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1.
PLoS Pathog ; 19(4): e1010893, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37014917

RESUMEN

In settings with high tuberculosis (TB) endemicity, distinct genotypes of the Mycobacterium tuberculosis complex (MTBC) often differ in prevalence. However, the factors leading to these differences remain poorly understood. Here we studied the MTBC population in Dar es Salaam, Tanzania over a six-year period, using 1,082 unique patient-derived MTBC whole-genome sequences (WGS) and associated clinical data. We show that the TB epidemic in Dar es Salaam is dominated by multiple MTBC genotypes introduced to Tanzania from different parts of the world during the last 300 years. The most common MTBC genotypes deriving from these introductions exhibited differences in transmission rates and in the duration of the infectious period, but little differences in overall fitness, as measured by the effective reproductive number. Moreover, measures of disease severity and bacterial load indicated no differences in virulence between these genotypes during active TB. Instead, the combination of an early introduction and a high transmission rate accounted for the high prevalence of L3.1.1, the most dominant MTBC genotype in this setting. Yet, a longer co-existence with the host population did not always result in a higher transmission rate, suggesting that distinct life-history traits have evolved in the different MTBC genotypes. Taken together, our results point to bacterial factors as important determinants of the TB epidemic in Dar es Salaam.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Humanos , Mycobacterium tuberculosis/genética , Tanzanía/epidemiología , Tuberculosis/epidemiología , Genotipo , Virulencia
2.
PLoS Comput Biol ; 18(1): e1009628, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-35025869

RESUMEN

Genome-wide association studies rely on the statistical inference of untyped variants, called imputation, to increase the coverage of genotyping arrays. However, the results are often suboptimal in populations underrepresented in existing reference panels and array designs, since the selected single nucleotide polymorphisms (SNPs) may fail to capture population-specific haplotype structures, hence the full extent of common genetic variation. Here, we propose to sequence the full genomes of a small subset of an underrepresented study cohort to inform the selection of population-specific add-on tag SNPs and to generate an internal population-specific imputation reference panel, such that the remaining array-genotyped cohort could be more accurately imputed. Using a Tanzania-based cohort as a proof-of-concept, we demonstrate the validity of our approach by showing improvements in imputation accuracy after the addition of our designed add-on tags to the base H3Africa array.


Asunto(s)
Genética de Población , Estudio de Asociación del Genoma Completo , Genotipo , Polimorfismo de Nucleótido Simple/genética , Biología Computacional/métodos , Genética de Población/métodos , Genética de Población/normas , Estudio de Asociación del Genoma Completo/métodos , Estudio de Asociación del Genoma Completo/normas , Humanos , Masculino , Tanzanía
3.
Parasitol Res ; 121(5): 1295-1304, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35230547

RESUMEN

Zoonotic larvae of the family Anisakidae found in several fish species represent a serious risk in public health since they may cause food-borne anisakidosis in humans. Chile has culinary preferences including eating raw fish in many traditional preparations. In the present study, a total of 180 fish specimens representing three different fish species, i.e., Chilean hake (Merluccius gayi), snoek (Thyrsites atun), and sea bream (Brama australis), were caught at central coast of Chile. Parasitological examination was performed on musculature and abdominal cavity for subsequent extraction and quantification of anisakid larvae. Estimation of infection parameters, such as prevalence, was performed indicating 100% (CI: 0.94-1.0) prevalence of anisakid L3 in Chilean hakes and snoeks. Moreover, sea breams reached a prevalence of 35% (CI: 0.23-0.48). Prevalence of anisakid larvae in muscle was also analyzed showing values of 18.6% (CI: 0.097-0.309) in Chilean hakes, 15% (CI: 0.07-0.26) in snoeks, and 1.7% (CI: 0-0.089) in sea breams. Meanwhile, prevalence of anisakid larvae in internal organs showed highest values for peritoneum (100% and 83.3%) for snoeks and Chilean hakes, respectively, for liver (96.7%) and gonads (86.6%) in Chilean hakes, and for intestine (98.3%) in snoeks. Molecular analysis of collected anisakid L3 unveiled presence of two potentially zoonotic nematode species, i.e., Pseudoterranova cattani and Anisakis pegreffii. P. cattani was found in Chilean hakes and snoeks being the first molecular host species report for Chilean snoeks. Besides, A. pegreffii was also identified in these species being the first molecular report on this regard. These findings are relevant for better understanding of epidemiology of anisakiasis in Chilean coasts and for public health issues considering potential risk of human population due to its culinary preferences in eating raw fish.


