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Background: The incidence of mycotic infections, especially of Candida, has gradually increased over the past few years. In clinical practice, azoles are the most frequently used antifungal agents and the growing incidence of systemic candidiasis and resistance to antifungals have become a matter of concern worldwide. Virulence factors in Candida spp. may be critical for predicting the response of antifungal drugs. Objectives: This study aimed to identify the relationship between virulence factors and the antifungal susceptibility of Candida. Methodology: This cross-sectional study was conducted on a sample of 55 Candida strains isolated from vulvovaginal samples of patients in the reproductive age group, presenting with signs and symptoms of vulvovaginitis in a large tertiary care hospital in central India. Results: A majority of the Candida were sensitive to three tested drugs (89% to amphotericin B, 76.4% to fluconazole, and 89.1% to voriconazole). Resistance to fluconazole was highest at 16.4%. No significant relationships were identified between antifungal sensitivity of the three azoles with biofilm formation, phospholipase, or proteinase synthesis. Conclusions: High level of antifungal resistance to the three antifungals, especially to voriconazole, is worrisome; however, none of the virulence markers have a significant association with antifungal sensitivity of Candida species. This finding rules out the effect of the virulence of the pathogen on drug response.
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BACKGROUND: The epidemiology, clinical profile and outcome of paediatric candidemia vary considerably by age, healthcare settings and prevalent Candida species. Despite these differences, few comprehensive studies are undertaken. This nationwide study addresses this knowledge gap. METHODS: 487 children who contracted ICU-acquired candidemia at 23 Indian tertiary care centres were assessed for 398 variables spanning demography, clinical characteristics, microbiology, treatment and outcome. RESULTS: Both neonates (5.0 days; range = 3.0-9.5) and non-neonatal children (7.0 days; range = 3.0-13.0) developed candidemia early after ICU admission. Majority of neonates were premature (63.7%) with low birthweight (57.1%). Perinatal asphyxia (7.3%), pneumonia (8.2%), congenital heart disease (8.4%) and invasive procedures were common comorbidities, and antibiotic use (94.1%) was widespread. C tropicalis (24.7%) and C albicans (20.7%) dominated both age groups. Antifungal treatment (66.5%) and removal of central catheters (44.8%) lagged behind. Overall resistance was low; however, emergence of resistant C krusei and C auris needs attention. The 30-day crude mortality was 27.8% (neonates) and 29.4% (non-neonates). Logistic regression identified admission to public sector ICUs (OR = 5.64), mechanical ventilation (OR = 2.82), corticosteroid therapy (OR = 8.89) and antifungal therapy (OR = 0.22) as independent predictors of 30-day crude mortality in neonates. Similarly, admission to public sector ICUs (OR = 3.62), mechanical ventilation (OR = 3.13), exposure to carbapenems (OR = 2.18) and azole antifungal therapy (OR = 0.48) were independent predictors for non-neonates. CONCLUSIONS: Our findings reveal a distinct epidemiology, including early infection with a different spectrum of Candida species, calling for appropriate intervention strategies to reduce candidemia morbidity and mortality. Independent factors identified in our regression models can help tackle these challenges.
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Purpose. Rapid and accurate detection of carbapenem resistance is a critical requirement for the selection of appropriate therapy and initiation of infection control measures. Although several tests are available, their use is limited by one or more factors. Phenotypic tests are lengthy, have variable sensitivity and specificity and do not generally identify the carbapenemase. Molecular assays overcome many of these issues but cost can be a barrier to adoption, particularly in low-resource settings. To address the need for affordable, molecular tools, we have assessed the performance characteristics of loop-mediated isothermal amplification (LAMP)-based assays for the major carbapenemase genes, blaNDM, blaKPC, blaOXA-48, blaOXA-23 blaVIM and blaIMP.Methodology. The assays were validated using 1849 Gram-negative Indian clinical isolates obtained from seven hospitals and diagnostic centres.Results. The assays had diagnostic sensitivities of 98.14â%, 98.92â%, 100â%, 98.48â%, and diagnostic specificities of 98.94â%, 99.61â%, 97.42â%, 99.38â% for blaNDM, blaOXA-48, blaOXA-23 and blaVIM, respectively. Due to a low number of isolates positive for blaKPC and blaIMP, the performance characteristics of assays for these two genes could not be suitably evaluated.Conclusion. The performance characteristics suggest suitability for diagnostic and surveillance purposes.
