Fatores de risco para Infecções relacionadas à Assistência à Saúde causadas por Enterobacteriaceae produtoras de Klebsiella pneumoniae carbapenemase: um estudo de caso controle

Objective: To evaluate the risk factors for healthcare-associated infections caused by Klebsiella pneumoniae carbapenemase producing Enterobacteriaceae. Method: This is a retrospective case-control study that consisted of a sample of 82 infected patients and 164 controls, totaling 246 patients. Data collection was performed between January and May 2017 through search in the Automated Hospital Infection Control System and in the electronic patient records.Results: Patients previously colonized with gram-negative microorganisms (OR: 10.7, 95% CI: 2-60, p=0.007), with cancer (OR: 20.8, 95% CI: 4-120, p<0.001), using a double lumen catheter (OR: 30.5, 95% CI: 2-382, p=0.008), with pressure injury (OR: 136.2, 95% CI: 11- 1623, p<0.001) and Intensive Care Unit stay (OR: 1.4, 95% CI: 1.2-1.6, p <0.001) had a greater chance of developing Healthcare-associated Infections caused by KPC-producing Enterobacteriaceae than the control group. The area under the ROC curve showed a good overall performance (0.99, 95% CI: 0.992-0.998) of the final logistic regression model. Conclusion: Previous colonization, cancer, double lumen catheter use, pressure injury and ICU stay were very important risk factors for the acquisition of infections in the hospital environment.  Objetivo: Evaluar los factores de riesgo para infecciones relacionadas con la asistencia sanitaria causadas por Enterobacteriaceae productoras de carbapenemas.Método: Este es un estudio retrospectivo de casos y controles que consistió en una muestra de 82 pacientes infectados y 164 controles, totalizando 246 pacientes. La recopilación de datos se realizó entre enero y mayo de 2017 mediante la búsqueda en el Sistema Automatizado de Control de Infecciones Hospitalarias y en los registros electrónicos de pacientes.Resultados: Pacientes previamente colonizados con microorganismos gramnegativos (OR: 10.7, 95% CI: 2-60, p=0.007), con cáncer (OR: 20.8, 95% CI: 4-120, p<0.001), utilizando una catéter de doble luz (OR: 30.5, 95% CI: 2-382, p=0.008), con lesión por presión (OR: 136.2, 95% CI: 11- 1623, p<0.001) y permanecer en la Unidad de Cuidados Intensivos (OR: 1.4, 95% CI: 1.2-1.6, p <0.001) fueron más propensos a desarrollar infecciones causadas por Enterobacteriaceae productoras de carbapenemas que el grupo control. El área bajo la curva ROC mostró un buen rendimiento general (0,99; IC 95%: 0,992-0,998) del modelo de regresión logística final.Conclusión: La colonización previa, el cáncer, el uso de catéteres de doble luz, la lesión por presión y la estadía en la UCI fueron factores de riesgo muy importantes para la adquisición de infecciones en el entorno hospitalario.Objetivo: Avaliar os fatores de risco para infecções relacionadas à assistência à saúde causadas por Enterobactérias produtoras de Klebsiella pneumoniae carbapenemase.Método: Estudo de caso-controle, retrospectivo que foi composto por uma amostra de 82 pacientes infectados e 164 controles, totalizando 246 pacientes. A coleta de dados foi realizada entre janeiro e maio de 2017, por meio de busca no Sistema Automatizado de Controle de Infecção Hospitalar e nos prontuários eletrônicos dos pacientes.Resultados: Pacientes previamente colonizados com microrganismos gram-negativos (OR: 10,7, IC 95%: 2-60, p=0,007), com câncer (OR: 20,8, IC 95%: 4-120, p<0,001), utilizando cateter de duplo lúmen (OR: 30,5, IC 95%: 2-382, p=0,008), com lesão por pressão (OR: 136,2, IC 95%: 11-1623, p<0,001) e internação na Unidade de Terapia Intensiva (OR: 1,4, IC 95%: 1,2-1,6, p<0,001) tiveram maior chance de desenvolver infecções relacionadas à assistência à saúde causadas por Enterobactérias produtoras de Klebsiella pneumoniae carbapenemase quando comparadas ao grupo controle. A área sob a curva ROC apresentou um bom desempenho geral do modelo final de regressão logística (0,99, IC95%: 0,992-0,998).Conclusão: Colonização prévia, câncer, uso de cateter de duplo lúmen, lesão por pressão e permanência na UTI foram fatores de risco muito importantes para a aquisição de infecções no ambiente hospitalar

