Alterações ao Doppler tecidual em pacientes com a forma aguda da doença de chagas / Alterations to tissue Doppler in patients with acute form of chagas disease

Fundamento: Recentemente tem ocorrido aumento do número de casos agudos de doença de Chagas, principalmente causados por transmissão oral. A maioria dos pacientes mostra boa evolução, apresentando sintomatologia compatívelcom processo infeccioso sistêmico, porém sem alterações cardíacas significativas ao exame físico, eletrocardiograma eecocardiograma transtorácico.Objetivo: Avaliar alterações ecocardiográficas com análise do Doppler tecidual em pacientes com doença de Chagas aguda. Métodos: Foram avaliados pacientes com diagnóstico de doença de Chagas aguda confirmada por exame parasitológico direto. Esses pacientes foram submetidos a exame físico, eletrocardiograma e ecocardiograma transtorácico, sendocomparados com um grupo controle.Resultados: Foram avaliados 12 casos com doença de Chagas aguda e 15 indivíduos no grupo controle. As variáveis que apresentaram diferenças significativas foram: ondas S’ lateral de VE (DCA = 0,09 ± 0,02 m/seg; GC = 0,11 ± 0,02 m/seg; p = 0,024); E’ lateral (DCA = 0,13 ± 0,03 m/seg; GC = 0,18 ± 0,03 m/seg; p = 0,001); E’ septal do VE (DCA = 0,10± 0,03 m/seg; GC = 0,14 ± 0,03 m/seg; p = 0,008), A’ lateral do VE (DCA = 0,08 ± 0,03 m/seg; GC = 0,12 ± 0,01 m/seg;p = 0,003), onda S’ do VD (DCA = 0,12 ± 0,02 m/seg; GC = 0,17 ± 0,02 m/seg; p < 0,001) e TAPSE (DCA = 1,95 ±0,41 cm; GC = 2,37 ± 0,25 cm; p = 0,006). Conclusões: Em pacientes com doença de Chagas aguda, mesmo quando apresentam evolução benigna, podem ocorrer alterações subclínicas detectadas principalmente ao Doppler tecidual. Essas alterações podem ser importantes na avaliação do tratamento da fase aguda e na sua evolução a longo prazo.

Background: Recently there has been an increased number of cases of acute Chagas disease primarily caused by oral transmission. Most patients have a good outcome, presenting symptoms consistent with systemic infectious process, but no significant cardiac abnormalities on physical examination, electrocardiogram and echocardiogram.Objective: To evaluate echocardiographic changes with tissue Doppler analysis in patients with acute Chagas disease.Methods: We evaluated patients with acute Chagas disease confirmed by cytological examination. These patients underwent a physical examination, eletrocardiogram and transthoracic echocardiography, and compared with a control group. Results: We evaluated 12 patients with acute Chagas disease and 15 subjects in the control group. Variables that showed significant diferences were waves S ‘side of LV (DCA = 0.09 ± 0.02m/sec; CG = 0.11 ± 0.02 m/sec; p = 0.024); and ‘side (DCA = 0.13 ± 0.03 m/sec; CG = 0.18 ±0.03 m/sec; p = 0.001); Septal E ‘LV (DCA = 0.10 ± 0.03 m/sec; CG = 0.14 ± 0.03 m/sec; p = 0.008), A’ lateral LV (DCA = 0.08 ± 0.03 m/sec;CG = 0 12 ± 0.01 m/sec; p = 0,003), S wave ‘RV (DCA = 0.12 ± 0.02 m/sec; CG = 0.17 ± 0.02 m/sec; p < 0.001) and TAPSE (DCA = 1,95cm ± 0.41; CG = 2.37 ± 0.25 cm; p = 0.006). Conclusions: In patients with acute Chagas disease, even when present benign, there may be subclinical alterations detected primarilyby tissue Doppler. These changes may be important in the treatment of acute and its long-term evolution.

Chronic Heart Disease after Treatment of Oral Acute Chagas Disease.

We describe the recurrence of cardiac abnormalities in a patient treated during the acute phase of Chagas disease after outpatient follow-up of 5 years.

