O impacto da pandemia da covid-19 na microbiota intestinal do lactente / The impact of the covid-19 pandemic on the infant gut microbiota / El impacto de la pandemia de covid-19 en la microbiota intestinal del lactante

A COVID-19 resultou em milhares de óbitos e até o presente momento assola diversos pacientes com as suas implicações. Uma das consequências da doença foi o isolamento social, realizado por quase todos os países, o que configurou a alteração de diversos padrões de convivência e principalmente de exposição a outros agentes não patogênicos e patogênicos essenciais para o desenvolvimento da microbiota. Com isso, o seguinte projeto tem como objetivo a descrição dos impactos da pandemia da COVID-19 na microbiota intestinal de lactentes do período pandêmico e as consequências geradas no sistema imunológico imaturo, prejudicando seu desenvolvimento e maturação. A metodologia consiste na análise e seleção de artigos científicos publicados nos últimos 10 anos com auxílio de Descritores em Ciências da Saúde (DeCS) específicos nas línguas inglesa e portuguesa para o tema da pesquisa, sendo a combinação dos descritores feita por meio de operadores booleanos. Conclui-se que a composição da microbiota intestinal é iniciada intraútero e influenciada pela via de parto, contato pele a pele após o nascimento e pela presença da amamentação materna. A modificação das práticas durante a pandemia da COVID-19, pode alterar a microbiologia neonatal, assim como impactar na maturação do sistema imunológico do lactente, predispondo futuramente à doenças gastrointestinais, metabólicas e atópicas, como asma.

COVID-19 has resulted in thousands of deaths and until now is affecting many patients with its implications. One of the consequences of the disease was social isolation, carried out by almost all countries, which resulted in changes in different patterns of coexistence and mainly exposure to other non-pathogenic and pathogenic agents essential for the development of the microbiota. Therefore, the following project aims to describe the impacts of the COVID-19 pandemic on the microbiota of infants during the pandemic period and the consequences generated on the immature immune system, damaging its development and maturation and relating microbiology, essentially intestinal, throughout the project. The methodology consists of the analysis and selection of scientific articles published in the last 10 years with the help of specific Health Sciences Descriptors in English and Portuguese for the research topic, with the combination of descriptors made using Boolean operators. It is concluded that the composition of the intestinal microbiota begins in utero and is influenced by the mode of delivery, skin-to- skin contact after birth, and the presence of maternal breastfeeding. Modifying practices during the COVID-19 pandemic may alter neonatal microbiology and impact the maturation of the infant's immune system, potentially predisposing them to future gastrointestinal, metabolic, and atopic diseases such as asthma.

El COVID-19 ha provocado miles de muertes y todavía afecta a muchos pacientes con sus implicaciones. Una de las consecuencias de la enfermedad fue el aislamiento social, llevado a cabo por casi todos los países, que resultó en cambios en diferentes patrones de convivencia y principalmente exposición a otros agentes patógenos y no patógenos esenciales para el desarrollo de la microbiota. Com eso, el siguiente proyecto tiene como objetivo describir los impactos de la pandemia de COVID-19 en la microbiota de los lactantes durante el periodo pandémico y las consecuencias generadas sobre el sistema inmunológico inmaduro, perjudicando su desarrollo y maduración y relacionando la microbiología, fundamentalmente intestinal, a lo largo del proyecto. La metodología consiste en el análisis y selección de artículos científicos publicados en los últimos 10 años con la ayuda de Descriptores en Ciencias de la Salud específicos en inglés y portugués para el tema de investigación, con la combinación de descriptores realizada mediante operadores booleanos. Se concluye que la composición de la microbiota intestinal comienza intraútero y está influenciada por la vía de parto, el contacto piel a piel después del nacimiento y la presencia de la lactancia materna. La modificación de las prácticas durante la pandemia de COVID-19 puede alterar la microbiología neonatal y afectar la maduración del sistema inmunológico del lactante, predisponiéndolo potencialmente a enfermedades gastrointestinales, metabólicas y atópicas en el futuro, como la asma.

Cytokine gene polymorphisms in populations from Parana, Southern Brazil.

In this study, were genotyped 22 single nucleotide polymorphisms (SNPs) in 13 genes that encode the pro-inflammatory (IL-1α, IL-1ß, IL-1R, IL-4Rα, IL-12, IFN-γ, TNF-α, and IL-2) and anti-inflammatory (IL-1RA, TGF-ß, IL-4, IL-6 and IL-10) cytokines of 350 individuals by PCR-SSP (polymerase chain reaction - sequence specific primer). A total of 473 individuals were genotyped for IL17A and IL17F genes by PCR-RFLP (restriction fragment length polymorphism). The sample consisted of healthy and unrelated subjects from a mixed population from Parana state, in the South region of Brazil. The frequency analyses and genotype data are available in the Supplementary materials and are accessible at Allele Frequency Net Database (AFND).