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Proteínas Bacterianas/genética , Bacterias Gramnegativas/enzimología , Bacterias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/microbiología , Técnicas de Amplificación de Ácido Nucleico/métodos , beta-Lactamasas/genética , Proteínas Bacterianas/metabolismo , Bacterias Gramnegativas/clasificación , Bacterias Gramnegativas/genética , Infecciones por Bacterias Gramnegativas/diagnóstico , Humanos , beta-Lactamasas/metabolismoRESUMEN
During the last two decades, nontuberculous mycobacteria (NTM) have gained in importance but there is still a paucity of data, particularly for environmental isolates. We studied, over a period of two years, the spatio-temporal features of NTM isolates obtained from different environmental sources in Wardha district, India. A total of 1398 samples (699 each of soil and water) were tested and 170 (12.2%) yielded NTM isolates, including 123 from soil and 47 from water samples. Out of 170 NTM isolates, 107 (63%) belonged to potentially pathogenic mycobacteria (PPM) and 63 (37%) to the less pathogenic mycobacterial (LPM) group. Overall, maximum isolation was obtained in rainy season (20.3%) followed by winter (13.5%), post rainy (8.7%) and summer seasons (5.8%). Mycobacterium fortuitum, Mycobacterium gordonae and Mycobacterium avium complex (MAC) were common isolates followed by Mycobacterium flavescens, Mycobacterium scrofulaceum, Mycobacterium simiae and Mycobacterium marinum. From soil, isolation of NTM was highest from grounds used for community gatherings (42.8%) followed by soil from residential premises (27.7%) and near the wells (26.0%). From drinking water sources, highest NTM isolation was obtained from wells (15.4%) followed by treated water tanks (6.9%), household receptacles (6.3%), hand pumps (5.6%) and tap water supply (3.5%). Isolation from natural canal water was 6.6%, while from drainage and waste water ponds isolation was 8.3%. The results of the study revealed that in Wardha district, NTM are present both in the soil and drinking water. As NTM can be pathogenic, particularly in immune-compromised individuals, these can be of potential risk to the human population.
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Microbiología Ambiental , Micobacterias no Tuberculosas/clasificación , Análisis Espacio-Temporal , ADN Espaciador Ribosómico , Humanos , India , Micobacterias no Tuberculosas/genética , Micobacterias no Tuberculosas/aislamiento & purificación , Filogenia , ARN Ribosómico/genética , Microbiología del Suelo , Microbiología del AguaRESUMEN
Enteric fever is an invasive infection predominantly caused by Salmonella enterica serovars Typhi and Paratyphi A. The pathogens have evolved from other nontyphoidal salmonellaeto become invasive and host restricted. Emergence of antimicrobial resistance in typhoidal salmonellae in some countries is a major therapeutic concern as the travelers returning from endemic countries carry resistant strains to non endemic areas. In order to understand the epidemiology and to design disease control strategies molecular typing of the pathogen is very important. We performed Multilocus Sequence Typing (MLST) of 251 S. Typhi and 18 S. Paratyphi strains isolated from enteric fever patients from seven centers across India during 2010-2013to determine the population structure and prevalence of MLST sequence types in India. MLST analysis revealed the presence of five sequence types (STs) of typhoidal salmonellae in India namely ST1, ST2 and ST3 for S. Typhi and ST85 and ST129 for S. Paratyphi A.S. Typhi strains showed monophyletic lineage and clustered in to 3 Sequence Types-ST1, ST2 and ST3 and S. Paratyphi A isolates segregated in two sequence types ST85 and ST129 respectively. No association was found between antimicrobial susceptibility and sequence types. This study found ST1 as the most prevalent sequence type of S. Typhi in India followed by ST2, which is in concordance with previous studies and MLST database. In addition a rare sequence type ST3 has been found which is reported for the first time from the Indian subcontinent. Amongst S. Paratyphi A, the most common sequence type is ST129 as also reported from other parts of world. This distribution and prevalence suggest the common spread of the sequence types across the globe and these findings can help in understanding the disease distribution.