Chronic Heart Disease after Treatment of Oral Acute Chagas Disease / Cardiopatia Crônica após Tratamento de Doença de Chagas Aguda Oral

Abstract We describe the recurrence of cardiac abnormalities in a patient treated during the acute phase of Chagas disease after outpatient follow-up of 5 years.

Resumo Descreve-se a recorrência de alterações cardíacas em paciente tratado na fase aguda de doença de Chagas, após seguimento ambulatorial de 5 anos.

Polymerase chain reaction-based method for the identification of Leishmania (Viannia) braziliensis and Leishmania (Viannia) guyanensis in mucosal tissues conserved in paraffin.

INTRODUCTION: In the Americas, mucosal leishmaniasis is primarily associated with infection by Leishmania (Viannia) braziliensis. However, Leishmania (Viannia) guyanensis is another important cause of this disease in the Brazilian Amazon. In this study, we aimed at detecting Leishmaniadeoxyribonucleic acid (DNA) within paraffin-embedded fragments of mucosal tissues, and characterizing the infecting parasite species. METHODS: We evaluated samples collected from 114 patients treated at a reference center in the Brazilian Amazon by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses. RESULTS: Direct examination of biopsy imprints detected parasites in 10 of the 114 samples, while evaluation of hematoxylin and eosin-stained slides detected amastigotes in an additional 17 samples. Meanwhile, 31/114 samples (27.2%) were positive for Leishmania spp. kinetoplast deoxyribonucleic acid (kDNA) by PCR analysis. Of these, 17 (54.8%) yielded amplification of the mini-exon PCR target, thereby allowing for PCR-RFLP-based identification. Six of the samples were identified as L. (V.) braziliensis, while the remaining 11 were identified as L. (V.) guyanensis. CONCLUSIONS: The results of this study demonstrate the feasibility of applying molecular techniques for the diagnosis of human parasites within paraffin-embedded tissues. Moreover, our findings confirm that L. (V.) guyanensisis a relevant causative agent of mucosal leishmaniasis in the Brazilian Amazon.

Polymerase chain reaction-based method for the identification of Leishmania (Viannia) braziliensis and Leishmania (Viannia) guyanensis in mucosal tissues conserved in paraffin

ABSTRACTINTRODUCTION: In the Americas, mucosal leishmaniasis is primarily associated with infection by Leishmania (Viannia) braziliensis. However, Leishmania (Viannia) guyanensis is another important cause of this disease in the Brazilian Amazon. In this study, we aimed at detecting Leishmaniadeoxyribonucleic acid (DNA) within paraffin-embedded fragments of mucosal tissues, and characterizing the infecting parasite species.METHODS: We evaluated samples collected from 114 patients treated at a reference center in the Brazilian Amazon by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses.RESULTS: Direct examination of biopsy imprints detected parasites in 10 of the 114 samples, while evaluation of hematoxylin and eosin-stained slides detected amastigotes in an additional 17 samples. Meanwhile, 31/114 samples (27.2%) were positive for Leishmania spp. kinetoplast deoxyribonucleic acid (kDNA) by PCR analysis. Of these, 17 (54.8%) yielded amplification of the mini-exon PCR target, thereby allowing for PCR-RFLP-based identification. Six of the samples were identified as L. (V.) braziliensis, while the remaining 11 were identified as L. (V.) guyanensis.CONCLUSIONS: The results of this study demonstrate the feasibility of applying molecular techniques for the diagnosis of human parasites within paraffin-embedded tissues. Moreover, our findings confirm that L. (V.) guyanensisis a relevant causative agent of mucosal leishmaniasis in the Brazilian Amazon.

Tegumentary leishmaniasis in the State of Amazonas: what have we learned and what do we need?