Asunto(s)
Anisakiasis , Anisakis , Ascaridoidea , Enfermedades de los Peces , Gadiformes , Perciformes , Animales , Anisakiasis/epidemiología , Anisakiasis/veterinaria , Anisakis/genética , Ascaridoidea/genética , Chile/epidemiología , Enfermedades de los Peces/epidemiología , Peces , Humanos , Larva/genética , Prevalencia
4.
Mem Inst Oswaldo Cruz ; 115: e200520, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33533871

RESUMEN

BACKGROUND: The evaluation of procedures for drug susceptibility prediction of Mycobacterium tuberculosis based on genomic data against the conventional reference method test based on culture is realistic considering the scenario of growing number of tools proposals based on whole-genome sequences (WGS). OBJECTIVES: This study aimed to evaluate drug susceptibility testing (DST) outcome based on WGS tools and the phenotypic methods performed on isolates of M. tuberculosis Lineage 1 from the state of Pará, Brazil, generally associated with low levels of drug resistance. METHODOLOGY: Culture based DST was performed using the Proportion Method in Löwenstein-Jensen medium on 71 isolates that had been submitted to WGS. We analysed the seven main genome sequence-based tools for resistance and lineage prediction applied to M. tuberculosis and for comparison evaluation we have used the Kappa concordance test. FINDINGS: When comparing the WGS-based tools against the DST, we observed the highest level of agreement using TB-profiler. Among the tools, TB-profiler, KvarQ and Mykrobe were those which identified the largest number of TB-MDR cases. Comparing the four most sensitive tools regarding resistance prediction, agreement was observed for 43 genomes. MAIN CONCLUSIONS: Drug resistance profiling using next-generation sequencing offers rapid assessment of resistance-associated mutations, therefore facilitating rapid access to effective treatment.


Asunto(s)
Antituberculosos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/genética , Antituberculosos/uso terapéutico , Brasil , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/aislamiento & purificación , Preparaciones Farmacéuticas , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Secuenciación Completa del Genoma
5.
Exp Appl Acarol ; 84(2): 459-471, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33909190

RESUMEN

Ticks will diminish productivity among farm animals and transmit zoonotic diseases. We conducted a study to identify tick species infesting slaughter bulls from Adama City and to screen them for tick-borne pathogens. In 2016, 291 ticks were collected from 37 bulls in Adama, which were ready for slaughter. Ticks were identified morphologically. Total genomic DNA was extracted from ticks and used to test for Rickettsia spp. with real-time PCR. Species identification was done by phylogenetic analysis using sequencing that targeted the 23S-5S intergenic spacer region and ompA genes. Four tick species from two genera, Amblyomma and Rhipicephalus, were identified. Amblyomma cohaerens was the dominant species (n = 241, 82.8%), followed by Amblyomma variegatum (n = 22, 7.5%), Rhipicephalus pulchellus (n = 19, 6.5%), and Rhipicephalus decoloratus (n = 9, 3.0%). Among all ticks, 32 (11%) were positive for Rickettsia spp. and 15 (5.2%) of these were identified as R. africae comprising at least two genetic clades, occurring in A. variegatum (n = 10) and A. cohaerens (n = 5). The remainder of Rickettsia-positive samples could not be amplified due to low DNA yield. Furthermore, another 15 (5.2%) samples carried other pathogenic bacteria: Ehrlichia ruminantium (n = 9; 3.1%) in A. cohaerens, Ehrlichia sp. (n = 3; 1%) in Rh. pulchellus and A. cohaerens, Anaplasma sp. (n = 1; 0.5%) in A. cohaerens, and Neoehrlichia mikurensis (n = 2; 0.7%) in A. cohaerens. All ticks were negative for Bartonella spp., Babesia spp., Theileria spp., and Hepatozoon spp. We reported for the first time E. ruminatium, N. mikurensis, Ehrlichia sp., and Anaplasma sp. in A. cohaerens. Medically and veterinarily important pathogens were mostly detected from A. variegatum and A. cohaerens. These data are relevant for a One-health approach for monitoring and prevention of tick-borne disease transmission.