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Salmonella paratyphi A/genética , Salmonella typhi/genética , Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Genes Bacterianos , Filogenia , Salmonella paratyphi A/clasificación , Salmonella paratyphi A/efectos de los fármacos , Salmonella typhi/clasificación , Salmonella typhi/efectos de los fármacosRESUMEN
A house based survey was conducted during 2007-2009 in a representative sample of population in Wardha district implementing Directly Observed Treatment Short Course strategy for tuberculosis (TB) control since 2001. The objective was to estimate prevalence of bacillary pulmonary TB (PTB) in individuals aged 15 years or above, and to estimate trends in prevalence when compared to a previous survey carried out in mid 1980's. Two sputum samples (one spot, one early morning) collected from individuals having symptoms suggestive of PTB, history of previous anti-TB treatment (ATT) or abnormal pulmonary shadow on Mass Miniature Radiography (MMR) consistent with possibly or probably active tuberculosis were subjected to Ziehl-Neelsen microscopy and culture on Lowenstein-Jensen medium. Of 55,096 individuals registered into the survey, 50,332 (91.4%) were screened by interview for symptoms and history of ATT and/or by MMR. Of them, 4805 were eligible for sputum collection; both specimens were collected in 4285 (89.2%) and only one specimen in 27 (0.6%). A total of 86 bacillary cases were detected during the survey. Prevalence of bacillary PTB was estimated at 188.7 (140.3-236.9) per 100,000 populations. There was a decline of 61% in the prevalence of PTB over a period of 22 years.
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Tuberculosis Pulmonar/epidemiología , Adolescente , Adulto , Anciano , Femenino , Encuestas Epidemiológicas , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Prevalencia , Población Rural/estadística & datos numéricos , Esputo/microbiología , Población Urbana/estadística & datos numéricos , Adulto JovenRESUMEN
PURPOSE: A systematic epidemiological study on intensive care unit (ICU)-acquired candidemia across India. METHOD: A prospective, nationwide, multicentric, observational study was conducted at 27 Indian ICUs. Consecutive patients who acquired candidemia after ICU admission were enrolled during April 2011 through September 2012. Clinical and laboratory variables of these patients were recorded. The present study is an analysis of data specific for adult patients. RESULTS: Among 1,400 ICU-acquired candidemia cases (overall incidence of 6.51 cases/1,000 ICU admission), 65.2 % were adult. Though the study confirmed the already known risk factors for candidemia, the acquisition occurred early after admission to ICU (median 8 days; interquartile range 4-15 days), even infecting patients with lower APACHE II score at admission (median 17.0; mean ± SD 17.2 ± 5.9; interquartile range 14-20). The important finding of the study was the vast spectrum of agents (31 Candida species) causing candidemia and a high rate of isolation of Candida tropicalis (41.6 %). Azole and multidrug resistance were seen in 11.8 and 1.9 % of isolates. Public sector hospitals reported a significantly higher presence of the relatively resistant C. auris (8.2 vs. 3.9 %; p = 0.008) and C. rugosa (5.6 vs. 1.5 %; p = 0.001). The 30-day crude and attributable mortality rates of candidemia patients were 44.7 and 19.6 %, respectively. Logistic regression analysis revealed significant independent predictors of mortality including admission to public sector hospital, APACHE II score at admission, underlying renal failure, central venous catheterization and steroid therapy. CONCLUSION: The study highlighted a high burden of candidemia in Indian ICUs, early onset after ICU admission, higher risk despite less severe physiology score at admission and a vast spectrum of agents causing the disease with predominance of C. tropicalis.
