Host Determinants of Reinfection with Schistosomes in Humans: A Systematic Review and Meta-analysis

Background: Schistosomiasis is still a major public health burden in the tropics and subtropics. Although there is an effective chemotherapy (Praziquantel) for this disease, reinfection occurs rapidly after mass drug administration (MDA). Because the entire population do not get reinfected at the same rate, it is possible that host factors may play a dominant role in determining resistance or susceptibility to reinfection with schistosomes. Here, we systematically reviewed and meta-analyzed studies that reported associations between reinfection with the principal human-infecting species (S. mansoni, S. japonicum and S. haematobium) and host socio-demographic, epidemiological, immunological and genetic factors.Methodology/Principal Findings: PubMed, Scopus, Google Scholar, Cochrane Review Library and African Journals Online public databases were searched in October 2013 to retrieve studies assessing association of host factors with reinfection with schistosomes. Meta-analysis was performed to generate pooled odds ratios and standardized mean differences as overall effect estimates for dichotomous and continuous variables, respectively. Quality assessment of included studies, heterogeneity between studies and publication bias were also assessed. Out of the initial 2739 records, 109 studies were included in the analyses, of which only 32 studies with 37 data sets were eligible for quantitative data synthesis. Among several host factors identified, strong positive association was found with age and pre-treatment intensity, and only slightly for gender. These factors are major determinants of exposure and disease transmission. Significant positive association was found with anti-SWA IgG4 level, and a negative overall effect for association with IgE levels. This reconfirmed the concept that IgE/IgG4 balance is a major determinant of protective immunity against schistosomiasis. Other identified determinants were reported by a small number of studies to enable interpretation.Conclusions: Our data contribute to the understanding of host-parasite interaction as it affects reinfection, and is a potential tool to guide planning and tailoring of community interventions to target high-risk groups

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Pressão do líqüido cefalorraqueano: I conceito de índice de Ayala normal

O quociente raqueano de Ayala é um índice resultante do produto do volume de liquor retirado pela relação entre as pressões inicial e final. Em geral, nos manuais, considera-se normal o intervalo entre 5 e 7, sem se dar, entretanto, a devida importância ao volume retirado. Sendo o QR função dêsse volume, é evidente que o conceito de normalidade do índice de Ayala dependerá da quantidade de LCR extraído. Com base em 22 casos normais, foram calculados os limites de normalidade para cada volume retirado inteiro entre 2 e 15 ml. Nesse material foram verificados serem normais os índices entre 4 e 7 para o volume retirado de 10 ml. A partir dos dados de pressão obtidos com a retirada de volumes diversos, é possível o cálculo dos QR equivalentes e correspondentes à retirada de um volume-padrão, por meio de uma fórmula que foi deduzida

Convulsões na infância: aspectos eletrencefalográficos

The electroencephalographic records of 700 children, up to 6 years old, with a history of only convulsions without other clinical manifestations are analysed. The EEG findings in patients with febrileand non febrile convulsions,in waking and sleeping state and according to their age (0-2 and 3-6 years old), were compared statistically. From this study three main conclusions can be drawn: 1) there is a significant percentage of cerebral abnormalities among the children with isolated convulsions; 2) there is a significantly higher incidence of focal abnormalities in patients with non febrile convulsionsthan in those with febrile convulsions,suggesting that convulsions in each group may correspond to different cerebral conditions; 3) in the electroencephalographic study of these children with convulsions one must take into account the state of the patient during the recording (awake or asleep). It would be an error to consider results as they were of a homogeneous group.São analisados os resultados eletrencefalográficos de 700 crianças, com idade de 0 a 6 anos, que apresentaram convulsões isoladas, sem história ou manifestações clínicas de qualquer outra moléstia. Os resultados nos subgrupos de pacientes com convulsões febrise não febrissão analisados separadamente sob o ponto de vista estatístico, assim como nos subgrupos de 0-2 e 3-6 anos de idade. Análise similar foi feita nos subgrupos de pacientes examinados somente durante o sono ou em sono e em vigília, com finalidade de testar o fator técnico do exame. Deste estudo podem ser tiradas três conclusões principais: 1) nas crianças com convulsões isoladas aparecem sinais eletrencefalográficos que permitem diagnóstico da existência de lesão cerebral em uma incidência estatisticamente significante; 2) a incidência de lesões cerebrais focais nos casos de convulsões não febrisé também significativamente maior que nos casos de convulsões febris, oque sugere que as convulsões nesses grupos de pacientes dependem de condições cerebrais diferentes; 3) no estudo eletrencefalográfico das crianças com convulsões, deve ser tomado em consi- deração se o exame foi feito somente durante o sono ou se também em vigília, pois tais resultados não podem ser considerados em conjunto, sob pena de se incorrer em erro grosseiro.Escola Paulista de Medicina Section of Epilepsy Department of Neurology and Neurosurgery (Prof. P. W. Longo)UNIFESP, EPM, Section of Epilepsy Department of Neurology and Neurosurgery (Prof. P. W. Longo)SciEL

