Spatial patterns and temporal tendency of mortality related to Chagas disease in an endemic area of northeastern Brazil.

OBJECTIVE: To analyse spatial patterns and the temporal tendency of mortality related to Chagas disease, in order to identify priority control areas in the state of Sergipe, Northeast Brazil. METHODS: We conducted an ecological and time-series study with spatial analysis techniques on deaths from Chagas disease in the state of Sergipe (1996-2016). We used data from the Mortality Information System (SIM). The temporal analysis was performed using a statistical technique capable of describing changes in the trend pattern for the period. Thematic maps were elaborated from point and polygonal analyses. RESULTS: There were 247 deaths related to Chagas disease, with a mean of 11.7 deaths/year, most of them male (64%), and aged 50-59 years (21%) and 60-69 years (26%). Two segments with increasing, non-constant and significant trends were identified: 1996-2005 (APC = 21.6%; P = 0.01) and 2005-2016 (APC = 4.4%; P = 0.01), with APPC = 11.8% (P = 0.01). A positive and significant spatial autocorrelation with areas of higher risk of death was found in the southern region of the state. CONCLUSIONS: The trend of mortality related to Chagas disease in the state of Sergipe was increasing during the period analysed, with a heterogeneous distribution of cases. A main risk area was identified in the southern region of the state.

OBJECTIF: Analyser les profils spatiaux et la tendance temporelle de la mortalité liée à la maladie de Chagas, afin d'identifier les domaines de priorité de lutte dans l'Etat de Sergipe, dans le nord-est du Brésil. MÉTHODES: Nous avons mené une étude écologique et de séries chronologiques avec des techniques d'analyse spatiale sur les décès dus à la maladie de Chagas dans l'état de Sergipe (1996-2016). Nous avons utilisé les données du système d'information sur la mortalité (SIM). L'analyse temporelle a été réalisée à l'aide d'une technique statistique capable de décrire les changements dans le profil de tendance pour la période. Des cartes thématiques ont été élaborées à partir d'analyses ponctuelles et polygonales. RÉSULTATS: Il y a eu 247 décès liés à la maladie de Chagas, avec une moyenne de 11,7 décès/an, pour la plupart de sexe masculin (64%), et âgés de 50 à 59 ans (21%) et de 60 à 69 ans (26%). Deux segments avec des tendances à la hausse, non constantes et significatives ont été identifiés: 1996-2005 (APC = 21,6%; p = 0,01) et 2005-2016 (APC = 4,4%; p = 0,01), avec APPC = 11,8% (p = 0,01). Une autocorrélation spatiale positive et significative avec des zones à haut risque de décès a été trouvée dans la région sud de l'Etat. CONCLUSIONS: La tendance de la mortalité liée à la maladie de Chagas dans l'état de Sergipe a augmenté au cours de la période analysée , avec une répartition hétérogène des cas. Une principale zone à risque a été identifiée dans la région sud de l'Etat.

Fatal acute Chagas disease by Trypanosoma cruzi DTU TcI, Ecuador.

BACKGROUND: Chagas disease is caused by the haemoflagellate protozoan Trypanosoma cruzi. Currently, T. cruzi recognizes seven discrete typing units (DTUs): TcI to TcVI and Tcbat. The genetic diversity of T. cruzi is suspected to influence the clinical outcome. Acute clinical manifestations, which include myocarditis and meningoencephalitis, are sometimes fatal; occur most frequently in children and in immunocompromised individuals. Acute disease is often overlooked, leading to a poor prognosis. CASE PRESENTATION: A 38-year-old man from a subtropical area of the Andes mountains of Ecuador was hospitalized after 3 weeks of evolution with high fever, chills, an enlarged liver, spleen, and lymph nodes, as well as facial edema. ECG changes were also observed. T. cruzi was identified in blood smears, culture and amplification of DNA by PCR. Tests for anti-T. cruzi IgG and IgM and HIV were negative. Molecular typing by restriction fragment length polymorphism (PCR-RFLP) determined the parasite to DTU TcI. In the absence of a timely anti-T. cruzi medication, the patient died. CONCLUSIONS: This is a case of severe pathogenicity and the virulence of a DTU TcI strain in an adult patient. The severe acute Chagas disease was probably overlooked due to limited awareness and its low incidence. Our findings suggest that T. cruzi DTU TcI strains circulating in Ecuador are capable of causing fatal acute disease. Early diagnosis and prompt treatment is of paramount importance to avoid fatalities in acute infections.