Asunto(s)
Enfermedades de los Bovinos , Ixodidae , Rickettsia , Infestaciones por Garrapatas , Enfermedades por Picaduras de Garrapatas , Animales , Bovinos , Enfermedades de los Bovinos/epidemiología , Etiopía/epidemiología , Masculino , Filogenia , Rickettsia/genética , Infestaciones por Garrapatas/epidemiología , Infestaciones por Garrapatas/veterinaria , Enfermedades por Picaduras de Garrapatas/epidemiología , Enfermedades por Picaduras de Garrapatas/veterinaria
6.
Antimicrob Agents Chemother ; 64(10)2020 09 21.
Artículo en Inglés | MEDLINE | ID: mdl-32718966

RESUMEN

We analyzed 312 drug-resistant genomes of Mycobacterium tuberculosis isolates collected from HIV-coinfected and HIV-negative TB patients from nine countries with a high tuberculosis burden. We found that rifampicin-resistant M. tuberculosis strains isolated from HIV-coinfected patients carried disproportionally more resistance-conferring mutations in rpoB that are associated with a low fitness in the absence of the drug, suggesting these low-fitness rpoB variants can thrive in the context of reduced host immunity.


Asunto(s)
Infecciones por VIH , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Antituberculosos , Proteínas Bacterianas/genética , ARN Polimerasas Dirigidas por ADN/genética , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Pruebas de Sensibilidad Microbiana , Mutación , Mycobacterium tuberculosis/genética , Rifampin
7.
BMC Bioinformatics ; 19(1): 164, 2018 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-29716518

RESUMEN

BACKGROUND: Large sequence datasets are difficult to visualize and handle. Additionally, they often do not represent a random subset of the natural diversity, but the result of uncoordinated and convenience sampling. Consequently, they can suffer from redundancy and sampling biases. RESULTS: Here we present Treemmer, a simple tool to evaluate the redundancy of phylogenetic trees and reduce their complexity by eliminating leaves that contribute the least to the tree diversity. CONCLUSIONS: Treemmer can reduce the size of datasets with different phylogenetic structures and levels of redundancy while maintaining a sub-sample that is representative of the original diversity. Additionally, it is possible to fine-tune the behavior of Treemmer including any kind of meta-information, making Treemmer particularly useful for empirical studies.


Asunto(s)
Biología Computacional/métodos , Virus de la Influenza A/genética , Mycobacterium tuberculosis/genética , Filogenia , Programas Informáticos , Algoritmos , Bases de Datos Genéticas , Humanos , Almacenamiento y Recuperación de la Información
8.
Front Microbiol ; 12: 633396, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34489876

