Dengue in Brazil and Colombia: a study of knowledge, attitudes, and practices

Introduction This study was conducted in Brazil and Colombia,where dengue is endemic and vector control programs use chemical insecticides. Methods We identified knowledge, attitudes, and practices about dengue and determined the infestation levels of Aedes aegypti in one Brazilian and four Colombian communities. Results The surveys show knowledge of the vector, but little knowledge about diagnosis, prognosis, and treatment. Vector infestation indices show Brazil to have good relative control, while Colombia presents a high transmission risk. Conclusions Given the multidimensionality of dengue control, vertical control strategies are inadequate because they deny contextualized methods, alternative solutions, and local empowerment.

Plasma levels of immunoinflammatory markers in De Novo coronary atherosclerosis and coronary restenosis postangioplasty

OBJECTIVE: To compare circulating plasma levels of immunoinflammatory markers in patients with known de novo coronary artery disease and patients with postangioplasty restenosis. METHODS: Using enzymatic immunoabsorbent assay, we measured plasma levels of soluble interleukin-2 receptosr, tumor necrosis factor alpha, and soluble tumor necrosis alpha receptors I and II in 11 patients with restenosis postcoronary angioplasty (restenosis group), in 10 patients with primary atherosclerosis (de novo group) who were referred for coronary angiography because of stable or unstable angina, and in 9 healthy volunteers (control group). Levels of soluble interleukin-2 receptors were significantly higher in the de novo group compared with that in the restenosis and control groups. Levels were also higher in the restenosis group compared with that in the control group. Plasma levels of tumor necrosis alpha and receptor levels were significantly higher in the de novo group compared to with that in the restenosis and control groups, but levels in the restenosis group were not different from that in the controls. CONCLUSION: Coronary artery disease, either primary or secondary to restenosis, is associated with significant immunoinflammatory activity, which can be assessed by examining the extent of circulating plasma levels of inflammatory markers. Moreover, patients with de novo lesions appear to have increased inflammatory activity compared with patients with restenosis.

Cytokines and troponin-I in cardiac dysfunction after coronary artery grafting with cardiopulmonary bypass

OBJECTIVE: The association between cytokines and troponin-I with cardiac function after cardiac surgery with cardiopulmonary bypass remains a topic of continued investigation. METHODS: Serial measurements, within 24h following surgery, of tumor necrosis factor-alpha, its soluble receptors, and troponin-I were performed in patients with normal ejection fraction undergoing coronary artery bypass grafting. Ejection fraction was measured by radioisotopic ventriculography preoperatively, at 24h and at day 7 postoperatively. RESULTS: Of 19 patients studied (59±8.5 years), 10 (group 1) showed no changes in ejection fraction, 53±8% to 55±7%, and 9 (group 2) had a decrease in ejection fraction, 60±11% to 47±11% (p=0.015) before and 24h after coronary artery bypass grafting, respectively. All immunological variables, except tumor necrosis factor-alpha soluble receptor I at 3h postoperation (5.5± 0.5 in group 1 versus 5.9±0.2 pg/ml in group 2; p=0.048), were similar between groups. Postoperative troponin-I had an inverse correlation with ejection fraction at 24h (r= -0.44). CONCLUSIONS: Inflammatory activity, assessed based on tumor necrosis factor-alpha and its receptors, appears to play a minor role in cardiac dysfunction after cardiac surgery. Troponin I levels are inversely associated with early postoperative ejection fraction.

Further development of the baboon as a model for acute schistosomiasis

Baboons develop a syndrome, including eosinophilia and transient fever, after infection with carcariae of Schistosoma mansoni that is consistent with the human syndrome of acute schistosomiasis. Radiotelemetry can be used to follow the course of fever in infected baboons. Individual variations in intensity of disease were noted in baboons. These symptoms and signs were more closely linked to the onset of oviposition by the newly matured worms than they were to the presence of migrating schistosoma or maturing worms. The baboon is concluded to be a suitable and useful model for human acute schistosomiasis mansoni.

