The endemisation of schistosomiasis in Porto de Galinhas, Pernambuco, Brazil, 10 years after the first epidemic outbreak

In 2000, after heavy rains and floods in Porto de Galinhas, Pernambuco, Brazil, an outbreak of schistosomiasis was recorded, of which 62.2% (412 cases) were of the acute clinical form. Between 2001-2009, occasional findings of Biomphalaria snails parasitised by Schistosoma mansoni indicated that disease transmission was still occurring. This motivated a new epidemiological survey between August-December 2010 to provide an update of the occurrence of this health hazard and to investigate the process of disease endemisation at this locality. This survey gathered parasitological, clinical and malacological data. The results of this survey, compared with data from the year 2000 survey, showed the following: (i) over these 10 years, there were declines in the total percentage of cases and the percentage of acute forms, (ii) the acute clinical form now represents 23.3% in contrast with the 62.2% detected in 2000 and (iii) the current prevalence of schistosomiasis is 15.7%, while in 2000 32.1% of the individuals were diagnosed as parasitised. Today, the chronic clinical form represents 76.7% of the total number of cases diagnosed, thus showing that over the 10-year period the occurrences of clinical forms became inverted. These findings, together with visual observation of insalubrious environmental conditions, indicate that schistosomiasis has become endemic in Porto de Galinhas.

Malaria-related anaemia: a Latin American perspective

Malaria is the most important parasitic disease worldwide, responsible for an estimated 225 million clinical cases each year. It mainly affects children, pregnant women and non-immune adults who frequently die victims of cerebral manifestations and anaemia. Although the contribution of the American continent to the global malaria burden is only around 1.2 million clinical cases annually, there are 170 million inhabitants living at risk of malaria transmission in this region. On the African continent, where Plasmodium falciparum is the most prevalent human malaria parasite, anaemia is responsible for about half of the malaria-related deaths. Conversely, in Latin America (LA), malaria-related anaemia appears to be uncommon, though there is a limited knowledge about its real prevalence. This may be partially explained by several factors, including that the overall malaria burden in LA is significantly lower than that of Africa, that Plasmodium vivax, the predominant Plasmodium species in the region, appears to display a different clinical spectrus and most likely because better health services in LA prevent the development of severe malaria cases. With the aim of contributing to the understanding of the real importance of malaria-related anaemia in LA, we discuss here a revision of the available literature on the subject and the usefulness of experimental animal models, including New World monkeys, particularly for the study of the mechanisms involved in the pathogenesis of malaria.

Serologic follow-up of IgG responses against recombinant mycobacterial proteins ML0405, ML2331 and LID-1 in a leprosy hyperendemic area in Venezuela

Leprosy is a slowly evolving disease that occurs mainly in adults. In this study, the Mamaría Village, state of Portuguesa was selected because it had one of the highest prevalence rates (13.25%) of leprosy cases in 1997. Between 1998-2004, 20.2% of the 89 cases registered in this village were less than 15 years old and 61.8% were males. Pau-cibacillary (PB) lesions were the predominant clinical forms identified, although also multibacillary (MB) forms were found. Additionally, 76% of the patients were bacteriologically negative. At the time of diagnosis, 75% of the patients presented with grade 0 disabilities, 23% with grade 1 and 2% with grade 2. Serum samples were collected from 18 PB and 15 MB patients, in addition to 14 family contacts, at the beginning and end of treatment. All the groups were re-evaluated during a three-year period (2008-2011). The proteins used for evaluation were ML0405, ML2331 and LID-1. These mycobacterial proteins were highly specific for Mycobacterium leprae and the IgG responses decreased in both MB and PB patients during multidrug treatment. Our results suggest that these antigens could be used as markers for successful treatment of non-reactional lepromatous patients.