RESUMEN

Each day, approximately 27,000 people become ill with tuberculosis (TB), and 4,000 die from this disease. Pulmonary TB is the main clinical form of TB, and affects the lungs with a considerably heterogeneous manifestation among patients. Immunomodulation by an interplay of host-, environment-, and pathogen-associated factors partially explains such heterogeneity. Microbial communities residing in the host's airways have immunomodulatory effects, but it is unclear if the inter-individual variability of these microbial communities is associated with the heterogeneity of pulmonary TB. Here, we investigated this possibility by characterizing the microbial composition in the sputum of 334 TB patients from Tanzania, and by assessing its association with three aspects of disease manifestations: sputum mycobacterial load, severe clinical findings, and chest x-ray (CXR) findings. Compositional data analysis of taxonomic profiles based on 16S-rRNA gene amplicon sequencing and on whole metagenome shotgun sequencing, and graph-based inference of microbial associations revealed that the airway microbiome of TB patients was shaped by inverse relationships between Streptococcus and two anaerobes: Selenomonas and Fusobacterium. Specifically, the strength of these microbial associations was negatively correlated with Faith's phylogenetic diversity (PD) and with the accumulation of transient genera. Furthermore, low body mass index (BMI) determined the association between abnormal CXRs and community diversity and composition. These associations were mediated by increased abundance of Selenomonas and Fusobacterium, relative to the abundance of Streptococcus, in underweight patients with lung parenchymal infiltrates and in comparison to those with normal chest x-rays. And last, the detection of herpesviruses and anelloviruses in sputum microbial assemblage was linked to co-infection with HIV. Given the anaerobic metabolism of Selenomonas and Fusobacterium, and the hypoxic environment of lung infiltrates, our results suggest that in underweight TB patients, lung tissue remodeling toward anaerobic conditions favors the growth of Selenomonas and Fusobacterium at the expense of Streptococcus. These new insights into the interplay among particular members of the airway microbiome, BMI, and lung parenchymal lesions in TB patients, add a new dimension to the long-known association between low BMI and pulmonary TB. Our results also drive attention to the airways virome in the context of HIV-TB coinfection.

9.
F1000Res ; 10: 60, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33732436

RESUMEN

Background: Lineage 1 (L1) and 3 (L3) are two lineages of the Mycobacterium tuberculosis complex (MTBC) causing tuberculosis (TB) in humans. L1 and L3 are prevalent around the rim of the Indian Ocean, the region that accounts for most of the world's new TB cases. Despite their relevance for this region, L1 and L3 remain understudied. Methods: We analyzed 2,938 L1 and 2,030 L3 whole genome sequences originating from 69 countries. We reconstructed the evolutionary history of these two lineages and identified genes under positive selection. Results: We found a strongly asymmetric pattern of migration from South Asia toward neighboring regions, highlighting the historical role of South Asia in the dispersion of L1 and L3. Moreover, we found that several genes were under positive selection, including genes involved in virulence and resistance to antibiotics. For L1 we identified signatures of local adaptation at the esxH locus, a gene coding for a secreted effector that targets the human endosomal sorting complex, and is included in several vaccine candidates. Conclusions: Our study highlights the importance of genetic diversity in the MTBC, and sheds new light on two of the most important MTBC lineages affecting humans.


Asunto(s)
Mycobacterium tuberculosis , Genotipo , Humanos , Océano Índico , Mycobacterium tuberculosis/genética
10.
PLoS One ; 14(4): e0206334, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30978186

RESUMEN

BACKGROUND: Human tuberculosis (TB) is caused by seven phylogenetic lineages of the Mycobacterium tuberculosis complex (MTBC), Lineage 1-7. Recent advances in rapid genotyping of MTBC based on single nucleotide polymorphisms (SNP), allow for phylogenetically robust strain classification, paving the way for defining genotype-phenotype relationships in clinical settings. Such studies have revealed that, in addition to host and environmental factors, strain variation in the MTBC influences the outcome of TB infection and disease. In Tanzania, such molecular epidemiological studies of TB however are scarce in spite of a high TB burden. METHODS AND FINDINGS: Here we used SNP-typing to characterize a nationwide collection of 2,039 MTBC clinical isolates representative of 1.6% of all new and retreatment TB cases notified in Tanzania during 2012 and 2013. Four lineages, namely Lineage 1-4 were identified within the study population. The distribution and frequency of these lineages varied across regions but overall, Lineage 4 was the most frequent (n = 866, 42.5%), followed by Lineage 3 (n = 681, 33.4%) and 1 (n = 336, 16.5%), with Lineage 2 being the least frequent (n = 92, 4.5%). We found Lineage 2 to be independently associated with female sex (adjusted odds ratio [aOR] 2.14; 95% confidence interval [95% CI] 1.31 - 3.50, p = 0.002) and retreatment cases (aOR 1.67; 95% CI 0.95 - 2.84, p = 0. 065) in the study population. We found no associations between MTBC lineage and patient age or HIV status. Our sublineage typing based on spacer oligotyping on a subset of Lineage 1, 3 and 4 strains revealed the presence of mainly EAI, CAS and LAM families. Finally, we detected low levels of multidrug resistant isolates among a subset of 144 retreatment cases. CONCLUSIONS: This study provides novel insights into the MTBC lineages and the possible influence of pathogen-related factors on the TB epidemic in Tanzania.


