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.
Evidence on the optimal time to initiate antiretroviral therapy (ART) in the presence of toxoplasmic encephalitis (TE) is scarce. We compared the impact of early vs. delayed ART initiation on ...mortality and neurologic complications at discharge in a Brazilian population co-infected with HIV and TE.
We retrospectively evaluated data from 9 years of hospitalizations at a referral center in Manaus, Amazonas. All ART-naïve hospitalized patients were divided into early initiation treatment (EIT) (0-4 weeks) and delayed initiation treatment (DIT) (>4 weeks). The groups were compared using chi-square test and mortality at 16 weeks.
Four hundred sixty nine patients were included, of whom 357 (76.1%) belonged to the EIT group. The median CD4
lymphocyte count and CD4
/CD8
ratio were 53 cells/mm
and 0.09, respectively. Mortality rate and presence of sequelae were 4.9% (
= 23) and 41.6% (
= 195), respectively. Mortality was similar between groups (
= 0.18), although the EIT group had the highest prevalence of sequelae at discharge (
= 0.04). The hazard ratio for death at 16 weeks with DIT was 2.3 (
= 0.18). The necessity for intensive care unit admission, mechanical ventilation, and cardiopulmonary resuscitation were similar between groups.
In patients with AIDS and TE, early ART initiation might have a detrimental influence on the occurrence of sequelae.
Zymomonas mobilis has long attracted attention owing to its capacity to ferment hexose to ethanol. From a taxonomic viewpoint, Z. mobilis is a unique species of the genus Zymomonas, separated into ...three subspecies, Z. mobilis subsp. mobilis, Z. mobilis subsp. pomaceae and Z. mobilis subsp. francensis on the basis of physiological tests, which are often unreliable owing to the genetic proximity among these species. Currently, the use of molecular techniques is more appropriate for identification of these bacterial subspecies. In this study, the 32 strains of Z. mobilis present in the UFPEDA bacterial collection were characterized using molecular techniques, such as sequencing of the 16S rDNA gene and its theoretical restriction profile, classifying them as members of the subspecies, Z. mobilis subsp. mobilis. In addition, anaerobic cultivations were performed, which showed the biological diversity of the strains in terms of growth, sugar consumption and ethanol production. From these results, it was possible to identify the strain Z‐2‐80 as a promising bacterium for use in the fermentation process.
Significance and Impact of the Study
Zymomonas mobilis is a bacterium of great relevance to biotechnology, owing to its capacity to ferment hexose to ethanol. On a molecular basis, 32 isolates were identified as Z. mobilis subsp. mobilis. However, intraspecific diversity was identified when these were grown under strictly anaerobic conditions. The results obtained from this study suggest a strain of Z. mobilis as an alternative for use in the fermentation process.
Significance and Impact of the Study:Zymomonas mobilis is a bacterium of great relevance to biotechnology, owing to its capacity to ferment hexose to ethanol. On a molecular basis, 32 isolates were identified as Z. mobilis subsp. mobilis. However, intraspecific diversity was identified when these were grown under strictly anaerobic conditions. The results obtained from this study suggest a strain of Z. mobilis as an alternative for use in the fermentation process.
Despite toxoplasmosis being a common infection among human and other
warm-blooded animals worldwide, there are no findings about Toxoplasma
gondii evolutionary forms in ancient populations. The ...molecular
techniques used for amplification of genetic material have allowed
recovery of ancient DNA (aDNA) from parasites contained in mummified
tissues. The application of polymerase chain reaction (PCR) to
paleoparasitological toxoplasmosis research becomes a promising option,
since it might allow diagnosis, acquisition of paleoepidemiological
data, access to toxoplasmosis information related origin, evolution,
and distribution among the ancient populations. Furthermore, it makes
possible the analysis of parasite aDNA aiming at phylogenetic studies.
To standardize and evaluate PCR applicability to toxoplasmosis
paleodiagnostic, an experimental mummification protocol was tested
using desiccated tissues from mice infected with the ME49 strain cysts,
the chronic infection group (CIG), or infected with tachyzoites (RH
strain), the acute infection group (AIG). Tissues were subjected to DNA
extraction followed by PCR amplification of T. gondii B1 gene. PCR
recovered T. gondii DNA in thigh muscle, encephalon, heart, and lung
samples. AIG presented PCR positivity in encephalon, lungs, hearts, and
livers. Based on this results, we propose this molecular approach for
toxoplasmosis research in past populations.
Severe disease attributable to Plasmodium vivax infection is already well described worldwide; however, autopsies in these patients are scarce.
From 1996 to 2010, 19 patient deaths with a clinical ...diagnosis of P. vivax infection occurred in a tertiary care center in the Brazilian Amazon. Seventeen of these 19 deaths were fully autopsied. Clinical charts, macroscopic autopsy reports, and stored paraffinized tissue blocks were retrieved. Nested polymerase chain reaction was performed in paraffinized samples of spleen and lung to confirm P. vivax monoinfection. Immunohistofluorescence was used to detect P. vivax parasitized red blood cells (RBCs).
Of 17 autopsies, 13 revealed that death could be attributed to P. vivax infection; in the remaining 4, acute diseases other than malaria were found to be the cause of death. The primary complication in patients in which malaria contributed to death was acute respiratory distress syndrome (ARDS) and pulmonary edema associated with the accumulation of neutrophils in the interalveolar space (6 cases). Spleen rupture (3 cases) and multiorgan dysfunction syndrome (3 cases) were the second most common complications. One child evolving with coma was also characterized, but no parasite was detected in the brain tissue. In one patient who developed ARDS and presented negative peripheral parasitemia by the time of death, scattered parasitized red blood cells were seen inside pulmonary capillaries, suggesting some sequestration in the lung.