Cerebrospinal fluid sodium and potassium in normal and abnormal conditions

The authors have determined sodium and potassium contents of normal cerebrospinal fluid and the range of concentrations was from 140 to 150 mEq/1 for sodium, and for potassium it was from 2.3 to 3.4 mEq/1. These determinations were performed with the flamme photometer with internal lithium standard. When studying disorders of electrolyte and water metabolism in diseases of the central nervous system, they have observed 99 patients and determined both sodium an potassium contents in cerebrospinal fluid. In cases with hipo-osmolarity they have observed that the cerebrospinal fluid potassium content was in the range of normality generally. In cases of hyperosmolarity they have observed that 2/3 of the cases were in the range of normality, but in the remaining cases there was a little increase in the potassium content, and the greatest figure was 4.3 mEq/1. The results point out to the great value of the determination of cerebrospinal fluid sodium content in the early recognition of disorders of electrolyte and water metabolism in diseases of the central nervous system. On the other hand, the determination of cerebrospinal fluid potassium content has no practical value in the recognition of potassium metabolism disorders in the body.Os autores determinaram o conceito de normalidade para as taxas de sódio e potássio do líquor e verificaram, para o sódio, uma variação de 140 a 150 mEq/1 (média de 145 mEq/1) e, para o potássio, uma variação de 2,3 a 3,4 mEq/1 (média de 2,9 mEq/1), utilizando-se do fotômetro de chama. Estudando os distúrbios do equilíbrio hidrossalino em pacientes com afecções neurológicas graves, reuniram um grupo de 99 casos, incluindo variadas moléstias agudas e crônicas. Apreciando os resultados das dosagens do potássio nos pacientes com perturbações da osmolaridade do meio extracelular, verificaram relativa invariabilidade de sua taxa nos casos de hiposmolaridade parece existir algum paralelismo entre sódio e potássio, embora com dispersão muito grande. A maior taxa de potássio verificada foi de 4,3 mEq/1. Êstes resultados mostram que, enquanto a determinação da taxa de sódio no líquor tem grande sabor na caracterização de distúrbios do equilíbrio hidrossalino em pacientes neurológicos, a determinação da taxa do potássio no líquor não tem valor para o estudo de perturbação do seu metabolismo no organismo.Escola Paulista de MedicinaUNIFESP, EPMSciEL

O cálcio no líqüido céfalo-raqueano

Os autores estudaram o cálcio no líquido céfalo-raqueano de 217 pacientes portadores de diversas condições neurológicas e psiquiátricas, tendo sido examinadas 244 amostras. Procuraram demonstrar a importância de se considerar as duas frações, a difusível e a não difusível, na interpretação das alterações do cálcio total no líquido céfalo-raqueano. Como somente as modificações da fração difusível têm maior significado em patologia, estudaram todo o seu material visando o cálculo desta fração em cada amostra do líquor. Tendo encontrado uma relação logarítmica entre a taxa das proteínas totais e a taxa do cálcio, propuzeram uma fórmula para o cálculo da taxa de cálcio não difusível [(0,91 χ log. taxa de proteínas totais em mg%) - 1,3]. Baseados nesta fórmula elaboraram uma tabela que permite a dedução da fração não difusível do cálcio total. Os autores verificaram aumento da taxa do cálcio total em numerosas amostras de líquor em que havia aumento da taxa das proteínas, tais como nos casos de meningites, tumores encefálicos e raqueanos, hidrocefalias, neurolues, hemorragias intracranianas. Porém, nestes casos, após o desconto da fração não difusível, constataram valores dentro dos limites de normalidade. Deduzida a fração não difusível o material foi analizado do ponto de vista do cálcio difusível, sendo encontrado um aumento significativo desta fração na maioria dos casos de encefalite psicótica aguda azotêmica (Marchand), fato êste não assinalado na literatura compulsada pelos autores

Paper-strip electrophoresis of cerebrospinal fluid proteins and their practical value in Neurology