Inflammation in disseminated lesions: an analysis of CD4+, CD20+, CD68+, CD31+ and vW+ cells in non-ulcerated lesions of disseminated leishmaniasis

Disseminated leishmaniasis (DL) differs from other clinical forms of the disease due to the presence of many non-ulcerated lesions (papules and nodules) in non-contiguous areas of the body. We describe the histopathology of DL non-ulcerated lesions and the presence of CD4-, CD20-, CD68-, CD31- and von Willebrand factor (vW)-positive cells in the inflamed area. We analysed eighteen biopsies from non-ulcerated lesions and quantified the inflamed areas and the expression of CD4, CD20, CD68, CD31 and vW using Image-Pro software (Media Cybernetics). Diffuse lymphoplasmacytic perivascular infiltrates were found in dermal skin. Inflammation was observed in 3-73% of the total biopsy area and showed a significant linear correlation with the number of vW+ vessels. The most common cells were CD68+ macrophages, CD20+ B-cells and CD4+ T-cells. A significant linear correlation between CD4+ and CD20+ cells and the size of the inflamed area was also found. Our findings show chronic inflammation in all DL non-ulcerated lesions predominantly formed by macrophages, plasmacytes and T and B-cells. As the inflamed area expanded, the number of granulomas and extent of the vascular framework increased. Thus, we demonstrate that vessels may have an important role in the clinical evolution of DL lesions.

Estudio piloto sobre el manejo de la fluidoterapia intravenosa en pacientes adultos de un hospital de tercer nivel.

The purpose of intravenous fluid therapy (IFT) is to maintain or restore internal equilibrium by administering fluids and/or different electrolyte components. Its correct use and the prevention of complications arising from their misuse depend on the knowledge of the medical team on this subject. We analyzed this issue in different clinical areas of a tertiary hospital. MATERIAL AND METHODS We performed a descriptive cross-sectional pilot study via a questionnaire given to physicians specializing in internal medicine (IM) and digestive system surgery (SDS) who perform clinical practice in hospital units with unit dose drug dispensing system. We designed an anonymous questionnaire with 25 questions relative to knowledge of theory and practices, as well as the opinion of physicians regarding IFT. We evaluated the association between nominal qualitative variables with the Chi-square or Fisher's exact test. The behavior of the quantitative variables was assessed using the t-student test. The analysis of the data was generated using SAS/STAT, Version 9. RESULTS 28 questionnaires were collected from 13 surgeons and 15 digestive interns. Over 40% of specialists considered further education in IFT a necessity , especially regarding its prescription (SDS: 61.54%, IM: 71.43%). No statistically significant differences were found between the specialties in terms of perceived frequency of complications associated with IFT or in the frequency indication with the exception of hypovolemic shock, which is considered to be more prevalent in gastrointestinal surgery (p = 0.046). 90% of professionals prefer an individualized prescription. Statistically significant differences in terms of scores in the area of knowledge, with IM physicians achieving the highest scores (p = 0.014). There were also differences in attitude but they are not significant (p = 0.162). Knowledge of intravenous fluid increases with years of clinical experience (Spearman correlation coefficient = 0.386, p = 0.047). CONCLUSIONS The professionals who prescribe IFT perceive the need to design IFT training programs, together with the production of guides and consensus protocols.

Comparative analysis of the tissue inflammatory response in human cutaneous and disseminated leishmaniasis

Cutaneous leishmaniasis (CL) is the most frequent clinical form of tegumentary leishmaniasis and is characterised by a single or a few ulcerated skin lesions that may disseminate into multiple ulcers and papules, which characterise disseminated leishmaniasis (DL). In this study, cells were quantified using immunohistochemistry and haematoxylin and eosin staining (CD4+, CD68+, CD20+, plasma cells and neutrophils) and histopathology was used to determine the level of inflammation in biopsies from patients with early CL, late CL and DL (ulcers and papules). The histopathology showed differences in the epidermis between the papules and ulcers from DL. An analysis of the cells present in the tissues showed similarities between the ulcers from localised CL (LCL) and DL. The papules had fewer CD4+ T cells than the DL ulcers. Although both CD4+ cells and macrophages contribute to inflammation in early CL, macrophages are the primary cell type associated with inflammation intensity in late ulcers. The higher frequency of CD20+ cells and plasma cells in lesions demonstrates the importance of B cells in the pathogenesis of leishmaniasis. The number of neutrophils was the same in all of the analysed groups. A comparison between the ulcers from LCL and DL and the early ulcers and papules shows that few differences between these two clinical forms can be distinguished by observing only the tissue.