Asunto(s)
Mycobacterium tuberculosis/genética , Filogenia , Polimorfismo de Nucleótido Simple , Tuberculosis Pulmonar/genética , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tanzanía/epidemiología , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/microbiología
11.
Infect Genet Evol ; 73: 337-341, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31170529

RESUMEN

Lineage 1 (L1) is one of seven Mycobacterium tuberculosis complex (MTBC) lineages. The objective of this study was to improve the complex taxonomy of L1 using phylogenetic SNPs, and to look for the origin of the main L1 sublineage prevalent in Para, Brazil. We developed a high-throughput SNPs-typing assay based on 12-L1-specific SNPs. This assay allowed us to experimentally retrieve SNP patterns on nine of these twelve SNPs in 277 isolates previously tentatively assigned to L1 spoligotyping-based sublineages. Three collections were used: Pará-Brazil (71); RIVM, the Netherlands (102), Madagascar (104). One-hundred more results were generated in Silico using the PolyTB database. Based on the final SNPs combination, the samples were classified into 11 clusters (C1-C11). Most isolates within a SNP-based cluster shared a mutual spoligotyping-defined lineage. However, L1/EAI1-SOM (SIT48) and L1/EAI6-BGD1 (SIT591) showed a poor correlation with SNP data and are not monophyletic. L1/EAI8-MDG and L1/EAI3-IND belonged to C5; this result suggests that they share a common ancestor. L1.1.3/SIT129, a spoligotype pattern found in SNPs-cluster C6, was found to be shared between Pará/Brazil and Malawi. SIT129 was independently found to be highly prevalent in Mozambique, which suggests a migration history from East-Africa to Brazil during the 16th-18th slave trade period to Northern Brazil.


Asunto(s)
Variación Genética/genética , Mycobacterium tuberculosis/genética , Población Negra/genética , Brasil , Genotipo , Humanos , Madagascar , Mozambique , Países Bajos , Filogenia , Polimorfismo de Nucleótido Simple/genética , Tuberculosis/microbiología
12.
Infect Dis Poverty ; 7(1): 24, 2018 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-29580279

