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1.
BMC Microbiol ; 15: 268, 2015 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-26589993

RESUMEN

BACKGROUND: The zoonosis bovine tuberculosis (TB) is known to be responsible for a considerable proportion of extrapulmonary TB. In Mozambique, bovine TB is a recognised problem in cattle, but little has been done to evaluate how Mycobacterium bovis has contributed to human TB. We here explore the public health risk for bovine TB in Maputo, by characterizing the isolates from tuberculous lymphadenitis (TBLN) cases, a common manifestation of bovine TB in humans, in the Pathology Service of Maputo Central Hospital, in Mozambique, during one year. RESULTS: Among 110 patients suspected of having TBLN, 49 had a positive culture result. Of those, 48 (98%) were positive for Mycobacterium tuberculosis complex and one for nontuberculous mycobacteria. Of the 45 isolates analysed by spoligotyping and Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU-VNTR), all were M. tuberculosis. No M. bovis was found. Cervical TBLN, corresponding to 39 (86.7%) cases, was the main cause of TBLN and 66.7% of those where from HIV positive patients. We found that TBLN in Maputo was caused by a variety of M. tuberculosis strains. The most prevalent lineage was the EAI (n = 19; 43.2%). Particular common spoligotypes were SIT 48 (EAI1_SOM sublineage), SIT 42 (LAM 9), SIT 1 (Beijing) and SIT53 (T1), similar to findings among pulmonary cases. CONCLUSIONS: M. tuberculosis was the main etiological agent of TBLN in Maputo. M. tuberculosis genotypes were similar to the ones causing pulmonary TB, suggesting that in Maputo, cases of TBLN arise from the same source as pulmonary TB, rather than from an external zoonotic source. Further research is needed on other forms of extrapulmonary TB and in rural areas where there is high prevalence of bovine TB in cattle, to evaluate the risk of transmission of M. bovis from cattle to humans.


Asunto(s)
Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Ganglionar/epidemiología , Adolescente , Adulto , Anciano , Femenino , Variación Genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Tipificación Molecular , Mozambique/epidemiología , Mycobacterium bovis/aislamiento & purificación , Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/genética , Adulto Joven
3.
BMC Microbiol ; 10: 195, 2010 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-20663126

RESUMEN

BACKGROUND: Mozambique is one of the countries with the highest burden of tuberculosis (TB) in Sub-Saharan Africa, and information on the predominant genotypes of Mycobacterium tuberculosis circulating in the country are important to better understand the epidemic. This study determined the predominant strain lineages that cause TB in Mozambique. RESULTS: A total of 445 M. tuberculosis isolates from seven different provinces of Mozambique were characterized by spoligotyping and resulting profiles were compared with the international spoligotyping database SITVIT2.The four most predominant lineages observed were: the Latin-American Mediterranean (LAM, n = 165 or 37%); the East African-Indian (EAI, n = 132 or 29.7%); an evolutionary recent but yet ill-defined T clade, (n = 52 or 11.6%); and the globally-emerging Beijing clone, (n = 31 or 7%). A high spoligotype diversity was found for the EAI, LAM and T lineages. CONCLUSIONS: The TB epidemic in Mozambique is caused by a wide diversity of spoligotypes with predominance of LAM, EAI, T and Beijing lineages.


Asunto(s)
Variación Genética , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Pulmonar/microbiología , Adolescente , Adulto , Femenino , Humanos , Persona de Mediana Edad , Datos de Secuencia Molecular , Mozambique/epidemiología , Mycobacterium tuberculosis/clasificación , Tuberculosis Pulmonar/epidemiología , Adulto Joven
4.
BMC Infect Dis ; 9: 12, 2009 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-19196450