A comparative cross-sectional study on the prevalence and morbidity of schistosomiasis in a community in northeastern Brazil (1979-2010)

A cross-sectional study on the prevalence and morbidity of schistosomiasis was conducted in the main settlement of the municipality of Alhandra, in the southern coastal region of the state of Paraíba, in 2010. The results of this study were compared with the results of a previous study conducted in the same area in 1979. The systematic sampling per family conglomerate included approximately 10% of the resident population in the urban area of Alhandra. Faecal examinations were performed using the Kato-Katz method. The clinical forms of the disease were classified in accordance with FS Barbosa as Type I - intestinal form, Type II - hepatointestinal form and Type III - hepatosplenic form. The prevalence of the infection in 2010 was 10.05%, whereas in 1979 it was 46.6% among untreated patients. The percentages of the three clinical forms in 2010 were as follows: 95.3% Type I, 4.6% Type II and 0% Type III; in 1979, the percentages were 94.4%, 3% and 2.6% for Types I, II and III, respectively. In 1979, 6.07% of the Biomphalaria glabrata specimens (the intermediate host in this area) excreted cercariae, where in 2010 only 1.27% of the specimens caught excreted the parasite.

The mazEF toxin-antitoxin system as a novel antibacterial target in Acinetobacter baumannii

Although analysis of toxin-antitoxin (TA) systems can be instructive, to date, there is no information on the prevalence and identity of TA systems based on a large panel of Acinetobacter baumannii clinical isolates. The aim of the current study was to screen for functional TA systems among clinical isolates of A. baumannii and to identify the systems’ locations. For this purpose, we screened 85 A. baumannii isolates collected from different clinical sources for the presence of the mazEF, relBE and higBA TA genes. The results revealed that the genes coding for the mazEF TA system were commonly present in all clinical isolates of A. baumannii. Reverse transcriptase-polymerase chain reaction analysis showed that transcripts were produced in the clinical isolates. Our findings showed that TA genes are prevalent, harboured by chromosomes and transcribed within A. baumannii. Hence, activation of the toxin proteins in the mazEF TA system should be investigated further as an effective antibacterial strategy against this bacterium.

Ecoepidemiology, short history and control of Chagas disease in the endemic countries and the new challenge for non-endemic countries

Chagas disease is maintained in nature through the interchange of three cycles: the wild, peridomestic and domestic cycles. The wild cycle, which is enzootic, has existed for millions of years maintained between triatomines and wild mammals. Human infection was only detected in mummies from 4,000-9,000 years ago, before the discovery of the disease by Carlos Chagas in 1909. With the beginning of deforestation in the Americas, two-three centuries ago for the expansion of agriculture and livestock rearing, wild mammals, which had been the food source for triatomines, were removed and new food sources started to appear in peridomestic areas: chicken coops, corrals and pigsties. Some accidental human cases could also have occurred prior to the triatomines in peridomestic areas. Thus, triatomines progressively penetrated households and formed the domestic cycle of Chagas disease. A new epidemiological, economic and social problem has been created through the globalisation of Chagas disease, due to legal and illegal migration of individuals infected by Trypanosoma cruzi or presenting Chagas disease in its varied clinical forms, from endemic countries in Latin America to non-endemic countries in North America, Europe, Asia and Oceania, particularly to the United States of America and Spain. The main objective of the present paper was to present a general view of the interchanges between the wild, peridomestic and domestic cycles of the disease, the development of T. cruzi among triatomine, their domiciliation and control initiatives, the characteristics of the disease in countries in the Americas and the problem of migration to non-endemic countries.

Imaging of human leukemic T-cell xenografts in nude mice by radiolabeled monoclonal antibodies and F(ab')2 fragments.

