Severity of chronic experimental Chagas' heart disease parallels tumour necrosis factor and nitric oxide levels in the serum: models of mild and severe disease

Heart tissue inflammation, progressive fibrosis and electrocardiographic alterations occur in approximately 30% of patients infected by Trypanosoma cruzi, 10-30 years after infection. Further, plasma levels of tumour necrosis factor (TNF) and nitric oxide (NO) are associated with the degree of heart dysfunction in chronic chagasic cardiomyopathy (CCC). Thus, our aim was to establish experimental models that mimic a range of parasitological, pathological and cardiac alterations described in patients with chronic Chagas’ heart disease and evaluate whether heart disease severity was associated with increased TNF and NO levels in the serum. Our results show that C3H/He mice chronically infected with the Colombian T. cruzi strain have more severe cardiac parasitism and inflammation than C57BL/6 mice. In addition, connexin 43 disorganisation and fibronectin deposition in the heart tissue, increased levels of creatine kinase cardiac MB isoenzyme activity in the serum and more severe electrical abnormalities were observed in T. cruzi-infected C3H/He mice compared to C57BL/6 mice. Therefore, T. cruzi-infected C3H/He and C57BL/6 mice represent severe and mild models of CCC, respectively. Moreover, the CCC severity paralleled the TNF and NO levels in the serum. Therefore, these models are appropriate for studying the pathophysiology and biomarkers of CCC progression, as well as for testing therapeutic agents for patients with Chagas’ heart disease.

Silicon and rice disease management

The element silicon (Si) is not considered an essential nutrient for plant function. Nevertheless, Si is absorbed from soil in large amounts that are several fold higher than those of other essential macronutrients in certain plant species. Its beneficial effects have been reported in various situations, especially under biotic and abiotic stress conditions. The most significant effect of Si on plants, besides improving their fitness in nature and increasing agricultural productivity, is the restriction of parasitism. There has been a considerable amount of research showing the positive effect of Si in controlling diseases in important crops. Rice (Oryza sativa), in particular, is affected by the presence of Si, with diseases such as blast, brown spot and sheath blight becoming more severe on rice plants grown in Si-depleted soils. The hypothesis underlying the control of some diseases in both mono- and di-cots by Si has been confined to that of a mechanical barrier resulting from its polymerization in planta. However, some studies show that Si-mediated resistance against pathogens is associated with the accumulation of phenolics and phytoalexins as well as with the activation of some PR-genes. These findings strongly suggest that Si plays an active role in the resistance of some plants to diseases rather than forming a physical barrier that impedes penetration by fungal pathogens.

Association between the -174 G/C promoter polymorphism of the interleukin-6 gene and cardiovascular disease risk factors in Brazilian older women

In worldwide studies, interleukin-6 (IL-6) is implicated in age-related disturbances. The aim of the present report was to determine the possible association of IL-6 -174 C/G promoter polymorphism with the cytokine profile as well as with the presence of selected cardiovascular risk features. This was a cross-sectional study on Brazilian women aged 60 years or older. A sample of 193 subjects was investigated for impaired glucose regulation, diabetes, hypertension, and dyslipidemia. Genotyping was done by direct sequencing of PCR products. IL-6 and C-reactive protein were quantified by high-sensitivity assays. General linear regression models or the Student t-test were used to compare continuous variables among genotypes, followed by adjustments for confounding variables. The chi-square test was used to compare categorical variables. The genotypes were consistent with Hardy-Weinberg equilibrium proportions. In a recessive model, mean waist-to-hip ratio, serum glycated hemoglobin and serum glucose were markedly lower in C homozygotes (P = 0.001, 0.028, and 0.047, respectively). In a dominant hypothesis, G homozygotes displayed a trend towards higher levels of circulating IL-6 (P = 0.092). Non-parametric analysis revealed that impaired fasting glucose and hypertension were findings approximately 2-fold more frequent among G homozygous subjects (P = 0.042 and 0.043, respectively). Taken together, our results show that the IL-6 -174 G-allele is implicated in a greater cardiovascular risk. To our knowledge, this is the first investigation of IL-6 promoter variants and age-related disturbances in the Brazilian elderly population.