Prevalence of Chagas Disease Among Family Members of Previously Diagnosed Patients in Los Angeles, California.

Chagas disease (CD) in the United States is severely underdiagnosed, due to an absence of systematic screening as part of routine healthcare. We screened 189 relatives of 86 existing patients and found a CD prevalence of 7.4%. Screening close relatives of previously diagnosed individuals can effectively identify new CD cases.

Chagas disease.

Chagas disease is an anthropozoonosis from the American continent that has spread from its original boundaries through migration. It is caused by the protozoan Trypanosoma cruzi, which was identified in the first decade of the 20th century. Once acute infection resolves, patients can develop chronic disease, which in up to 30-40% of cases is characterised by cardiomyopathy, arrhythmias, megaviscera, and, more rarely, polyneuropathy and stroke. Even after more than a century, many challenges remain unresolved, since epidemiological control and diagnostic, therapeutic, and prognostic methods must be improved. In particular, the efficacy and tolerability profile of therapeutic agents is far from ideal. Furthermore, the population affected is older and more complex (eg, immunosuppressed patients and patients with cancer). Nevertheless, in recent years, our knowledge of Chagas disease has expanded, and the international networking needed to change the course of this deadly disease during the 21st century has begun.

Tissue and blood protozoa including toxoplasmosis, Chagas disease, leishmaniasis, Babesia, Acanthamoeba, Balamuthia, and Naegleria in solid organ transplant recipients- Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of tissue and blood protozoal infections in the pre- and post-transplant period. Significant new developments in the field have made it necessary to divide the previous single guideline published in 2013 into two sections, with the intestinal parasites separated from this guideline devoted to tissue and blood protozoa. The current update reflects the increased focus on donor screening and risk-based recipient monitoring for parasitic infections. Increased donor testing has led to new recommendations for recipient management of Toxoplasma gondii and Trypanosoma cruzi. Molecular diagnostics have impacted the field, with access to rapid diagnostic testing for malaria and polymerase chain reaction testing for Leishmania. Changes in Babesia treatment regimens in the immunocompromised host are outlined. The risk of donor transmission of free-living amebae infection is reviewed. Changing immigration patterns and the expansion of transplant medicine in developing countries has contributed to the recognition of parasitic infections as an important threat to transplant outcomes. Medications such as benznidazole and miltefosine are now available to US prescribers as access to treatment of tissue and blood protozoa is increasingly prioritized.

Cell therapies for Chagas disease.

In this review of cell therapies in Chagas disease, we cover aspects related to the disease, its treatment and world demographics, before proceeding to describe the preclinical and clinical trials performed using cell therapies in the search for an alternative therapy for the most severe and lethal form of this disease, chronic chagasic cardiomyopathy.

[Strategy to improve access to etiological treatment of Chagas disease at the first level of care in Argentina]. / Estrategia para mejorar el acceso al tratamiento etiológico para la enfermedad de Chagas en el primer nivel de atención en Argentina.

OBJECTIVE: Improve distribution of etiological treatment of Chagas disease by identifying barriers to the decentralization of treatment to the first level of care in Argentina. METHODS: A qualitative, exploratory, and descriptive study was conducted using semi-structured interviews of key actors belonging to the National Chagas Program and members of health teams at the first level of care, for the purpose of identifying barriers to diagnosis and treatment of Chagas disease at different levels (administrative, health agents, and community) that could affect a decentralized distribution strategy. Additionally, pilot decentralization was instituted in 10 primary health care centers in an Argentine province. RESULTS: Semi-structured interviews were conducted with 22 program heads and health professionals. Principal obstacles found were lack of systematic case-finding, poor coordination among levels of care and health system actors, lack of health team training on treatment, patient monitoring, and patient-related barriers. A pilot decentralization program was carried out and strategies were evaluated to optimize large-scale intervention. CONCLUSIONS: The results made it possible to improve implementation of the plan to decentralize treatment through better inter-program coordination, capitalization on existing monitoring and communication tools, and sensitization of health teams. Furthermore, recommendations were developed to improve diagnosis and treatment of Chagas disease.