MORTALIDADE INFANTIL EVITÁVEL E VULNERABILIDADE SOCIAL NO VALE DO JEQUITINHONHA, MINAS GERAIS, BRASIL

RESUMO Objetivo: analisar a ocorrência de mortalidade infantil segundo critérios de evitabilidade e de vulnerabilidade social no Vale do Jequitinhonha, Minas Gerais. Métodos: estudo transversal realizado com dados dos sistemas de informação do Ministério da Saúde, entre 2009 e 2014. Foi considerado o índice de vulnerabilidade social das cidades e as causas de morte foram classificadas conforme lista de causas evitáveis por intervenção do SUS. Foram calculadas as proporções, taxas corrigidas de mortalidade infantil geral e estratificadas. Diferenças foram avaliadas por meio do teste qui-quadrado em todo o período e entre os triênios 2009-11 e 2012-14. Resultados: a taxa de mortalidade infantil média foi de 21,7 óbitos /1.000 nascidos vivos. No total, 69,5% dos óbitos foram classificados como evitáveis. Foram observadas reduções de 34,9 e 26,5% nos óbitos evitáveis por ações de atenção à mulher na gestação (p=0,00) e ao recém-nascido (p=0,04), respectivamente, e aumento de 65,8% nos óbitos evitáveis por ações de atenção à mulher no parto (p=0,01). Foi demonstrada predominância de óbitos evitáveis nos municípios de mais vulnerabilidade social (p=0,00). Conclusões: os resultados destacaram a importância das causas evitáveis relacionadas ao cuidado em saúde no momento do parto e, apesar das reduções observadas, na gestação e ao recém-nascido. Também evidenciaram a maior proporção de óbitos evitáveis na população mais vulnerável. O desafio de reduzir essa mortalidade indica a urgência por ações que visem à redução das desigualdades sociais, bem como a necessidade de melhorias no acesso e na qualidade dos serviços assistenciais

Contributions of IFN-gamma and granulysin to the clearance of Plasmodium yoelii blood stage

P. vivax-infected Retics (iRetics) express human leukocyte antigen class I (HLA-I), are recognized by CD8+ T cells and killed by granulysin (GNLY) and granzymes. However, how Plasmodium infection induces MHC-I expression on Retics is unknown. In addition, whether GNLY helps control Plasmodium infection in vivo has not been studied. Here, we examine these questions using rodent infection with the P. yoelii 17XNL strain, which has tropism for Retics. Infection with P. yoelii caused extramedullary erythropoiesis, reticulocytosis and expansion of CD8+CD44+CD62L- IFN-gamma-producing T cells that form immune synapses with iRetics. We now provide evidence that MHC-I expression by iRetic is dependent on IFN-gamma-induced transcription of IRF-1, MHC-I and beta2-microglobulin (beta2-m) in erythroblasts. Consistently, CTLs from infected wild type (WT) mice formed immune synapses with iRetics in an IFN-gamma- and MHC-I-dependent manner. When challenged with P. yoelii 17XNL, WT mice cleared parasitemia and survived, while IFN-gamma KO mice remained parasitemic and all died. beta2-m KO mice that do not express MHC-I and have virtually no CD8+ T cells had prolonged parasitemia, and 80% survived. Because mice do not express GNLY, GNLY-transgenic mice can be used to assess the in vivo importance of GNLY. Parasite clearance was accelerated in GNLY-transgenic mice and depletion of CD8+ T cells ablated the GNLY-mediated resistance to P. yoelii. Altogether, our results indicate that in addition to previously described mechanisms, IFN-gamma promotes host resistance to the Retic-tropic P. yoelii 17XNL strain by promoting MHC-I expression on iRetics that become targets for CD8+ cytotoxic T lymphocytes and GNLY

Investigação dos óbitos infantil e fetal no Vale do Jequitinhonha, Minas Gerais, Brasil