RESUMEN

BACKGROUND: The identification and differentiation of strains of Mycobacterium tuberculosis by DNA fingerprinting has provided a better understanding of the epidemiology and tracing the transmission of tuberculosis. We set out to determine if there was a relationship between the risk of belonging to a group of tuberculosis patients with identical mycobacterial DNA fingerprint patterns and the HIV sero-status of the individuals in a high TB incidence peri-urban setting of Kampala, Uganda. METHODS: One hundred eighty three isolates of Mycobacterium tuberculosis from 80 HIV seropositive and 103 HIV seronegative patients were fingerprinted by standard IS6110-RFLP. Using the BioNumerics software, strains were considered to be clustered if at least one other patient had an isolate with identical RFLP pattern. RESULTS: One hundred and eighteen different fingerprint patterns were obtained from the 183 isolates. There were 34 clusters containing 54% (99/183) of the patients (average cluster size of 2.9), and a majority (96.2%) of the strains possessed a high copy number (> or = 5 copies) of the IS6110 element. When strains with <5 bands were excluded from the analysis, 50.3% (92/183) were clustered, and there was no difference in the level of diversity of DNA fingerprints observed in the two sero-groups (adjusted odds ratio [aOR] 0.85, 95%CI 0.46-1.56, P = 0.615), patients aged <40 years (aOR 0.53, 95%CI 0.25-1.12, P = 0.100), and sex (aOR 1.12, 95%CI 0.60-2.06, P = 0.715). CONCLUSION: The sample showed evidence of a high prevalence of recent transmission with a high average cluster size, but infection with an isolate with a fingerprint found to be part of a cluster was not associated with any demographic or clinical characteristics, including HIV status.


Asunto(s)
Dermatoglifia del ADN , Seropositividad para VIH/epidemiología , Mycobacterium tuberculosis/genética , Polimorfismo de Longitud del Fragmento de Restricción , Tuberculosis Pulmonar/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Adolescente , Adulto , Técnicas de Tipificación Bacteriana , Análisis por Conglomerados , ADN Bacteriano/análisis , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/aislamiento & purificación , Oportunidad Relativa , Prevalencia , Factores de Riesgo , Análisis de Secuencia de ADN , Tuberculosis Pulmonar/microbiología , Uganda/epidemiología , Adulto Joven
5.
Microbes Infect ; 10(6): 699-705, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18485780

RESUMEN

Drug-resistant tuberculosis (TB), including the more severe forms of multidrug- and extensively drug-resistant forms, is an increasing public health concern globally. In Sweden the majority of patients with TB are immigrants from countries with a high incidence of TB including the drug-resistant forms. In this study, the spread of resistant TB in Sweden was investigated by molecular fingerprinting. Isolates resistant to at least one of the drugs, isoniazid, rifampicin, ethambutol or streptomycin, from 400 patients collected between 1994 and 2005, were studied by restriction fragment length polymorphism (RFLP) and by spoligotyping. Thirty-five clusters of patients infected with strains with identical RFLP and spoligotyping patterns (2-96 patients per cluster), comprising a total of 203 patients, were found. One large outbreak of isoniazid resistant tuberculosis was identified, involving 96 patients, mainly from the Horn of Africa. To identify chains of transmission, molecular epidemiological characterization of TB isolates should, if possible, be performed on isolates from all new TB patients.


Asunto(s)
Epidemiología Molecular , Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Antituberculosos/uso terapéutico , Técnicas de Tipificación Bacteriana , Brotes de Enfermedades , Femenino , Humanos , Isoniazida/uso terapéutico , Masculino , Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/efectos de los fármacos , Polimorfismo de Longitud del Fragmento de Restricción , Suecia/epidemiología , Suecia/etnología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico
6.
BMC Infect Dis ; 8: 101, 2008 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-18662405

RESUMEN

BACKGROUND: The poor peri-urban areas of developing countries with inadequate living conditions and a high prevalence of HIV infection have been implicated in the increase of tuberculosis (TB). Presence of different lineages of Mycobacterium tuberculosis has been described in different parts of the world. This study determined the predominant strain lineages that cause TB in Rubaga division, Kampala, Uganda, and the prevalence of resistance to key anti-tuberculosis drugs in this community. METHODS: This was a cross-sectional study of newly diagnosed sputum smear-positive patients aged >or= 18 years. A total of 344 isolates were genotyped by standard spoligotyping and the strains were compared with those in the international spoligotype database (SpolDB4). HIV testing and anti-tuberculosis drug susceptibility assays for isoniazid and rifampicin were performed and association with the most predominant spoligotypes determined. RESULTS: A total of 33 clusters were obtained from 57 spoligotype patterns. According to the SpolDB4 database, 241 (70%) of the isolates were of the T2 family, while CAS1-Kili (3.5%), LAM9 (2.6%), CAS1-Delhi (2.6%) were the other significant spoligotypes. Furthermore, a major spoligotype pattern of 17 (4.5%) strains characterized by lack of spacers 15-17 and 19-43 was not identified in SpolDB4. A total of 92 (26.7%) of the patients were HIV sero-positive, 176 (51.2%) sero-negative, while 76 (22.1%) of the patients did not consent to HIV testing. Resistance to isoniazid was found in 8.1% of strains, while all 15 (4.4%) strains resistant to rifampicin were multi-drug resistant. Additionally, there was no association between any strain types in the sample with either drug resistance or HIV sero-status of the patients. CONCLUSION: The TB epidemic in Kampala is localized, mainly caused by the T2 family of strains. Strain types were neither associated with drug resistance nor HIV sero-status.


