Seroprevalence of Triatoma virus (Dicistroviridae: Cripaviridae) antibodies in Chagas disease patients

Background: Chagas disease is caused by Trypanosoma cruzi, and humans acquire the parasite by exposure to contaminated feces from hematophagous insect vectors known as triatomines. Triatoma virus (TrV) is the sole viral pathogen of triatomines, and is transmitted among insects through the fecal-oral route and, as it happens with T. cruzi, the infected insects release the virus when defecating during or after blood uptake. Methods: In this work, we analysed the occurrence of anti-TrV antibodies in human sera from Chagas disease endemic and non-endemic countries, and developed a mathematical model to estimate the transmission probability of TrV from insects to man, which ranged between 0.00053 and 0.0015. Results: Our results confirm that people with Chagas disease living in Bolivia, Argentina and Mexico have been exposed to TrV, and that TrV is unable to replicate in human hosts. Conclusions: We presented the first experimental evidence of antibodies against TrV structural proteins in human sera.

On an acute case of Chagas disease in a region under vector control in the state of São Paulo, Brazil

Desde a década de 1970 não se notificavam casos autóctones de doença de Chagas aguda em São Paulo. em março de 2006 a Vigilância Epidemiológica registrou óbito por doença de Chagas aguda, em Itaporanga, de paciente de seis anos de idade. Exame histopatológico post mortem realizado no Hospital das Clínicas da Faculdade de Medicina de Botucatu confirmou o diagnóstico. Consultamos prontuários de hospitais e entrevistamos profissionais de saúde envolvidos além de familiares do paciente. Descrevemos medidas adotadas in loco para identificar a via de transmissão, reservatórios e vetores. Discutimos as possíveis fontes de infecção. Na região não foram identificados outros casos humanos, vetores ou reservatórios vertebrados infectados por Trypanosoma cruzi. Salientamos a importância de manter a vigilância, mesmo em áreas onde a transmissão de doença de Chagas está interrompida e naquelas ainda infestadas por triatomíneos. Deve-se admitir a hipótese diagnóstica de doença de Chagas quando observados: edema palpebral (uni ou bilateral), insuficiência cardíaca, miocardite, pericardite, anasarca, quadros similares aos de síndrome nefrótica ou glomerulonefrite sem causas outras aparentes, em pacientes com dados epidemiológicos positivos. Encontro, mesmo em raras ocasiões, de triatomíneos na região ou ainda contato com alimento contaminável com formas infectantes de T. cruzi.

Chagas disease and triatomine biology (Heteroptera, Triatominae), with emphasis on aspects of spermatogenesis

A century after the discovery of Chagas disease, it is still one of the most important parasitic diseases affecting humans. The subfamily Triatominae is important in medical health, because these insects are vectors of Trypanosoma cruzi, the etiologic agent of Chagas disease. These insects are also of important cytological relevance because they have particular cell characteristics, such as persistence of nucleolar material in spermatogenesis. The germ cells of the animal kingdom have chromatoid bodies (CBs) in their cytoplasm that can originate from nucleolar material that is fragmented in the early stages of spermatogenesis and plays an important role in cellular communication between the spermatids during spermiogenesis. Currently, there are few studies on the function and formation of the CB in nucleologenesis, especially with emphasis on the ultrastructure of the cells involved in spermatogenesis of insects. Considering the importance of knowledge about the triatomine fauna, we conducted a study of the biogeography and reports of these insects and a survey of patients with Chagas disease in the northwestern region of São Paulo State. Data collected from 1995 to 2009 indicated 700 individuals with Chagas disease, demonstrating a range of 0 to 40 years, which shows that the disease may be active in this region. Moreover, of the 1150 patients treated for cardiomyopathy, 44% were chagasic. Regarding the triatomines noted and captured in the period from 2004 to 2009, the species were Triatoma sordida and Rhodnius neglectus, with T. sordida being the most abundant. In addition, some triatomines were infected by T. cruzi in various developmental stages. We also analyzed the nucleolar cycle and fibrillarin nucleolar protein expression in CB of spermatogenic cells of T. infestans and T. sordida, using histological, ultrastructural and immunocytochemical techniques. The results revealed fibrillarin nucleolar protein expression in the nucleus and in some cytoplasmic spots of germ cells during spermatogenesis in triatomines. These data suggest that fibrillarin could be a constituent of CB, which was most likely derived from nucleolar fragmentation. This is the first time that fibrillarin protein expression has been shown in CB during spermatogenesis progression in triatomines. Knowledge about the biology of triatomines was deepened in this study and, in particular, the structural and ultrastructural aspects of spermatogenesis in triatomines. This study showed that the disease may be active in the northwestern region of São Paulo and expanded our knowledge of the biology of triatomines, the main vectors of Chagas disease. © FUNPEC-RP.