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Antifúngicos/uso terapéutico , Candida/aislamiento & purificación , Candidemia/epidemiología , Candidiasis/epidemiología , Infección Hospitalaria/epidemiología , Unidades de Cuidados Intensivos/estadística & datos numéricos , APACHE , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Candidemia/tratamiento farmacológico , Candidiasis/tratamiento farmacológico , Infección Hospitalaria/tratamiento farmacológico , Femenino , Humanos , Incidencia , India , Modelos Logísticos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND & OBJECTIVES: The SXT element, also known as 'constin' (conjugable, self transmissible, integrating element) is an integrating conjugative element (ICE) in Vibrio cholerae discovered in the chromosome of epidemic V. cholerae O139 strain MO10 (SXT MO10 ) which arose in late 1992 in Chennai, India. SXT related ICEs have become widespread and currently, most if not all Asian V. cholerae clinical isolates contain SXT related ICEs. The present study attempts to determine the presence of SXT Int gene in V. cholerae recovered between 2005 to 2007 in a tertiary care hospital, demonstrate its conjugal nature and also detect co-presence and co-transfer of plasmids in representative isolates. METHODS: This prospective study was done on 116 V. cholerae isolates [114- O1 (107 ogawa and 7 inaba) and 2 - Non O1 Non O139 V. cholerae] from watery stools between 2005 to 2007 recovered from equal number of patients. PCR was carried out using SXT Int specific primers that produced a 592 bp internal fragment of SXT element, and rifampicin resistant strain of E.coli K-12 was used as recipient in conjugation experiments to study transfer of SXT, as also co-transfer of resistance to tetracycline, erythromycin, and nalidixic acid. Antibiotic susceptibility was performed against various antibiotics. RESULTS: Of the 116 isolates, 110 (94.8%) were positive for SXT element by PCR. It was demonstrated in 94.7 per cent of the O1, and 100 per cent of non O1 non O139 V. cholerae. All 2005 isolates, 25 per cent of 2006 isolates and 96.6 per cent of 2007 isolates were positive for SXT. Thirty two drug resistance patterns were observed and the 2007 isolates showed resistance to as many as eight antibiotics. The resistance of SXT positive isolates was higher than those of SXT negative and the typical drug resistance pattern corresponding to SXT ET and SXT MO10 was shown by only one V. cholerae O1 isolate. Successful conjugal transfer of SXT was seen in 31 (88.6%) of the 35 isolates studied without any co-transfer while, presence of plasmids was observed in two of the 31 donor V. cholerae studied. INTERPRETATION & CONCLUSIONS: The demonstration of SXT element and its successful horizontal transfer in V. cholerae isolates studied emphasizes the need for its detection to monitor antibiotic resistance and dissemination in V. cholerae.
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Proteínas Bacterianas/metabolismo , Cólera/microbiología , Vibrio cholerae/aislamiento & purificación , Vibrio cholerae/metabolismo , Proteínas Bacterianas/genética , Elementos Transponibles de ADN , Farmacorresistencia Bacteriana , Humanos , Secuencias Repetitivas Esparcidas , Estudios Prospectivos , Vibrio cholerae/efectos de los fármacos , Vibrio cholerae/genéticaRESUMEN
Peritonitis is a common problem in patients undergoing peritoneal dialysis. However, peritonitis due to Cunninghamella (C.) bertholletiae, a fungus of the class Zygomycetes, is rare. We present a case of fungal peritonitis in a patient on continuous ambulatory peritoneal dialysis due to kidney rejection. Direct examination of the patient's peritoneal fluid showed fungal hyphae, and the culture was identified as C. bertholletiae. A cumulative dose of 1,600 mg fluconazole was given to the patient intraperitoneally over a one-week period. When his condition had stabilised, oral antifungal treatment was administered for two weeks. After removal of the Tenckhoff catheter, the patient was discharged with arteriovenous fistulation for haemodialysis. Zygomycosis due to C. bertholletiae is often fatal and non-responsive to systemic antifungal therapy. This case is the first from India with a successful outcome, and highlights the importance of early detection and intervention for successful outcome of peritonitis caused by C. bertholletiae.