Monoclonal antibodies (MoAb) that react with the T-lymphocyte markers called cluster of differentiation CD5 and CD2 were labeled with iodine 131 (131I) and were injected intravenously in nude mice bearing solid subcutaneous xenografts derived from the human T-cell leukemia line Ichikawa. Both MoAb anti-CD5 and anti-CD2 yielded favorable mean tumor to whole-body ratios of 3.8 and 5.1, respectively. These ratios were further increased up to 10.0 for MoAb anti-CD5 and 15.5 for MoAb anti-CD2 by using their F(ab')2 fragments. The tumors could be imaged clearly by external scanning after injection of F(ab')2 fragments from both MoAb. F(ab')2 fragments from MoAb anti-CD2 and of a third MoAb recognizing the clonotypic determinant (Ti) of the antigen receptor expressed by the human T-cell line Jurkat were injected in mice bearing intrasplenic Jurkat xenografts. A selective localization of both fragments in tumor tissue was demonstrated with mean tumor to whole-body ratios of 7.5 and 4.1 for MoAb anti-CD2 and anti-Ti, respectively. These in vivo experimental results may provide useful information for the potential use of radiolabeled MoAb and fragments in the diagnosis and treatment of patients with T-cell lymphoma and different other forms of T-cell malignancies.

Modulation of Trypanosoma cruzi-specific T-cell responses after chemotherapy for chronic Chagas disease

The aim of this review is to describe the contributions of the knowledge of T-cell responses to the understanding of the physiopathology and the responsiveness to etiological treatment during the chronic phase of Chagas disease.T-helper (Th)1 and interleukin (IL)-10Trypanosoma cruzi-specific T-cells have been linked to the asymptomatic phase or to severe clinical forms of the disease, respectively orvice versa, depending on the T. cruziantigen source, the patient’s location and the performed immunological assays. Parasite-specific T-cell responses are modulated after benznidazole (BZ) treatment in chronically T. cruzi-infected subjects in association with a significant decrease in T. cruzi-specific antibodies. Accumulating evidence has indicated that treatment efficacy during experimental infection with T. cruziresults from the combined action of BZ and the activation of appropriate immune responses in the host. However, strong support of this interaction in T. cruzi-infected humans remains lacking. Overall, the quality of T-cell responses might be a key factor in not only disease evolution, but also chemotherapy responsiveness. Immunological parameters are potential indicators of treatment response regardless of achievement of cure. Providing tools to monitor and provide early predictions of treatment success will allow the development of new therapeutic options.

Gene expression profiling of isolated tumour cells from anaplastic large cell lymphomas: insights into its cellular origin, pathogenesis and relation to Hodgkin lymphoma.

Anaplastic large cell lymphoma (ALCL) is a main type of T-cell lymphomas and comprises three distinct entities: systemic anaplastic lymphoma kinase (ALK) positive, systemic ALK(-) and cutaneous ALK(-) ALCL (cALCL). Little is known about their pathogenesis and their cellular origin, and morphological and immunophenotypical overlap exists between ALK(-) ALCL and classical Hodgkin lymphoma (cHL). We conducted gene expression profiling of microdissected lymphoma cells of five ALK(+) and four ALK(-) systemic ALCL, seven cALCL and sixteen cHL, and of eight subsets of normal T and NK cells. The analysis supports a derivation of ALCL from activated T cells, but the lymphoma cells acquired a gene expression pattern hampering an assignment to a CD4(+), CD8(+) or CD30(+) T-cell origin. Indeed, ALCL display a down-modulation of many T-cell characteristic molecules. All ALCL types show significant expression of NFkappaB target genes and upregulation of genes involved in oncogenesis (e.g. EZH2). Surprisingly, few genes are differentially expressed between systemic and cALCL despite their different clinical behaviour, and between ALK(-) ALCL and cHL despite their different cellular origin. ALK(+) ALCL are characterized by expression of genes regulated by pathways constitutively activated by ALK. This study provides multiple novel insights into the molecular biology and pathogenesis of ALCL.

