Interferon gamma release assays for detection of latent Mycobacterium tuberculosis in older Hispanic people.

BACKGROUND: Interferon gamma release assays (IGRAs) are used to detect latent Mycobacterium tuberculosis (M.tb) infection (LTBI) in adults, but their performance in older people is not well-established. We evaluated IGRAs for LTBI detection in older Hispanic recent TB contacts (ReC) or community controls (CoC). METHODS: Cross-sectional assessment of LTBI with T-SPOT.TB and/or QuantiFERON-Gold in-tube or -Plus assay in older (≥60 years) and adult (18-50 years) Hispanic people. RESULTS: We enrolled 193 CoC (119 adults, 74 older persons) and 459 ReC (361 adults, 98 older persons). LTBI positivity increased with age in CoC (19%-59%, P<0.001), but was similar in ReC (59%-69%, P=0.329). Older people had lower concordance between IGRAs (kappa 0.465 vs 0.688 in adults) and more inconclusive results (indeterminate/borderline 11.6% vs 5.8% in adults, P=0.012). With simultaneous IGRAs, inconclusive results were resolved as positive or negative with the other IGRA. The magnitude of response to M.tb peptides in IGRAs was similar among age groups, but responsiveness to mitogens was lower in older people. CONCLUSIONS: IGRAs are suitable for LTBI detection in older people. Discordant and inconclusive findings are more prevalent in older people, but results are resolved when IGRA is repeated with a different IGRA test.

A prospective cross-sectional study of tuberculosis in elderly Hispanics reveals that BCG vaccination at birth is protective whereas diabetes is not a risk factor.

BACKGROUND: Aging increases the risk of tuberculosis (TB) and its adverse outcomes, but most studies are based on secondary analyses, and few are in Hispanics. Diabetes is a risk factor for TB in adults, but its contribution in the elderly is unknown. We aimed to identify the role of diabetes and other risk factors for TB in elderly Hispanics. METHODS: Cross-sectional study among newly-diagnosed TB patients, recent contacts (ReC), or community controls (CoC) totaling 646 participants, including 183 elderly (>60 years; 43 TB, 80 ReC, 60 CoC) and 463 adults (18 to 50 years; 80 TB, 301 ReC and 82 CoC). Host characteristics associated with TB and latent Mycobacterium tuberculosis infection (LTBI) were identified in the elderly by univariable and confirmed by multivariable logistic regression. RESULTS: LTBI was more prevalent among the elderly CoC (55% vs. 23.2% in adults; p<0.001), but not in ReC (elderly 71.3% vs. adult 63.8%); p = 0.213). Risk factors for TB in the elderly included male sex (adj-OR 4.33, 95% CI 1.76, 10.65), smoking (adj-OR 2.55, 95% CI 1.01, 6.45) and low BMI (adj-OR 12.34, 95% CI 4.44, 34.33). Unexpectedly, type 2 diabetes was not associated with TB despite its high prevalence (adj-OR 0.38, 95% CI 0.06, 2.38), and BCG vaccination at birth was protective (adj-OR 0.16, 95% CI 0.06, 0.45). CONCLUSIONS: We report novel distinctions in TB risk factors in the elderly vs. adults, notably in diabetes and BCG vaccination at birth. Further studies are warranted to address disparities in this vulnerable, understudied population.

Dipstick urinalysis for diabetes screening in TB patients.

INTRODUCTION: Diabetes knowledge among TB patients can contribute to improved TB treatment outcomes, but lack of diabetes diagnosis awareness is a limitation in developing countries. Given its low cost, the sensitivity of urine glucose dipsticks for diabetes screening in TB patients was assessed. METHODS: Glycosuria was assessed in 90 newly diagnosed TB patients (38 with diabetes) in south Texas, USA (n = 20) and northeast Mexico (n = 70) during January 2009-December 2010. RESULTS: Glycosuria was detected in 65% of the diabetic patients with chronic hyperglycemia (positive predictive value 91%, negative predictive value 84%). CONCLUSION: We propose that TB clinics with limited budgets where portable glucometers may not be available conduct universal screening for diabetes with urine dipsticks. This could be followed by blood glucose or HbA1c testing in the subset of patients requiring confirmation or higher sensitivity assessment, to improve the comanagement of TB and diabetes.

Validation of Mycobacterium tuberculosis Rv1681 protein as a diagnostic marker of active pulmonary tuberculosis.

