RESUMEN
The advent of Mycobacterium tuberculosis strain genotyping has allowed differentiation between disease relapse and exogenous re-infection. We report here a remarkable case of multiply recurrent tuberculosis in a patient living with HIV. Between 1995 and 2009, a young HIV-infected intravenous drug user, who was reluctant to comply with anti-retroviral treatment, underwent at least five tuberculosis episodes caused by three distinct M. tuberculosis strains sharply differentiated by drug susceptibility profile, genotype and infectious source. Eventually, the patient died during a relapse of tuberculosis due to a notorious multidrug-resistant outbreak-strain, which infected him during a prolonged hospitalization in the epicentre of such outbreak. Whether recurrent tuberculosis is due to a new infection or to reactivation of a previous one is a century-long controversial question. In our patient, both conditions alternated throughout his 15 years of living with HIV. Cases such as this might not be exceptional in certain underprivileged suburban areas of Argentina and should raise concern over three pending issues in tuberculosis control policies, namely secondary preventing therapy, institutional infection control and patient follow-up throughout the health network system.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Resistente a Múltiples Medicamentos/complicaciones , Tuberculosis Pulmonar/complicaciones , Adulto , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Argentina , Técnicas de Tipificación Bacteriana , Elementos Transponibles de ADN/genética , ADN Bacteriano/análisis , Farmacorresistencia Bacteriana Múltiple , Resultado Fatal , Genotipo , Humanos , Masculino , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/crecimiento & desarrollo , Cooperación del Paciente , Recurrencia , Factores de Riesgo , Factores de Tiempo , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/fisiopatología , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/fisiopatologíaRESUMEN
Strains of Mycobacterium tuberculosis were compared using two DNA fingerprinting techniques: Restriction Fragment Length Polymorphism (RFLP) and Double-Repetitive-Element-PCR (DRE-PCR). Two of these strains: IH1 (susceptible to isoniazid) and IH2 (resistant to isoniazid) were recovered from cases of pulmonary tuberculosis which occurred in two brothers who lived together. The first one was recognized on July 1999, and the second was diagnosed one year later. IH1 and IH2 showed the same pattern of bands with both molecular tests. These results suggest that single drug chemoprophylaxis may occasionally select resistant strains for that drug, which can eventually cause disease and be recognized through these tests. Strains IH3, IH4 and IH5 were obtained from sputum samples of 3 different patients, and intra-laboratory cross-contamination was suspected when it was realized that the 3 positive materials had been consecutively processed the same day by the same worker in the same biological safety cabinet. Again, the 3 strains revealed identical band patterns with RFLP and DRE-PCR, confirming the posed suspicion. The results with DRE-PCR were obtained after only 8 hours of work, without the need for subcultures. This procedure allows quick correction of treatment conducts, avoiding unnecessary exposure of people and bacteria to antimicrobial drugs.
Asunto(s)
Antituberculosos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Mycobacterium tuberculosis/clasificación , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Adulto , Antituberculosos/administración & dosificación , Antituberculosos/uso terapéutico , Técnicas Bacteriológicas , Dermatoglifia del ADN , Quimioterapia Combinada , Contaminación de Equipos , Infecciones por VIH/complicaciones , Humanos , Isoniazida/administración & dosificación , Isoniazida/farmacología , Isoniazida/uso terapéutico , Masculino , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Longitud del Fragmento de Restricción , Selección Genética , Tuberculosis Resistente a Múltiples Medicamentos/complicaciones , Tuberculosis Resistente a Múltiples Medicamentos/prevención & control , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiologíaRESUMEN
In order to determine the possible relationship among HIV patients coinfected with multidrug resistant tuberculosis strains who had been receiving clinical assistance in our Hospital, clinical and epidemiological information from 28 patients was collected. DNA fingerprinting by restriction fragment length polymorphism (RFLP) pattern was performed on the mycobacterial isolates from these patients, using the restriction enzyme Pvull and IS 6110 as genetic marker. A unique RFLP pattern was found in 10 isolates from 10 different patients who had a disease caused by a single strain. Our findings confirm RFLP as a reliable and useful tool to analyze TB transmission.