OBJETIVO: analisar os fatores relacionados à não investigação dos óbitos fetal e infantil ocorridos no Vale do Jequitinhonha, Minas Gerais. MÉTODOS: trata-se de estudo ecológico que teve, como unidades de análise, todos os 33 municípios da Região Ampliada de Saúde Jequitinhonha, Minas Gerais. Nesses municípios foi aplicado um questionário a um membro do Comitê de Prevenção do Óbito Infantil e Fetal com questões sobre a composição dos comitês, mecanismos de investigação do óbito infantil, fatores dificultadores para a investigação dos óbitos e critérios de evitabilidade entre os anos 2007 e 2012. Foi feita análise descritiva com frequências simples, com o intuito de descrever o perfil dos municípios estudados. RESULTADOS: dos 598 óbitos infantis e 477 fetais registrados, apenas 22,2 e 18,4% foram investigados, respectivamente. Constatou-se a existência de problemas de infraestrutura, técnico-operacionais e políticos que interferiram na prática de investigação. CONCLUSÃO: a operacionalização da investigação do óbito infantil e fetal, apesar de exigido por lei, apresenta deficiências, o que acarreta elevado número de óbitos não investigados no período do estudo, o que poderá comprometer as ações para a redução da mortalidade infantil e fetal e a qualidade da assistência infantil

The CD14+CD16+ inflammatory monocyte subset displays increased mitochondrial activity and effector function during acute Plasmodium vivax malaria

Infection with Plasmodium vivax results in strong activation of monocytes, which are important components of both the systemic inflammatory response and parasite control. The overall goal of this study was to define the role of monocytes during P. vivax malaria. Here, we demonstrate that P. vivax-infected patients display significant increase in circulating monocytes, which were defined as CD14(+)CD16- (classical), CD14(+)CD16(+) (inflammatory), and CD14loCD16(+) (patrolling) cells. While the classical and inflammatory monocytes were found to be the primary source of pro-inflammatory cytokines, the CD16(+) cells, in particular the CD14(+)CD16(+) monocytes, expressed the highest levels of activation markers, which included chemokine receptors and adhesion molecules. Morphologically, CD14(+) were distinguished from CD14lo monocytes by displaying larger and more active mitochondria. CD14(+)CD16(+) monocytes were more efficient in phagocytizing P. vivax-infected reticulocytes, which induced them to produce high levels of intracellular TNF-alpha and reactive oxygen species. Importantly, antibodies specific for ICAM-1, PECAM-1 or LFA-1 efficiently blocked the phagocytosis of infected reticulocytes by monocytes. Hence, our results provide key information on the mechanism by which CD14(+)CD16(+) cells control parasite burden, supporting the hypothesis that they play a role in resistance to P. vivax infection

A human type 5 adenovirus-based Trypanosoma cruzi therapeutic vaccine re-programs immune response and reverses chronic cardiomyopathy

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a prototypical neglected tropical disease. Specific immunity promotes acute phase survival. Nevertheless, one-third of CD patients develop chronic chagasic cardiomyopathy (CCC) associated with parasite persistence and immunological unbalance. Currently, the therapeutic management of patients only mitigates CCC symptoms. Therefore, a vaccine arises as an alternative to stimulate protective immunity and thereby prevent, delay progression and even reverse CCC. We examined this hypothesis by vaccinating mice with replication-defective human Type 5 recombinant adenoviruses (rAd) carrying sequences of amastigote surface protein-2 (rAdASP2) and trans-sialidase (rAdTS) T. cruzi antigens. For prophylactic vaccination, naive C57BL/6 mice were immunized with rAdASP2+rAdTS (rAdVax) using a homologous prime/boost protocol before challenge with the Colombian strain. For therapeutic vaccination, rAdVax administration was initiated at 120 days post-infection (dpi), when mice were afflicted by CCC. Mice were analyzed for electrical abnormalities, immune response and cardiac parasitism and tissue damage. Prophylactic immunization with rAdVax induced antibodies and H-2Kb-restricted cytotoxic and interferon (IFN)gamma-producing CD8+ T-cells, reduced acute heart parasitism and electrical abnormalities in the chronic phase. Therapeutic vaccination increased survival and reduced electrical abnormalities after the prime (analysis at 160 dpi) and the boost (analysis at 180 and 230 dpi). Post-therapy mice exhibited less heart injury and electrical abnormalities compared with pre-therapy mice. rAdVax therapeutic vaccination preserved specific IFNgamma-mediated immunity but reduced the response to polyclonal stimuli (anti-CD3 plus anti-CD28), CD107a+ CD8+ T-cell frequency and plasma nitric oxide (NO) levels. Moreover, therapeutic rAdVax reshaped immunity in the heart tissue as reduced the number of perforin+ cells, preserved the number of IFNgamma+ cells, increased the expression of IFNgamma mRNA but reduced inducible NO synthase mRNA. Vaccine-based immunostimulation with rAd might offer a rational alternative for re-programming the immune response to preserve and, moreover, recover tissue injury in Chagas\u27 heart disease