Aspirin treatment exacerbates oral infections by Trypanosoma cruzi.

Oral transmission of the protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas disease, has been documented in Latin American countries. The reported cases of infection were due to the ingestion of contaminated fresh fruit, juices, or sugar cane juice. There have been few studies on the physiopathology of the disease in oral transmission cases. Gastritis is a common ailment that can be caused by poor dietary habits, intake of alcohol or other gastric irritants, bacterial infection, or by the widespread use of non-steroidal anti-inflammatory drugs (NSAIDs). This study investigated in a mouse model whether gastric mucosal injury, induced by aspirin, would affect the course of disease in animals infected with T. cruzi by the oral route. The CL14 and G strains of T. cruzi, both of low infectivity, were used. To this end, groups of BALB/c mice were treated during 5 days with aspirin (100 mg kg(-1)) before oral infection with T. cruzi metacyclic forms (4 × 10(5) or 5 × 10(7) parasites/mouse). Histological analysis and determination of nitric oxide and TNF-α were performed in gastric samples obtained 5 days after infection. Parasitemia was monitored from the thirteenth day after infection. The results indicate that aspirin treatment of mice injured their gastric mucosa and facilitated invasion by both CL14 and G strains of T. cruzi. Strain CL14 caused more severe infection compared to the G strain, as larger numbers of amastigote nests were found in the stomach and parasitemia levels were higher. Our study is novel in that it shows that gastric mucosal damage caused by aspirin, a commonly used NSAID, facilitates T. cruzi infection by the oral route.

Cerebral trypanosomiasis in a renal transplant recipient.

Chagas disease is a lifelong, systemic, parasitic infection caused by the protozoan Trypanosoma cruzi. The main form of disease transmission is vector borne, but vertical transmission, such as by organ transplantation from a chronically infected donor, is also possible. The brain tumor-like form can occur years after infection and has been described in patients with acquired immunodeficiency syndrome, and in a very few cases in transplant recipients. We describe the case of a kidney transplant patient who was human immunodeficiency virus negative and infected with T. cruzi, and developed cerebral trypanosomiasis that was successfully treated with benznidazole at 7 mg/kg/day for 60 days. The risk of Chagas disease transmission should not be underestimated in renal transplant patients, even in non-endemic areas. Chagas disease can present as a tumor-like brain lesion, very difficult to differentiate from other opportunistic infectious or neoplastic processes. Frequent monitoring for T. cruzi infection is essential to promptly implement treatment, which, in our patient, proved to be effective and safe.

Sympathetic glial cells and macrophages develop different responses to Trypanosoma cruzi infection or lipopolysaccharide stimulation.

Nitric oxide (NO) participates in neuronal lesions in the digestive form of Chagas disease and the proximity of parasitised glial cells and neurons in damaged myenteric ganglia is a frequent finding. Glial cells have crucial roles in many neuropathological situations and are potential sources of NO. Here, we investigate peripheral glial cell response to Trypanosoma cruzi infection to clarify the role of these cells in the neuronal lesion pathogenesis of Chagas disease. We used primary glial cell cultures from superior cervical ganglion to investigate cell activation and NO production after T. cruzi infection or lipopolysaccharide (LPS) exposure in comparison to peritoneal macrophages. T. cruzi infection was greater in glial cells, despite similar levels of NO production in both cell types. Glial cells responded similarly to T. cruzi and LPS, but were less responsive to LPS than macrophages were. Our observations contribute to the understanding of Chagas disease pathogenesis, as based on the high susceptibility of autonomic glial cells to T. cruzi infection with subsequent NO production. Moreover, our findings will facilitate future research into the immune responses and activation mechanisms of peripheral glial cells, which are important for understanding the paradoxical responses of this cell type in neuronal lesions and neuroprotection.

Selective testing for Trypanosoma cruzi: the first year after implementation at Canadian Blood Services.

