ABSTRACT This narrative review summarizes the main aspects underlying the new coronavirus SARS-CoV-2, its epidemiology, pathophysiology, pointing to differences of SARS-CoV-2 main receptors ACE2, in terms of expression and the amount of soluble ACE2 in the circulation of children, men and women, and also in those with risk factors such as the smokers and pregnant women or presenting with comorbidities (diabetes, obesity, hypertension and other cardiovascular diseases, renal and CNS pre-existing diseases). Clinical manifestations in adults and children were also described, emphasizing the particularities already seen in children, regarding signs, symptoms, viral excretion time and the involvement of all organs and systems. The COVID-19 in the pediatric population was divided into two sections: one dedicated to previously healthy children and adolescents with COVID-19, and the other to those who live with comorbidities and acquired COVID-19. A few paragraphs were reserved to the recently described severe multisystemic inflammatory syndrome associated with COVID-19 (MIS-C) that shares certain characteristics with Kawasaki disease. Some studies on the infection in pregnant and postpartum women, as well as neonates were shown. This review has also covered the laboratory diagnosis of COVID-19, passing through the imaging diagnosis made by the chest tomography revealing ground glass patching opacities, and results of non-specific exams such as the total blood with lymphopenia, the coagulation tests with increased prothrombin times, as well as marked increments of the D-dimer, troponin and proinflammatory cytokines. In the section devoted to the specific laboratory diagnosis of COVID-19, the most used RT-PCR protocols were described and some studies on the serological diagnosis with IgA, IgM and IgG detection were detailed, including the use of rapid immunochromatographic assays and discussing the ideal period after the onset of symptoms to perform each type of test. In the end, the management of pediatric patients with COVID-19 based mainly on supportive measures has been briefly commented.

Objective: Cocaine use disorders (CUDs) represent a major public health problem in many countries. To better understand the interaction between the environmental modulations and phenotype, the aim of the present study was to investigate the DNA methylation pattern of CUD patients, who had concomitant cocaine and crack dependence, and healthy controls. Methods: We studied DNA methylation profiles in the peripheral blood of 23 CUD patients and 24 healthy control subjects using the Illumina Infinium HumanMethylation450 BeadChip arrays. Results: Comparison between CUD patients and controls revealed 186 differentially methylated positions (DMPs; adjusted p-value [adjP] < 10-5) related to 152 genes, with a subset of CpGs confirmed by pyrosequencing. DNA methylation patterns discriminated CUD patients and control groups. A gene network approach showed that the EHMT1, EHMT2, MAPK1, MAPK3, MAP2K1, and HDAC5 genes, which are involved in transcription and chromatin regulation cellular signaling pathways, were also associated with cocaine dependence. Conclusion: The investigation of DNA methylation patterns may contribute to a better understanding of the biological mechanisms involved in CUD.

Objetivo:Avaliar a acurácia de um teste de liberação de interferon-gama (QuantiFERON-TB Gold in Tube) para diagnosticar a infecção pelo Mycobacterium tuberculosisem uma população pediátrica.Métodos: Avaliaram-se 195 crianças previamente vacinadas com BCG, sendo 184 sadias, sem evidência clínica ou epidemiológica de infecção pelo M. tuberculosis, e 11 com infecção, definida de acordo com critérios clínicos, radiológicos e laboratoriais. Obteve-se uma amostra de sangue de cada criança, processada conforme as instruções do fabricante. Avaliou-se o desempenho do ensaio por meio de uma curva de características operacionais (curva Receiver Operating Characteristic - ROC).Resultados: No grupo de 184 crianças não infectadas, 130 (70,6%) eram menores de quatro anos (média de 35 meses). Nesse grupo, 177 crianças (96,2%) tiveram resultado negativo do teste, seis (3,2%) apresentaram resultado indeterminado e uma (0,5%) teve resultado positivo. No grupo de 11 crianças com infecção, a idade média era de 58,5 meses e duas (18%) apresentaram resultado negativo. A curva ROC determinou uma área sob a curva de 0,88 (IC95% 0,82-0,92; p<0,001), evidenciando um valor preditivo positivo de 81,8% para o teste (IC95% 46,3-97,4). A sensibilidade do teste foi de 81,8% (IC95% 48,2-97,2) e a especificidade, de 98,8% (IC95% 96-99,8).Conclusões: No presente estudo, o desempenho do QuantiFERON-TB Gold in Tubepara o diagnóstico da infecção pelo M. tuberculosis foi adequado quando utilizado em uma população pediátrica jovem.