Asunto(s)
Brotes de Enfermedades , Farmacorresistencia Bacteriana/genética , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Tuberculosis Pulmonar/epidemiología , Adolescente , Adulto , Antibióticos Antituberculosos/farmacología , Anticuerpos Antibacterianos/inmunología , Técnicas de Tipificación Bacteriana , Estudios Transversales , Femenino , Genotipo , Seronegatividad para VIH , Seropositividad para VIH/epidemiología , VIH-1/inmunología , Humanos , Isoniazida/farmacología , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Epidemiología Molecular , Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/inmunología , Prevalencia , Rifampin/farmacología , Esputo/microbiología , Tuberculosis Pulmonar/inmunología , Tuberculosis Pulmonar/microbiología , Uganda/epidemiología
7.
PLoS Negl Trop Dis ; 12(1): e0006147, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29346413

RESUMEN

Bovine tuberculosis is a zoonotic disease with largely unknown impact in Africa, with risk factors such as HIV and direct contact with animals or consumption of Mycobacterium bovis infected animal products. In order to understand and quantify this risk and design intervention strategies, good epidemiological studies are needed. Such studies can include molecular typing of M. bovis isolates. The aim of this study was to apply these tools to provide novel information concerning the distribution of bovine tuberculosis in cattle in Mozambique and thereby provide relevant information to guide policy development and strategies to contain the disease in livestock, and reduce the risk associated with transmission to humans. A collection of 178 M. bovis isolates was obtained from cattle in Mozambique. Using spoligotyping and regions of difference analysis, we classified the isolates into clonal complexes, thus reporting the first characterisation of M. bovis strains in this region. Data from MIRU-VNTR typing was used to compare isolates from a number of African countries, revealing a deeply geographically structured diversity of M. bovis. Eastern Africa appears to show high diversity, suggesting deep evolution in that region. The diversity of M. bovis in Africa does not seem to be a function of recent importation of animals, but is probably maintained within each particular region by constant reinfection from reservoir animals. Understanding the transmission routes of M. bovis in Mozambique and elsewhere is essential in order to focus public health and veterinary resources to contain bovine tuberculosis.


Asunto(s)
Transmisión de Enfermedad Infecciosa , Variación Genética , Mycobacterium bovis/clasificación , Tuberculosis Bovina/epidemiología , Tuberculosis Bovina/transmisión , Zoonosis/epidemiología , Zoonosis/transmisión , Animales , Bovinos , Genotipo , Epidemiología Molecular , Tipificación Molecular , Mozambique/epidemiología , Mycobacterium bovis/genética , Mycobacterium bovis/aislamiento & purificación
8.
Clin Infect Dis ; 35(2): 146-55, 2002 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-12087520

RESUMEN

We investigated the means by which drug resistance emerges among drug-susceptible Mycobacterium tuberculosis strains during antituberculosis therapy. Patients who experienced failure of treatment for active pulmonary tuberculosis, who initially received diagnoses of infection with drug-susceptible M. tuberculosis, and who had had at least 3 isolates tested for drug susceptibility were selected from a 6-year period in the Estonian National Reference Laboratory archive. Eleven patients from whom 35 sequential isolates of M. tuberculosis had been obtained were recruited into the study. Their clinical data and treatment charts were analyzed and correlated with drug-susceptibility patterns and IS6110 restriction fragment-length polymorphism (RFLP) profiles. Six patients excreted isogenic drug-susceptible M. tuberculosis strains, whereas, in the other 5 patients, the isolated strain shifted from a susceptible to a resistant phenotype. In all cases, this shift correlated to a shift in RFLP pattern, which showed reinfection with a new strain. Exogenous reinfection with drug-resistant M. tuberculosis may be misinterpreted as the emergence of drug resistance if molecular testing techniques are not used.