BACKGROUND: Various testing strategies may reduce the risk of Chagas disease transmission in nonendemic, low-prevalence countries. Results of the first year of selective testing of at-risk donors at Canadian Blood Services are reported. STUDY DESIGN AND METHODS: Since February 2009, platelets were not produced from at-risk donors. Since May 2010, at-risk donors were tested for Trypanosoma cruzi antibodies. Donors testing positive were interviewed about risk factors, and lookback studies were initiated. RESULTS: There were 7255 at-risk donors of 421,979 donors screened (1.72%). Risk factors were born in Latin America (50.6%), mother or maternal grandmother born in Latin America (28%), and 6 months or more travel history or residence in Latin America (19%). Sixteen (16) at-risk donors had T. cruzi repeat-reactive test results of whom 13 confirmed positive. Eleven of 13 were born in Latin America (nine in Paraguay and two in Argentina), and the other two were born in Canada but had short-term travel history and mothers who had been born in Latin America. Ten of the donors spoke German as their first language (all of those born in Paraguay and one born in Canada). There were 148 previous donations (176 components transfused) evaluated by lookback, of which 28% of recipients could be tested. None were positive. CONCLUSION: Selective testing has mitigated a small risk to the blood supply with very few false-positive results. Most positive donors were born in a risk country, with a concentration of German-speaking immigrants from Paraguay. Residency or travel alone were not clear risk factors.

Ecological niche modeling as a tool for understanding distributions and interactions of vectors, hosts, and etiologic agents of Chagas disease.

Chagas disease, or American Trypanosomiasis, is a tropical parasitic disease caused by the flagellate protozoan Trypanosoma cruzi, which is in turn transmitted by blood-sucking insects of the subfamily Triatominae (family Reduviidae). Because no drugs or vaccines are available to cure Chagas disease in its chronic phase, vectorial control (i.e., insecticide spraying) constitutes the principal means by which to impair Chagas disease transmission. Environmental and social factors have caused changes in the epidemiology of this disease-it was originally restricted to Latin America, but is now becoming a global heath concern in non-endemic areas as a consequence of human migrations. In Brazil, despite the fact that the most effective vector has been controlled, other triatomine species infest and colonize domiciliary habitats and can transmit the pathogen. As a consequence, Chagas disease transmission continues: the prevalence of the disease remains at ∼12 million people, with ∼200,000 new cases per year in 15 countries of Latin America, making control actions still necessary. Understanding the environmental requirements and geographic distributions of vectors is key to guiding control measures, and understanding better epidemiologic aspects of the disease. Ecologic niche modeling is a relatively new tool that permits such insights--as a consequence, here, we present an overview of insights gained using this approach in understanding of Chagas disease.

Natural products and Chagas' disease: a review of plant compounds studied for activity against Trypanosoma cruzi.

Here, we review studies that have investigated the activity of plant-derived compounds against Trypanosoma cruzi, the etiologic agent of Chagas' disease. In the last decade, more than 300 species belonging to almost 100 families have been evaluated for activity, and here we describe the compounds isolated; 85 references are cited.

Large urban outbreak of orally acquired acute Chagas disease at a school in Caracas, Venezuela.

BACKGROUND: Trypanosoma cruzi oral transmission is possible through food contamination by vector's feces. Little is known about the epidemiology and clinical features of microepidemics of orally acquired acute Chagas disease (CD). METHODS: A case-control, cohort-nested, epidemiological study was conducted during an outbreak of acute CD that affected a school community. Structured interviews were designed to identify symptoms and sources of infection. Electrocardiograms were obtained for all patients. Specific serum antibodies were assessed by immunoenzimatic and indirect hemagglutination tests. In some cases, parasitemia was tested directly or by culture, animal inoculation, and/or a polymerase chain reaction technique. RESULTS: Infection was confirmed in 103 of 1000 exposed individuals. Of those infected, 75% were symptomatic, 20.3% required hospitalization, 59% showed ECG abnormalities, parasitemia was documented in 44, and 1 child died. Clinical features differed from those seen in vectorial transmission. The infection rate was significantly higher among younger children. An epidemiological investigation incriminated contaminated fresh guava juice as the sole source of infection. CONCLUSIONS: This outbreak was unique, because it affected a large, urban, predominantly young, middle-class, otherwise healthy population and resulted in an unprecedented public health emergency. Rapid diagnosis and treatment avoided higher lethality. Food-borne transmission of T. cruzi may occur more often than is currently recognized.