Objective:To evaluate the accuracy of an interferongamma release assay (QuantiFERON-TB Gold in Tube) for diagnosing Mycobacterium tuberculosis infection in a young pediatric population.Methods: 195 children previously vaccinated with BCG were evaluated, being 184 healthy individuals with no clinical or epidemiological evidence of mycobacterial infection, and 11 with Mycobacterium tuberculosis infection, according to clinical, radiological, and laboratory parameters. A blood sample was obtained from each child and processed according to the manufacturer's instructions. The assay performance was evaluated by a Receiver Operating Characteristic (ROC) curve.Results: In the group of 184 non-infected children, 130 (70.6%) were under the age of four years (mean age of 35 months). In this group, 177 children (96.2%) had negative test results, six (3.2%) had indeterminate results, and one (0.5%) had a positive result. In the group of 11 infected children, the mean age was 58.5 months, and two of them (18%) had negative results. The ROC curve had an area under the curve of 0.88 (95%CI 0.82-0.92; p<0.001), disclosing a predictive positive value of 81.8% for the test (95%CI 46.3-97.4). The assay sensitivity was 81.8% (95%CI 48.2-97.2) and the specificity was 98.8% (95%CI 96-99.8).Conclusions: In the present study, the QuantiFERON-TB Gold in Tube performance for diagnosing M. tuberculosis infection was appropriate in a young pediatric population.

Objetivo: Evaluar la precisión de una prueba de liberación de interferón gama (QuantiFERON-TB Gold in Tube) para el diagnóstico de la infección por el Mycobacterium tuberculosis en una población pediátrica.Métodos: Se evaluaron 195 niños previamente vacunados con BCG, siendo 184 niños sanos sin evidencia clínica o epidemiológica de infección por el M. tuberculosis, y 11 niños con infección, definida conforme a criterios clínicos, radiológicos y laboratoriales. Se obtuvo una muestra de sangre de cada niño, que fue procesada conforme a las instrucciones del fabricante. El desempeño del ensayo fue evaluado mediante una curva de características operacionales (curva ROC).Resultados: En el grupo de 184 niños no infectados, 130 (70,6%) tenían menos que cuatro años (promedio de 35 meses). En este grupo control, 177 niños (96,2%) tuvieron un resultado negativo de la prueba, mientras que 6 niños (3,2%) presentaron resultado indeterminado, y un niño (0,5%) tuvo un resultado positivo. En el grupo de 11 niños con infección, el promedio de edad era de 58,5 meses, y 2 niños (18%) presentaron resultado negativo. La curva ROC determinó un área bajo la curva de 0,876 (95%IC 0,82-0,92; p<0,001), evidenciando un valor predictivo positivo del 81,8% para la prueba (95%IC 46,3-97,4). La sensibilidad de la prueba fue de 81,8% (95%IC, 48,2-97,2) y la especificidad de 98,8% (95%IC, 96-99,8).Conclusión: En el presente estudio, el desempeño del QuantiFERON-TB Gold in Tube para el diagnóstico de la infección por el M. tuberculosis fue adecuado cuando utilizado en una población pediátrica joven.

Os autores discutem, a partir do conceito evolutivo, como a resposta de estresse, nas suas possibilidades de fuga e luta e de imobilidade tônica, pode levar a uma nova compreensão etiológica do transtorno de estresse pós-traumático. Através da análise dos agrupamentos de sintomas desse diagnóstico - revivência, evitação e hiperexcitação -, procuram correlacionar os achados neurobiológicos e evolutivos. As descobertas atuais sobre a genética do transtorno de estresse pós-traumático são resumidas e colocadas nessa perspectiva evolutiva, dentro de conceitos que possibilitam o entendimento da interação gene/ambiente, como a epigenética. Propõem que a pesquisa dos fatores de risco do transtorno de estresse pós-traumático deva ser investigada do ponto de vista fatorial, onde a somatória destes aumenta o risco de desenvolvimento do quadro, não sendo possível a procura da causa do transtorno de forma única. A pesquisa de genes candidatos no transtorno de estresse pós-traumático deve levar em consideração todos os sistemas associados aos processos de respostas ao estresse, sistemas dos eixos hipotálamo-hipofisário-adrenal e simpático, mecanismos de aprendizado, formação de memórias declarativas, de extinção e esquecimento, da neurogênese e da apoptose, que envolvem vários sistemas de neurotransmissores, neuropeptídeos e neuro-hormônios.