Schistosoma mansoni Stomatin Like Protein-2 Is Located in the Tegument and Induces Partial Protection against Challenge Infection

Schistosomiasis is a parasitic disease causing serious chronic morbidity in tropical countries. Together with the publication of the transcriptome database, a series of new vaccine candidates were proposed based on their functional classification. However, the prediction of vaccine candidates from sequence information or even by proteomics or microarrays data is somewhat speculative and there remains the considerable task of functional analysis of each new gene/protein. In this study, we present the characterization of one of these molecules, a stomatin like protein 2 (SmStoLP-2). Sequence analysis predicts signals that could contribute to protein membrane association and mitochondrial targeting, which was confirmed by differential extractions of schistosome tegument membranes and mitochondria. Additionally, confocal microscope analysis showed SmStoLP-2 present in the tegument of 7-day-old schistosomula and adult worms. Studies in patients living in endemic areas for schistosomiasis revealed high levels of IgG1, IgG2, IgG3 and IgA anti-SmStoLP-2 antibodies in individuals resistant to reinfection. Recombinant SmStoLP-2 protein, when used as vaccine, induced significant levels of protection in mice. This reduction in worm burden was associated with a typical Th1-type immune response. These results indicate that SmStoLP-2 could be useful in association with other antigens for the composition of a vaccine against schistosomiasis

Adolescent health in rural Ghana: A cross-sectional study on the co-occurrence of infectious diseases, malnutrition and cardio-metabolic risk factors.

In sub-Saharan Africa, infectious diseases and malnutrition constitute the main health problems in children, while adolescents and adults are increasingly facing cardio-metabolic conditions. Among adolescents as the largest population group in this region, we investigated the co-occurrence of infectious diseases, malnutrition and cardio-metabolic risk factors (CRFs), and evaluated demographic, socio-economic and medical risk factors for these entities. In a cross-sectional study among 188 adolescents in rural Ghana, malarial infection, common infectious diseases and Body Mass Index were assessed. We measured ferritin, C-reactive protein, retinol, fasting glucose and blood pressure. Socio-demographic data were documented. We analyzed the proportions (95% confidence interval, CI) and the co-occurrence of infectious diseases (malaria, other common diseases), malnutrition (underweight, stunting, iron deficiency, vitamin A deficiency [VAD]), and CRFs (overweight, obesity, impaired fasting glucose, hypertension). In logistic regression, odds ratios (OR) and 95% CIs were calculated for the associations with socio-demographic factors. In this Ghanaian population (age range, 14.4-15.5 years; males, 50%), the proportions were for infectious diseases 45% (95% CI: 38-52%), for malnutrition 50% (43-57%) and for CRFs 16% (11-21%). Infectious diseases and malnutrition frequently co-existed (28%; 21-34%). Specifically, VAD increased the odds of non-malarial infectious diseases 3-fold (95% CI: 1.03, 10.19). Overlap of CRFs with infectious diseases (6%; 2-9%) or with malnutrition (7%; 3-11%) was also present. Male gender and low socio-economic status increased the odds of infectious diseases and malnutrition, respectively. Malarial infection, chronic malnutrition and VAD remain the predominant health problems among these Ghanaian adolescents. Investigating the relationships with evolving CRFs is warranted

Importance of TLR2 on Hepatic Immune and Non-Immune Cells to Attenuate the Strong Inflammatory Liver Response During Trypanosoma cruzi Acute Infection

Trypanosoma cruzi, an obligate intracellular protozoan, is the etiological agent of Chagas Disease that represents an important public health burden in Latin America. The infection with this parasite can lead to severe complications in cardiac, liver and gastrointestinal tissue depending on the strain of parasite and host genetics. Recently, we reported a fatal liver injury in T. cruzi infected B6 mice. However, the local immune response against this parasite is poorly understood. This work highlights some of the molecular and cellular mechanisms involved in liver pathology during the acute phase of infection. Using two mouse strains with different genetic backgrounds and responses to infection, B6 and BALB/c, we found that infected B6 mice develop a strong pro-inflammatory environment associated with high TLR9 expression. Conversely, infected BALB/c mice showed a more balanced inflammatory response in liver. Moreover, higher TLR2 and TLR4 expression were found only in hepatocytes from BALB/c. These data emphasize the importance of an adequate integration of signalling between immune and non-immune cells to define the outcome of infection. In addition, the pre-treatment with TLR2-agonist reverts the strong pro-inflammatory environment in T. cruzi infected B6 mice. These results could be useful in the understanding and design of novel immune strategies in controlling liver pathologies