Asunto(s)
Antibióticos Antituberculosos/uso terapéutico , Antituberculosos/uso terapéutico , Técnicas de Tipificación Bacteriana/métodos , Genética Microbiana/métodos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiología , Adulto , Anciano , Dermatoglifia del ADN , Esquema de Medicación , Farmacorresistencia Bacteriana/genética , Etambutol/uso terapéutico , Femenino , Humanos , Isoniazida/uso terapéutico , Kanamicina/uso terapéutico , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/efectos de los fármacos , Polimorfismo de Longitud del Fragmento de Restricción , Pirazinamida/uso terapéutico , Recurrencia , Estudios Retrospectivos , Rifampin/uso terapéutico , Estreptomicina/uso terapéutico , Insuficiencia del Tratamiento , Tuberculosis Pulmonar/genética
10.
Microbes Infect ; 6(14): 1320-5, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15555539

RESUMEN

Isolates of Mycobacterium avium complex (MAC) were cultured from sputum samples obtained from patients in Guinea-Bissau, West Africa. Twenty-eight isolates hybridising with MAC probe (AccuProbe) were further characterised by different molecular techniques: hybridisation with species-specific probes (AccuProbe) for M. avium and M. intracellulare, partial sequencing of 16S rRNA gene and PCR detection of the DT1-DT6 sequences and the macrophage-induced gene (mig). Only one of the 28 isolates reacted with the M. avium probe and four with the M. intracellulare probe. Two isolates expressed the DT1 sequence, and three the DT6. The mig was detected in 18 (64%) of the isolates. Sequencing of 16S rRNA had the greatest discriminative power of the typing methods applied, without strong correlation with any other technique. Clinical MAC isolates from Guinea-Bissau demonstrated a wide genetic diversity among the members of M. avium complex that might reflect on biotope variation.


Asunto(s)
Variación Genética , Complejo Mycobacterium avium/genética , Complejo Mycobacterium avium/aislamiento & purificación , Infección por Mycobacterium avium-intracellulare/microbiología , ADN Bacteriano/química , ADN Bacteriano/aislamiento & purificación , ADN Ribosómico/química , ADN Ribosómico/aislamiento & purificación , Genes Bacterianos , Genes de ARNr , Guinea Bissau , Humanos , Epidemiología Molecular , Complejo Mycobacterium avium/clasificación , Hibridación de Ácido Nucleico , Reacción en Cadena de la Polimerasa , ARN Bacteriano/genética , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Esputo/microbiología
11.
Microbes Infect ; 6(3): 272-8, 2004 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15026014

RESUMEN

In a previous study of Mycobacterium tuberculosis complex isolates from Guinea-Bissau in West Africa, we identified a unique group of strains, designated here as the Guinea-Bissau family of strains, which, although genotypically closely related, phenotypically demonstrated a considerable heterogeneity. We conducted here a detailed genotypic analysis of a subset (n = 35) of these isolates. Based on the data obtained, and by comparison of known corresponding genes in mycobacteria outside the M. tuberculosis complex, we propose that the Guinea-Bissau strains belong to a unique branch of the M. tuberculosis complex tree in between classical M. tuberculosis and classical M. bovis. These observations are discussed in their significance in M. tuberculosis complex classification.


Asunto(s)
Catalasa , Proteínas de Unión al ADN , Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/genética , Filogenia , Polimorfismo Genético , Amidohidrolasas/genética , Proteínas Bacterianas/genética , Técnicas de Tipificación Bacteriana , Dermatoglifia del ADN , Girasa de ADN/genética , ADN Bacteriano/genética , Genes Bacterianos , Genotipo , Guinea Bissau , Epidemiología Molecular , Mycobacterium tuberculosis/aislamiento & purificación , Oxidorreductasas/genética , Polimorfismo de Longitud del Fragmento de Restricción , Proteínas Represoras/genética , Análisis de Secuencia de ADN , Eliminación de Secuencia , Factores de Transcripción/genética
12.
Lakartidningen ; 99(23): 2618-9, 2622-3, 2002 Jun 06.
Artículo en Sueco | MEDLINE | ID: mdl-12101614