RESUMEN

BACKGROUND: Differences in rural and urban settings could account for distinct characteristics in the epidemiology of tuberculosis (TB). We comparatively studied epidemiological features of TB and helminth co-infections in adult patients from rural and urban settings of Tanzania. METHODS: Adult patients (≥ 18 years) with microbiologically confirmed pulmonary TB were consecutively enrolled into two cohorts in Dar es Salaam, with ~ 4.4 million inhabitants (urban), and Ifakara in the sparsely populated Kilombero District with ~ 400 000 inhabitants (rural). Clinical data were obtained at recruitment. Stool and urine samples were subjected to diagnose helminthiases using Kato-Katz, Baermann, urine filtration, and circulating cathodic antigen tests. Differences between groups were assessed by χ2, Fisher's exact, and Wilcoxon rank sum tests. Logistic regression models were used to determine associations. RESULTS: Between August 2015 and February 2017, 668 patients were enrolled, 460 (68.9%) at the urban and 208 (31.1%) at the rural site. Median patient age was 35 years (interquartile range [IQR]: 27-41.5 years), and 454 (68%) were males. Patients from the rural setting were older (median age 37 years vs. 34 years, P = 0.003), had a lower median body mass index (17.5 kg/m2 vs. 18.5 kg/m2, P <  0.001), a higher proportion of recurrent TB cases (9% vs. 1%, P <  0.001), and in HIV/TB co-infected patients a lower median CD4 cell counts (147 cells/µl vs. 249 cells/µl, P = 0.02) compared to those from urban Tanzania. There was no significant difference in frequencies of HIV infection, diabetes mellitus, and haemoglobin concentration levels between the two settings. The overall prevalence of helminth co-infections was 22.9% (95% confidence interval [CI]: 20.4-27.0%). The significantly higher prevalence of helminth infections at the urban site (25.7% vs. 17.3%, P = 0.018) was predominantly driven by Strongyloides stercoralis (17.0% vs. 4.8%, P <  0.001) and Schistosoma mansoni infection (4.1% vs. 16.4%, P <  0.001). Recurrent TB was associated with living in a rural setting (adjusted odds ratio [aOR]: 3.97, 95% CI: 1.16-13.67) and increasing age (aOR: 1.06, 95% CI: 1.02-1.10). CONCLUSIONS: Clinical characteristics and helminth co-infections pattern differ in TB patients in urban and rural Tanzania. The differences underline the need for setting-specific, tailored public health interventions to improve clinical management of TB and comorbidities.


Asunto(s)
Coinfección/epidemiología , Helmintiasis , Población Rural/estadística & datos numéricos , Tuberculosis , Población Urbana/estadística & datos numéricos , Adolescente , Adulto , Estudios de Cohortes , Femenino , Helmintiasis/complicaciones , Helmintiasis/epidemiología , Helmintiasis/parasitología , Humanos , Masculino , Persona de Mediana Edad , Tanzanía/epidemiología , Tuberculosis/complicaciones , Tuberculosis/epidemiología , Tuberculosis/parasitología , Adulto Joven
13.
Tuberculosis (Edinb) ; 113: 125-129, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30514494

RESUMEN

Tuberculosis (TB) is an infectious disease with a higher risk for infection and disease among household contacts (HHC). Here, we report a molecular epidemiology-based approach to study disease transmission and the genetic characteristics of Mycobacterium tuberculosis (Mtb) strains among HHC in the city of Belem, the capital of the state of Para in north Brazil. The study included 63 TB patients belonging to 26 HHC groups (HHC1 to HHC26). Spoligotyping and 24-loci Mycobacterial Interspersed Repetitive Unit - Variable Number of Tandem Repeat (MIRU-VNTR) revealed indistinguishable bacterial genotypes among 26 patients in 14 (53.8%) HHC groups. Drug susceptibility testing (DST) revealed that 45 (71.4%) of the Mtb isolates were multidrug resistant. The major cluster composed of isolates from five HHCs and on three of these, whole genome sequencing (WGS) was performed confirming their high genetic similarity. These results pinpoint the need for improved vigilance for TB control in households in the city of Belém. When comparing WGS versus phenotypic resistance detection methods as DST and Minimum Inhibitory Concentration (MIC) our data suggest that depending on the colonies selection, results may present variation.


Asunto(s)
Trazado de Contacto , ADN Bacteriano/genética , Composición Familiar , Mycobacterium tuberculosis/genética , Tuberculosis/microbiología , Tuberculosis/transmisión , Adolescente , Adulto , Anciano , Antituberculosos/uso terapéutico , Técnicas Bacteriológicas , Brasil/epidemiología , Niño , Farmacorresistencia Bacteriana Múltiple/genética , Femenino , Genotipo , Humanos , Secuencias Repetitivas Esparcidas , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Epidemiología Molecular , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/patogenicidad , Fenotipo , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Secuencias Repetidas en Tándem , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/transmisión , Secuenciación Completa del Genoma , Adulto Joven
14.
J Infect ; 73(4): 326-35, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27394403