The authors discuss, from the evolutionary concept, how flight and fight responses and tonic immobility can lead to a new understanding of posttraumatic stress disorder. Through the analysis of symptom clusters (revivals, avoidance and hyperexcitation), neurobiological and evolutionary findings are correlated. The current discoveries on posttraumatic stress disorder genetics are summarized and analyzed in this evolutionary perspective, using concepts to understand the gene-environment interaction, such as epigenetic. The proposal is that the research of susceptibility factors in posttraumatic stress disorder must be investigated from the factorial point of view, where their interactions increase the risk of developing the disorder, preventing a unique search of the cause of this disorder. The research of candidate genes in posttraumatic stress disorder must take into consideration all the systems associated with processes of stress response, such as the hypothalamus-pituitary-adrenal and sympathetic axes, mechanisms of learning, formation and extinguishing of declarative memories, neurogenesis and apoptosis, which involve many systems of neurotransmitters, neuropeptides and neurohormones.

Infection by unusual microorganisms can be one of the clinical manifestations of primary immunodeficiency (PID). We report on a four-month-old child with pneumonia caused by the fungus Acremonium kiliense as the first clinical manifestation of chronic granulomatous disease. We emphasize the importance of an active search for unusual organisms in immunodeficient patients, and a precise diagnosis and early institution of specific treatment against such microorganisms for the reduction of the morbidity and mortality of these patients.

A poliomielite associada à vacina oral é definida como a forma paralítica da poliomielite anterior aguda decorrente da cepa vacinal. Uma vez que o comportamento da cepa vacinal é semelhante ao do vírus selvagem, epidemiologicamente podemos distinguir dois tipos de poliomielite associada à vacina, os casos em que o paciente foi vacinado e os casos em que o paciente teve contato com pessoas que receberam a vacina. Apresentamos o caso de um lactente não vacinado, que apresentou quadro de poliomielite anterior aguda associada à vacina oral, cujo irmão havia recebido a vacina Sabin 20 dias antes do início do quadro clínico. Na cultura de fezes do paciente foi isolado o poliovírus tipo 3, cepa vacinal, que apresentava mutação do nucleotídeo 472 (C<FONT FACE="Symbol">®</font>U) na região 5' não codificadora, a qual está significativamente relacionada com a maior virulência da cepa.

Poliomyelitis associated with live strain vaccine is defined as the paralytic form of the acute anterior poliomyelitis related to the vaccine strain. Since these strains behave similarly to the wild-type virus, we can differentiate, epidemiologically, two types of vaccine-associated poliomyelitis: cases in which the patient was vaccinated and cases in which the patient had had contact with vaccinated individuals. We herein present the case of an unvaccinated child, with a clinical picture of an acute anterior poliomyelitis associated with the live strain vaccine, whose brother received the Sabin vaccine 20 days before the onset of the symptoms. Vaccine strain of the type 3 poliovirus was isolated in fecal culture and a presented mutation in nucleotide 472 (C<FONT FACE="Symbol">®</font>U) in the 5' non-coding region, which is strongly related to the higher strain virulence.

