180 research outputs found
Ecological host fitting of Trypanosoma cruzi TcI in Bolivia: mosaic population structure, hybridization and a role for humans in Andean parasite dispersal.
An improved understanding of how a parasite species exploits its genetic repertoire to colonize novel hosts and environmental niches is crucial to establish the epidemiological risk associated with emergent pathogenic genotypes. Trypanosoma cruzi, a genetically heterogeneous, multi-host zoonosis, provides an ideal system to examine the sylvatic diversification of parasitic protozoa. In Bolivia, T. cruzi I, the oldest and most widespread genetic lineage, is pervasive across a range of ecological clines. High-resolution nuclear (26 loci) and mitochondrial (10 loci) genotyping of 199 contemporaneous sylvatic TcI clones was undertaken to provide insights into the biogeographical basis of T. cruzi evolution. Three distinct sylvatic parasite transmission cycles were identified: one highland population among terrestrial rodent and triatomine species, composed of genetically homogenous strains (Ar = 2.95; PA/L = 0.61; DAS = 0.151), and two highly diverse, parasite assemblages circulating among predominantly arboreal mammals and vectors in the lowlands (Ar = 3.40 and 3.93; PA/L = 1.12 and 0.60; DAS = 0.425 and 0.311, respectively). Very limited gene flow between neighbouring terrestrial highland and arboreal lowland areas (distance ~220 km; FST = 0.42 and 0.35) but strong connectivity between ecologically similar but geographically disparate terrestrial highland ecotopes (distance >465 km; FST = 0.016-0.084) strongly supports ecological host fitting as the predominant mechanism of parasite diversification. Dissimilar heterozygosity estimates (excess in highlands, deficit in lowlands) and mitochondrial introgression among lowland strains may indicate fundamental differences in mating strategies between populations. Finally, accelerated parasite dissemination between densely populated, highland areas, compared to uninhabited lowland foci, likely reflects passive, long-range anthroponotic dispersal. The impact of humans on the risk of epizootic Chagas disease transmission in Bolivia is discussed
Urban Policies and Health In Developing Countries: The Case of Maputo (Mozambique) and Cochabamba (Bolivia)
Urban planning and related policies can contribute to improvement in health. Recent epidemiological and quantitative Health Impact Assessment (HIA) studies in Europe and North America suggest that a change from passive (car) to active transportation (cycling, walking)
and public transport in daily life could improve health. HIA studies are still largely lacking in low and middle-income countries. We conducted a scoping study to evaluate the availability of data to conduct quantitative HIA in two cities from two low-income countries. We collected information through interviews with different local agents, from the National Institute of Statistics and by conducting field work to identify the built environment and mobility characteristics in the respective cities. Conducting a quantitative HIA in Maputo (Mozambique) is currently not possible, mainly because there is no appropriate data on mortality, road traffic accidents and physical activity of the general population. However, in Cochabamba (Bolivia) it might be possible when the mobility plan will be available (currently under development), in which data on traffic flows, mobility surveys and transport modal shares will become available. The current
paper describes two examples of the opportunities and difficulties to conduct quantitative HIA in low- and middle-income countries, highlighting the limited availability of data (quantitatively and qualitatively) on transport and urban planning and health outcomes
The burden of congenital Chagas disease and implementation of molecular diagnostic tools in Latin America
It is estimated that between 8000 and 15 000 Trypanosoma cruzi infected babies are born every year to infected mothers in Chagas disease endemic countries. Currently, poor access to and performance of the current diagnostic algorithm, based on microscopy at birth and serology at 8-12 months after delivery, is one of the barriers to congenital Chagas disease (CCD) control. Detection of parasite DNA using molecular diagnostic tools could be an alternative or complement to current diagnostic methods, but its implementation in endemic regions remains limited. Prompt diagnosis and treatment of CCD cases would have a positive clinical and epidemiological impact. In this paper, we analysed the burden of CCD in Latin America, and the potential use of molecular tests to improve access to early diagnosis and treatment of T. cruzi infected newborns.Fil: Picado, Albert. Foundation for Innovative New Diagnostics; SuizaFil: Cruz, Israel. Foundation for Innovative New Diagnostics; SuizaFil: Redard Jacot, Maël. Foundation for Innovative New Diagnostics; SuizaFil: Schijman, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Torrico, Faustino. Universidad Mayor de San Simón; Bolivia. Fundación CEADES; BoliviaFil: Sosa-Estani, Sergio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina. Drugs for Neglected Diseases initiative; BrasilFil: Katz, Zachary. Foundation for Innovative New Diagnostics; SuizaFil: Ndung'u, Joseph Mathu. Foundation for Innovative New Diagnostics; Suiz
Trypanosoma cruzi IIc: phylogenetic and phylogeographic insights from sequence and microsatellite analysis and potential impact on emergent Chagas disease.