Biologic and genetics aspects of chagas disease at endemic areas

The etiologic agent of Chagas Disease is the Trypanosoma cruzi, transmitted through blood-sucking insect vectors of the Triatominae subfamily, representing one of the most serious public health concerns in Latin America. There are geographic variations in the prevalence of clinical forms and morbidity of Chagas disease, likely due to genetic variation of the T. cruzi and the host genetic and environmental features. Increasing evidence has supported that inflammatory cytokines and chemokines are responsible for the generation of the inflammatory infiltrate and tissue damage. Moreover, genetic polymorphisms, protein expression levels, and genomic imbalances are associated with disease progression. This paper discusses these key aspects. Large surveys were carried out in Brazil and served as baseline for definition of the control measures adopted. However, Chagas disease is still active, and aspects such as host-parasite interactions, genetic mechanisms of cellular interaction, genetic variability, and tropism need further investigations in the attempt to eradicate the disease. Copyright 2012 Marilanda Ferreira Bellini et al.

Entoepidemiology of Chagas disease in the Western region of the State of Sao Paulo from 2004 to 2008, and cytogenetic analysis in Rhodnius neglectus (Hemiptera, Triatominae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Study on Chagas disease occurrence in the municipality of Monte Negro, State of Rondônia, Brazilian Amazon

Introduction: Studies on Chagas disease deal with the perspective of its occurrence in the Amazon region, which is directly correlated to the population growth and the spread of the bug biotope. The state of Rondônia has an immense source of vectors (Triatomine) and reservoirs of Trypanosoma cruzi. Environmental changes brought forth by the deforestation in the region may cause vector behavior changes and bring these vectors to a closer contact with humans, increasing the probability of vector infection. Methods: This study was carried out to check the occurrence of Chagas disease in the municipality of Monte Negro, Rondônia, Brazil, based on a random sampling of the farms and people wherein blood collection from the population and capturing triatomines were done. The blood samples were submitted to serologic tests to detect antibodies of the IgG class against T. cruzi. The triatomines that were collected had their digestive tract checked for the presence of trypanosomatidae with morphology resembling that of the T. cruzi. Results: The population examined was mostly from other states. From the 322 bugs examined on the microscope, 50% showed parasites with morphology compatible with T. cruzi. From the serology of 344 random samples of human blood, 1.2% was found positive, 6% showed inconclusive results, and 92.8% were negative. Conclusions: Monte Negro shows low prevalence of human infection by T. cruzi and none active vector transmission; however, preventive and surveying measures, which are not performed until now, shall be taken due to the abundance of vectors infected by trypanosomatidae.

Antigenic variation in surface proteins of Trypanosoma cruzi (Chagas' disease)

Chagas' disease, a devastating illness in the Western Hemisphere, is caused by the protozoan parasite Trypanosoma cruzi. Transmission is via bloodsucking insect vectors, congenitally, or through blood transfusion and/or organ transplantation. A significant percentage of heart-related illnesses and deaths each year are attributable to the number of persons with Chagas' disease. Currently, there is no FDA-approved routine screening of the U.S. blood supply being conducted by blood banks. The only current commercial assays available for detection of Trypanosoma cruzi are based on South American isolates, which may differ antigenically from those found in the US. In this study, the assay used intact parasites as antigen in an ELISA-type assay. Therefore, serological differences presumably reflected variations in surface antigens. The basis of differential antibody binding to these antigens is unknown. In this study, biochemical characterization and genetic polymorphism analysis will be performed on three defined surface proteins of T. cruzi epimastigotes.^

Aquatic ecology monitoring: water quality, fish, fish catch, sanitation and disease vectors: monitoring No. 5, 6th-9th October 2009

The survey covered by this report was undertaken between 6 th and 9th October 2009 as a follow-up on the during construction surveys of the Bujagali Hydropwer Project (BHPP). In addition to two pre-construction baseline surveys in April 2000 and April 2006, four monitoring surveys have so far been undertaken i.e. in September 2007, April 2008, April 2009 and the present one, in October 2009. The 2009 biannual monitoring surveys were conducted at an upstream and a downstream transect of the BHPP with emphasis on the following aspects: 1. water quality determinants 2. biology and ecology of fishes and food webs 3. fish stock and fish catch including economic aspects of catch and 4. sanitation/vector studies (bilharzias and river blindness)

Aquatic ecology monitoring: water quality, fish, fish catch, sanitation and disease vectors: monitoring no. 8, 6– 10th April 2011

The result reported were from a monitoring survey no.8 undertaken between 6th and 10th April 2011 during construction period of the Bujagali Hydropwer Project (BHPP). Two pre-construction, baseline surveys in April 2000 and April 2006 were conducted and so far,durin construction phase of the project, seven monitoring surveys have been undertaken i.e. in September 2007, April 2008, April 2009,October 2009, April 2010, September 2010 and the present one, in April 2011. Since 2009 biannual monitoring surveys have been conducted at an upstream and a downstream transect of the BHPP with emphasis on the following aspects: Water quality determinants Biology and ecology of fishes and food webs Fish stock and fish catch including economic aspects of catch and Sanitation/vector studies (bilharzias and river blindness)

Aquatic ecology monitoring: water quality, fish, fish catch, sanitation and disease vectors: monitoring no. 10 and reservoir baseline, 23rd – 30th April 2012