This study evaluated the occurrence of American tegumentary leishmaniasis (ATL) in the State of Amazonas, Brazil, in the last 30 years with emphasis on the last 10 years (2001 to 2010). The disease was predominantly observed in males (76.2%), in the 21- to 30-year-old age group (26.6%) and in extractive workers (43.7%); 3.3% of the cases were the mucosal form. The endemic channel shows the disease seasonality, with a predominance of cases at the beginning and end of each year. The number of cases by municipality in the period of 2001-2010 shows the maintenance of the endemic in the localities where the highest numbers of cases have always been registered, namely, Manaus, Rio Preto da Eva, Itacoatiara and Presidente Figueiredo. The comparison of data from 2001 to 2005 and from 2006 to 2010 showed the emergence of this disease in municipalities that had been previously unaffected. In the last years, there has been a significant increase in the activities of control, diagnosis and treatment of leishmaniasis in the State of Amazonas. In conclusion, the historical series of ATL analyzed in this study suggests that the transmission foci remain and are even expanding, though without continuous transmission in the intra- or peridomicile settings. Moreover, the disease will persist in the Amazon while the factors associated with infection acquisition relative to forest exploitation continue to have economic appeal. There is a real expectation of wide variations in disease incidence that can be influenced by climate and economic aspects.

Chagas disease in the State of Amazonas: history, epidemiological evolution, risks of endemicity and future perspectives.

Chagas disease (CD) is a parasitic infection that originated in the Americas and is caused by Trypanosoma cruzi. In the last few years, the disease has spread to countries in North America, Asia and Europe due to the migration of Latin Americans. In the Brazilian Amazon, CD has an endemic transmission, especially in the Rio Negro region, where an occupational hazard was described for piaçaveiros (piassaba gatherers). In the State of Amazonas, the first chagasic infection was reported in 1977, and the first acute CD case was recorded in 1980. After initiatives to integrate acute CD diagnostics with the malaria laboratories network, reports of acute CD cases have increased. Most of these cases are associated with oral transmission by the consumption of contaminated food. Chronic cases have also been diagnosed, mostly in the indeterminate form. These cases were detected by serological surveys in cardiologic outpatient clinics and during blood donor screening. Considering that the control mechanisms adopted in Brazil's classic transmission areas are not fully applicable in the Amazon, it is important to understand the disease behavior in this region, both in the acute and chronic cases. Therefore, the pursuit of control measures for the Amazon region should be a priority given that CD represents a challenge to preserving the way of life of the Amazon's inhabitants.

Tegumentary leishmaniasis in the State of Amazonas: what have we learned and what do we need?

This study evaluated the occurrence of American tegumentary leishmaniasis (ATL) in the State of Amazonas, Brazil, in the last 30 years with emphasis on the last 10 years (2001 to 2010). The disease was predominantly observed in males (76.2%), in the 21- to 30-year-old age group (26.6%) and in extractive workers (43.7%); 3.3% of the cases were the mucosal form. The endemic channel shows the disease seasonality, with a predominance of cases at the beginning and end of each year. The number of cases by municipality in the period of 2001-2010 shows the maintenance of the endemic in the localities where the highest numbers of cases have always been registered, namely, Manaus, Rio Preto da Eva, Itacoatiara and Presidente Figueiredo. The comparison of data from 2001 to 2005 and from 2006 to 2010 showed the emergence of this disease in municipalities that had been previously unaffected. In the last years, there has been a significant increase in the activities of control, diagnosis and treatment of leishmaniasis in the State of Amazonas. In conclusion, the historical series of ATL analyzed in this study suggests that the transmission foci remain and are even expanding, though without continuous transmission in the intra- or peridomicile settings. Moreover, the disease will persist in the Amazon while the factors associated with infection acquisition relative to forest exploitation continue to have economic appeal. There is a real expectation of wide variations in disease incidence that can be influenced by climate and economic aspects.

Chagas disease in the State of Amazonas: history, epidemiological evolution, risks of endemicity and future perspectives

Chagas disease (CD) is a parasitic infection that originated in the Americas and is caused by Trypanosoma cruzi. In the last few years, the disease has spread to countries in North America, Asia and Europe due to the migration of Latin Americans. In the Brazilian Amazon, CD has an endemic transmission, especially in the Rio Negro region, where an occupational hazard was described for piaçaveiros (piassaba gatherers). In the State of Amazonas, the first chagasic infection was reported in 1977, and the first acute CD case was recorded in 1980. After initiatives to integrate acute CD diagnostics with the malaria laboratories network, reports of acute CD cases have increased. Most of these cases are associated with oral transmission by the consumption of contaminated food. Chronic cases have also been diagnosed, mostly in the indeterminate form. These cases were detected by serological surveys in cardiologic outpatient clinics and during blood donor screening. Considering that the control mechanisms adopted in Brazil's classic transmission areas are not fully applicable in the Amazon, it is important to understand the disease behavior in this region, both in the acute and chronic cases. Therefore, the pursuit of control measures for the Amazon region should be a priority given that CD represents a challenge to preserving the way of life of the Amazon's inhabitants.