Dengue in Brazil - situation, transmission and control: a proposal for ecological control

This article discusses dengue in terms of its conceptual and historical aspects, epidemiological and clinical/pathological nature, and evolution up to the present situation in Brazil. The author discusses the ecological relationship in both the production of dengue and its control. Comparison is made between traditional dengue-control programs and a proposed socially-controlled program of an ecological nature without the use of insecticides. Stress is placed on interdisciplinary technical and scientific activity, broadbased participation by communities in discussing methodological aspects involving them, and prospective evaluation comparing the communities selected for intervention and control communities with regard to clinical and subclinical dengue cases and vector infestation rates in relation to climatic, socio-economic, and behavioural factors.

Infected erythrocyte choline carrier inhibitors: exploring some potentialities inside Plasmodium phospholipid metabolism for eventual resistance acquisition

We have developed a model for designing antimalarial drugs based on interference with an essential metabolism developed by Plasmodium during its intraerythrocytic cycle, phospholipid (PL) metabolism. The most promising drug interference is choline transporter blockage, which provides Plasmodium with a supply of precursor for synthesis of phosphatidylcholine (PC), the major PL of infected erythrocytes. Choline entry is a limiting step in this metabolic pathway and occurs by a facilitated-diffusion system involving an asymmetric carrier operating according to a cyclic model. Choline transport in the erythrocytes is not sodium dependent nor stereospecific as demonstrated using stereoisomers of alpha and beta methylcholine. These last two characteristics along with distinct effects of nitrogen substitution on transport rate demonstrate that choline transport in the infected erythrocyte possesses characteristics quite distinct from that of the nervous system. This indicates a possible discrimination between the antimalarial activity (inhibition of choline transport in the infected erythrocyte) and a possible toxic effect through inhibition of choline entry in synaptosomes. Apart from the de novo pathway of choline, PC can be synthesized by N-methylation from phosphatidylethanolamine (PE). There is a de novo pathway for PE biosynthesis from ethanolamine in infected cells but phosphatidylserine (PS) decarboxylation also occurs. In addition, PE can be directly and abundantly synthesized from serine decarboxylation into ethanolamine, a pathway which is absent from the host. The variety of the pathways that exist for the biosynthesis of one given PL led us to investigate whether an equilibrium can occur between all PL metabolic pathways. Indeed, if alternative (compensative) pathway(s) can operate after blockage of the de novo PC biosynthesis pathway this would indicate a potential mechanism for resistance acquisition. Up until now, there is no evidence of such a compensative process occurring in Plasmodium-infected erythrocytes under physiological conditions. Besides, the discovery of a highly parasite-specific pathway (serine decarboxylation and the presence of PS synthase) constitutes a very attractive and promising target, which could be attacked if resistances are built up against choline analogs. Indeed, potential inhibitions of the serine decarboxylase pathway could be very useful in acting instead of, or in surgery with, choline analogs.

Cytokines in the modulation of eosinophilia

In this review we discuss our recently results showing interleukin 5 (IL-5) involvement in eosinophil migration and in the maintenance of eosinophilia in blood, bone marrow, lung and peritoneal cavity, in a visceral larva migrans syndrome model using guinea-pigs infected with Toxocara canis. We also describe the sequential release of TNF-alpha and IL-8 during the course of infection, and the interaction between these cytokines and IL-5 during infection. Finally we propose a new biological role for IL-5, at least in our model, as a modulator of IL-8 release and secretion.

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

The trypanosomatid evolution workshop London School of Hygiene and Tropical Medicine

The trypanosome evolution workshop, a joint meeting of the University of Exeter and the London School of Hygiene and Tropical Medicine, focused on topics relating to trypanosomatid and vector evolution. The meeting, sponsored by The Wellcome Trust, The Special Programme for Research and Training in Tropical Disease of World Health Organization and the British Section of the Society of Protozoologists, brought together an international group of experts who presented papers on a wide range of topics including parasite and vector phylogenies, molecular methodology and relevant biogeographical data.