Trypanosoma cruzi trans-sialidase: enhancement of virulence in a murine model of Chagas' disease.

Trypanosoma cruzi, the etiological agent of Chagas' disease, expresses a trans-sialidase at highest levels in infective trypomastigotes, where it attaches to the plasma membrane by a glycophosphoinositol linkage. Bound enzyme sheds into the extracellular milieu in a soluble form. Experiments performed in vitro suggest that the trans-sialidase participates in several parameters of T. cruzi-host interactions, like cell adhesion and complement resistance. However, the role that membrane-bound and soluble trans-sialidase plays in the infection of mammals is not understood. To begin to study the role the enzyme may play in vivo, T. cruzi trypomastigotes were inoculated subcutaneously into mice that had been sensitized for various times with the purified protein. A single dose of either endogenous or recombinant trans-sialidase injected into the connective tissues of BALB/c mice greatly enhanced parasitemia and mortality. Maximum enhancement was achieved with 1-2-h priming. Injection of the enzyme after the parasites had been established in the inoculation site had little, if any, consequence in modifying virulence. The enhancement did not seem to be through a direct effect of the enzyme on trypomastigote-host cell interactions because it occurred when the sites of trans-sialidase sensitization and parasite inoculation were physically separate. Rather, virulence enhancement seemed to depend on inflammatory cells, since priming with trans-sialidase had no significant effect in severe combined immunodeficiency mice, which lack functional T and B lymphocytes. However, antibody response to T. cruzi in the trans-sialidase-primed BALB/c mice was the same as in the control animals. Virulence enhancement was specific for the trans-sialidase because it did not occur in mice primed with Newcastle virus sialidase, which has the same substrate specificity as the T. cruzi enzyme, or with the sialidase from the bacterium Vibrio cholerae, whose substrate specificity is broader than the trypanosome sialidase. Furthermore, no enhancement of virulence occurred after sensitization with another adhesion protein (penetrin) purified from T. cruzi trypomastigotes and engineered bacteria, nor with bacterial lipopolysaccharide. The virulence-promoting activity of soluble trans-sialidase in the mouse model may be physiologically relevant because it was achieved with tiny doses, approximately 1-2 microgram/kg, raising the possibility that neutralization of the enzyme with specific probes could impair the development of Chagas' disease. In fact, a monoclonal antibody specific for the tandem repeat in the trans-sialidase COOH terminus enhanced infection of BALB/c mice, in agreement with earlier experiments in vitro, whereas antibodies against an amino acid sequence in the Cys region had the opposite effect.

Acute Chagas' disease in postrenal transplant and treatment with benzonidazole.

Transplanted organs may act as a route of transmission of infectious diseases, such as Chagas' disease. The aim of this study was to describe the transmission of the Trypanosoma cruzi through a renal transplant and the anatomo-clinical evolution of the patient after treatment with benzonidazole. The patient was a 31-year-old white male from the State of Minas Gerais in Brazil. He had renal failure secondary to diabetes and later received a kidney from a cadaveric donor. The patient was undergoing immunosuppression therapy with azathioprine, cyclosporine A, and prednisone. After the transplant, he developed an acute phase of Chagas' disease and complications from diabetes and died 2 months later. In the autopsy, T cruzi amastigotes were found in the transplanted kidney, heart, bladder, liver, and pancreas. An important reduction in the parasitemia was obtained through the treatment of the infection with benzonidazole; however, the patient died due to complications from diabetes associated with tissue lesions caused by T cruzi.

May the epimastigote form of Trypanosoma cruzi be infective?

For many years it has been considered that there are three basic developmental stages of Trypanosoma cruzi: Epimastigote (Epi), Amastigote (Ama) and Trypomastigote (Typo). Epi and Ama are able to divide while Trypo does not divide. Epi are not infective while Ama and Trypo are able to infect host cells. Here we review the available data for the epimastigote form. Taken together the data show that (a) there are intermediate forms between epimastigotes and trypomastigotes in axenic cultures as well as between amastigote and trypomastigote forms within the cells (both in vitro and in vivo), and (c) that the intermediate forms, here designated as "Transitional Epimastigote", most of the time considered as epimastigotes, are able to infect cells. The recognition of the existence of this stage is of practical importance for those work with T. cruzi. Many laboratories working only with T. cruzi in axenic cultures usually consider to work with nonpathogenic cultures. This attitude needs to be changed requiring special care by those working with this protozoan to avoid accidental infections in the laboratory. In view of these observation a new scheme for the life cycle of T. cruzi is proposed.