Impact of benznidazole on infection course in mice experimentally infected with Trypanosoma cruzi I, II, and IV.

American trypanosomiasis is an emerging zoonosis in the Brazilian Amazon. Studies on benznidazole (BZ) chemotherapy with Trypanosoma cruzi from this region have great relevance, given the different discrete typing units (DTUs) that infect humans in the Amazon and other regions of Brazil. We performed a parasitological, histopathological, and molecular analysis of mice inoculated with strains of T. cruzi I, II, and IV that were BZ-treated during the acute phase of infection. Groups of Swiss mice were inoculated; 13 received oral BZ, whereas the other 13 comprised the untreated controls. Unlike parasitemia, the infectivity and mortality did not vary among the DTUs. Trypanosoma cruzi DNA was detected in all tissues analyzed and the proportion of organs parasitized varied with the parasite DTU. The BZ treatment reduced the most parasitological parameters, tissue parasitism and the inflammatory processes at all infection stages and for all DTUs. However, the number of significant reductions varied according to the DTU and infection phase.

Comparative pathogenicity in Swiss mice of Trypanosoma cruzi IV from northern Brazil and Trypanosoma cruzi II from southern Brazil.

The geographical heterogeneity of Chagas disease (ChD) is mainly caused by genetic variability of the etiological agent Trypanosoma cruzi. Our hypothesis was that the pathogenicity for mice may vary with the genetic lineage (or Discrete Typing Unit - DTU) of the parasite. To test this hypothesis, parasitological and histopathological evaluations were performed in mice inoculated with strains belonging to the DTU T. cruzi IV (TcIV) from the State of Amazonas (northern Brazil), or the DTU T. cruzi II (TcII) from the State of Paraná (southern Brazil). Groups of 10 Swiss mice were inoculated with eight strains of TcIV obtained from acute cases (7) from two outbreaks of orally acquired ChD, and from the triatomine Rhodnius robustus (1) from Amazonas; and three strains of TcII obtained from chronic patients in Paraná. We evaluated the pre-patent period, patent period, maximum peak of parasitemia, day of maximum peak of parasitemia, area under the parasitemia curve, inflammatory process, and tissue parasitism in the acute phase. TcIV was less virulent than TcII, and showed significantly (p < 0.005) lower parasitemia levels. Although the levels of tissue parasitism did not differ statistically, mice infected with TcIV displayed significantly (p < 0.001) fewer inflammatory processes than mice infected with TcII. This supported the working hypothesis, since TcIV from Amazonas was less pathogenic than TcII from Paraná; and agreed with the lower severity of human cases of ChD in the Amazon region.

Historical analysis of the records of sylvan yellow fever in the State of Amazonas, Brazil, from 1996 to 2009.

INTRODUCTION: Yellow fever is a non-contagious infectious disease, highly lethal, transmitted by the Aedes, Haemagogus and Sabethes. METHODS: Descriptive retrospective study of the yellow fever cases in Amazonas, between 1996 and 2009. RESULTS: Forty two cases of yellow fever were confirmed, with 30 deaths, 10% of which were foreigners. CONCLUSIONS: The presence of Aedes aegypti and Aedes albopictus in both rural Amazonas and its capital demonstrates the dispersion of these vectors and underscores the need for better and continuous epidemiological and entomological control.

Outbreak of acute Chagas disease associated with oral transmission in the Rio Negro region, Brazilian Amazon.

INTRODUCTION: Chagas disease is considered as emerging in the Brazilian Amazon, usually occurring in acute outbreaks. METHODS: We describe 17 cases of acute Chagas disease in Rio Negro, Amazonas. RESULTS: There were 15 males (average age, 31.3 years), all positive for Trypanosoma cruzi in fresh blood smear examination, and 14 positive by xenodiagnosis and PCR. The top clinical manifestations were fever, asthenia, abdominal pain, and palpitations. Electrocardiograms featured low-voltage QRS, anterosuperior divisional block, and right bundle branch block associated with anterosuperior divisional block. CONCLUSIONS: All patients had consumed açaí products from Monte Alegre in the rural area around Santa Izabel do Rio Negro, Brazil.