Genetic Polymorphisms of IL17 and Chagas Disease in the South and Southeast of Brazil.

The aim of this study was to investigate possible associations between genetic polymorphisms of IL17A G197A (rs2275913) and IL17F T7488C (rs763780) with Chagas Disease (CD) and/or the severity of left ventricular systolic dysfunction (LVSD) in patients with chronic Chagas cardiomyopathy (CCC). The study with 260 patients and 150 controls was conducted in the South and Southeast regions of Brazil. The genotyping was performed by PCR-RFLP. The A allele and A/A genotype of IL17A were significantly increased in patients and their subgroups (patients with CCC; patients with CCC and LVSD; and patients with CCC and severe LVSD) when compared to the control group. The analysis according to the gender showed that the A/A genotype of IL17A was more frequent in female with LVSD and mild to moderate LVSD and also in male patients with LVSD. The frequency of IL17F T/C genotype was higher in male patients with CCC and severe LVSD and in female with mild to moderate LVSD. The results suggest the possible involvement of the polymorphisms of IL17A and IL17F in the susceptibility to chronic Chagas disease and in development and progression of cardiomyopathy.

Gene Association with Leprosy: A Review of Published Data.

Leprosy is a chronic infectious disease caused by an obligate intracellular bacterium known as Mycobacterium leprae. Exposure to the bacillus is necessary, but this alone does not mean an individual will develop clinical symptoms of the disease. In recent years, several genes have been associated with leprosy and the innate immune response pathways converge on the main hypothesis that genes are involved in the susceptibility for the disease in two distinct steps: for leprosy per se and in the development of the different clinical forms. These genes participate in the sensing, main metabolic pathway of immune response activation and, subsequently, on the evolution of the disease into its clinical forms. The aim of this review is to highlight the role of innate immune response in the context of leprosy, stressing their participation in the signaling and targeting processes in response to bacillus infection and on the evolution to the clinical forms of the disease.

Killer Cell Immunoglobulin-like Receptors and Their HLA Ligands are Related with the Immunopathology of Chagas Disease.

The aim of this study was to investigate the influence of killer cell immunoglobulin-like receptor (KIR) genes and their human leucocyte antigen (HLA) ligands in the susceptibility of chronic Chagas disease. This case-control study enrolled 131 serologically-diagnosed Chagas disease patients (59 men and 72 women, mean age of 60.4 ± 9.8 years) treated at the University Hospital of Londrina and the Chagas Disease Laboratory of the State University of Maringa. A control group was formed of 165 healthy individuals - spouses of patients or blood donors from the Regional Blood Bank in Maringa (84 men and 81 women, with a mean age of 59.0 ± 11.4 years). Genotyping of HLA and KIR was performed by PCR-SSOP. KIR2DS2-C1 in the absence of KIR2DL2 (KIR2DS2+/2DL2-/C1+) was more frequent in Chagas patients (P = 0.020; Pc = 0.040; OR = 2.14) and, in particular, those who manifested chronic chagasic cardiopathy-CCC (P = 0.0002; Pc = 0.0004; OR = 6.64; 95% CI = 2.30-18.60) when compared to the control group, and when CCC group was compared to the patients without heart involvement (P = 0.010; Pc = 0.020; OR = 3.97). The combination pair KIR2DS2+/2DL2-/KIR2DL3+/C1+ was also positively associated with chronic chagasic cardiopathy. KIR2DL2 and KIR2DS2 were related to immunopathogenesis in Chagas disease. The combination of KIR2DS2 activating receptor with C1 ligand, in the absence of KIR2DL2, may be related to a risk factor in the chronic Chagas disease and chronic chagasic cardiopathy.

Evidence of HLA-DQB1 Contribution to Susceptibility of Dengue Serotype 3 in Dengue Patients in Southern Brazil.