B-cell infiltration and frequency of cytokine producing cells differ between localized and disseminated human cutaneous leishmaniases

Biopsies from human localized cutaneous lesions (LCL n = 7) or disseminated lesions (DL n = 8) cases were characterized according to cellular infiltration,frequency of cytokine (IFN-g, TNF-alpha) or iNOS enzyme producing cells. LCL, the most usual form of the disease with usually one or two lesions, exhibits extensive tissue damage. DL is a rare form with widespread lesions throughout the body; exhibiting poor parasite containment but less tissue damage. We demonstrated that LCL lesions exhibit higher frequency of B lymphocytes and a higher intensity of IFN-gamma expression. In both forms of the disease CD8+ were found in higher frequency than CD4+ T cells. Frequency of TNF-alpha and iNOS producing cells, as well as the frequency of CD68+ macrophages, did not differ between LCL and DL. Our findings reinforce the link between an efficient control of parasite and tissue damage, implicating higher frequency of IFN-gamma producing cells, as well as its possible counteraction by infiltrated B cells and hence possible humoral immune response in situ.

Identification of casein kinase 1, casein kinase 2, and cAMP-dependent protein kinase-like activities in Trypanosoma evansi

Trypanosoma evansi contains protein kinases capable of phosphorylating endogenous substrates with apparent molecular masses in the range between 20 and 205 kDa. The major phosphopolypeptide band, pp55, was predominantly localized in the particulate fraction. Anti-alpha and anti-beta tubulin monoclonal antibodies recognized pp55 by Western blot analyses, suggesting that this band corresponds to phosphorylated tubulin. Inhibition experiments in the presence of emodin, heparin, and 2,3-bisphosphoglycerate indicated that the parasite tubulin kinase was a casein kinase 2 (CK2)-like activity. GTP, which can be utilized instead of ATP by CK2, stimulated rather than inactivated the phosphorylation of tubulin in the parasite homogenate and particulate fraction. However, GTP inhibited the cytosolic CK2 responsible for phosphorylating soluble tubulin and other soluble substrates. Casein and two selective peptide substrates, P1 (RRKDLHDDEEDEAMSITA) for casein kinase (CK1) and P2 (RRRADDSDDDDD) for CK2, were recognized as substrates in T. evansi. While the enzymes present in the soluble fraction predominantly phosphorylated P1, P2 was preferentially labeled in the particulate fractions. These results demonstrated the existence of CK1-like and CK2-like activities primarily located in the parasite cytosolic and membranous fractions, respectively. Histone II-A and kemptide (LRRASVA) also behaved as suitable substrates, implying the existence of other Ser/Thr kinases in T. evansi. Cyclic AMP only increased the phosphorylation of histone II-A and kemptide in the cytosol, demonstrating the existence of soluble cAMP-dependent protein kinase-like activities in T. evansi. However, no endogenous substrates for this enzyme were identified in this fraction. Further evidences were obtained by using PKI (6-22), a reported inhibitor of the catalytic subunit of mammalian cAMP-dependent protein kinases, which specifically hindered the cAMP-dependent phosphorylation of histone II-A and kemptide in the parasite soluble fraction. Since the sum of the values obtained in the parasite cytosolic and particulate fractions were always higher than the values observed in the total T. evansi lysate, the kinase activities examined here appeared to be inhibited in the original extract.