Novel methicillin-resistant coagulase-negative Staphylococcus clone isolated from patients with haematological diseases at the Blood Bank Centre of Amazon, Brazil.

Methicillin-resistant Staphylococcus remains a severe public health problem worldwide. This research was intended to identify the presence of methicillin-resistant coagulase-negative staphylococci clones and their staphylococcal cassette chromosome mec (SCCmec)-type isolate from patients with haematologic diseases presenting bacterial infections who were treated at the Blood Bank of the state of Amazonas in Brazil. Phenotypic and genotypic tests, such as SCCmec types and multilocus sequence typing (MLST), were developed to detect and characterise methicillin-resistant isolates. A total of 26 Gram-positive bacteria were isolated, such as: Staphylococcus epidermidis (8/27), Staphylococcus intermedius (4/27) and Staphylococcus aureus (4/27). Ten methicillin-resistant staphylococcal isolates were identified. MLST revealed three different sequence types: S. aureus ST243, S. epidermidis ST2 and a new clone of S. epidermidis, ST365. These findings reinforce the potential of dissemination presented by multi-resistant Staphylococcus and they suggest the introduction of monitoring actions to reduce the spread of pathogenic clonal lineages of S. aureus and S. epidermidis to avoid hospital infections and mortality risks.

Historical analysis of the records of sylvan yellow fever in the State of Amazonas, Brazil, from 1996 to 2009

Introduction Yellow fever is a non-contagious infectious disease, highly lethal, transmitted by the Aedes, Haemagogus and Sabethes. Methods Descriptive retrospective study of the yellow fever cases in Amazonas, between 1996 and 2009. Results Forty two cases of yellow fever were confirmed, with 30 deaths, 10% of which were foreigners. Conclusions The presence of Aedes aegypti and Aedes albopictus in both rural Amazonas and its capital demonstrates the dispersion of these vectors and underscores the need for better and continuous epidemiological and entomological control. .

Trypanosoma cruzi I and IV stocks from Brazilian Amazon are divergent in terms of biological and medical properties in mice.

BACKGROUND: In the Brazilian Amazon, clinical and epidemiological frameworks of Chagas disease are very dissimilar in relation to the endemic classical areas of transmission, possibly due to genetic and biological characteristics of the circulating Trypanosoma cruzi stocks. Twenty six T. cruzi stocks from Western Amazon Region attributed to the TcI and TcIV DTUs were comparatively studied in Swiss mice to test the hypothesis that T. cruzi clonal structure has a major impact on its biological and medical properties. METHODOLOGY/PRINCIPAL FINDINGS: Seventeen parameters were assayed in mice infected with 14 T. cruzi strains belonging to DTU TcI and 11 strains typed as TcIV. In comparison with TcI, TcIV stocks promoted a significantly shorter pre-patent period (p<0.001), a longer patent period (p<0.001), higher values of mean daily parasitemia (p = 0.009) and maximum of parasitemia (p = 0.015), earlier days of maximum parasitemia (p<0.001) and mortality (p = 0.018), higher mortality rates in the acute phase (p = 0.047), higher infectivity rates (p = 0.002), higher positivity in the fresh blood examination (p<0.001), higher positivity in the ELISA at the early chronic phase (p = 0.022), and a higher positivity in the ELISA at the late chronic phase (p = 0.003). On the other hand TcI showed higher values of mortality rates in the early chronic phase (p = 0.014), higher frequency of mice with inflammatory process in any organ (p = 0.005), higher frequency of mice with tissue parasitism in any organ (p = 0.027) and a higher susceptibility to benznidazole (p = 0.002) than TcIV. Survival analysis showing the time elapsed from the day of inoculation to the beginning of the patent period was significantly shorter for TcIV strains and the death episodes triggered following the infection with TcI occurred significantly later in relation to TcIV. The notable exceptions come from positivity in the hemocultures and PCR, for which the results were similar. CONCLUSION/SIGNIFICANCE: T. cruzi stocks belonging to TcI and TcIV DTUs from Brazilian Amazon are divergent in terms of biological and medical properties in mice.