Gut permeability to lactulose and mannitol differs in treated Crohn's disease and celiac disease patients and healthy subjects

The gut barrier monitors and protects the gastrointestinal tract from challenges such as microorganisms, toxins and proteins that could act as antigens. There is evidence that gut barrier dysfunction may act as a primary disease mechanism in intestinal disorders. The aim of the present study was to evaluate the barrier function towards sugars after the appropriate treatment of celiac disease and Crohn's disease patients and compare the results with those obtained with healthy subjects. Fifteen healthy volunteers, 22 celiac disease patients after 1 year of a gluten-free diet, and 31 Crohn's disease patients in remission were submitted to an intestinal permeability test with 6.0 g lactulose and 3.0 g mannitol. Six-hour urinary lactulose excretion in Crohn's disease patients was significantly higher than in both celiac disease patients (0.42 vs 0.15%) and healthy controls (0.42 vs 0.07%). Urinary lactulose excretion was significantly higher in celiac disease patients than in healthy controls (0.15 vs 0.07%). Urinary mannitol excretion in Crohn's disease patients was the same as healthy controls (21 vs 21%) and these values were significantly higher than in celiac disease patients (10.9%). The lactulose/mannitol ratio was significantly higher in Crohn's disease patients in comparison to celiac disease patients (0.021 vs 0.013) and healthy controls (0.021 vs 0.003) and this ratio was also significantly higher in celiac disease patients compared to healthy controls (0.013 vs 0.003). In spite of treatment, differences in sugar permeability were observed in both disease groups. These differences in the behavior of the sugar probes probably reflect different mechanisms for the alterations of intestinal permeability.

Vitamin D and Kidney disease: what we know and what we do not know

Vitamin D deficiency is common in the chronic kidney disease (CKD) population. CKD has been recognized as a significant public health problem and CKD patients are at increased risk of total and cardiovascular morbidity and mortality. There are increasing epidemiological data suggesting that vitamin D deficiency may play a role in overall morbidity and mortality associated with CKD. The vitamin D hormonal system is classically implicated in the regulation of calcium homeostasis and bone metabolism but there is ample evidence to support the claim that extra renal conversion of 25(OH)D to 1.25(OH)2 has significant biological roles beyond those traditionally ascribed to vitamin D. Based on the current state of evidence this review intends to give an update on novel biological and clinical insights with relevance to the steroid hormone vitamin D specifically in patients with kidney disease.

Schistosomiasis mansoni and severe gastrointestinal cytomegalovirus disease in a patient with acquired immunodeficiency syndrome

The behavior of the Schistosoma mansoni infection in patients with AIDS has not been explored. The case of a young woman with schistosomiasis mansoni, AIDS, and cytomegalovirus disease is reported. The authors suggest that the helminth was not a bystander in this case, or rather, by interfering with the host's immune response, it set the stage for the development and/or aggravation of the viral infection.

Insights into the clinical and functional significance of cardiac autonomic dysfunction in Chagas disease

INTRODUCTION: Exclusive or associated lesions in various structures of the autonomic nervous system occur in the chronic forms of Chagas disease. In the indeterminate form, the lesions are absent or mild, whereas in the exclusive or combined heart and digestive disease forms, they are often more pronounced. Depending on their severity these lesions can result mainly in cardiac parasympathetic dysfunction but also in sympathetic dysfunction of variable degrees. Despite the key autonomic effect on cardiovascular functioning, the pathophysiological and clinical significance of the cardiac autonomic dysfunction in Chagas disease remains unknown. METHODS: Review of data on the cardiac autonomic dysfunction in Chagas disease and their potential consequences, and considerations supporting the possible relationship between this disturbance and general or cardiovascular clinical and functional adverse outcomes. RESULTS: We hypothesise that possible consequences that cardiac dysautonomia might variably occasion or predispose in Chagas disease include: transient or sustained arrhythmias, sudden cardiac death, adverse overall and cardiovascular prognosis with enhanced morbidity and mortality, an inability of the cardiovascular system to adjust to functional demands and/or respond to internal or external stimuli by adjusting heart rate and other hemodynamic variables, and immunomodulatory and cognitive disturbances. CONCLUSIONS: Impaired cardiac autonomic modulation in Chagas disease might not be a mere epiphenomenon without significance. Indirect evidences point for a likely important role of this alteration as a primary predisposing or triggering cause or mediator favouring the development of subtle or evident secondary cardiovascular functional disturbances and clinical consequences, and influencing adverse outcomes.

Exercise-induced ventricular arrhythmias and vagal dysfunction in Chagas disease patients with no apparent cardiac involvement

INTRODUCTION : Exercise-induced ventricular arrhythmia (EIVA) and autonomic imbalance are considered as early markers of heart disease in Chagas disease (ChD) patients. The objective of the present study was to verify the differences in the occurrence of EIVA and autonomic maneuver indexes between healthy individuals and ChD patients with no apparent cardiac involvement. METHODS : A total of 75 ChD patients with no apparent cardiac involvement, aged 44.7 (8.5) years, and 38 healthy individuals, aged 44.0 (9.2) years, were evaluated using echocardiography, symptom-limited treadmill exercise testing and autonomic function tests. RESULTS : The occurrence of EIVA was higher in the chagasic group (48%) than in the control group (23.7%) during both the effort and the recovery phases. Frequent ventricular contractions occurred only in the patient group. Additionally, the respiratory sinus arrhythmia index was significantly lower in the chagasic individuals compared with the control group. CONCLUSIONS : ChD patients with no apparent cardiac involvement had a higher frequency of EIVA as well as more vagal dysfunction by respiratory sinus arrhythmia. These results suggest that even when asymptomatic, ChD patients possess important arrhythmogenic substrates and subclinical disease.