Asunto(s)
Dermatoglifia del ADN , Brotes de Enfermedades , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Pulmonar/transmisión , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/microbiología , Adulto , Argentina/epidemiología , ADN Bacteriano/genética , Femenino , Humanos , Isoniazida , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Polimorfismo de Longitud del Fragmento de Restricción , Rifampin , Tuberculosis Resistente a Múltiples Medicamentos/complicaciones , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/microbiologíaRESUMEN
Multidrug-resistant tuberculosis has emerged over the last two years at Carrasco Hospital, located in Rosario city. Nosocomial transmission among 7 AIDS patients admitted into the same ward between June and December/94 was supported by temporal clustering of cases, matching drug susceptibility, and identical IS6110 fingerprints. Among 8 non-HIV chronic cases without evidence of reciprocal contact outside the hospital, two additional clusters of 2 and 4 cases, respectively, were identified. The latter was found to be generated by a strain genetically related to the one that infected AIDS patients. It is hypothesized that an ancestor strain, common to both, might have been brought into the hospital long before the outbreak was first suspected.
Asunto(s)
Infección Hospitalaria/transmisión , Tuberculosis Resistente a Múltiples Medicamentos/transmisión , Tuberculosis Pulmonar/transmisión , Síndrome de Inmunodeficiencia Adquirida/microbiología , Adulto , Argentina , Enfermedad Crónica , Infección Hospitalaria/microbiología , Dermatoglifia del ADN , ADN Bacteriano/genética , Etambutol , Humanos , Isoniazida , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Polimorfismo de Longitud del Fragmento de Restricción , Rifampin , Estreptomicina , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Pulmonar/microbiologíaRESUMEN
The frequency of Mycobacterium bovis detection in milk samples obtained from infected animals was explored in an intensive dairy area in Argentina. To this end, an "in house" polymerase chain reaction (PCR) method was developed using Mycobacterium tuberculosis Complex specific INS1-INS2 primers, and its performance was compared with that of bacteriological methods. The decontamination procedures previous to culture reduced M. bovis viability. The pathogen was identified in milk samples from 1 of 143 infected cows and in none of 43 uninfected ones. Even though PCR sensitivity was found to be 2-20 times higher than that of bacteriology in experimentally inoculated milk samples, all 186 field samples resulted negative by PCR, including the bacteriologically-confirmed one. In spite of the high prevalence of bovine tuberculosis in Argentinian dairy herds, the detection of M. bovis in milk is an unusual finding.
Asunto(s)
Técnicas Bacteriológicas , Leche/microbiología , Mycobacterium bovis/aislamiento & purificación , Tuberculosis Bovina/microbiología , Animales , Argentina/epidemiología , Bovinos , ADN Bacteriano/análisis , Femenino , Mycobacterium bovis/genética , Reacción en Cadena de la Polimerasa , Prevalencia , Sensibilidad y Especificidad , Tuberculosis Bovina/epidemiologíaRESUMEN
Fifteen episodes of Mycobacterium tuberculosis laboratory cross-contamination suspected between 1996 and 2001 at 6 laboratories in Buenos Aires City and suburbs were investigated by IS6110 RFLP. Thirteen episodes were confirmed. Even though BACTEC 460 produced the highest number of confirmed episodes in a single laboratory, the most extended one occurred while employing conventional culture procedures in solid medium. The double repetitive element-polymerase chain reaction (DRE-PCR) was applied to 8 of these episodes and produced concordant results with those of the RFLP. The DRE-PCR appears to be a valuable tool for the prompt identification of false positive cultures. The timely rectification of defects in laboratory protocols can avert false diagnoses of tuberculosis and unnecessary prolonged treatments.