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Cunninghamella/aislamiento & purificación , Fluconazol/administración & dosificación , Rechazo de Injerto/complicaciones , Fallo Renal Crónico/terapia , Mucormicosis/tratamiento farmacológico , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Peritonitis/tratamiento farmacológico , Antifúngicos/administración & dosificación , Vías de Administración de Medicamentos , Estudios de Seguimiento , Humanos , Fallo Renal Crónico/complicaciones , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Mucormicosis/etiología , Mucormicosis/microbiología , Peritonitis/etiología , Peritonitis/microbiologíaRESUMEN
Integrative conjugative elements (ICEs) of the SXT/R391 family are self-transmissible mobile elements mainly involved in antibiotic resistance spread among γ-Proteobacteria, including Vibrio cholerae. We demonstrated that the recently described ICEVchInd5 is prevailing in V. cholerae O1 clinical strains isolated in Wardha province (Maharashtra, India) from 1994 to 2005. Genetic characterization by ribotyping and multiple-locus SSR analysis proved the same clonal origin for V. cholerae O1 isolates in Wardha province over an 11-year period and was used to assess the correlation between strain and ICE content among ours and different Indian reference strains. In silico analysis showed the existence of at least 3 sibling ICEs of ICEVchInd5 in V. cholerae O1 El Tor reference strains, isolated in the Indian subcontinent after 1992.
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Cólera/epidemiología , Cólera/microbiología , Secuencias Repetitivas Esparcidas , Vibrio cholerae O1/genética , Técnicas de Tipificación Bacteriana , Análisis por Conglomerados , Genotipo , Humanos , India/epidemiología , Epidemiología Molecular , Tipificación Molecular , Tipificación de Secuencias Multilocus , Ribotipificación , Vibrio cholerae O1/aislamiento & purificaciónRESUMEN
To study the possible importance of mycobacterial ES-31 serine protease for bacterial cell growth, the effect of serine and metalloprotease inhibitors, anti-tubercular drugs such as isoniazid and anti-ES-31 antibody, was evaluated on mycobacterial ES-31 serine protease in vitro and on bacilli in axenic and macrophage cultures. Serine protease inhibitors such as pefabloc, 3,4 dichloroisocoumarin, phenyl methyl sulfonyl fluoride (PMSF) and metalloprotease inhibitors such as ethylene diamine tetracetic acid (EDTA) and 1,10 phenanthroline inhibited 65-92% serine protease activity in vitro. Isoniazid showed 95% inhibition on mycobacterial ES-31 serine protease. These inhibitors also showed decreased bacterial growth in axenic culture and inhibition was further confirmed by a decreased amount of ES-31 serine protease in culture filtrate. In human macrophage culture, highly inhibitory pefabloc, 1,10 phenanthroline and isoniazid inhibited infectivity of virulent as well as avirulent M. tuberculosis bacilli to macrophages. It was observed that addition of mycobacterial ES-31 serine protease to macrophage culture enhanced the entry of bacilli and their multiplication in human macrophages. However, the addition of anti-ES-31 serine protease antibody strongly inhibited the mycobacterial growth as observed by decreased CFU count, showing the importance of mycobacterial ES-31 serine protease for entry of bacilli and their multiplication.
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Antituberculosos/farmacología , Proteínas Bacterianas/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Macrófagos/microbiología , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/crecimiento & desarrollo , Serina Proteasas/metabolismo , Células Cultivadas , Recuento de Colonia Microbiana , Humanos , Mycobacterium tuberculosis/enzimologíaRESUMEN
Acrophialophora fusispora is a soil-borne fungus, which is emerging as a human pathogen. Only four cases of human infection had been described previously. We describe three more cases, two from Europe and one from India. Since this fungus has been misidentified in several other cases, it is probably more frequent than first thought.