Contemporary autochthonous human Chagas disease in the USA.

Chagas disease is a leading cause of non-ischemic cardiomyopathy in Latin America and an infection of emerging importance in the USA. Recent studies have uncovered evidence of an active peridomestic cycle in southern states, yet autochthonous transmission to humans has been rarely reported. We conducted a systematic review of the literature and public health department reports to investigate suspected or confirmed locally acquired cases of Chagas in the USA. We found 76 cases of contemporary suspected or confirmed locally acquired Chagas disease, nearly ten times the case counts cited in the prior 50 years of scientific literature. Shared risk factors among cases include rural residence, history of hunting or camping, and agricultural or outdoor work. The results of this review suggest that the disease burden and risk of autochthonous Chagas infection is potentially higher in the USA than previously recognized.

Lizards and rabbits may increase Chagas infection risk in the Mediterranean-type ecosystem of South America.

Studies of host-parasite relationships largely benefit from adopting a multifactorial approach, including the complexity of multi-host systems and habitat features in their analyses. Some host species concentrate most infection and contribute disproportionately to parasite and vector population maintenance, and habitat feature variation creates important heterogeneity in host composition, influencing infection risk and the fate of disease dynamics. Here, we examine how the availability of specific groups of hosts and habitat features relate to vector abundance and infection risk in 18 vector populations along the Mediterranean-type ecosystem of South America, where the kissing bug Mepraia spinolai is the main wild vector of the parasite Trypanosoma cruzi, the etiological agent of Chagas disease. For each population, data on vectors, vertebrate host availability, vegetation, precipitation, and temperature were collected and analyzed. Vector abundance was positively related to temperature, total vegetation, and European rabbit availability. Infection risk was positively related to temperature, bromeliad cover, and reptile availability; and negatively to the total domestic mammal availability. The invasive rabbit is suggested as a key species involved in the vector population maintenance. Interestingly, lizard species -a group completely neglected as a potential reservoir-, temperature, and bromeliads were relevant factors accounting for infection risk variation across populations.

Geographic distribution of Trypanosoma cruzi genotypes detected in chronic infected people from Argentina. Association with climatic variables and clinical manifestations of Chagas disease.

Chronic Chagas disease affects large number of people in Latin America where it remains one of the biggest public health problems. Trypanosoma cruzi is genetically divided into seven discrete typing units (DTUs), TcI-TcVI and Tcbat, and exhibits differential distribution across vectors, host and transmission cycles. Clinical manifestations (cardiac, digestive and / or neurological) vary according to the geographical region; and the DTUs more frequently found in any of the chronic form of the disease, indeterminate or clinical, are TcI, TcII, TcV and TcVI. However, why they have a particular geographical distribution and how they affect the development of Chagas disease is still unknown. In this study, we assessed the geographic distribution of T. cruzi genotypes detected in chronic infected people from 57 localities of endemic regions of Argentina and analyzed their association with climatic variables. The prevalent DTUs detected in the whole population were TcV (47.4%) and TcVI (66.0%). TcI and TcII were identified in 5.2% each. All DTUs were detected in single and mixed infections (78.4% and 21.6%, respectively). TcV was found in infected people from localities with significantly higher average annual temperature, seasonal temperature and annual temperature range than those infected with TcVI. When we evaluated the association of DTUs with clinical manifestations of Chagas disease, the probability of finding TcVI in subjects with chronic Chagas cardiomyopathy (CCC) was higher than other DTUs, but without reaching statistical significance. Moreover, the probability of finding TcV in those who have not developed the disease after 20 years of infection was significantly higher than in CCC, either if it was present as unique DTU (reciprocal OR=4.95 95%CI: 1.42 to 17.27) (p=0.0117) or if it was also part of mixed infections (reciprocal OR=3.375; 95%CI: 1.227 to 9.276) (p=0.0264). There was no difference in the distribution of TcI between asymptomatic people and those with clinical manifestations, while TcII appeared more frequently in CCC cases, but without statiscal significance.