Trypanosoma cruzi, the etiological agent of Chagas disease, is highly genetically diverse. Numerous lines of evidence point to the existence of six stable genetic lineages or DTUs: TcI, TcIIa, TcIIb, TcIIc, TcIId, and TcIIe. Molecular dating suggests that T. cruzi is likely to have been an endemic infection of neotropical mammalian fauna for many millions of years. Here we have applied a panel of 49 polymorphic microsatellite markers developed from the online T. cruzi genome to document genetic diversity among 53 isolates belonging to TcIIc, a lineage so far recorded almost exclusively in silvatic transmission cycles but increasingly a potential source of human infection. These data are complemented by parallel analysis of sequence variation in a fragment of the glucose-6-phosphate isomerase gene. New isolates confirm that TcIIc is associated with terrestrial transmission cycles and armadillo reservoir hosts, and demonstrate that TcIIc is far more widespread than previously thought, with a distribution at least from Western Venezuela to the Argentine Chaco. We show that TcIIc is truly a discrete T. cruzi lineage, that it could have an ancient origin and that diversity occurs within the terrestrial niche independently of the host species. We also show that spatial structure among TcIIc isolates from its principal host, the armadillo Dasypus novemcinctus, is greater than that among TcI from Didelphis spp. opossums and link this observation to differences in ecology of their respective niches. Homozygosity in TcIIc populations and some linkage indices indicate the possibility of recombination but cannot yet be effectively discriminated from a high genome-wide frequency of gene conversion. Finally, we suggest that the derived TcIIc population genetic data have a vital role in determining the origin of the epidemiologically important hybrid lineages TcIId and TcIIe
Molecular detection and parasite load of Trypanosoma cruzi in digestive tract tissue of Chagas disease patients affected by megacolon
Chagas disease, caused by the Trypanosoma cruzi parasite in the Americas affects similar to 7 million people, 30% with cardiac tissue damage and 10-15% with digestive disorders. In this study, we have developed a protocol to detect the presence of the parasite and estimate its load in resected dysfunctional tissue segments of chronically infected patients with digestive megacolon. We have included samples from 43 individuals, 38/5 with positive/negative serology for Chagas disease and digestive syndromes. Samples of 1.5 to 2.0 cm(2) were taken from different points of the dysfunctional digestive tract in specialized centres in Cochabamba, Bolivia. T. cruzi cultures were performed by inoculation with NNN-LIT culture medium, and genomic material was obtained from the samples for multiplex qPCR with TaqMan probes targeting satellite nuclear DNA. Cultures failed to isolate T. cruzi but qPCR reached a sensitivity of 42.1% (16/38) with all three spots and in triplicate. A new quantification methodology using synthetic satellite DNA as quantitation standard revealed parasite loads ranging from 2.2 x 10(2) to 1.0 x 10(6) satellite DNA copies/mu l. Positive samples from the distal end showed a higher parasite load. The results of the present study strengthen and add further evidence to previous findings in an experimental mouse model of chronic T. cruzi infection, providing a valuable tool to improve scientific knowledge on the relevance of the digestive tract in parasite persistence, and underline the need of a better understanding of host-pathogen interaction in digestive tissues, considering pathophysiology, disease immunology and response to treatment
Clinical and immunological characteristics of tegumentary leishmaniasis cases in Bolivia
Background Tegumentary leishmaniasis (TL) is a parasitic disease that can present a cutaneous or mucocutaneous clinical form (CL and MCL, respectively). The disease is caused by different Leishmania species and transmitted by phlebotomine sand flies. Bolivia has one of the highest incidences of the disease in South America and the diagnosis is done by parasitological techniques. Our aim was to describe the clinical and immunological characteristics of CL and MCL patients attending the leishmaniasis reference center in Cochabamba, Bolivia, in order to gain updated clinical and epidemiological information, to evaluate the diagnostic methods used and to identify biomarkers related to clinical disease and its evolution. Methodology/Principal findings The study was conducted from September 2014 to November 2015 and 135 patients with lesions compatible with CL or MCL were included. Epidemiological and clinical data were collected using a semi-structured questionnaire. Two parasitological diagnostic methods were used: Giemsa-stained smears and culture of lesion aspirates. Blood samples obtained from participants were used to measure the concentrations of different cytokines. 