Effects of COVID-19 Pandemic in Patients with a Previous Phrenic Nerve Transfer for a Traumatic Brachial Plexus Palsy.

Background With the advent of the coronavirus disease 2019 (COVID-19) pandemic, some doubts have been raised regarding the potential respiratory problems that patients who previously underwent a phrenic nerve transfer could have. Objectives To analyze the effects of the coronavirus infection on two populations, one from Argentina and another from Taiwan. Specific objectives were: (1) to identify the rate of COVID in patients with a history of phrenic nerve transfer for treatment of palsy; (2) to identify the overall symptom profile; (3) to compare Argentinian versus Taiwanese populations; and (4) to determine if any phrenic nerve transfer patients are at particular risk of more severe COVID. Methods A telephonic survey that included data regarding the number of episodes of acute COVID-19 infection, the symptoms it caused, the presence or absence of potential or life-threatening complications, and the status of COVID-19 vaccination were studied. Intergroup comparisons were conducted using the nonparametric Mann-Whitney U test, with categorical variables conducted using either the Pearson χ2 analysis or the Fisher's exact test, as appropriate. Results A total of 77 patients completed the survey, 40 from Taiwan and 37 from Argentina. Fifty-five (71.4%) developed a diagnosis of COVID. However, among these, only four had any level of dyspnea reported (4/55 = 7.3%), all mild. There were also no admissions to hospital or an intensive care unit, no intubations, and no deaths. All 55 patients isolated themselves at home. Conclusions It can be concluded that an acute COVID-19 infection was very well tolerated in our patients. (Level of evidence 3b, case reports).

Endogenous origin of Pseudomonas aeruginosa infecting hospitalized patients in Ecuador.

Recent evidence suggests that Pseudomonas aeruginosa, a bacterium that has the ability to cause deadly infections in hospitalized patients, could originate in the patient's own flora. We employed the Oxford Nanopore platform to obtain whole genome sequences (WGS) from clinical and rectal screen P. aeruginosa strains belonging to 15 patients from two hospitals. Our study found evidence that clinical and rectal isolates were clonal, with some evidence suggesting that the infecting strain was present in the patient's intestine at the time of admission, ruling out hospital acquisition. The use of WGS analysis is crucial to detect alternative sources of P. aeruginosa to develop new preventive measures against these serious infections.

Exploring Viral Metagenomics in Pediatric Patients with Acute Respiratory Infections: Unveiling Pathogens beyond SARS-CoV-2.

The emergence of SARS-CoV-2 and the subsequent pandemic have prompted extensive diagnostic and clinical efforts to mitigate viral spread. However, these strategies have largely overlooked the presence of other respiratory viruses. Acute respiratory diseases in pediatric patients can be caused by a diverse range of viral agents, and metagenomics represents a powerful tool for their characterization. This study aimed to investigate the viral abundance in pediatric patients with acute respiratory symptoms who tested negative for SARS-CoV-2 during the Omicron pandemic wave. To achieve this, viral metagenomics and next-generation sequencing were employed on 96 nasopharyngeal swab samples, which were organized into 12 pools, with each pool consisting of eight individual samples. Metagenomic analysis revealed that the most prevalent viruses associated with acute disease in pediatric patients were respiratory syncytial virus (detected in all pools) and enteroviruses, which are known to cause significant morbidity and mortality in children. Additionally, clinically significant viruses such as mumps orthorubulavirus, human metapneumovirus, influenza A, and a wide array of human herpesviruses (1, 3-7) were identified. These findings highlight the extensive potential of viral metagenomics in identifying viruses other than SARS-CoV-2 that contribute to acute infections in children. Consequently, this methodology should garner clinical attention in terms of differential diagnosis and the development of public policies to address such conditions in the global pediatric population.

Clinical Profile of SARS-CoV-2 Infection: Mechanisms of the Cellular Immune Response and Immunogenetic Markers in Patients from Brazil.