RESUMEN

Resistance of Mycobacterium tuberculosis to antibiotics is a world wide problem. A study is reported with the aim to analyse the spread of resistant isolates of M tuberculosis complex from patients with tuberculosis in Sweden. The study is based on a sample of 192 M tuberculosis complex isolates from patients with drug resistant tuberculosis during 1994-2000. All isolates resistant to at least one of the drugs streptomycin, isoniazid, ethambutol and rifampicin were included in the study. Restriction fragment length polymorphism (RFLP) was performed, using IS6110 as a probe for hybridisation. Visualised bands were analysed by Gel Compar software. The majority of the isolates were from patients born in high TB prevalence countries. During the years 1996-2000 there was one major cluster generated from 34 isolates. In 1996-1998 there were two isolates per year, in 1999 it increased to 20 isolates, and eight cases in 2000. All strains were resistant to isoniazid. All patients in this cluster were found to be from Africa. In comparing the pattern in the T-base the strains matched with strain BEA-000007341 isolated from a patient in Rwanda. The majority of patients with drug resistant tuberculosis in Sweden are immigrants from countries with high incidence of tuberculosis. Spread of disease to the Swedish born population is uncommon. However, an increasingly prevalent clone of isoniazid resistant tuberculosis was found among African immigrants, mainly living in the Stockholm area.


Asunto(s)
Antituberculosos/uso terapéutico , Trazado de Contacto/métodos , Dermatoglifia del ADN/métodos , Isoniazida/uso terapéutico , Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/transmisión , Adolescente , Adulto , Anciano , Niño , Preescolar , Enfermedades Transmisibles Emergentes/prevención & control , Enfermedades Transmisibles Emergentes/transmisión , Humanos , Lactante , Persona de Mediana Edad , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Polimorfismo de Longitud del Fragmento de Restricción , Suecia/epidemiología , Suecia/etnología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/prevención & control
13.
PLoS One ; 8(8): e71999, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23940801

RESUMEN

The Beijing genotype is a lineage of Mycobacterium tuberculosis that is distributed worldwide and responsible for large epidemics, associated with multidrug-resistance. However, its distribution in Africa is less understood due to the lack of data. Our aim was to investigate the prevalence and possible transmission of Beijing strains in Mozambique by a multivariate analysis of genotypic, geographic and demographic data. A total of 543 M. tuberculosis isolates from Mozambique were spoligotyped. Of these, 33 were of the Beijing lineage. The genetic relationship between the Beijing isolates were studied by identification of genomic deletions within some Regions of Difference (RD), Restriction Fragment Length Polymorphism (RFLP) and Mycobacterial Interspersed Repetivie Unit - variable number tandem repeat (MIRU-VNTR). Beijing strains from South Africa, representing different sublineages were included as reference strains. The association between Beijing genotype, Human Immunodeficiency Virus (HIV) serology and baseline demographic data was investigated. HIV positive serostatus was significantly (p=0.023) more common in patients with Beijing strains than in patients with non-Beijing strains in a multivariable analysis adjusted for age, sex and province (14 (10.9%) of the 129 HIV positive patients had Beijing strains while 6/141 (4.3%) of HIV negative patients had Beijing strains). The majority of Beijing strains were found in the Southern region of Mozambique, particularly in Maputo City (17%). Only one Beijing strain was drug resistant (multi-drug resistant). By combined use of RD and spoligotyping, three genetic sublineages could be tentatively identified where a distinct group of four isolates had deletion of RD150, a signature of the "sublineage 7" recently emerging in South Africa. The same group was very similar to South African "sublineage 7" by RFLP and MIRU-VNTR, suggesting that this sublineage could have been recently introduced in Mozambique from South Africa, in association with HIV infection.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Coinfección/microbiología , Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/genética , Tuberculosis Pulmonar/microbiología , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Adulto , Coinfección/epidemiología , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Repeticiones de Minisatélite , Tipificación Molecular , Mozambique/epidemiología , Filogenia , Polimorfismo de Longitud del Fragmento de Restricción , Tuberculosis Pulmonar/epidemiología
14.
PLoS One ; 7(10): e46848, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23056484