59.2% (80/135) were leishmaniasis confirmed cases (CL: 71.3%; MCL: 28.7%). Sixty percent of the confirmed cases were positive by smears and 90.6% were positive by culture. 53.8% were primo-infections. Eotaxin and monokine induced by IFN-γ presented higher serum concentrations in the MCL clinical presentation compared to CL cases and no-cases. None of the cytokines presented different concentrations between primo-infections and secondary infections due to treatment failure. Conclusions/Significance In Bolivia, parasitological diagnosis remains the reference standard in diagnosis of leishmaniasis because of its high specificity, whereas the sensitivity varies over a wide range leading to loss of cases. Until more accurate tools are implemented, all patients should be tested by both smears and culture of lesion aspirates to minimize the risk of false negatives. Our results showed higher concentrations of several cytokines in MCL compared to CL, but no differences were observed between CL and no-cases. In addition, none of the cytokines differed between primary and secondary infections. These results highlight the need of further research to identify biomarkers of susceptibility and disease progression, in addition to looking at the local cellular immune responses in the lesions
Strengthening the Bolivian pharmacovigilance system: New surveillance strategies to improve care for Chagas disease and tuberculosis.
"Chagas disease (CD) and tuberculosis (TB) are important
health problems in Bolivia. Current treatments for both
infections require a long period of time, and adverse drug
reactions (ADRs) are frequent. This study aims to strengthen the
Bolivian pharmacovigilance system, focusing on CD and TB. A
situation analysis of pharmacovigilance in the Department of
Cochabamba was performed. The use of a new local case report
form (CRF) was implemented, together with the CRF established by the Unidad de Medicamentos y Tecnolog\xC3\xADa en Salud
(UNIMED), in several healthcare centers. Training and follow-up
on drug safety monitoring and ADR reporting was provided to all
health professionals involved in CD and TB treatment. A
comparative analysis of the reported ADRs using the CRF provided
by UNIMED, the new CRF proposal, and medical records, was also performed. Our results showed that out of all patients starting
treatment for CD, 37.9% suffered ADRs according to the medical
records, and 25.3% of them were classified as moderate/severe
(MS). Only 47.4% of MS ADRs were reported to UNIMED. Regarding
TB treatment, 9.9% of all patients suffered ADRs, 44% of them
were classified as MS, and 75% of MS ADRs were reported to
UNIMED. These findings show that the reinforcement of the
Bolivian pharmacovigilance system is an ambitious project that
should involve a long-term perspective and the engagement of
national health workers and other stakeholders at all levels.
Continuity and perseverance are essential to achieve a solid ADR
reporting system, improving patient safety, drug efficacy and
adherence to treatment.
Rapid diagnostic tests duo as alternative to conventional serological assays for conclusive Chagas disease diagnosis
Chagas disease is caused by the parasite Trypanosoma cruzi. It
affects several million people, mainly in Latin America, and
severe cardiac and/or digestive complications occur in ~30% of
the chronically infected patients. Disease acute stage is mostly
asymptomatic and infection goes undiagnosed. In the chronic
phase direct parasite detection is hampered due to its concealed
presence and diagnosis is achieved by serological methods, like
ELISA or indirect hemagglutination assays. Agreement in at least
two tests must be obtained due to parasite wide antigenic
variability. These techniques require equipped labs and trained
personnel and are not available in distant regions. As a result,
many infected people often remain undiagnosed until it is too
late, as the two available chemotherapies show diminished
efficacy in the advanced chronic stage. Easy-to-use rapid
diagnostic tests have been developed to be implemented in remote
areas as an alternative to conventional tests. They do not need
electricity, nor cold chain, they can return results within an
hour and some even work with whole blood as sample, like Chagas
Stat-Pak (ChemBio Inc.) and Chagas Detect Plus (InBIOS Inc.).