Asunto(s)
Técnicas Bacteriológicas , ADN Bacteriano/análisis , Contaminación de Equipos , Laboratorios de Hospital , Mycobacterium tuberculosis/aislamiento & purificación , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Longitud del Fragmento de Restricción , Tuberculosis/diagnóstico , Aerosoles , Argentina , Técnicas Bacteriológicas/instrumentación , Medios de Cultivo , Reacciones Falso Positivas , Humanos , Radiometría/instrumentación , Manejo de Especímenes , Esterilización/métodosAsunto(s)
Microscopía/métodos , Mycobacterium tuberculosis/aislamiento & purificación , Colorantes de Rosanilina/normas , Esputo/microbiología , África Central , Factores de Confusión Epidemiológicos , Reacciones Falso Positivas , Guías como Asunto , Humanos , Humedad , Control de Calidad , América del Sur , Factores de Tiempo , Clima Tropical , XilenosAsunto(s)
Infecciones por VIH/complicaciones , Mycobacterium tuberculosis/genética , Tuberculosis Pulmonar/complicaciones , Dermatoglifia del ADN , ADN Bacteriano/análisis , Genoma Bacteriano , Infecciones por VIH/microbiología , Humanos , Mycobacterium tuberculosis/aislamiento & purificación , Polimorfismo de Longitud del Fragmento de Restricción , Tuberculosis Pulmonar/microbiologíaRESUMEN
The effect of the human immunodeficiency virus (HIV) on mycobacterial antibody production was investigated. Using an enzyme-linked immunosorbent assay (ELISA) for detecting IgG against Mycobacterium tuberculosis PPD, it was observed that individuals at risk of HIV infection show a pattern of humoral response to the tubercle bacillus similar to that previously found in the immunocompetent population not exposed to risk factors: 6 of 12 (50.0%) tuberculosis cases had elevated levels of antibodies to PPD and 27 of 30 (90.0%) asymptomatic individuals had antibody levels within the normal range. In an HIV-seropositive group without AIDS indicator diseases, 8 of 22 (36.4%) tuberculous patients had detectable mycobacterial antibodies whereas 156 of 164 (95.1%) non-tuberculous subjects did not. Among AIDS cases, only 1 of 20 (5.0%) patients with tuberculosis and none of 53 non-tuberculous subjects showed a positive result. The study evidenced an increasing humoral unresponsiveness to PPD in the progression of HIV infection to AIDS. Thus, a serodiagnostic method for detecting tuberculosis such as the ELISA here employed noticeably decreases its utility in the latency stage of the HIV infection, and it is practically useless in clinical AIDS.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Anticuerpos Antibacterianos/biosíntesis , Infecciones por VIH/complicaciones , Mycobacterium tuberculosis/inmunología , Tuberculosis/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Síndrome de Inmunodeficiencia Adquirida/inmunología , Adulto , Infecciones por VIH/inmunología , Seropositividad para VIH/inmunología , Humanos , Inmunoglobulina G/biosíntesis , Tuberculina/inmunología , Tuberculosis/diagnóstico , Tuberculosis/inmunologíaRESUMEN
A steep upsurge of human immunodeficiency virus (HIV)-associated multidrug-resistant tuberculosis (MDR-TB) was recently observed at a referral treatment center in Buenos Aires City. Between January 1994 and June 1995, TB isolates resistant to at least five drugs were recovered from 101 of 272 HIV-infected inpatients. Highly resistant isolates from 77 patients underwent restriction fragment length polymorphism study with IS6110. After cross-contamination was eliminated, a single TB strain was found to have caused disease in 68 patients with a history of on-site exposure. The frequency of smear-positive pulmonary disease was higher among these patients than among non-MDR-TB HIV-infected patients (50/68 vs. 60/148, P < .001), and the 1-year survival was dramatically reduced (5/68 vs. 92/148). The strain involved in the outbreak was traced back to patients hospitalized in 1992. Institutional infection control policies were and may still be inadequate to contain the spread of TB among immunodepressed subjects, as is the case in other large urban hospitals in Argentina.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/transmisión , Infección Hospitalaria/microbiología , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos/transmisión , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Adulto , Argentina/epidemiología , Infección Hospitalaria/transmisión , Femenino , Humanos , Masculino , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Polimorfismo de Longitud del Fragmento de Restricción , Estudios Retrospectivos , Tuberculosis Resistente a Múltiples Medicamentos/complicaciones , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/microbiologíaRESUMEN