Association of the solute carrier family 11 member 1 gene polymorphisms with susceptibility to leprosy in a Brazilian sample

Natural resistance-associated macrophage protein 1/solute carrier family 11 member 1 gene (Nramp1/Slc11a1) is a gene that controls the susceptibility of inbred mice to intracellular pathogens. Polymorphisms in the human Slc11a1/Nramp1 gene have been associated with host susceptibility to leprosy. This study has evaluated nine polymorphisms of the Slc11a1/Nramp1 gene [(GT)n, 274C/T, 469+14G/C, 577-18G/A, 823C/T, 1029 C/T, 1465-85G/A, 1703G/A, and 1729+55del4] in 86 leprosy patients (67 and 19 patients had the multibacillary and the paucibacillary clinical forms of the disease, respectively), and 239 healthy controls matched by age, gender, and ethnicity. The frequency of allele 2 of the (GT)n polymorphism was higher in leprosy patients [p = 0.04, odds ratio (OR) = 1.49], whereas the frequency of allele 3 was higher in the control group (p = 0.03; OR = 0.66). Patients carrying the 274T allele (p = 0.04; OR = 1.49) and TT homozygosis (p = 0.02; OR = 2.46), such as the 469+14C allele (p = 0.03; OR = 1.53) of the 274C/T and 469+14G/C polymorphisms, respectively, were more frequent in the leprosy group. The leprosy and control groups had similar frequency of the 577-18G/A, 823C/T, 1029C/T, 1465-85G/A, 1703G/A, and 1729+55del4 polymorphisms. The 274C/T polymorphism in exon 3 and the 469+14G/C polymorphism in intron 4 were associated with susceptibility to leprosy, while the allele 2 and 3 of the (GT)n polymorphism in the promoter region were associated with susceptibility and protection to leprosy, respectively.

Colorectal Cancer Classification and Cell Heterogeneity: A Systems Oncology Approach.

Colorectal cancer is a heterogeneous disease that manifests through diverse clinical scenarios. During many years, our knowledge about the variability of colorectal tumors was limited to the histopathological analysis from which generic classifications associated with different clinical expectations are derived. However, currently we are beginning to understand that under the intense pathological and clinical variability of these tumors there underlies strong genetic and biological heterogeneity. Thus, with the increasing available information of inter-tumor and intra-tumor heterogeneity, the classical pathological approach is being displaced in favor of novel molecular classifications. In the present article, we summarize the most relevant proposals of molecular classifications obtained from the analysis of colorectal tumors using powerful high throughput techniques and devices. We also discuss the role that cancer systems biology may play in the integration and interpretation of the high amount of data generated and the challenges to be addressed in the future development of precision oncology. In addition, we review the current state of implementation of these novel tools in the pathological laboratory and in clinical practice.

Leprosy in children and adolescents under 15 years old in an urban centre in Brazil

This original study describes the intra-urban distribution of cases of leprosy in residents under 15 years old in Salvador, Bahia, Brazil; the study also identifies the environment in which Mycobacterium leprae is being transmitted. The cases were distributed by operational classification, clinical forms, type of contact and the addresses were geo-referenced by neighborhood. Between 2007 and 2011, were reported 145 cases of leprosy in target population living in Salvador, corresponding to detection rates of 6.21, 6.14, 5.58, 5.41 and 6.88/100,000 inhabitants, respectively. The spatial distribution of the disease was focal. Of the 157 neighborhoods of Salvador, 44 (28.6%) notified cases of leprosy and in 22 (50%) of these were detected more than 10 cases per 100,000 inhabitants. The infectious forms were found in 40% of cases. Over 90% of cases had been living in Salvador for more than five years. Overall, 52.6% reported having had contact with another infected individual inside the household and 25% in their social circle. In Salvador, M. leprae transmission is established. The situation is a major concern, since transmission is intense at an early age, indicating that this endemic disease is expanding and contacts extend beyond individual households.