OBJECTIVES: The aim of this study is to evaluate some mechanisms of the immune response of people infected with SARS-CoV-2 in both acute infection and early and late convalescence phases. METHODS: This is a cohort study of 70 cases of COVID-19, confirmed by RT-PCR, followed up to 60 days. Plasma Samples and clinical data were. Viral load, blood count, indicators inflammation were the parameters evaluated. Cellular immune response was evaluated by flow cytometry and Luminex immunoassays. RESULTS: In the severe group, hypertension was the only reported comorbidity. Non severe patients have activated memory naive CD4+ T cells. Critically ill patients have central memory CD4+ T cell activation. Severe COVID-19 patients have both central memory and activated effector CD8+ T cells. Non-severe COVID-19 cases showed an increase in IL1ß, IL-6, IL-10 and TNF and severely ill patients had higher levels of the cytokines IL-6, IL-10 and CXCL8. CONCLUSIONS: The present work showed that different cellular responses are observed according to the COVID-19 severity in patients from Brazil an epicenter the pandemic in South America. Also, we notice that some cytokines can be used as predictive markers for the disease outcome, possibility implementation of strategies effective by health managers.

Exploring viral metagenomics in pediatric patients with acute respiratory infections: Unveiling pathogens beyond SARS-CoV-2

The emergence of SARS-CoV-2 and the subsequent pandemic have prompted extensive diagnostic and clinical efforts to mitigate viral spread. However, these strategies have largely overlooked the presence of other respiratory viruses. Acute respiratory diseases in pediatric patients can be caused by a diverse range of viral agents, and metagenomics represents a powerful tool for their characterization. This study aimed to investigate the viral abundance in pediatric patients with acute respiratory symptoms who tested negative for SARS-CoV-2 during the Omicron pandemic wave. To achieve this, viral metagenomics and next-generation sequencing were employed on 96 nasopharyngeal swab samples, which were organized into 12 pools, with each pool consisting of eight individual samples. Metagenomic analysis revealed that the most prevalent viruses associated with acute disease in pediatric patients were respiratory syncytial virus (detected in all pools) and enteroviruses, which are known to cause significant morbidity and mortality in children. Additionally, clinically significant viruses such as mumps orthorubulavirus, human metapneumovirus, influenza A, and a wide array of human herpesviruses (1, 3–7) were identified. These findings highlight the extensive potential of viral metagenomics in identifying viruses other than SARS-CoV-2 that contribute to acute infections in children. Consequently, this methodology should garner clinical attention in terms of differential diagnosis and the development of public policies to address such conditions in the global pediatric population.

Characteristics of Respiratory Syncytial Virus versus Influenza Infection in Hospitalized Patients of Peru: A Retrospective Observational Study.

Respiratory syncytial virus (RSV) and influenza infections are important causes of respiratory illness associated with hospitalizations in children in Peru; however, comparisons of RSV and influenza hospitalization across all age groups are not available in Peru. Therefore, we conducted an observational, retrospective study between May 2015 and October 2021 using hospitalization from RSV and influenza infection data obtained from SUSALUD (open data) in Peru to compare the baseline characteristics of sex, age, region, and infection type. For the study, 2696 RSV-infected and 1563 influenza-infected hospitalized patients from different age groups were included. Most hospitalizations from RSV infection and the influenza virus occurred in children <5 years of age (86.1% vs. 32.2%, respectively). Compared with influenza infection, RSV infection was less likely to occur in individuals ≥5 years of age (adjusted odds ratio (aOR) = 0.07; 95% confidence interval (CI), 0.06−0.08; p < 0.0001; compared to <5 years of age), and more likely to occur in highlands (aOR = 1.75; 95% CI, 1.46−2.07; p < 0.0001, compared to coast region), and jungle region (aOR = 1.75; 95% CI, 1.27−2.41; p = 0.001, compared to coast region). Among the respiratory complications, RSV pneumonia was less likely to occur between different age groups (aOR = 0.29; 95% CI, 0.22−0.37; p < 0.0001, compared to <5 years of age), compared with influenza pneumonia. These findings on the RSV-hospitalization and its complications are helpful for health services planning and may increase awareness of the Peruvian population's RSV and influenza disease burden.

Acute infection with Platynosomum illiciens (Trematoda: Dicrocoeliidae) as a clinically relevant and potentially fatal disease in Falco sparverius (Aves: Falconidae) in Brazil.