Utilizando a técnica de imunofluorescência indireta, foram demonstradas imunoglobulinas G e M, no soro humano, contra o Cryptosporidium, coccídeo implicado recentemente como agente de doença intestinal humana, principalmente em pacientes imunocomprometidos. Foi obtida positividade de 62% para imunoglobulinas G e M nos soros das crianças immunocompetentes com oocistos nas fezes e, respectivamente, 20% e 40%, nos soros das crianças sem oocistos. Nos pacientes adultos , com o vírus da imunodeficiência humana e excreção fecal do parasita, foram encontrados índices de positividade de 57% da IgG mas apenas 2% para IgM e aqueles com excreção não determinada apresentaram 23% da IgG. Crianças com o vírus da imunodeficiência humana, apresentaram apenas 14% da IgG e foram negativas quanto à IgM. Os resultados apontaram para a utilidade do teste, associado a outras técnicas parasitológicas, em estudos populacionais retrospectivos ou diagnósticos na infecção aguda e, ainda, que a resposta imune humoral a este protozoário necessita de maiores investigações, nos pacientes imunocomprometidos, principalmente crianças.

Cryptosporidium sp., a coccidian parasite usually found in the faeces of cattle, has been recently implicated as an agent of human intestinal disease, mainly in immunocompromised patients. In the study realized, by an indirect immunofluorescence technique, specific immunoglobulins (IgG and IgM) have been demonstrated in human serum against Cryptosporidium oocysts. Purified oocysts were used as antigens in the indirect immunofluorecence assay. After analyzing this test in sera from selected groups of patients, the frequency of both specific IgG and IgM of immunocompetent children who were excreting oocysts in their faeces was 62% and in children with negative excretion of oocysts was 20% and 40%, respectively. In adults infected with the human immunodeficiency virus (HIV) and who were excreting Cryptosporidium in their stools, the frequency was 57% for IgG but only 2% for IgM. Twenty three percent of immunocompromised adults with not determined excretion of oocysts in their stools had anti-Cryptosporidium IgG in their sera. Children infected with human immunodeficiency virus had no IgM and only 14% had IgG detectable in their sera. The indirect immunoflorescence assay, when used with other parasitological techniques appears to be useful for retrospective population studies and for diagnosis of acute infection. The humoral immune response of HIV positive patients to this protozoan agent needs clarification.

Utilizando a técnica de imunofluorescência indireta, foram demonstradas imunoglobulinas G e M, no soro humano, contra o Cryptosporidium, coccídeo implicado recentemente como agente de doença intestinal humana, principalmente em pacientes imunocomprometidos. Foi obtida positividade de 62% para imunoglobulinas G e M nos soros das crianças immunocompetentes com oocistos nas fezes e, respectivamente, 20% e 40%, nos soros das crianças sem oocistos. Nos pacientes adultos , com o vírus da imunodeficiência humana e excreção fecal do parasita, foram encontrados índices de positividade de 57% da IgG mas apenas 2% para IgM e aqueles com excreção não determinada apresentaram 23% da IgG. Crianças com o vírus da imunodeficiência humana, apresentaram apenas 14% da IgG e foram negativas quanto à IgM. Os resultados apontaram para a utilidade do teste, associado a outras técnicas parasitológicas, em estudos populacionais retrospectivos ou diagnósticos na infecção aguda e, ainda, que a resposta imune humoral a este protozoário necessita de maiores investigações, nos pacientes imunocomprometidos, principalmente crianças.

Cryptosporidium sp., a coccidian parasite usually found in the faeces of cattle, has been recently implicated as an agent of human intestinal disease, mainly in immunocompromised patients. In the study realized, by an indirect immunofluorescence technique, specific immunoglobulins (IgG and IgM) have been demonstrated in human serum against Cryptosporidium oocysts. Purified oocysts were used as antigens in the indirect immunofluorecence assay. After analyzing this test in sera from selected groups of patients, the frequency of both specific IgG and IgM of immunocompetent children who were excreting oocysts in their faeces was 62% and in children with negative excretion of oocysts was 20% and 40%, respectively. In adults infected with the human immunodeficiency virus (HIV) and who were excreting Cryptosporidium in their stools, the frequency was 57% for IgG but only 2% for IgM. Twenty three percent of immunocompromised adults with not determined excretion of oocysts in their stools had anti-Cryptosporidium IgG in their sera. Children infected with human immunodeficiency virus had no IgM and only 14% had IgG detectable in their sera. The indirect immunoflorescence assay, when used with other parasitological techniques appears to be useful for retrospective population studies and for diagnosis of acute infection. The humoral immune response of HIV positive patients to this protozoan agent needs clarification.