BACKGROUND: Data on global trends in resistance to antituberculosis drugs are lacking. METHODS: We expanded the survey conducted by the World Health Organization and the International Union against Tuberculosis and Lung Disease to assess trends in resistance to antituberculosis drugs in countries on six continents. We obtained data using standard protocols from ongoing surveillance or from surveys of representative samples of all patients with tuberculosis. The standard sampling techniques distinguished between new and previously treated patients, and laboratory performance was checked by means of an international program of quality assurance. RESULTS: Between 1996 and 1999, patients in 58 geographic sites were surveyed; 28 sites provided data for at least two years. For patients with newly diagnosed tuberculosis, the frequency of resistance to at least one antituberculosis drug ranged from 1.7 percent in Uruguay to 36.9 percent in Estonia (median, 10.7 percent). The prevalence increased in Estonia, from 28.2 percent in 1994 to 36.9 percent in 1998 (P=0.01), and in Denmark, from 9.9 percent in 1995 to 13.1 percent in 1998 (P=0.04). The median prevalence of multidrug resistance among new cases of tuberculosis was only 1.0 percent, but the prevalence was much higherin Estonia (14.1 percent), Henan Province in China (10.8 percent), Latvia (9.0 percent), the Russian oblasts of Ivanovo (9.0 percent) and Tomsk (6.5 percent), Iran (5.0 percent), and Zhejiang Province in China (4.5 percent). There were significant decreases in multidrug resistance in France and the United States. In Estonia, the prevalence in all cases increased from 11.7 percent in 1994 to 18.1 percent in 1998 (P<0.001). CONCLUSIONS: Multidrug-resistant tuberculosis continues to be a serious problem, particularly among some countries of eastern Europe. Our survey also identified areas with a high prevalence of multidrug-resistant tuberculosis in such countries as China and Iran.
Asunto(s)
Antituberculosos , Resistencia a Múltiples Medicamentos , Salud Global , Tuberculosis/tratamiento farmacológico , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Recolección de Datos , Humanos , Mycobacterium tuberculosis/efectos de los fármacos , Prevalencia , MuestreoRESUMEN
Strains of Mycobacterium tuberculosis were compared using two DNA fingerprinting techniques: Restriction Fragment Length Polymorphism (RFLP) and Double-Repetitive-Element-PCR (DRE-PCR). Two of these strains: IH1 (susceptible to isoniazid) and IH2 (resistant to isoniazid) were recovered from cases of pulmonary tuberculosis which occurred in two brothers who lived together. The first one was recognized on July 1999, and the second was diagnosed one year later. IH1 and IH2 showed the same pattern of bands with both molecular tests. These results suggest that single drug chemoprophylaxis may occasionally select resistant strains for that drug, which can eventually cause disease and be recognized through these tests. Strains IH3, IH4 and IH5 were obtained from sputum samples of 3 different patients, and intra-laboratory cross-contamination was suspected when it was realized that the 3 positive materials had been consecutively processed the same day by the same worker in the same biological safety cabinet. Again, the 3 strains revealed identical band patterns with RFLP and DRE-PCR, confirming the posed suspicion. The results with DRE-PCR were obtained after only 8 hours of work, without the need for subcultures. This procedure allows quick correction of treatment conducts, avoiding unnecessary exposure of people and bacteria to antimicrobial drugs.