Platynosomum illiciens is a dicrocoeliid trematode from the biliary tract of warm-blooded vertebrates (felines, primates, marsupials, and birds) reported in different parts of the world. Although the veterinary relevance of platynosomosis in mammals, especially in domestic felines, has been increasingly evidenced in the scientific literature, studies involving avian disease caused by P. illiciens are comparatively scarce. In the present study, a female specimen of the American kestrel, Falco sparverius L., found dead, in November 2019, in Brazil, was necropsied. Parietal biliary effusion in the celomatic cavity was observed, suggesting biliary transudation and gallbladder stasis, which possibily preceded the distension and rupture of gallbladder noted during necropsy. In the microscopic analysis of the bile content, small trematodes were found and characterized as immature stages of Platynosomum after the morphological study. Partial sequences of the cox-1 gene enabled the identification of P. illiciens, with 100% similarity with previously sequenced sympatric isolates from mammals. The finding of immature specimens in a ruptured gallbladder strongly suggests a role for the parasite in biliary flow dysfunction, indicating acute platynosomosis as a clinically relevant and potentially fatal condition that has not yet been discussed.

Evaluation of Molecular Test for the Discrimination of "Naked" DNA from Infectious Parvovirus B19 Particles in Serum and Bone Marrow Samples.

Low levels of parvovirus B19 (B19V) DNA can be detected in the circulation and in different tissue of immunocompetent individuals for months or years, which has been linked to inflammatory diseases such as cardiomyopathy, rheumatoid arthritis, hepatitis, and vasculitis. However, the detection of B19V DNA does not necessarily imply that infectious virions are present. This study aimed to evaluate the method based on the Benzonase® treatment for differentiation between the infectious virions from "naked" DNA in serum and bone marrow (BM) samples to be useful for the B19V routine diagnosis. In addition, we estimated the period of viremia and DNAemia in the sera and bone marrow of nonhuman primates experimentally infected with B19V. Serum samples from ten patients and from four cynomolgus monkeys experimentally infected with B19V followed up for 60 days were used. Most of the human serum samples became negative after pretreatment; however, only decreased viral DNA loads were observed in four patients, indicating that these samples still contained the infectious virus. Reduced B19V DNA levels were observed in animals since 7th dpi. At approximately 45th dpi, B19V DNA levels were below 105 IU/mL after Benzonase® pretreatment, which was not a consequence of active B19V replication. The test based on Benzonase® pretreatment enabled the discrimination of "naked DNA" from B19V DNA encapsidated in virions. Therefore, this test can be used to clarify the role of B19V as an etiological agent associated with atypical clinical manifestations.

Finding and treating early-stage HIV infections: A cost-effectiveness analysis of the Sabes study in Lima, Peru.

Background: Sabes, a treatment-as-prevention intervention among men who have sex with men and transgender women in Lima, Peru, was developed to identify HIV during early primary infection (<3 months from acquisition) through monthly serologic assays and HIV RNA tests. Newly diagnosed individuals were rapidly linked to care and offered to initiate ART. In this study we sought to study the cost-effectiveness of Sabes compared to the standard of care (SOC) for HIV testing and initiation of treatment. Methods: We adapted a compartmental model of HIV transmission to evaluate the cost-effectiveness of the Sabes approach compared to the SOC using a government health care perspective, 20-year time horizon, and 3% annual discounting. We estimated the proportion of cases of HIV detected during early primary infection, reduction in HIV incidence and prevalence, incremental cost-effectiveness ratio (ICER), and net monetary benefit. We analyzed costs using data from the Sabes study, the Peruvian Ministry of Health, published literature, and expert consultation. Findings: The Sabes intervention is projected to identify 9294 early primary HIV infections in Lima, Peru over 20 years. The intervention costs $6,896 per early primary infection diagnosed and by 2038 is expected to decrease the fraction of early infections among prevalent infections by 62%. Sabes is expected to improve health, resulting in greater total discounted QALYs per person than the SOC (16·7 vs 16·4, respectively). Sabes had an ICER of $1431 (22% per capita GDP in Peru) per QALY compared to SOC. Interpretation: Our analysis suggests that in Lima, Peru the Sabes intervention could be a cost-effective approach to reduce the burden of HIV even under stringent cost-effectiveness criteria. This finding suggests that programs that use frequent HIV testing, rapid linkage to care and initiation of ART should be considered as part of a comprehensive HIV prevention strategy. Funding: National Institutes of Health.

Cell wall glycolipids from Corynebacterium pseudotuberculosis strains with different virulences differ in terms of composition and immune recognition.