RESUMEN

UNLABELLED: A hundred years ago the prevalence of tuberculosis (TB) in Sweden was one of the highest in the world. In this study we conducted a population-based search for distinct strains of Mycobacterium tuberculosis complex isolated from patients born in Sweden before 1945. Many of these isolates represent the M. tuberculosis complex population that fueled the TB epidemic in Sweden during the first half of the 20(th) century. METHODS: Genetic relationships between strains that caused the epidemic and present day strains were studied by spoligotyping and restriction fragment length polymorphism. RESULTS: The majority of the isolates from the elderly population were evolutionary recent Principal Genetic Group (PGG)2/3 strains (363/409 or 88.8%), and only a low proportion were ancient PGG1 strains (24/409 or 5.9%). Twenty-two were undefined. The isolates demonstrated a population where the Euro-American superlineage dominated; in particular with Haarlem (41.1%) and T (37.7%) spoligotypes and only 21.2% belonged to other spoligotype families. Isolates from the elderly population clustered much less frequently than did isolates from a young control group population. CONCLUSIONS: A closely knit pool of PGG2/3 strains restricted to Sweden and its immediate neighbours appears to have played a role in the epidemic, while PGG1 strains are usually linked to migrants in todaýs Sweden. Further studies of these outbreak strains may give indications of why the epidemic waned.


Asunto(s)
Epidemias/estadística & datos numéricos , Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/fisiología , Tuberculosis/epidemiología , Tuberculosis/microbiología , Anciano , Anciano de 80 o más Años , Cromosomas Bacterianos/genética , Farmacorresistencia Bacteriana/genética , Femenino , Humanos , Masculino , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Polimorfismo de Longitud del Fragmento de Restricción , Especificidad de la Especie , Suecia/epidemiología
15.
PLoS One ; 6(4): e18601, 2011 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-21533101

RESUMEN

The Guinea-Bissau family of strains is a unique group of the Mycobacterium tuberculosis complex that, although genotypically closely related, phenotypically demonstrates considerable heterogeneity. We have investigated 414 M. tuberculosis complex strains collected in Guinea-Bissau between 1989 and 2008 in order to further characterize the Guinea-Bissau family of strains. To determine the strain lineages present in the study sample, binary outcomes of spoligotyping were compared with spoligotypes existing in the international database SITVIT2. The major circulating M. tuberculosis clades ranked in the following order: AFRI (n = 195, 47.10%), Latin-American-Mediterranean (LAM) (n = 75, 18.12%), ill-defined T clade (n = 53, 12.8%), Haarlem (n = 37, 8.85%), East-African-Indian (EAI) (n = 25, 6.04%), Unknown (n = 12, 2.87%), Beijing (n = 7, 1.68%), X clade (n = 4, 0.96%), Manu (n = 4, 0.97%), CAS (n = 2, 0.48%). Two strains of the LAM clade isolated in 2007 belonged to the Cameroon family (SIT61). All AFRI isolates except one belonged to the Guinea-Bissau family, i.e. they have an AFRI_1 spoligotype pattern, they have a distinct RFLP pattern with low numbers of IS6110 insertions, and they lack the regions of difference RD7, RD8, RD9 and RD10, RD701 and RD702. This profile classifies the Guinea-Bissau family, irrespective of phenotypic biovar, as part of the M. africanum West African 2 lineage, or the AFRI_1 sublineage according to the spoligtyping nomenclature. Guinea-Bissau family strains display a variation of biochemical traits classically used to differentiate M. tuberculosis from M. bovis. Yet, the differential expression of these biochemical traits was not related to any genes so far investigated (narGHJI and pncA). Guinea-Bissau has the highest prevalence of M. africanum recorded in the African continent, and the Guinea-Bissau family shows a high phylogeographical specificity for Western Africa, with Guinea-Bissau being the epicenter. Trends over time however indicate that this family of strains is waning in most parts of Western Africa, including Guinea-Bissau (p = 0.048).


Asunto(s)
Mycobacterium tuberculosis/clasificación , Secuencia de Bases , Cartilla de ADN , Genotipo , Guinea Bissau , Humanos , Fenotipo , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción
16.
PLoS One ; 6(1): e16647, 2011 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-21304944