Participation of cytokines in the necrotic-inflammatory lesions in the heart and skeletal muscles of Calomys callosus infected with Trypanosoma cruzi

Calomys callosus, a sylvatic reservoir of Trypanosoma cruzi, when infected with the Colombian strain (Biodeme Type III, T. cruzi I ) develops necrotic-inflammatory lesions and intense early fibrogenesis in the heart and skeletal muscles, that spontaneously regress. Participation of pro-inflammatory and pro-fibrogenic cytokines, such as tumor necrosis factor-alpha (TNF-alpha), gamma interferon (IFN-gamma) , and tumor growth factor-beta (TGF-beta), in the pathogenesis of the lesions is herein studied. Eighty C. callosus weighing 20 to 30 g were used. Seventy of them were inoculated with the Colombian strain (10(5) blood forms) and 10 were maintained as intact non-infected controls. After infection, C. callosus were sacrificed at different time-points from 15 to 70 days. The heart and skeletal muscle were processed for histopathology and cryopreserved for immunohistochemistry. Early necrotic lesions of parasitized skeletal muscle and myocardium with intense inflammatory lesions were present. Search for the in situ presence of TNF-alpha and IFN-gamma, was performed using rat-IgG anti-mouse antibodies against these cytokines. For the in situ search of TGF-beta, rabbit IgG anti-mouse antibodies were used. Immunolabeling of the cytokines in tissues of infected C. callosus was successful. The cytokines TNF-alpha, IFN-gamma , and TGF-beta were detected in the cytoplasm of macrophages and in the necrotic material from 15 to 45 days post-infection, decreasing their intensity until complete disappearance by the 65th day, which correlated with subsiding histopathological lesions. These findings suggest the participation of these cytokines in the control of parasite multiplication, in the development of an early fibrogenesis and in the regression of fibrotic-inflammatory lesions observed in C. callosus.

Cellular and genetic mechanisms involved in the generation of protective and pathogenic immune responses in human Chagas disease

Perhaps one of the most intriguing aspects of human Chagas disease is the complex network of events that underlie the generation of protective versus pathogenic immune responses during the chronic phase of the disease. While most individuals do not develop patent disease, a large percentage may develop severe forms that eventually lead to death. Although many efforts have been devoted to deciphering these mechanisms, there is still much to be learned before we can fully understand the pathogenesis of Chagas disease. It is clear that the host's immune response is decisive in this process. While characteristics of the parasite influence the immune response, it is becoming evident that the host genetic background plays a fundamental role in the establishment of pathogenic versus protective responses. The involvement of three complex organisms, host, parasite and vector, is certainly one of the key aspects that calls for multidisciplinary approaches towards the understanding of Chagas disease. We believe that now, one hundred years after the discovery of Chagas disease, it is imperative to continue with highly interactive research in order to elucidate the immune response associated with disease evolution, which will be essential in designing prophylactic or therapeutic interventions.

A comparative evaluation of endemic and non-endemic region of visceral leishmaniasis (Kala-azar) in India with ground survey and space technology

In visceral leishmaniasis, phlebotomine vectors are targets for control measures. Understanding the ecosystem of the vectors is a prerequisite for creating these control measures. This study endeavours to delineate the suitable locations of Phlebotomus argentipes with relation to environmental characteristics between endemic and non-endemic districts in India. A cross-sectional survey was conducted on 25 villages in each district. Environmental data were obtained through remote sensing images and vector density was measured using a CDC light trap. Simple linear regression analysis was used to measure the association between climatic parameters and vector density. Using factor analysis, the relationship between land cover classes and P. argentipes density among the villages in both districts was investigated. The results of the regression analysis indicated that indoor temperature and relative humidity are the best predictors for P. argentipes distribution. Factor analysis confirmed breeding preferences for P. argentipes by landscape element. Minimum Normalised Difference Vegetation Index, marshy land and orchard/settlement produced high loading in an endemic region, whereas water bodies and dense forest were preferred in non-endemic sites. Soil properties between the two districts were studied and indicated that soil pH and moisture content is higher in endemic sites compared to non-endemic sites. The present study should be utilised to make critical decisions for vector surveillance and controlling Kala-azar disease vectors.

Acute Chagas disease in El Salvador 2000-2012 - Need for surveillance and control

Several parasitological studies carried out in El Salvador between 2000-2012 showed a higher frequency of acute cases of Chagas disease than that in other Central American countries. There is an urgent need for improved Chagas disease surveillance and vector control programs in the provinces where acute Chagas disease occurs and throughout El Salvador as a whole.