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Ascomicetos/patogenicidad , Infecciones Fúngicas del Ojo/microbiología , Enfermedades Pulmonares Fúngicas/microbiología , Adulto , Anciano , Ascomicetos/clasificación , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: In vitro interferon-gamma (IFN-gamma) assays have emerged as novel alternatives to the tuberculin skin test (TST) for the diagnosis of latent tuberculosis (TB) infection. These assays have been evaluated in low incidence countries, mainly in adults, and have been shown to be more specific than TST. Because few studies have been done in high incidence countries, and because paediatric data are limited, we compared a whole-blood IFN-gamma assay with TST among hospitalized Indian children. METHODS: Between July 2004 and June 2005, a total of 105 consecutively admitted children (median age 6 years; 82% had BCG scars) in whom TB was suspected or had history of contact with an index case were recruited at a rural hospital in India. All children underwent TST, and the QuantiFERON-TB-Gold In Tube (QFT) assay. RESULTS: The overall prevalence of TB infection was similar with both tests. With a TST cut-off point of > or =10mm, 10 of 105 (9.5%; 95% CI 3.8, 15.2) children were TST positive. With a cut-off point of IFN-gamma> or =0.35IU/ml, 11 of 105 (10.5%; 95% CI 4.5, 16.4) were QFT positive. The concordance between TST and QFT was substantial (agreement 95.2%; kappa [kappa] 0.73; 95% CI for kappa 0.53, 0.92). Agreement between TST and QFT results was 100% (kappa 1.0) in BCG scar-negative children as compared to 94% (kappa 0.63) in scar-positive children. BCG was not associated with the results of either TST or QFT (P>0.05 for both tests). The number of children with bacteriologically confirmed active TB was too small to permit the estimation of sensitivity of the tests. CONCLUSIONS: In a rural, predominantly BCG-vaccinated paediatric population in India, the TST and QFT assay produced comparable results. BCG vaccination did not significantly affect either TST or QFT results. Larger studies are needed to compare the sensitivity of the IFN-gamma assay with that of the TST in children with bacteriologically and/or clinically confirmed TB.
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Interferón gamma/sangre , Prueba de Tuberculina , Tuberculosis/diagnóstico , Niño , Preescolar , Femenino , Humanos , India , Lactante , Masculino , Sensibilidad y Especificidad , Estadística como AsuntoRESUMEN
RATIONALE: Although interferon-gamma (IFN-gamma) assays are promising alternatives to the tuberculin skin test (TST), their serial testing performance is unknown. OBJECTIVE: To compare TST and IFN-gamma conversions and reversions in healthcare workers. METHODS: We prospectively followed-up 216 medical and nursing students in India who underwent baseline and repeat testing (after 18 mo) with TST and QuantiFERON-TB Gold In-Tube (QFT). TST conversions were defined as reactions greater than or equal to 10 mm, with increments of 6 or 10 mm over baseline. QFT conversions were defined as baseline IFN-gamma less than 0.35 and follow-up IFN-gamma greater than or equal to 0.35 or 0.70 IU/ml. QFT reversions were defined as baseline IFN-gamma greater than or equal to 0.35 and follow-up IFN-gamma less than 0.35 IU/ml. RESULTS: Of the 216 participants, 48 (22%) were TST-positive, and 38 (18%) were QFT-positive at baseline. Among 147 participants with concordant baseline negative results, TST conversions occurred in 14 (9.5%; 95% confidence interval [CI] = 5.3-15.5) using the 6 mm increment definition, and 6 (4.1%; 95% CI = 1.5-8.7) using the 10 mm increment definition. QFT conversions occurred in 17/147 participants (11.6%; 95% CI = 6.9-17.9) using the definition of IFN-gamma greater than or equal to 0.35 IU/ml, and 11/147 participants (7.5%; 95% CI = 3.8-13.0) using IFN-gamma greater than or equal to 0.70 IU/ml. Agreement between TST (10 mm increment) and QFT conversions (>or= 0.70 IU/ml) was 96% (kappa = 0.70). QFT reversions occurred in 2/28 participants (7%) with baseline concordant positive results, as compared with 7/10 participants (70%) with baseline discordant results (p < 0.001). CONCLUSIONS: IFN-gamma assay shows promise for serial testing, but repeat results need to be interpreted carefully. To meaningfully interpret serial results, the optimal thresholds to distinguish new infections from nonspecific variations must be determined.