Dengue infection (DI) transmitted by arthropod vectors is the viral disease with the highest incidence throughout the world, an estimated 300 million cases per year. In addition to environmental factors, genetic factors may also influence the manifestation of the disease; as even in endemic areas, only a small proportion of people develop the most serious form. Immune-response gene polymorphisms may be associated with the development of cases of DI. The aim of this study was to determine allele frequencies in the HLA-A, B, C, DRB1, DQA1, and DQB1 loci in a Southern Brazil population with dengue virus serotype 3, confirmed by the ELISA serological method, and a control group. The identification of the HLA alleles was carried out using the SSO genotyping PCR program (One Lambda), based on Luminex technology. In conclusion, this study suggests that DQB1∗06:11 allele could act as susceptible factors to dengue virus serotype 3, while HLA-DRB1∗11 and DQA1∗05:01 could act as resistance factors.

Frequências fenotípicas dos grupos sanguíneos Kell, Duffy e Kidd em doadores de sangue do Hemonúcleo de Apucarana, sul do Brasil / Phenotypic frequencies of the Kell, Duffy and Kidd blood groups in blood donors from Apucarana Blood Center, southern Brazil

Objetivo: O objetivo desse estudo foi determinar as frequências fenotípicas dos grupos sanguíneos Kell, Duffy e Kidd em uma população paranaense. Métodos: Foram avaliadas as frequências desses grupos sanguíneos em 1.759 doadores de sangue fenotipados no Hemonúcleo de Apucarana, sul do Brasil. A fenotipagem foi realizada pela aglutinação em gel-teste e os dados foram obtidos pelo sistema Report Smith-Access, da rede Hemepar. Resultados: Essa população apresentou uma distribuição das frequências fenotípicas de Kell, Kidd e Duffy compatível com populações caucasianas. Para averiguar esse fato, nós comparamos nossos dados com aqueles de uma população da mesma região do Paraná, composta principalmente por caucasianos. O fenótipo Fy(a+b-) foi mais frequente na população de Apucarana do que na população de Maringá (22,68 vs. 12,50%, P<0,001), enquanto que o fenótipo Fy (a+b+) foi menos frequente (37,24 vs. 48,0%, P<0,001). Conclusão: As frequências fenotípicas de três grupos sanguíneos foram determinadas e poderão ser utilizadas pelos Serviços de Hematologia e Hemoterapia na busca de unidades de concentrados de hemácias com fenótipos desejados e no cálculo da incidência de doadores compatíveis, em casos de receptores com múltiplos aloanticorpos, além de poderem ser utilizadas para comparações antropológicas e em estudos de associação com doenças.

Genetic susceptibility to Chagas disease: an overview about the infection and about the association between disease and the immune response genes.

Chagas disease, which is caused by the flagellate parasite Trypanosoma cruzi, affects 8-10 million people in Latin America. The disease is endemic and is characterised by acute and chronic phases that develop in the indeterminate, cardiac, and/or gastrointestinal forms. The immune response during human T. cruzi infection is not completely understood, despite its role in driving the development of distinct clinical manifestations of chronic infection. Polymorphisms in genes involved in the innate and specific immune response are being widely studied in order to clarify their possible role in the occurrence or severity of disease. Here we review the role of classic and nonclassic MHC, KIR, and cytokine host genetic factors on the infection by T. cruzi and the clinical course of Chagas disease.

Role of HLA, KIR, MICA, and cytokines genes in leprosy.

Many genes including HLA, KIR, and MICA genes, as well as polymorphisms in cytokines have been investigated for their role in infectious disease. HLA alleles may influence not only susceptibility or resistance to leprosy, but also the course of the disease. Some combinations of HLA and KIR may result in negative as well as positive interactions between NK cells and infected host cells with M. leprae, resulting in activation or inhibition of NK cells and, consequently, in death of bacillus. In addition, studies have demonstrated the influence of MICA genes in the pathogenesis of leprosy. Specifically, they may play a role in the interaction between NK cells and infected cells. Finally, pro- and anti-inflammatory cytokines have been influencing the clinical course of leprosy. Data from a wide variety of sources support the existence of genetic factors influencing the leprosy pathogenesis. These sources include twin studies, segregation analyses, family-based linkage and association studies, candidate gene association studies, and, most recently, genome-wide association studies (GWAS). The purpose of this brief review was to highlight the importance of some immune response genes and their correlation with the clinical forms of leprosy, as well as their implications for disease resistance and susceptibility.

Class-I human leukocyte alleles in leprosy patients from Southern Brazil.