Evolutionary Control of Infectious Disease: Prospects for Vectorborne and Waterborne Pathogens

Evolutionary theory may contribute to practical solutions for control of disease by identifying interventions that may cause pathogens to evolve to reduced virulence. Theory predicts, for example, that pathogens transmitted by water or arthropod vectors should evolve to relatively high levels of virulence because such pathogens can gain the evolutionary benefits of relatively high levels of host exploitation while paying little price from host illness. The entrance of Vibrio cholerae into South America in 1991 has generated a natural experiment that allows testing of this idea by determining whether geographic and temporal variations in toxigenicity correspond to variation in the potential for waterborne transmission. Preliminary studies show such correspondences: toxigenicity is negatively associated with access to uncontaminated water in Brazil; and in Chile, where the potential for waterborne transmission is particularly low, toxigenicity of strains declined between 1991 and 1998. In theory vector-proofing of houses should be similarly associated with benignity of vectorborne pathogens, such as the agents of dengue, malaria, and Chagas' disease. These preliminary studies draw attention to the need for definitive prospective experiments to determine whether interventions such as provisioning of uncontaminated water and vector-proofing of houses cause evolutionary reductions in virulence

Evolution of the clinical and epidemiological knowledge about Chagas disease 90 years after its discovery

Three different periods may be considered in the evolution of knowledge about the clinical and epidemiological aspects of Chagas disease since its discovery: (a) early period concerning the studies carried out by Carlos Chagas in Lassance with the collaboration of other investigators of the Manguinhos School. At that time the disease was described and the parasite, transmitters and reservoirs were studied. The coexistence of endemic goiter in the same region generated some confusion about the clinical forms of the disease; (b) second period involving uncertainty and the description of isolated cases, which lasted until the 1940 decade. Many acute cases were described during this period and the disease was recognized in many Latin American countries. Particularly important were the studies of the Argentine Mission of Regional Pathology Studies, which culminated with the description of the Romaña sign in the 1930 decade, facilitating the diagnosis of the early phase of the disease. However, the chronic phase, which was the most important, continued to be difficult to recognize; (c) period of consolidation of knowledge and recognition of the importance of Chagas disease. Studies conducted by Laranja, Dias and Nóbrega in Bambuí updated the description of Chagas heart disease made by Carlos Chagas and Eurico Villela. From then on, the disease was more easily recognized, especially with the emphasis on the use of a serologic diagnosis; (d) period of enlargement of knowledges on the disease. The studies on denervation conducted in Ribeirão Preto by Fritz Köberle starting in the 1950 decade led to a better understanding of the relations between Chagas disease and megaesophagus and other visceral megas detected in endemic areas.

Reduction in morbidity and mortality from childhood diarrhoeal disease after species A rotavirus vaccine introduction in Latin America : a review

Countries in Latin America were among the first to implement routine vaccination against species A rotavirus (RVA). We evaluate data from Latin America on reductions in gastroenteritis and RVA disease burden following the introduction of RVA vaccine. Published literature was reviewed to identify case-control studies of vaccine effectiveness and population-based studies examining longitudinal trends of diarrhoeal disease reduction after RVA vaccine introduction in Latin American countries. RVA vaccine effectiveness and impact on gastroenteritis mortality and hospitalization rates and RVA hospitalization rates are described. Among middle-income Latin American countries with published data (Mexico, Brazil, El Salvador and Panama), RVA vaccine contributed to a gastroenteritis-associated mortality reduction of 22-41%, a gastroenteritis-associated hospitalization reduction of 17-51% and a RVA hospitalization reduction of 59-81% among children younger than five years of age. In Brazil and El Salvador, case-control studies demonstrated that a full RVA vaccination schedule was 76-85% effective against RVA hospitalization; a lower effectiveness of 46% was seen in Nicaragua, the only low-income country with available data. A growing body of literature offers convincing evidence of "real world" vaccine program successes in Latin American settings, which may be expanded as more countries in the region include RVA vaccine in their immunization programs.