Nonetheless, in order to qualify a rapidly diagnosed positive
patient for treatment, conventional serological confirmation is
obligatory, which might risk its start. In this study two rapid
tests based on distinct antigen sets were used in parallel as a
way to obtain a fast and conclusive Chagas disease diagnosis
using whole blood samples. Chagas Stat-Pak and Chagas Detect
Plus were validated by comparison with three conventional tests
yielding 100% sensitivity and 99.3% specificity over 342
patients seeking Chagas disease diagnosis in a reference centre
in Sucre (Bolivia). Combined used of RDTs in distant regions
could substitute laborious conventional serology, allowing
immediate treatment and favouring better adhesion to it
Usefulness of Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry in the Characterization of Leishmania Strains Causing Tegumentary Leishmaniasis in Bolivia versus hsp70 Gene Sequencing
Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) is a proteomic technique with proven efficiency in the identification of microorganisms, such as bacteria, fungi, and parasites. The present study aimed to evaluate the usefulness of MALDI-TOF MS for the characterization of Leishmania species circulating in Bolivia using hsp70 gene sequencing as a reference technique. 55 Leishmania strains that were isolated from patients with tegumentary leishmaniasis were analyzed. MALDI-TOF MS identified two species of the L. braziliensis complex (L. braziliensis, n = 26; L. braziliensis outlier, n = 18), one species of the L. guyanensis complex (L. guyanensis, n = 1), one species of the L. lainsoni complex (L. lainsoni, n = 2), and two species of the complex (, n = 5; and L. garnhami, n = 3). All of the strains were correctly identified at the subgenus, genus, and complex level, but 10 of them (18%) were misidentified as other species within the same complex by the hsp70 gene sequencing, with 7 of these corresponding to possible hybrids. Thus, one L. braziliensis corresponded to L. peruviana, two L. braziliensis corresponded to L. braziliensis / L. peruviana possible hybrids, two corresponded to , and three L. garnhami and two corresponded to / possible hybrids. Accordingly, MALDI-TOF MS could be used as an alternative to molecular techniques for the identification of Leishmania spp., as it is low cost, simple to apply, and able to quickly produce results. In Bolivia, its application would allow for the improvement of the management of patient follow-ups, the updating of the epidemiological data of the Leishmania species, and a contribution to the control of tegumentary leishmaniasis. IMPORTANCE The objective of the study was to evaluate the usefulness of MALDI-TOF MS for the characterization of Leishmania species circulating in Bolivia, in comparison with the sequencing of the hsp70 gene. In our study, all of the isolates could be identified, and no misidentifications were observed at the complex level. Although the equipment implies a high initial investment in our context, MALDI-TOF MS can be used in different areas of microbiology and significantly reduces the cost of testing. Once the parasite culture is obtained, the technique quickly yields information by accessing a free database that is available online. This would allow for the improvement of the management of patients and follow-ups, the updating of the epidemiological data of the species, and a contribution to the control of tegumentary leishmaniasis in Bolivia. Likewise, it can be used to determine a specific treatment to be given, according to the causal species of Leishmania, when there are protocols in this regard in the area
Intradomiciliary and peridomiciliary captures of sand flies (Diptera: Psychodidae) in the leishmaniasis endemic area of Chapare province, Tropic of Cochabamba, Bolivia
In South America, cutaneous leishmaniasis is the most frequent clinical form of leishmaniasis. Bolivia is one of the countries with higher incidence, with 33 cases per 100,000 individuals, and the disease is endemic in 70% of the territory. In the last decade, the number of cases has increased, the age range has expanded, affecting children under 5 years old, and a similar frequency between men and women is found. An entomological study with CDC light traps was conducted in three localities (Chipiriri, Santa Elena and Pedro Domingo Murillo) of the municipality of Villa Tunari, one of the main towns in the Chapare province (Department of Cochabamba, Bolivia). A total of 16 specimens belonging to 6 species of the genus Lutzomyia were captured: Lu. aragaoi, Lu. andersoni, Lu. antunesi, Lu. shawi, Lu. yuilli yuilli and Lu. auraensis. Our results showed the presence of two incriminated vectors of leishmaniasis in an urbanized area and in the intradomicile. More entomological studies are required in the Chapare province to confirm the role of vector sand flies, the intradomiciliary transmission of the disease and the presence of autochthonous cases of cutaneous leishmaniasis
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