Caseous lymphadenitis (CLA) is an infectious disease caused by Corynebacterium pseudotuberculosis in small ruminants and is characterized by the development of granulomas in the lymph nodes, spleen, liver, and lungs. Although little is known about the host-pathogen relationship of this bacterium, it was previously reported that the pathogen's lipids are important for its taxonomic classification and survival inside macrophages. However, there are no studies regarding the composition of these molecules. In this study, cell wall glycolipids from two C. pseudotuberculosis strains presenting different virulence profiles were purified and its composition was characterized. A difference was observed between the electrophoretic and chromatogram profiles for cell wall components from the two strains, mainly among molecules with low molecular weights. IgM from sheep with acute CLA recognized antigens with an estimated molecular weight of 11 kDa of the low-pathogenicity strain, while low-molecular weight antigens from the high-pathogenicity strain presented a lower recognition by these antibodies. Mass spectrometry analysis showed that the cell wall of the high-pathogenicity strain contained glycolipids with high amounts of unsaturated fatty acids and glycerophosphoinositols, which may contribute to the capacity of this strain to cause severe disease. In conclusion, it is indicated that cell wall non-protein antigens can play a key role in C. pseudotuberculosis virulence.

Pathogenesis of Bovine alphaherpesvirus 2 in calves following different routes of inoculation / Patogênese do alfaherpesvírus bovino 2 em bezerros inoculados por diferentes vias

Bovine alphaherpesvirus 2 (BoHV-2) is the agent of herpetic mammilitis (BHM), a cutaneous and self-limiting disease affecting the udder and teats of cows. The pathogenesis of BoHV-2 is pourly understood, hampering the development of therapeutic drugs, vaccines and other control measures. This study investigated the pathogenesis of BoHV-2 in calves after inoculation through different routes. Three- to four-months seronegative calves were inoculated with BoHV-2 (107TCID50.mL-1) intramuscular (IM, n=4), intravenous (IV, n=4) or transdermal (TD) after mild scarification (n=4) and submitted to virological, clinical and serological monitoring. Calves inoculated by the IV route presented as light increase in body temperature between days 6 to 9 post-inoculation (pi). Virus inoculation by the TD route resulted in mild inflammatory lesions at the sites of inoculation, characterized by hyperemia, small vesicles, mild exudation and scab formation, between days 2 and 8pi. Virus or viral DNA was detected by PCR in the crusts/swabs collected from lesions of 3 out of 4 animals inoculated TD from day 2 to 8pi. Viremia was detected in 3/4 animals of the IM group (from day 4 to 8pi); in 2/4 animals of the IV group (days 6 and 8pi) but not in the TD group. Calves from all inoculated groups seroconverted to BoHV-2 in titers from 4 to 64, as indicated by virus-neutralizing (VN) assays performed in sera collected at day 15pi. Administration of dexamethasone (Dex) to the inoculated calves at day 48pi, did not result in virus reactivation as indicated by lack of virus detection in the blood and/or in inoculation sites and no increase in VN antibody titers. These results demonstrated that BoHV-2 was able to replicate efficiently in calves following different routes of exposure, produced viremia after IM and IV inoculation and was not reactivated by Dex treatment.(AU)

O alfaherpesvírus bovino 2 (BoHV-2) é um agente etiológico da mamilite herpética (BHM), uma doença cutânea e autolimitante do úbere e tetos de vacas. Pouco se sabe sobre a patogênese do BoHV-2, dificultando o desenvolvimento de medicamentos terapêuticos e vacinas. Este estudo investigou a patogênese do BoHV-2 em bezerros após a inoculação por diferentes vias. Bezerros soronegativos de três a quatro meses foram inoculados com BoHV-2 (107TCID50.mL-1) por via intramuscular (IM, n=4), por via intravenosa (IV, n=4) ou transdérmica (TD, n=4) após escarificação leve e submetidos a monitoramento virológico, clínico e sorológico. Os bezerros inoculados pela via IV apresentaram aumento leve da temperatura corporal entre os dias 6 a 9 pós-inoculação (pi). A inoculação do vírus pela via TD resultou em lesões inflamatórias leves nos locais de inoculação, caracterizadas por hiperemia, pequenas vesículas, exsudação leve e formação de crostas, entre os dias 2 e 8pi. O vírus ou DNA viral foi detectado por PCR nas crostas/swabs coletados de lesões de 3 de 4 animais inoculados TD do dia 2 ao 8pi. Viremia foi detectada em 3/4 dos animais do grupo IM (do dia 4 ao 8pi); em 2/4 animais do grupo IV (dias 6 e 8pi), mas não no grupo TD. Bezerros de todos os grupos inoculados soroconverteram o BoHV-2 em títulos de 4 a 64, conforme indicado por ensaios de vírus-neutralização (VN) realizados em soro coletado no dia 15pi. Administração de dexametasona (Dex) nos bezerros inoculados no dia 48pi, não resultou em reativação do vírus, como indicado pela falta de detecção de vírus no sangue e/ou nos locais de inoculação e pela ausência de aumento nos títulos de anticorpos. Estes resultados demonstraram que o BoHV-2 foi capaz de replicar eficientemente em bezerros seguindo diferentes vias de inoculação, produziu viremia após a inoculação IM e IV e não foi reativado pelo tratamento com Dex.(AU)