RESUMEN

OBJECTIVES: We evaluated the ability of the Xpert(®) MTB/RIF assay to detect Mycobacterium tuberculosis in whole blood of children with tuberculosis in tuberculosis endemic settings with high rates of HIV infection. METHODS: From June 2011 to September 2012 we prospectively enrolled children with symptoms or signs suggestive of tuberculosis at three research centres in Tanzania and Uganda. After clinical assessment, respiratory specimens were collected for microscopy and culture, as well as whole blood for Xpert(®) MTB/RIF. Children were classified according to standardised case definitions. RESULTS: A total of 232 children were evaluated; 14 (6.0%) had culture-confirmed tuberculosis. The Xpert(®) MTB/RIF assay detected M. tuberculosis in 5/232 (2.2%) blood samples with 1 (0.4%) error reading and presumably 1 (0.4%) false-positive result. The sensitivity of the assay in children with culture-confirmed (1/14) versus no tuberculosis (1/117) was 7.1% (95% CI, 1.3-31.5). Three of the five Xpert(®) MTB/RIF positive patients had negative cultures, but were classified as probable tuberculosis cases. Assay sensitivity against a composite reference standard (culture-confirmed, highly probable or probable tuberculosis) was 5.4% (95% CI, 2.1-13.1). CONCLUSION: Whole blood Xpert(®) MTB/RIF demonstrated very poor sensitivity, although it may enhance the diagnostic yield in select cases, with culture-negative tuberculosis.


Asunto(s)
Sangre/microbiología , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/microbiología , Tuberculosis/diagnóstico , Tuberculosis/microbiología , Niño , Preescolar , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Infecciones por VIH/microbiología , Infecciones por VIH/virología , Humanos , Masculino , Microscopía , Estudios Prospectivos , Sensibilidad y Especificidad , Esputo/microbiología , Tanzanía/epidemiología , Tuberculosis/complicaciones , Tuberculosis/epidemiología , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/epidemiología , Uganda/epidemiología , Organización Mundial de la Salud
15.
Nat Genet ; 48(12): 1535-1543, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27798628

RESUMEN

Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration.


Asunto(s)
ADN Bacteriano/análisis , Genómica/métodos , Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/genética , Polimorfismo Genético/genética , Tuberculosis/microbiología , Genotipo , Salud Global , Humanos , Mycobacterium tuberculosis/aislamiento & purificación , Filogeografía , Tuberculosis/genética
16.
PLoS One ; 10(9): e0138413, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26418678

RESUMEN

OBJECTIVE: We examined the effect of an instructional video about the production of diagnostic sputum on case detection of tuberculosis (TB), and evaluated the acceptance of the video. TRIAL DESIGN: Randomized controlled trial. METHODS: We prepared a culturally adapted instructional video for sputum submission. We analyzed 200 presumptive TB cases coughing for more than two weeks who attended the outpatient department of the governmental Municipal Hospital in Mwananyamala (Dar es Salaam, Tanzania). They were randomly assigned to either receive instructions on sputum submission using the video before submission (intervention group, n = 100) or standard of care (control group, n = 100). Sputum samples were examined for volume, quality and presence of acid-fast bacilli by experienced laboratory technicians blinded to study groups. RESULTS: Median age was 39.1 years (interquartile range 37.0-50.0); 94 (47%) were females, 106 (53%) were males, and 49 (24.5%) were HIV-infected. We found that the instructional video intervention was associated with detection of a higher proportion of microscopically confirmed cases (56%, 95% confidence interval [95% CI] 45.7-65.9%, sputum smear positive patients in the intervention group versus 23%, 95% CI 15.2-32.5%, in the control group, p <0.0001), an increase in volume of specimen defined as a volume ≥3ml (78%, 95% CI 68.6-85.7%, versus 45%, 95% CI 35.0-55.3%, p <0.0001), and specimens less likely to be salivary (14%, 95% CI 7.9-22.4%, versus 39%, 95% CI 29.4-49.3%, p = 0.0001). Older age, but not the HIV status or sex, modified the effectiveness of the intervention by improving it positively. When asked how well the video instructions were understood, the majority of patients in the intervention group reported to have understood the video instructions well (97%). Most of the patients thought the video would be useful in the cultural setting of Tanzania (92%). CONCLUSIONS: Sputum submission instructional videos increased the yield of tuberculosis cases through better quality of sputum samples. If confirmed in larger studies, instructional videos may have a substantial effect on the case yield using sputum microscopy and also molecular tests. This low-cost strategy should be considered as part of the efforts to control TB in resource-limited settings. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201504001098231.