RESUMEN

In molecular epidemiological studies of drug resistant Mycobacterium tuberculosis (TB) in Sweden a large outbreak of an isoniazid resistant strain was identified, involving 115 patients, mainly from the Horn of Africa. During the outbreak period, the genomic pattern of the outbreak strain has stayed virtually unchanged with regard to drug resistance, IS6110 restriction fragment length polymorphism and spoligotyping patterns. Here we present the complete genome sequence analyses of the index isolate and two isolates sampled nine years after the index case as well as experimental data on the virulence of this outbreak strain. Even though the strain has been present in the community for nine years and passaged between patients at least five times in-between the isolates, we only found four single nucleotide polymorphisms in one of the later isolates and a small (4 amino acids) deletion in the other compared to the index isolate. In contrast to many other evolutionarily successful outbreak lineages (e.g. the Beijing lineage) this outbreak strain appears to be genetically very stable yet evolutionarily successful in a low endemic country such as Sweden. These findings further illustrate that the rate of genomic variation in TB can be highly strain dependent, something that can have important implications for epidemiological studies as well as development of resistance.


Asunto(s)
Brotes de Enfermedades , Farmacorresistencia Bacteriana/genética , Inestabilidad Genómica , Isoniazida/farmacología , Mycobacterium tuberculosis/genética , Tuberculosis/epidemiología , Humanos , Mycobacterium tuberculosis/patogenicidad , Mycobacterium tuberculosis/fisiología , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido Simple , Suecia/epidemiología
17.
Int J Infect Dis ; 14 Suppl 3: e142-7, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20395161

RESUMEN

OBJECTIVES: To investigate the effect of human T-lymphotropic virus type 1 (HTLV-1) on CD4 counts and mortality in tuberculosis (TB) patients with or without human immunodeficiency virus (HIV). METHODS: A prospective study on 280 hospitalized patients with pulmonary TB was performed in Guinea-Bissau, 1994-1997, including HIV, CD4 counts and clinical outcome. We compared the CD4 count levels at the time of inclusion between HIV-negative and HIV-positive patients, with or without HTLV-1. Mortality was determined while patients were on treatment for TB. RESULTS: Median CD4% was significantly higher in HIV-positive subjects co-infected with HTLV-1 compared to HTLV-1-negative patients. Two hundred thirty-three individuals were included in the analysis of mortality, and among HIV-negative subjects the mortality was 18.6/100 person-years . In HIV-2-positive HTLV-1-negative subjects the mortality was 39.5/100 person-years and in HIV-2/HTLV-1 co-infected patients it was 113.6/100 person-years (adjusted mortality rate ratio 4.7, 95% CI 1.5-14.4; p < 0.01). When all HIV-positive patients were analyzed together, corresponding mortality rates were 53.5/100 person-years and 104.8/100 person-years , respectively (not significant). CONCLUSIONS: HIV/HTLV-1 co-infected patients hospitalized for pulmonary TB had a high mortality and had significantly higher CD4% compared to only HIV-positive subjects. This may imply that HTLV-1 has an adverse effect on the immune system in HIV-infected subjects, independently of the CD4 count, that makes co-infected subjects more vulnerable to TB.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/mortalidad , Infecciones por VIH/complicaciones , Infecciones por VIH/mortalidad , VIH-2 , Infecciones por HTLV-I/complicaciones , Infecciones por HTLV-I/mortalidad , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/mortalidad , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Recuento de Linfocito CD4 , Relación CD4-CD8 , Femenino , Guinea Bissau/epidemiología , Infecciones por VIH/inmunología , VIH-1 , Infecciones por HTLV-I/inmunología , Humanos , Masculino , Tuberculosis Pulmonar/inmunología
18.
PLoS One ; 5(5): e10893, 2010 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-20531942