Pathogenesis of Bovine alphaherpesvirus 2 in calves following different routes of inoculation / Patogênese do alfaherpesvírus bovino 2 em bezerros inoculados por diferentes vias

Bovine alphaherpesvirus 2 (BoHV-2) is the agent of herpetic mammilitis (BHM), a cutaneous and self-limiting disease affecting the udder and teats of cows. The pathogenesis of BoHV-2 is pourly understood, hampering the development of therapeutic drugs, vaccines and other control measures. This study investigated the pathogenesis of BoHV-2 in calves after inoculation through different routes. Three- to four-months seronegative calves were inoculated with BoHV-2 (107TCID50.mL-1) intramuscular (IM, n=4), intravenous (IV, n=4) or transdermal (TD) after mild scarification (n=4) and submitted to virological, clinical and serological monitoring. Calves inoculated by the IV route presented as light increase in body temperature between days 6 to 9 post-inoculation (pi). Virus inoculation by the TD route resulted in mild inflammatory lesions at the sites of inoculation, characterized by hyperemia, small vesicles, mild exudation and scab formation, between days 2 and 8pi. Virus or viral DNA was detected by PCR in the crusts/swabs collected from lesions of 3 out of 4 animals inoculated TD from day 2 to 8pi. Viremia was detected in 3/4 animals of the IM group (from day 4 to 8pi); in 2/4 animals of the IV group (days 6 and 8pi) but not in the TD group. Calves from all inoculated groups seroconverted to BoHV-2 in titers from 4 to 64, as indicated by virus-neutralizing (VN) assays performed in sera collected at day 15pi. Administration of dexamethasone (Dex) to the inoculated calves at day 48pi, did not result in virus reactivation as indicated by lack of virus detection in the blood and/or in inoculation sites and no increase in VN antibody titers. These results demonstrated that BoHV-2 was able to replicate efficiently in calves following different routes of exposure, produced viremia after IM and IV inoculation and was not reactivated by Dex treatment.(AU)

O alfaherpesvírus bovino 2 (BoHV-2) é um agente etiológico da mamilite herpética (BHM), uma doença cutânea e autolimitante do úbere e tetos de vacas. Pouco se sabe sobre a patogênese do BoHV-2, dificultando o desenvolvimento de medicamentos terapêuticos e vacinas. Este estudo investigou a patogênese do BoHV-2 em bezerros após a inoculação por diferentes vias. Bezerros soronegativos de três a quatro meses foram inoculados com BoHV-2 (107TCID50.mL-1) por via intramuscular (IM, n=4), por via intravenosa (IV, n=4) ou transdérmica (TD, n=4) após escarificação leve e submetidos a monitoramento virológico, clínico e sorológico. Os bezerros inoculados pela via IV apresentaram aumento leve da temperatura corporal entre os dias 6 a 9 pós-inoculação (pi). A inoculação do vírus pela via TD resultou em lesões inflamatórias leves nos locais de inoculação, caracterizadas por hiperemia, pequenas vesículas, exsudação leve e formação de crostas, entre os dias 2 e 8pi. O vírus ou DNA viral foi detectado por PCR nas crostas/swabs coletados de lesões de 3 de 4 animais inoculados TD do dia 2 ao 8pi. Viremia foi detectada em 3/4 dos animais do grupo IM (do dia 4 ao 8pi); em 2/4 animais do grupo IV (dias 6 e 8pi), mas não no grupo TD. Bezerros de todos os grupos inoculados soroconverteram o BoHV-2 em títulos de 4 a 64, conforme indicado por ensaios de vírus-neutralização (VN) realizados em soro coletado no dia 15pi. Administração de dexametasona (Dex) nos bezerros inoculados no dia 48pi, não resultou em reativação do vírus, como indicado pela falta de detecção de vírus no sangue e/ou nos locais de inoculação e pela ausência de aumento nos títulos de anticorpos. Estes resultados demonstraram que o BoHV-2 foi capaz de replicar eficientemente em bezerros seguindo diferentes vias de inoculação, produziu viremia após a inoculação IM e IV e não foi reativado pelo tratamento com Dex.(AU)

A unique immune signature of serum cytokine and chemokine dynamics in patients with Zika virus infection from a tropical region in Southern Mexico.