Se compararon cepas de Mycobacterium tuberculosis utilizando 2 procedimientos de ADN fingerprinting: polimorfismo de los fragmentos de restricción (RFLP) y Double-Repetitive-Element-PCR (DRE-PCR). Dos de las cepas: IH1 (susceptible a isoniazida) e IH2 (resistente a isoniazida) se recuperaron a partir de casos de tuberculosis pulmonar que ocurrieron en dos hermanos convivientes. La primera fue aislada en julio de 1999 y la segunda un año después. IH1 e IH2 mostraron el mismo patrón de bandas por ambos procedimientos. Estos resultados sugieren que la quimioprofilaxis con una sola droga puede ocasionalmente seleccionar mutantes resistentes, las cuales pueden causar enfermedad y ser reconocidas por estos procedimientos. Las cepas IH3, IH4 e IH5 fueron aisladas de 3 pacientes diferentes, y examinadas por probable contaminación cruzada dentro del laboratorio ya que fueron procesadas el mismo día, por el mismo operador y en la misma cabina de seguridad biológica. Nuevamente, las 3 cepas revelaron el mismo patrón de bandas por RFLP y por DRE-PCR, confirmando la sospecha. Los resultados de la DRE-PCR se obtuvieron luego de 8 horas de trabajo, sin necesidad de subcultivos. Esta técnica permitiría la rápida correción de pautas de tratamiento, evitando la exposición innecesaria de personas y bacterias a drogas antimicrobianas.
Asunto(s)
Adulto , Humanos , Masculino , Antituberculosos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Mycobacterium tuberculosis/clasificación , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Antituberculosos/administración & dosificación , Antituberculosos/uso terapéutico , Técnicas Bacteriológicas , Dermatoglifia del ADN , Quimioterapia Combinada , Contaminación de Equipos , Infecciones por VIH/complicaciones , Isoniazida/administración & dosificación , Isoniazida/farmacología , Isoniazida/uso terapéutico , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Polimorfismo de Longitud del Fragmento de Restricción , Reacción en Cadena de la Polimerasa/métodos , Selección Genética , Tuberculosis Resistente a Múltiples Medicamentos/complicaciones , Tuberculosis Resistente a Múltiples Medicamentos/prevención & control , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiologíaRESUMEN
The frequency of Mycobacterium bovis detection in milk samples obtained from infected animals was explored in an intensive dairy area in Argentina. To this end, an [quot ]in house[quot ] polymerase chain reaction (PCR) method was developed using Mycobacterium tuberculosis Complex specific INS1-INS2 primers, and its performance was compared with that of bacteriological methods. The decontamination procedures previous to culture reduced M. bovis viability. The pathogen was identified in milk samples from 1 of 143 infected cows and in none of 43 uninfected ones. Even though PCR sensitivity was found to be 2-20 times higher than that of bacteriology in experimentally inoculated milk samples, all 186 field samples resulted negative by PCR, including the bacteriologically-confirmed one. In spite of the high prevalence of bovine tuberculosis in Argentinian dairy herds, the detection of M. bovis in milk is an unusual finding.
RESUMEN
Fifteen episodes of Mycobacterium tuberculosis laboratory cross-contamination suspected between 1996 and 2001 at 6 laboratories in Buenos Aires City and suburbs were investigated by IS6110 RFLP. Thirteen episodes were confirmed. Even though BACTEC 460 produced the highest number of confirmed episodes in a single laboratory, the most extended one occurred while employing conventional culture procedures in solid medium. The double repetitive element-polymerase chain reaction (DRE-PCR) was applied to 8 of these episodes and produced concordant results with those of the RFLP. The DRE-PCR appears to be a valuable tool for the prompt identification of false positive cultures. The timely rectification of defects in laboratory protocols can avert false diagnoses of tuberculosis and unnecessary prolonged treatments.