RESUMEN

BACKGROUND: Drug resistant (DR) and multi-drug resistant (MDR) tuberculosis (TB) is increasing worldwide. In some parts of the world 10% or more of new TB cases are MDR. The Beijing genotype is a distinct genetic lineage of Mycobacterium tuberculosis, which is distributed worldwide, and has caused large outbreaks of MDR-TB. It has been proposed that certain lineages of M. tuberculosis, such as the Beijing lineage, may have specific adaptive advantages. We have investigated the presence and transmission of DR Beijing strains in the Swedish population. METHODOLOGY/PRINCIPAL FINDINGS: All DR M. tuberculosis complex isolates between 1994 and 2008 were studied. Isolates that were of Beijing genotype were investigated for specific resistance mutations and phylogenetic markers. Seventy (13%) of 536 DR strains were of Beijing genotype. The majority of the patients with Beijing strains were foreign born, and their country of origin reflects the countries where the Beijing genotype is most prevalent. Multidrug-resistance was significantly more common in Beijing strains than in non-Beijing strains. There was a correlation between the Beijing genotype and specific resistance mutations in the katG gene, the mabA-inhA-promotor and the rpoB gene. By a combined use of RD deletions, spoligotyping, IS1547, mutT gene polymorphism and Rv3135 gene analysis the Beijing strains could be divided into 11 genomic sublineages. Of the patients with Beijing strains 28 (41%) were found in altogether 10 clusters (2-5 per cluster), as defined by RFLP IS6110, while 52% of the patients with non-Beijing strains were in clusters. By 24 loci MIRU-VNTR 31 (45%) of the patients with Beijing strains were found in altogether 7 clusters (2-11 per cluster). Contact tracing established possible epidemiological linkage between only two patients with Beijing strains. CONCLUSIONS/SIGNIFICANCE: Although extensive outbreaks with non-Beijing TB strains have occurred in Sweden, Beijing strains have not taken hold, in spite of the proximity to high prevalence countries such as Russia and the Baltic countries. The Beijing sublineages so far introduced in Sweden may not be adapted to spread in the Scandinavian population.


Asunto(s)
Farmacorresistencia Bacteriana/genética , Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/transmisión , Adolescente , Adulto , Anciano , Niño , Preescolar , China , Femenino , Genoma Bacteriano/genética , Genotipo , Humanos , Lactante , Masculino , Persona de Mediana Edad , Mutación/genética , Mycobacterium tuberculosis/aislamiento & purificación , Filogenia , Polimorfismo Genético , Suecia/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/genética , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Adulto Joven
19.
J Acquir Immune Defic Syndr ; 48(5): 607-10, 2008 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-18645510

RESUMEN

BACKGROUND: Few and inconclusive results have been presented regarding the influence of human T-lymphotropic virus 1 (HTLV-1) infection on the risk of acquiring tuberculosis (TB). METHODS: In 1994-1997, we performed a prospective study on hospitalized adult patients with pulmonary TB in Guinea-Bissau and compared the clinical outcome in HIV-2 and HIV-negative patients. We determined the prevalence of HTLV-1 in all patients screened and diagnosed with TB in that study and compared the infection rate with a serosurvey of HTLV-1 in a population sample from a community-based study conducted at the same time and in the same city. RESULTS: In the TB group, a total of 32 (11.4%) of 280 patients were positive for HTLV-1. This was significantly higher compared with the population-based group in which 74 (3.5%) of 2117 were HTLV-1 positive [crude odds ratio (OR) = 3.6; 95% confidence interval (CI) 2.2 to 5.6, P < 0.001]. However, in a logistic regression analysis controlling for age, gender, and HIV result, the difference was no longer significant (OR = 1.61; 95% CI 0.95 to 2.70, P = 0.074). In HIV-negative patients, no association was found between HTLV-1 and TB (OR = 1.18; 95% CI 0.48 to 2.89, P = 0.71), whereas a significant association was found in HIV-positive patients (OR = 2.41; 95% CI 1.26 to 4.61, P = 0.008). CONCLUSIONS: The immunosuppressive effect of HTLV-1 alone was not enough to increase the risk of TB in a highly endemic country, but HTLV-1 increased the risk of TB among HIV-infected individuals.


Asunto(s)
Infecciones por VIH/complicaciones , Anticuerpos Anti-HTLV-I/sangre , Infecciones por HTLV-I/epidemiología , Tuberculosis Pulmonar/complicaciones , Adulto , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , VIH-2/aislamiento & purificación , Infecciones por HTLV-I/complicaciones , Infecciones por HTLV-I/virología , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Tuberculosis Pulmonar/epidemiología
20.
Emerg Infect Dis ; 8(11): 1347-9, 2002 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-12453368

RESUMEN

We present a short summary of recent observations on the global distribution of the major clades of the Mycobacterium tuberculosis complex, the causative agent of tuberculosis. This global distribution was defined by data-mining of an international spoligotyping database, SpolDB3. This database contains 11708 patterns from as many clinical isolates originating from more than 90 countries. The 11708 spoligotypes were clustered into 813 shared types. A total of 1300 orphan patterns (clinical isolates showing a unique spoligotype) were also detected.


Asunto(s)
Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis/microbiología , Bases de Datos Factuales , Filogenia , Tuberculosis/epidemiología
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