , Arboviruses/physiology , Blood Proteins/genetics , Complement C3b Inactivator Proteins/genetics , Heterozygote , Humans , Male , Mutation , Thrombotic Microangiopathies/genetics , Young AdultABSTRACT
In a Plasmodium vivax infection, it was shown a proportionally increased on gametocyte distribution within the bone marrow aspirant, suggesting a role of this organ as a reservoir for this parasite stage. Here, we evaluated the ex vivo cytoadhesive capacity of P. vivax gametocytes to bone marrow endothelial cells (HBMEC) and investigated the involvement of some receptors in the cytoadhesion process by using transfected CHO cells (CHO-ICAM1, CHO-CD36 and CHO-VCAM), wild type (CHO-K1) or deficient in heparan and chondroitin sulfate (CHO-745). Ex-vivo cytoadhesion assays were performed using a total of 44 P. vivax isolates enriched in gametocyte stages by Percoll gradient in the different cell lines. The majority of isolates (88.9%) were able to adhere to HBMEC monolayer. ICAM1 seemed to be the sole receptor significantly involved. CD-36 was the receptor with higher adhesion rate, despite no significance was noticed when compared to CHO-745. We demonstrated that gametocyte P. vivax adheres ex vivo to bone marrow endothelial cells. Moreover, P. vivax gametocytes display the ability to adhere to all CHO cells investigated, especially to CHO-ICAM1. These findings bring insights to the comprehension of the role of the bone marrow as a P. vivax reservoir and the potential impact on parasite transmission to the vector.