Asunto(s)
Mycobacterium tuberculosis/aislamiento & purificación , Educación del Paciente como Asunto/métodos , Esputo/microbiología , Tuberculosis Pulmonar/diagnóstico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Tanzanía , Tuberculosis Pulmonar/microbiología
17.
Mem. Inst. Oswaldo Cruz ; 115: e200520, 2020. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1154871

RESUMEN

BACKGROUND The evaluation of procedures for drug susceptibility prediction of Mycobacterium tuberculosis based on genomic data against the conventional reference method test based on culture is realistic considering the scenario of growing number of tools proposals based on whole-genome sequences (WGS). OBJECTIVES This study aimed to evaluate drug susceptibility testing (DST) outcome based on WGS tools and the phenotypic methods performed on isolates of M. tuberculosis Lineage 1 from the state of Pará, Brazil, generally associated with low levels of drug resistance. METHODOLOGY Culture based DST was performed using the Proportion Method in Löwenstein-Jensen medium on 71 isolates that had been submitted to WGS. We analysed the seven main genome sequence-based tools for resistance and lineage prediction applied to M. tuberculosis and for comparison evaluation we have used the Kappa concordance test. FINDINGS When comparing the WGS-based tools against the DST, we observed the highest level of agreement using TB-profiler. Among the tools, TB-profiler, KvarQ and Mykrobe were those which identified the largest number of TB-MDR cases. Comparing the four most sensitive tools regarding resistance prediction, agreement was observed for 43 genomes. MAIN CONCLUSIONS Drug resistance profiling using next-generation sequencing offers rapid assessment of resistance-associated mutations, therefore facilitating rapid access to effective treatment.


Asunto(s)
Humanos , Tuberculosis Resistente a Múltiples Medicamentos/genética , Farmacorresistencia Bacteriana Múltiple/genética , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Antituberculosos/farmacología , Brasil , Preparaciones Farmacéuticas , Pruebas de Sensibilidad Microbiana , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Secuenciación Completa del Genoma , Mycobacterium tuberculosis/aislamiento & purificación , Antituberculosos/uso terapéutico
18.
BMJ Case Rep ; 20122012 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-22605838

RESUMEN

Data on non-tuberculous Mycobacteria (NTM) infection in non-HIV patients in Tanzania are scarce. However, NTM infections are emerging in Africa as in many parts of the world. Healthcare providers and physicians working in high tuberculosis incidence regions should also consider NTM as one of the differential diagnosis. A 35-year-old Tanzanian man presented with history of cough, fever, chest pain and night sweats for 4 weeks. The patient had a history of tuberculosis 4 years ago. On physical examination, there were no significant findings. Sputum smears were positive for acid fast bacilli, while Xpert MTB/RIF showed negative results. Culture and subsequent differentiation confirmed Mycobacterium intracellulare infection. With no specific national guidelines at our setting the patient received standard antituberculosis treatment and is kept under close follow-up.


Asunto(s)
Infección por Mycobacterium avium-intracellulare/diagnóstico , Antituberculosos/uso terapéutico , Diagnóstico Diferencial , Seronegatividad para VIH , Humanos , Masculino , Persona de Mediana Edad , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Tanzanía/epidemiología , Tuberculosis/epidemiología
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