The results reported on were from a monitoring survey No. 10 undertaken between 23 rd and 29th April 2012 during construction period of the Bujagali Hydropower Project (BHPP). Two pre-construction, baseline surveys in April 2000 and April 2006 were conducted and so far, during construction phase of the project, nine monitoring surveys have been undertaken i.e. in September 2007, April 2008, April 2009, October 2009, April 2010, September 2010, April 2011, September 2011and the present one, in April 2012. Since 2009 biannual monitoring surveys have been conducted at an upstream and a downstream transect of the BHPP with emphasis on the following aspects: water quality determinants biology and ecology of fishes and food webs fish stock and fish catch including economic aspects of catch and sanitation/vector studies (bilharzias and river blindness) During this survey, baseline assessment of the above mentioned studies was conducted in the reservoir behind the dam, including studies on algae, zooplankton and benthic macroinvertebrates which had been restrained since April 2008. The findings of baseline assessment of the reservoir are also contained in this report and are compared with those obtained from Transect 1(Upstream) and Transect 2 (Downstream).

Aquatic ecology monitoring, water quality, fish, fish catch, sanitation and disease vectors: monitoring no. 11, 4th – 9th September 2012

This monitoring survey No. 11 undertaken between 4th and 9th September 2012 is the second one to be conducted after completion of construction of Bujagali Hydropower Dam. Two pre-construction baseline surveys in April 2000 and April 2006 were conducted and during construction phase, eight monitoring surveys (September 2007, April 2008, April 2009, October 2009, April 2010, September 2010, April 2011, September 2011) were conducted.

Aquatic ecology monitoring: water quality, fish, fish catch, sanitation and disease vectors: monitoring No.7, 4-7th September 2010

The results reported on were from a monitoring survey No.7 undertaken between 4 th and 7th September 2010 during construction period of the Bujagali Hydropower Project (BHPP). Two pre-construction, baseline surveys in April 2000 and April 2006 were conducted and so far, during construction phase of the project, six monitoring surveys have been undertaken i.e. in September 2007, April 2008, April 2009, October 2009, April 2010 and the present one, in September 2010. Since 2009 biannual monitoring surveys have been conducted at an upstream and a downstream transect of the BHPP with emphasis on the following aspects: I. water quality determinants 2. biology and ecology of fishes and food webs 3. fish stock and fish catch including economic aspects of catch and 4. sanitation/vector studies (bilharzias and river blindness)

Aquatic ecology monitoring: water quality, fish, fish catch, sanitation and disease vectors: monitoring no.12, 25th-30th April 2013

Bujagali hydropower dam construction is now completed and a reservoir behind the dam has been created, extending all the way up to Kalange-Makwanzi, an upstream transects. During the 10th monitoring survey-April 2012, a third transect was established in the mid of the reservoir where it runs up to 30 m deep and sampled similarly as at the two original sampling transects, Kalange-Makwanzi and Buyala-Kikubamutwe for comparative purposes. This monitoring survey No. 12 undertaken between 25th and 30th April 2013 is the third one to be conducted after completion of construction of Bujagali Hydropower Dam. Two pre-construction baseline surveys in April 2000 and April 2006 were conducted and during construction phase, eight monitoring surveys (September 2007, April 2008, April 2009, October 2009, April 2010, September 2010, April 2011, September 2011) were conducted. Since 2009 biannual monitoring surveys have been conducted at an upstream and a downstream transect of the BHPP with emphasis on the following aspects: water quality determinants, biology and ecology of fishes and food webs, fish stock and fish catch including economic aspects of catch and sanitation/vector studies (bilharzias and river blindness). In the post-construction monitoring surveys, the assessments of algae, zooplankton and benthic macro-invertebrates which had been restrained since April 2008 were also included.

Towards the enantioselective synthesis of Plakortide P and its application to the development of drugs for the treatment of Chagas disease

The primary focus of this thesis was the asymmetric peroxidation of α,β-unsaturated aldehydes and the development of this methodology to include the synthesis of bioactive chiral 1,2-dioxane and 1,2-dioxalane rings. In Chapter 1 a review detailing the new and improved methods for the acyclic introduction of peroxide functionality to substrates over the last decade was discussed. These include a detailed examination of metal-mediated transformations, chiral peroxidation using organocatalytic means and the improvements in methodology of well-established peroxidation pathways. The second chapter discusses the method by which peroxidation of our various substrates was attempted and the optimisation studies associated with these reactions. The method by which the enantioselectivity of our β-peroxyaldehydes was determined is also reviewed. Chapters 3 and 4 focus on improving the enantioselectivity associated with our asymmetric peroxidation reaction. A comprehensive analysis exploring the effect of solvent, concentration and temperature on enantioselectivity was examined. The effect that different catalytic systems have on enantioselectivity and reactivity was also investigated in depth. Chapter 5 details the various transformations that β-peroxyaldehydes can undergo and the manipulation of these transformations towards the establishment of several routes for the formation of chiral 1,2-dioxane and 1,2-dioxalane rings. Chapter 6 details the full experimental procedures, including spectroscopic and analytical data for the compounds prepared during this research.