INTRODUCTION: The present study was designed to investigate a possible role of HLA (histocompatibility leucocyte antigen) class-I alleles (HLA-A, -B, and -C) in leprosy patients from Southern Brazil. METHODS: Two hundred and twenty-five patients with leprosy and 450 individuals for the control group were involved in this research. HLA genotyping was performed through PCR-SSO protocols (One Lambda, USA); the frequency of these alleles was calculated in each group by direct counting, and the frequencies were then compared. RESULTS: There was an association between HLA-A*11 (6.9% vs 4.1%, p=0.0345, OR=1.72, 95% CI=1.05-2.81), HLA-B*38 (2.7% vs. 1.1%, p=0.0402, OR=2.44, 95% CI=1.05-5.69), HLA-C*12 (9.4% vs. 5.4%, p=0.01, OR=1.82, 95% CI=1.17-2.82), and HLA-C*16 (3.1% vs. 6.5%, p=0.0124, OR=0.47, 95% CI=0.26-0.85) and leprosy per se. In addition, HLA-B*35, HLA-C*04, and HLA-C*07 frequencies were different between lepromatous (LL) and tuberculoid (TT) patients. However, after adjusting for the number of alleles compared, Pc values became nonsignificant. CONCLUSIONS: Although our results do not support the previous findings that HLA class-I alleles play a role in leprosy pathogenesis, we suggest new studies because of the importance of the association between the HLA and KIR in the innate immune response to leprosy.

Class-I human leukocyte alleles in leprosy patients from Southern Brazil / Alelos leucocitários humanos em pacientes com hanseníase do sul do Brasil

INTRODUCTION: The present study was designed to investigate a possible role of HLA (histocompatibility leucocyte antigen) class-I alleles (HLA-A, -B, and -C) in leprosy patients from Southern Brazil. METHODS: Two hundred and twenty-five patients with leprosy and 450 individuals for the control group were involved in this research. HLA genotyping was performed through PCR-SSO protocols (One Lambda, USA); the frequency of these alleles was calculated in each group by direct counting, and the frequencies were then compared. RESULTS: There was an association between HLA-A*11 (6.9 percent vs 4.1 percent, p=0.0345, OR=1.72, 95 percent CI=1.05-2.81), HLA-B*38 (2.7 percent vs. 1.1 percent, p=0.0402, OR=2.44, 95 percent CI=1.05-5.69), HLA-C*12 (9.4 percent vs. 5.4 percent, p=0.01, OR=1.82, 95 percent CI=1.17-2.82), and HLA-C*16 (3.1 percent vs. 6.5 percent, p=0.0124, OR=0.47, 95 percent CI=0.26-0.85) and leprosy per se. In addition, HLA-B*35, HLA-C*04, and HLA-C*07 frequencies were different between lepromatous (LL) and tuberculoid (TT) patients. However, after adjusting for the number of alleles compared, Pc values became nonsignificant. CONCLUSIONS: Although our results do not support the previous findings that HLA class-I alleles play a role in leprosy pathogenesis, we suggest new studies because of the importance of the association between the HLA and KIR in the innate immune response to leprosy.

INTRODUÇÃO: O presente estudo foi desenhado para investigar um possível papel para os alelos HLA (histocompatibility leucocyte antigen) de classe I (HLA-A, -B, and -C) em pacientes com hanseníase do sul do Brasil. MÉTODOS: Duzentos e vinte e cinco pacientes com hanseníase e 450 indivíduos para o grupo-controle foram envolvidos nesse estudo. O genótipo HLA foi determinado por protocolos PCR-SSO (One Lambda, USA) e, a frequência desses alelos foi calculada em cada grupo por contagem direta e, após, comparadas. RESULTADOS: Houve associação entre HLA-A*11 (6,9 por cento vs 4,1 por cento; p = 0,0345; OR = 1,72; CI = 1,05 - 2,81), HLA-B*38 (2,7 por cento vs 1,1; p = 0,0402; OR = 2,44; CI 95 por cento = 1,05-5,69), HLA-C*12 (9,4 por cento vs 5,4 por cento; p = 0,01; OR = 1,82; CI 95 por cento = 1,17-2,82) e HLA-C*16 (3,1 vs 6,5 por cento; p = 0,0124; OR = 0,47; CI 95 por cento = 0,26-0,85) e hanseníase per se. Além disso, as frequências de HLA-B*35, HLA-C*04 e HLA-C*07 foram diferentes entre os pacientes com as formas lepromatosa (LL) e tuberculoide (TT). Contudo, após o ajuste para o número de alelos comparados, os valores de p se tornaram não significativos. CONCLUSÕES: Embora nossos resultados não sustentem as conclusões anteriores de que os alelos HLA de classe I desempenham um papel na associação com a patogênese da hanseníase, sugerimos novos estudos devido à importância da associação entre HLA e KIR na resposta imune inata à hanseníase.