OBJECTIVES: To describe the kinetics of circulating cytokines and chemokines in humans with ZIKAV infection. METHODS: Serum levels of different immune mediators in patients with ZIKAV infection were measured at distinct stages of the disease, as well as in culture supernatants from human monocytes infected with a clinical ZIKAV isolate. We also looked for clinical features associated with specific immune signatures among symptomatic patients. RESULTS: We evaluated 23 ZIKAV-infected patients. Their mean age was 32 ± 8.3 years and 65% were female. ZIKAV patients showed elevated IL-9, IL-17A, and CXCL10 levels at acute stages of the disease. At day 28, levels of CCL4 and CCL5 were increased, whereas IL-1RA, CXCL8 and CCL2 were decreased. At baseline, IL-7 was increased among patients with headache, whereas CCL2, and CCL3 were decreased in patients with bleeding and rash, respectively. Our clinical ZIKAV isolate induced a broad immune response in monocytes that did not resemble the signature observed in ZIKAV patients. CONCLUSIONS: We showed a unique immune signature in our cohort of ZIKAV-infected patients. Our study may provide valuable evidence helpful to identify immune correlates of protection against ZIKAV.

Rapamycin Treatment Reduces Acute Myocarditis Induced by Trypanosoma cruzi Infection.

Chagas disease affects millions of people mainly in Latin America and is a protozoan illness caused by the parasite Trypanosoma cruzi. Chagasic cardiomyopathy is the leading cause of mortality of infected patients, due to compromised electrical and mechanical cardiac function induced by tissue remodeling, especially fibrosis, and lymphocytic infiltration. Some cellular biochemical pathways can be protective to the heart, and we tested if the in vivo activation of the autophagic machinery by rapamycin could reduce parasite-induced myocarditis. Regarding the expression of LC3, an autophagy marker, we observed its upregulation in the cardiac tissue of infected untreated mice. However, after rapamycin treatment, an autophagy inducer, infected mice showed reduced electrical cardiac dysfunctions, myocarditis, cardiac damage, and reduced production of pro-inflammatory cytokines by the heart. On the other hand, the parasite's life cycle was not affected, and we observed no modulations in cardiac tissue or blood parasitemia. Our data indicate that, at least partially, autophagy induction controls inflammation in the heart¸ illustrating the complexity of the pathways that concur to the development of the infection.

Epidemiological profile of acute Chagas disease in individuals infected by oral transmission in northern Brazil

Abstract INTRODUCTION: Oral infection by Trypanosoma cruzi is currently the most important route of transmission of acute Chagas disease (ACD) in the North region of Brazil, and the reported outbreaks are usually related to ingestion of contaminated food, especially unprocessed açaí pulp. METHODS A retrospective cohort study was performed to analyze the epidemiological profile of individuals with suspected cases of ACD in the municipality of Breves, located in the state of Pará, Brazil. Therefore, notifications of suspected cases of ACD were collected from the Municipal Health Department of Breves from January 2007 to December 2017. RESULTS A total of 265 individuals were registered, and the majority were male (54.7%; 145/265). Age ranged from nine months to 79 years, with a greater number of notifications for individuals aged between 1 and 39 years (71.3%; 189/265). Most of them had a low level of education (74.3%, 197/265), were living in rural and urban areas (58.9%; 156/265 and 37.7%; 100/265, respectively). Infection occurred mainly in the domestic environment (96.2%; 255/265) through oral transmission (98.1%; 260/265). There were a greater number of notifications in November, December and January. CONCLUSIONS These data showed that oral transmission of T. cruzi has become increasingly high in the study region, and health education programs need to be implemented as strategies to ensure good manufacturing practices of unprocessed food.

Transmission of Toxoplasma gondii Infection Due to Bone Marrow Transplantation: Validation by an Experimental Model.