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Personal de Salud , Interferón gamma/análisis , Tamizaje Masivo/métodos , Prueba de Tuberculina , Tuberculosis/diagnóstico , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Sensibilidad y Especificidad , Estudiantes de Medicina , Estudiantes de Enfermería , Tuberculosis/genéticaRESUMEN
BACKGROUND: T cell-based interferon-gamma (IFN-gamma) release assays (IGRAs) are novel tests for latent tuberculosis infection (LTBI). It has been suggested that T cell responses may be correlated with bacterial burden and, therefore, IGRAs may have a role in monitoring treatment response. We investigated IFN-gamma responses to specific TB antigens among Indian health care workers (HCWs) before, and after LTBI preventive therapy. METHODS: In 2004, we established a cohort of HCWs who underwent tuberculin skin testing (TST) and a whole-blood IGRA (QuantiFERON-TB-Gold In-Tube [QFT-G], Cellestis Ltd, Victoria, Australia) at a rural hospital in India. HCWs positive by either test were offered 6 months of isoniazid (INH) preventive therapy. Among the HCWs who underwent therapy, we prospectively followed-up 10 nursing students who were positive by both tests at baseline. The QFT-G assay was repeated 4 and 10 months after INH treatment completion (i.e. approximately 12 months and 18 months after the initial testing). IFN-gamma responses to ESAT-6, CFP-10 and TB7.7 peptides were measured using ELISA, and IFN-gamma >/=0.35 IU/mL was used to define a positive QFT-G test result. RESULTS: All participants (N = 10) reported direct contact with smear-positive TB patients at baseline, during and after LTBI treatment. All participants except one started treatment with high baseline IFN-gamma responses (median 10.0 IU/mL). The second QFT-G was positive in 9 of 10 participants, but IFN-gamma responses had declined (median 5.0 IU/mL); however, this difference was not significant (P = 0.10). The third QFT-G assay continued to be positive in 9 of 10 participants, with persistently elevated IFN-gamma responses (median 7.9 IU/mL; P = 0.32 for difference against baseline average). CONCLUSION: In an environment with ongoing, intensive nosocomial exposure, HCWs had strong IFN-gamma responses at baseline, and continued to have persistently elevated responses, despite LTBI treatment. It is plausible that persistence of infection and/or re-infection might account for this phenomenon. Our preliminary findings need confirmation in larger studies in high transmission settings. Specifically, research is needed to study T cell kinetics during LTBI treatment, and determine the effect of recurrent exposures on host cellular immune responses.
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CONTEXT: Mycobacterium tuberculosis infection in health care workers has not been adequately studied in developing countries using newer diagnostic tests. OBJECTIVES: To estimate latent tuberculosis infection prevalence in health care workers using the tuberculin skin test (TST) and a whole-blood interferon gamma (IFN-gamma) assay; to determine agreement between the tests; and to compare their correlation with risk factors. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional comparison study of 726 health care workers aged 18 to 61 years (median age, 22 years) with no history of active tuberculosis conducted from January to May 2004, at a rural medical school in India. A total of 493 (68%) of the health care workers had direct contact with patients with tuberculosis and 514 (71%) had BCG vaccine scars. INTERVENTIONS: Tuberculin skin testing was performed using 1-TU dose of purified protein derivative RT23, and the IFN-gamma assay was performed by measuring IFN-gamma response to early secreted antigenic target 6, culture filtrate protein 10, and a portion of tuberculosis antigen TB7.7. MAIN OUTCOME MEASURES: Agreement between TST and the IFN-gamma assay, and comparison of the tests with respect to their association with risk factors. RESULTS: A large proportion of the health care workers were latently infected; 360 (50%) were positive by either TST or IFN-gamma assay, and 226 (31%) were positive by both tests. The prevalence estimates of TST and IFN-gamma assay positivity were comparable (41%; 95% confidence interval [CI], 38%-45% and 40%; 95% CI, 37%-43%, respectively). Agreement between the tests was high (81.4%; kappa = 0.61; 95% CI, 0.56-0.67). Increasing age and years in the health profession were significant risk factors for both IFN-gamma assay and TST positivity. BCG vaccination had little impact on TST and IFN-gamma assay results. CONCLUSIONS: Our study showed high latent tuberculosis infection prevalence in Indian health care workers, high agreement between TST and IFN-gamma assay, and similar association between positive test results and risk factors. Although TST and IFN-gamma assay appear comparable in this population, they have different performance and operational characteristics; therefore, the decision to select one test over the other will depend on the population, purpose of testing, and resource availability.