This paper is based on the study of the protein profile of the cerebrospinal fluid of 300 neurological patients. This material was analysed in the same way as that one performed by Matiar and Schmidt (1958) and it was found almost the same results. These findings suggested the great value of the cerebrospinal fluid gamma-globulin concentration in the neurological differential diagnosis. In order to enlarge these studies in our own material, it was tried to find some correlation between albumin and globulin fractions expressed in mg/100 ml. The logarithm of albumin concentration was plotted graphically against the logarithm of globulin concentration; each disease was noted down as different symbols. It was verified linear bilogarithmic correlation between albumin and each globulin fraction. Graphs with albumin/alpha-globulin or with albumin/beta-globulin showed absence of characteristic disease behaviour. On the contrary, the graph with albumin/gamma-globulin showed a typical behaviour for neurolues and brain cysticercosis data. Assuming that the cases of spinal block may very well indicate the condition where the changes of the spinal fluid proteins were due to a modification of permeability of the blood-brain barrier, it was calculated the regression equation for the various gamma-globulin concentrations of these cases. It was found that most of the cases of brain tumors, intracranial hemorrhages, meningitis and polyradiculoneuritis were in perfect agreement with the cases of spinal block, suggesting that in these cases the protein changes were due to a modification of permeability of the blood-brain barrier. On the contrary, the great majority of the cases of neurolues and brain cysticercosis did not follow this pattern, suggesting that there was an increase of the spinal fluid gamma-globulin which must be originated intrathecally. These findings point out to two different mechanisms in the changes of the protein profile of cerebrospinal fluid and, therefore, electrophoresis did not allow the diagnosis of a determined neurological disorder, but it shows the particular physiopathological mechanism involved.O presente trabalho é baseado no estudo dos perfis eletroforéticos das proteínas do líquido cefalorraqueano de 300 pacientes normais ou portadores de diversas entidades neurológicas. Analisando êste material, os autores verificaram que a gama-globulina é a fração protêica cuja variação tem grande importância na prática neurológica para o diagnóstico diferencial. A principal conclusão a que chegaram indica que há dois diferentes mecanismos que atuam na alteração do perfil eletroforético das proteínas do líquor: a) alteração da permeabilidade da barreira hêmato-encefálica; b) liberação intratecal de gama-globulina. Portanto, o método eletroforético não permite o diagnóstico de determinada entidade neurológica, mas indica o mecanismo fisiopatológico em atividade

Eletroforese em papel das proteínas do líquido cefalorraqueano e seu valor prático em clínica neurológica

This paper is based on the study of the protein profile of the cerebrospinal fluid of 300 neurological patients. This material was analysed in the same way as that one performed by Matiar and Schmidt (1958) and it was found almost the same results. These findings suggested the great value of the cerebrospinal fluid gamma-globulin concentration in the neurological differential diagnosis. In order to enlarge these studies in our own material, it was tried to find some correlation between albumin and globulin fractions expressed in mg/100 ml. The logarithm of albumin concentration was plotted graphically against the logarithm of globulin concentration; each disease was noted down as different symbols. It was verified linear bilogarithmic correlation between albumin and each globulin fraction. Graphs with albumin/alpha-globulin or with albumin/beta-globulin showed absence of characteristic disease behaviour. On the contrary, the graph with albumin/gamma-globulin showed a typical behaviour for neurolues and brain cysticercosis data. Assuming that the cases of spinal block may very well indicate the condition where the changes of the spinal fluid proteins were due to a modification of permeability of the blood-brain barrier, it was calculated the regression equation for the various gamma-globulin concentrations of these cases. It was found that most of the cases of brain tumors, intracranial hemorrhages, meningitis and polyradiculoneuritis were in perfect agreement with the cases of spinal block, suggesting that in these cases the protein changes were due to a modification of permeability of the blood-brain barrier. On the contrary, the great majority of the cases of neurolues and brain cysticercosis did not follow this pattern, suggesting that there was an increase of the spinal fluid gamma-globulin which must be originated intrathecally. These findings point out to two different mechanisms in the changes of the protein profile of cerebrospinal fluid and, therefore, electrophoresis did not allow the diagnosis of a determined neurological disorder, but it shows the particular physiopathological mechanism involved.O presente trabalho é baseado no estudo dos perfis eletroforéticos das proteínas do líquido cefalorraqueano de 300 pacientes normais ou portadores de diversas entidades neurológicas. Analisando êste material, os autores verificaram que a gama-globulina é a fração protêica cuja variação tem grande importância na prática neurológica para o diagnóstico diferencial. A principal conclusão a que chegaram indica que há dois diferentes mecanismos que atuam na alteração do perfil eletroforético das proteínas do líquor: a) alteração da permeabilidade da barreira hêmato-encefálica; b) liberação intratecal de gama-globulina. Portanto, o método eletroforético não permite o diagnóstico de determinada entidade neurológica, mas indica o mecanismo fisiopatológico em atividade.Escola Paulista de Medicina Serviço de NeurologiaUNIFESP, EPM, Serviço de NeurologiaSciEL