Biomarkers for susceptibility to infection and disease severity in human malaria

Malaria remains a major infectious disease that affects millions of people. Once infected with Plasmodium parasites, a host can develop a broad range of clinical presentations, which result from complex interactions between factors derived from the host, the parasite and the environment. Intense research has focused on the identification of reliable predictors for exposure, susceptibility to infection and the development of severe complications during malaria. Although most promising markers are based on the current understanding of malaria immunopathogenesis, some are also focused more broadly on mechanisms of tissue damage and inflammation. Taken together, these markers can help optimise therapeutic strategies and reduce disease burden. Here, we review the recent advances in the identification of malarial biomarkers, focusing on those related to parasite exposure and disease susceptibility. We also discuss priorities for research in biomarkers for severe malaria.

Risks of endemicity, morbidity and perspectives regarding the control of Chagas disease in the Amazon Region

Chagas disease, in the Amazon Region as elsewhere, can be considered an enzootic disease of wild animals or an anthropozoonosis, an accidental disease of humans that is acquired when humans penetrate a wild ecosystem or when wild triatomines invade human dwellings attracted by light or searching for human blood. The risk of endemic Chagas disease in the Amazon Region is associated with the following phenomena: (i) extensive deforestation associated with the displacement of wild mammals, which are the normal sources of blood for triatomines, (ii) adaptation of wild triatomines to human dwellings due to the need for a new source of blood for feeding and (iii) uncontrolled migration of human populations and domestic animals that are already infected with Trypanosoma cruzi from areas endemic for Chagas disease to the Amazon Region. Several outbreaks of severe acute cases of Chagas disease, as well as chronic cases, have been described in the Amazon Region. Control measures targeted to avoiding endemic Chagas disease in the Amazon Region should be the following: improving health education in communities, training public health officials and communities for vector and Chagas disease surveillance and training local physicians to recognise and treat acute and chronic cases of Chagas diseases as soon as possible.

Unveiling healthy carriers and subclinical infections among household contacts of leprosy patients who play potential roles in the disease chain of transmission

Leprosy transmission still occurs despite the availability of highly effective treatment. The next step towards successfully eliminating leprosy is interrupting the chain of transmission of the aetiological agent, Mycobacterium leprae. In this investigation, we provide evidence that household contacts (HHCs) of leprosy patients might not only have subclinical infections, but may also be actively involved in bacilli transmission. We studied 444 patients and 1,352 contacts using anti-phenolic glycolipid-I (PGL-I) serology and quantitative polymerase chain reaction (qPCR) to test for M. leprae DNA in nasal swabs. We classified the patients according to the clinical form of their disease and the contacts according to the characteristics of their index case. Overall, 63.3% and 34.2% of patients tested positive by ELISA and PCR, respectively. For HHCs, 13.3% had a positive ELISA test result and 4.7% had a positive PCR test result. The presence of circulating anti-PGL-I among healthy contacts (with or without a positive PCR test result from nasal swabs) was considered to indicate a subclinical infection. DNA detected in nasal swabs also indicates the presence of bacilli at the site of transmission and bacterial entrance. We suggest that the concomitant use of both assays may allow us to detect subclinical infection in HHCs and to identify possible bacilli carriers who may transmit and disseminate disease in endemic regions. Chemoprophylaxis of these contacts is suggested.

Identification of serological biomarkers of infection, disease progression and treatment efficacy for leprosy

Although leprosy is curable with drug treatment, the identification of biomarkers of infection, disease progression and treatment efficacy would greatly help to reduce the overall prevalence of the disease. Reliable biomarkers would also reduce the incidence of grade-2 disability by ensuring that those who are most at risk are diagnosed and treated early or offered repeated treatments in the case of relapse. In this study, we examined the reactivity of sera from lepromatous and tuberculoid leprosy patients (LPs) against a panel of 12 recombinant Mycobacterium leprae proteins and found that six proteins were strongly recognised by multibacillary (MB) patients, while only three were consistently recognised by paucibacillary patients. To better understand the dynamics of patient antibody responses during and after drug therapy, we measured antibody titres to four recombinant proteins, phenolic glycolipid-I and lipoarabinomannan at baseline and up to two years after diagnosis to investigate the temporal changes in the antibody titres. Reactivity patterns to individual antigens and decreases in antibody titres were patient-specific. Antibody titres to proteins declined more rapidly vs. those to carbohydrate and glycolipid antigens. Compared to baseline values, increases in antibody titres were observed during reactional episodes in one individual. Additionally, antibody responses against a subset of antigens that provided a good prognostic indicator of disease progression were analysed in 51 household contacts of MB index cases for up to two years. Although the majority of these contacts showed no change or exhibited decreases in antibody titres, seven individuals developed higher titres towards one or more of these antigens and one individual with progressively higher titres was diagnosed with borderline lepromatous leprosy 19 months after enrolment. The results of this study indicate that antibody titres to specific M. leprae antigens can be used to monitor treatment efficacy in LPs and assess disease progression in those most at risk for developing this disease.