In 13 of 17 deceased patients, P. vivax infection was the plausible cause of death. However, more studies are needed to understand pathogenesis related to severe disease.
COVID-19 manifests as a milder disease in children than adults, but the underlying mechanisms are not fully characterized. Here we assess the difference in cellular or humoral immune responses of ...pediatric and adult COVID-19 patients to see if these factors contribute to the severity dichotomy. Children's non-specific immune profile is dominated by naive lymphocytes and HLA-DR
CX3CR1
dendritic cells; meanwhile, children show strong specific antibody and T cell responses for viral structural proteins, with their T cell responses differing from adults by having weaker CD8
TNF
T cells responses to S peptide pool but stronger responses to N and M peptide pools. Finally, viral mRNA is more abundant in pediatric patients. Our data thus support a scenario in which SARS-CoV-2 infected children contribute to transmission yet are less susceptible to COVID-19 symptoms due to strong and differential responses to the virus.
Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung ...injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART).
ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH2O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure ≤30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle.
If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.
ClinicalTrials.gov Identifier: NCT01374022.
The relationship between malaria and undernutrition is controversial and complex. Synergistic associations between malnutrition and malaria morbidity and mortality have been suggested, as well as ...undernutrition being protective against infection, while other studies found no association. We sought to evaluate the relationship between the number of malaria episodes and nutritional statuses in a cohort of children below 15 years of age living in a rural community in the Brazilian Amazon.
Following a baseline survey of clinical, malaria and nutritional assessment including anthropometry measurements and hemoglobin concentration, 202 children ranging from 1 month to 14 years of age were followed for one year through passive case detection for malaria episodes. After follow-up, all children were assessed again in order to detect changes in nutritional indicators associated with malaria infection. We also examined the risk of presenting malaria episodes during follow-up according to presence of stunting at baseline. Children who suffered malaria episodes during follow-up presented worse anthropometric parameters values during this period. The main change was a reduction of the linear growth velocity, associated with both the number of episodes and how close the last or only malaria episode and the second anthropometric assessment were. Changes were also observed for indices associated with chronic changes, such as weight-for-age and BMI-for-age, which conversely, were more frequently observed in children with the last or only episode occurring between 6 and 12 months preceding the second nutritional assessment survey. Children with inadequate height-for-age at baseline (Z-score < -2) presented lower risk of suffering malaria episodes during follow-up as assessed by both the log-rank test (p =0.057) and the multivariable Cox-proportional hazards regression (Hazard Ratio = 0.31, 95%CI 0.10; 0.99 p=0.049).
Malaria was associated with impaired nutritional status amongst children in an endemic area of the Western Brazilian Amazon where P. vivax predominates. Our data all supports that the association presents differential effects for each age group, suggesting distinct pathophysiology pathways. We were also able to demonstrate that undernourishment at baseline was protective to malaria during follow-up. These findings support an intriguing interaction between these conditions in the rural Amazon and the need for a more integrative approach by health systems in endemic areas.
Beta2‐adrenergic receptor (B2AR) signaling is known to impair Th1‐cell differentiation and function in a cAMP‐dependent way, leading to inhibition of cell proliferation and decreased production of ...IL‐2 and IFN‐γ. CD4+ Foxp3+ Treg cells play a key role in the regulation of immune responses and are essential for maintenance of self‐tolerance. Nevertheless, very little is known about adrenergic receptor expression in Treg cells or the influence of noradrenaline on their function. Here we show that Foxp3+ Treg cells express functional B2AR. B2AR activation in Treg cells leads to increased intracellular cAMP levels and to protein kinase A (PKA)‐dependent CREB phosphorylation. We also found that signaling via B2AR enhances the in vitro suppressive activity of Treg cells. B2AR‐mediated increase in Treg‐cell suppressive function was associated with decreased IL‐2 mRNA levels in responder CD4+ T cells and improved Treg‐cell‐induced conversion of CD4+ Foxp3− cells into Foxp3+ induced Treg cells. Moreover, B2AR signaling increased CTLA‐4 expression in Treg cells in a PKA‐dependent way. Finally, we found that PKA inhibition totally prevented the B2AR‐mediated increase in Treg‐cell suppressive function. Our data suggest that sympathetic fibers are able to regulate Treg‐cell suppressive activity in a positive manner through B2AR signaling.
Southeastern Brazil has been suffering a rapid expansion of a severe sylvatic yellow fever virus (YFV) outbreak since late 2016, which has reached one of the most populated zones in Brazil and South ...America, heretofore a yellow fever-free zone for more than 70 years. In the current study, we describe the complete genome of 12 YFV samples from mosquitoes, humans and non-human primates from the Brazilian 2017 epidemic. All of the YFV sequences belong to the modern lineage (sub-lineage 1E) of South American genotype I, having been circulating for several months prior to the December 2016 detection. Our data confirm that viral strains associated with the most severe YF epidemic in South America in the last 70 years display unique amino acid substitutions that are mainly located in highly conserved positions in non-structural proteins. Our data also corroborate that YFV has spread southward into Rio de Janeiro state following two main sylvatic dispersion routes that converged at the border of the great metropolitan area comprising nearly 12 million unvaccinated inhabitants. Our original results can help public health authorities to guide the surveillance, prophylaxis and control measures required to face such a severe epidemiological problem. Finally, it will also inspire other workers to further investigate the epidemiological and biological significance of the amino acid polymorphisms detected in the Brazilian 2017 YFV strains.
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