Toxoplasmosis is an opportunistic infectious disease and may present a fatal outcome for human bone marrow transplant (BMT) recipients, due to the rapid disease course in immunosuppressed individuals. Several reports about occurrence of toxoplasmosis after BMT have been published in the literature, but this disease has been associated mainly due to reactivation of latent infection rather than primary infection. Even though there are reports of acute toxoplasmosis in recipients who were seronegative for T. gondii, suggesting transmission of infection after BMT, the source of infection in those cases has not been clearly demonstrated, whether it is due to the transplantation procedure by itself or from environmental source. Thus, the present study aimed to observe if it could be possible to demonstrate the parasite's ability to infect bone marrow (BM) cells and cause toxoplasmosis, when using an experimental model. Our results showed that 11% of hematopoietic and 7.1% of nonhematopoietic lineages may become infected when using in vitro experiments. Also, in vivo experiments demonstrated that, when C57BL/6 mice were infected with RH-RFP or ME-49-GFP T. gondii strains, the BM cells may be infected at different time points of infection. The parasites were detected by both fluorescent microscopy and qPCR. Also, when those BM samples were collected and used for BMT, the transplanted animals presented high rates of mortality and 87.5% of them became seropositive for T. gondii. Taken together, our results clearly demonstrated that it is possible to acquire primary T. gondii infection from the donor cells after BMT. Therefore, we are emphasizing that, before transplantation, serological screening for T. gondii infection from both donors and recipients, in addition to DNA search for this parasite from donor bone marrow cells, are necessary procedures to avoid the risk of T. gondii infection for immunocompromised patients.

Reduction of HIV-1 Reservoir Size and Diversity After 1 Year of cART Among Brazilian Individuals Starting Treatment During Early Stages of Acute Infection.

The aim of early combined antiretroviral therapy (cART) of HIV is to limit the seeding of the viral reservoir during the initial phase of infection and, consequently, decrease intrahost viral diversity. Here, we assessed the effect of early cART on size and complexity of the proviral reservoir. Peripheral blood mononuclear cell (PBMC) and plasma samples were obtained from ten HIV-infected Brazilian individuals diagnosed at the acute phase of infection, before (PREART) and 12 months (M12ART) after suppressive cART. HIV proviral reservoir size was determined by quantitative real-time PCR; intrahost viral diversity of the env C2-V3 region was assessed by single genome amplification or next-generation sequencing in PBMC and plasma, respectively. Mean nucleotide diversity (π) and normalized Shannon entropy (HSN) were used to infer the complexity of the viral population. Compared to PREART, M12ART saw an immunological recovery with a gain of ∼200 CD4+ T cells (P = 0.008) and a normalization of the CD4/CD8 ratio [1.0 (IQR: 0.88-1.18), P = 0.016], as well as a significant decrease in HIV-1 RNA (∼4 log, P = 0.004) and DNA (∼1 log, P = 0.002) levels. The median time to achieve viral suppression was 3 months (IQR: 2.8-5.8 months). The high intermixing between sequences from both visits suggests that the HIV-1 DNA reservoir remained remarkably stable under cART. After 1 year of cART, there was a minor reduction in proviral π (PreART = 0.20 vs. M12ART = 0.10; P = 0.156) but a significant decrease in HSN (PreART = 0.41 vs. M12ART = 0.25; P = 0.019). We found no correlation between π or HSN at PreART and the rate of HIV DNA decay, T CD4+ counts, or CD4/CD8 ratio at M12ART. Based on a small cohort of Brazilian infected individuals under early cART and analyses of the env region, 1 year of follow-up suggested a reservoir size reduction, allowed a significant decrease of HIV-1 complexity, and achieved immunological restoration regardless of the initial HIV-1 plasma viral load, CD4+ T cell counts, or HIV-1 subtype. However, further studies in the Brazilian setting aiming a longer follow-up and larger cohort are required in this field.

Immature granulocytes index as early marker of sepsis.