Integrated vector management targeting Anopheles darlingi populations decreases malaria incidence in an unstable transmission area, in the rural Brazilian Amazon.

BACKGROUND: Studies on vector behaviour should be conducted in order to evaluate the effectiveness of vector control measures on malaria protection in endemic areas of Latin America, where P. vivax predominates. This work aims to investigate the fauna of anopheline mosquitoes and verify the impact of integrated vector management in two colonization projects in the Careiro Municipality, Western Brazilian Amazon. METHODS: Four mosquitoes' captures were carried out from August 2008 to March 2010, with an interval of six months between each collection. Since September 2009 a large programme to reduce the burden of malaria has started in the two communities by distribution of insecticide-treated bed nets (ITN) and intensification of indoor residual spraying (IRS). Human biting rates (HBRs), entomological inoculation rates (EIRs), malaria incidence rate (MIR) and Plasmodium carrier's prevalence were used as outcomes to estimate the impact of the control measures. RESULTS: A total of 3,189 anophelines were collected, belonging to 13 species. Anopheles darlingi was the predominant species in the period (42.6%), followed by Anopheles albitarsis (38.4%). An. darlingi HBRs showed a notable decreasing trend from the start to the end of the study. Conversely, An. albitarsis increased its contribution to overall HBRs throughout the study. For An. darlingi there was a significant positive correlation between HBRs and MIR (p = 0.002). Anopheles albitarsis HBRs showed a significant negative correlation with the corresponding MIR (p = 0.045). EIR from total anophelines and from An. darlingi and An. albitarsis presented decreasing patterns in the successive collections. Four species of anophelines (An. darlingi, An. albitarsis, Anopheles braziliensis and Anopheles nuneztovari) were naturally infected with Plasmodium, albeit at very low infection rates. There were a decrease in the MIR for both vivax and falciparum malaria and in the prevalence of Plasmodium vivax and Plasmodium falciparum carriers during the period of study. CONCLUSIONS: There is strong evidence of association between the density of An. darlingi and the incidence of malaria in the studies sites, further highlighting the importance of this vector in malaria transmission in this region. An. darlingi susceptibility to control using ITN and IRS is likely to be high in the rural settlements studied.

Trypanosoma cruzi IV causing outbreaks of acute Chagas disease and infections by different haplotypes in the Western Brazilian Amazonia.

BACKGROUND: Chagas disease is an emergent tropical disease in the Brazilian Amazon Region, with an increasing number of cases in recent decades. In this region, the sylvatic cycle of Trypanosoma cruzi transmission, which constitutes a reservoir of parasites that might be associated with specific molecular, epidemiological and clinical traits, has been little explored. The objective of this work is to genetically characterize stocks of T. cruzi from human cases, triatomines and reservoir mammals in the State of Amazonas, in the Western Brazilian Amazon. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed 96 T. cruzi samples from four municipalities in distant locations of the State of Amazonas. Molecular characterization of isolated parasites from cultures in LIT medium or directly from vectors or whole human blood was performed by PCR of the non-transcribed spacer of the mini-exon and of the 24 S alfa ribosomal RNA gene, RFLP and sequencing of the mitochondrial cytochrome c oxidase subunit II (COII) gene, and by sequencing of the glucose-phosphate isomerase gene. The T. cruzi parasites from two outbreaks of acute disease were all typed as TcIV. One of the outbreaks was triggered by several haplotypes of the same DTU. TcIV also occurred in isolated cases and in Rhodnius robustus. Incongruence between mitochondrial and nuclear phylogenies is likely to be indicative of historical genetic exchange events resulting in mitochondrial introgression between TcIII and TcIV DTUs from Western Brazilian Amazon. TcI predominated among triatomines and was the unique DTU infecting marsupials. CONCLUSION/SIGNIFICANCE: DTU TcIV, rarely associated with human Chagas disease in other areas of the Amazon basin, is the major strain responsible for the human infections in the Western Brazilian Amazon, occurring in outbreaks as single or mixed infections by different haplotypes.