INTRODUCTION: Sepsis induces the recruitment of immature neutrophils into the circulation. An immature granulocyte percentage (IG%) count greater than 3% has been shown to be an indicator for the risk of sepsis. The aim of this study was to evaluate the IG% as predictor of sepsis compared to blood culture results and sepsis diagnostic confirmation. METHODS: The study included individuals (n = 301) of both sexes aged ≥18 years who underwent Hospital São Lucas examinations between January and November 2017. For all the patients, IG%, as well as blood culture results, were evaluated. All examinations were obtained from Clinical Laboratory database. Data were analyzed through the SPSS program version 18.0. RESULTS: There was statistical association between blood culture and IG% results (P = 0.009) and between sepsis confirmation and IG% on Pearson chi-square test (P < 0.001). An IG% cutoff point of 2.0% was able to exclude sepsis based on clinical diagnosis with a specificity of 90.9% and a sensitivity of 38.5%. The cutoff value in ROC analyses of IG% based on blood culture results was 0.3% and 0.4% based on clinical diagnosis. CONCLUSION: Our study demonstrated that IG% <2.0% are helpful on the exclusion of sepsis diagnosis with a very high specificity (90.9%). The IG% is a useful additional marker for sepsis diagnosis allowing the early initiation of therapy and better possibilities of recovery.

Acute Toxoplasma gondii infection alters the number of neurons and the proportion of enteric glial cells in the duodenum in Wistar rats.

BACKGROUND: Toxoplasma gondii infection can occur through the ingestion of raw meat that contains tissue cysts or food that contains oocysts. Through the ingestion of oocysts, the parasite crosses the intestinal barrier, where the enteric nervous system is located. The objective was to investigate the kinetics of neuronal and glial responses during acute T. gondii infection. METHODS: We used 45 Wistar rats that were divided into a control group and infected groups that were evaluated at 6, 12, 24, 48, 72 hours, 7 days, 10 days, and 15 days after infection. The rats received 5000 sporulated oocysts of the parasite orally. To detect neurons and enteric glia cells, the myenteric and submucosal plexuses of the duodenum underwent double-labeling immunohistochemical techniques to evaluate HuC/HuD and S100, HuC/HuD and ChAT, and HuC/HuD and nNOS. KEY RESULTS: We observed a reduction of the total neuron population in the submucosal plexus 72 hours after infection. Cholinergic neurons decreased in the submucosal plexus 15 days after infection, and nitrergic neurons decreased in the myenteric plexus 72 hours after infection. A decrease in the number of glial cells was observed 7 days after infection in the submucosal plexus, and an increase in the enteric glial cell (EGC)/neuron ratio was found in both plexuses 48 hours after infection. CONCLUSIONS AND INFERENCES: We found decrease of neurons and increase in the EGC/neuron ratio in both plexuses caused by acute T. gondii infection, with major alterations 72 hours after oral infection. The number of cholinergic neurons decreased in the submucosal plexus, and the number of nitrergic neurons decreased in the myenteric plexus. A decrease in the number of enteric glial cells was observed in the submucosal plexus, and an increase in the enteric glial cell/neuron ratio was observed in both ganglionate plexuses of the duodenum.

Reduction of inflammation and T cell activation after 6 months of cART initiation during acute, but not in early chronic HIV-1 infection.

OBJECTIVES: To investigate the impact of early combined antiretroviral therapy (cART) on inflammation biomarkers and immune activation during acute and early chronic HIV-1 infection. METHODS: We included 12 acute (AHI), 11 early chronic (EcHI), and 18 late chronic HIV-1-infected (LcHI) individuals who were treated with cART and 18 HIV-1-uninfected (HIV-neg) individuals. Plasmatic levels of inflammation biomarkers, CD8+CD38+HLA-DR+ T cell frequencies, CD4 T cell counts, CD4/CD8 ratio, total HIV-1 DNA and plasmatic viral load were evaluated. Mann-Whitney test, Pearson and Spearman correlation, and linear regression models were used for statistical analyses. RESULTS: IP-10, IL-18, and sCD163 were significantly elevated at pre-ART in the AHI and EcHI groups, showing a significant reduction after 6 months of cART in the AHI group, achieving similar levels to the HIV-neg group. For the EcHI group, the IP-10 and sCD163 levels were also significantly reduced on M6-ART; however, IP-10 levels remained higher than in the HIV-neg group, and no significant reduction of IL-18 levels was observed. The CD8+ T cell activation levels were elevated in the AHI and EcHI groups at pre-ART and showed a significant reduction on M6-ART, but they were similar to levels seen for HIV-neg only after 12 months of cART. At pre-ART, IP-10 levels but not IL-18 levels were positively correlated with HIV-1 viral load in the AHI group. CONCLUSIONS: Early initiation of cART in HIV infection can reduce systemic inflammation, but the earlier normalization of the inflammation markers was only observed when cART was initiated in the acute phase of infection. A slower dynamic of reduction was observed for CD8+ T cell activation.