The development of an accurate antigen detection assay for the diagnosis of active tuberculosis (TB) would represent a major clinical advance. Here, we demonstrate that the Mycobacterium tuberculosis Rv1681 protein is a biomarker for active TB with potential diagnostic utility. We initially identified, by mass spectroscopy, peptides from the Rv1681 protein in urine specimens from 4 patients with untreated active TB. Rabbit IgG anti-recombinant Rv1681 detected Rv1681 protein in lysates and culture filtrates of M. tuberculosis and immunoprecipitated it from pooled urine specimens from two TB patients. An enzyme-linked immunosorbent assay formatted with these antibodies detected Rv1681 protein in unconcentrated urine specimens from 11/25 (44%) TB patients and 1/21 (4.8%) subjects in whom TB was initially clinically suspected but then ruled out by conventional methods. Rv1681 protein was not detected in urine specimens from 10 subjects with Escherichia coli-positive urine cultures, 26 subjects with confirmed non-TB tropical diseases (11 with schistosomiasis, 5 with Chagas' disease, and 10 with cutaneous leishmaniasis), and 14 healthy subjects. These results provide strong validation of Rv1681 protein as a promising biomarker for TB diagnosis.

Rapid DNA extraction for specific detection and quantitation of Mycobacterium tuberculosis DNA in sputum specimens using Taqman assays.

Rapid tuberculosis (TB) detection is critical for disease control, and further quantitation of Mycobacterium tuberculosis (Mtb) in sputum is valuable for epidemiological and clinical studies. We evaluated a simple, robust and cost-efficient in-house DNA extraction and downstream Taqman approach for detection and quantitation of Mtb genomes from sputum of newly-diagnosed TB patients and non-TB controls. DNA was extracted using guanidine isothiocyanate and silica-based spin columns in less than 2 h, stored frozen, and Taqman assays were used to detect Mtb with IS6110 and quantify it targeting RD1 and IS1081. The Taqmans had a sensitivity >95% in 108 culture-confirmed TB patients and specificity of 100% in 43 non-TB controls. Genome counts were correlated with the Mycobacterial Growth Indicator Tubes' (MGIT) time-to-detection values (1/TTD × 1000; rho = 0.66; p < 0.001) in 91 TB patients (33 excluded with MGIT contamination). This linear relationship was nearly identical between mycobacteria isolated from sputum and H37Rv Mtb grown in-vitro to its log phase. TB treatment between 3 and 7 days was associated with lower 1/TTD × 1000 values but not with genome counts. Together, our protocol provides rapid, specific, inexpensive and quantitative detection of Mtb DNA in fresh or stored sputa making it a robust tool for prompt TB diagnosis, and with potential use for clinical and epidemiologic studies.

Cross-sectional assessment reveals high diabetes prevalence among newly-diagnosed tuberculosis cases.

OBJECTIVE: To estimate the contribution of clinically-confirmed diabetes mellitus to tuberculosis (TB) rates in communities where both diseases are prevalent as a way to identify opportunities for TB prevention among diabetic patients. METHODS: This is a prospective study in which TB patients ≥ 20 years old at TB clinics in the Texas-Mexico border were tested for diabetes. The risk of tuberculosis attributable to diabetes was estimated from statistics for the corresponding adult population. FINDINGS: The prevalence of diabetes among TB patients was 39% in Texas and 36% in Mexico. Diabetes contributed 25% of the TB cases studied, whereas human immunodeficiency virus (HIV) infection contributed 5% or fewer. Among TB patients, fewer Mexicans than Texans were aware that they had diabetes before this study (4% and 19%, respectively). Men were also less frequently aware than women that they had diabetes (P = 0.03). Patients who knew that they had diabetes before the study had an 8-year history of the disease, on average, before being diagnosed with TB. CONCLUSION: Patients with diabetes are at higher risk of contracting TB than non-diabetic patients. Integrating TB and diabetes control programmes worldwide would facilitate TB prevention among diabetes patients and increase the number of diabetics who learn of their condition, particularly among males. Such a strategy would lead to earlier case detection and improve the management of both TB and diabetes.

La placenta en el embarazo múltiple: correlación anatomoclínica / The placenta in multiplo pregnancy: anatomo-clinical correlation

Se estudiaron 46 pacientes ingresadas con diagnóstico de embarazo múltiple. Una vez resuelto el embarazo, las placentas fueron enviadas a estudio anatomopatológico, poniendo especial atención al tipo de placentación (monocoriales, dicoriales etc). La edad de las pacientes estuvo entre los 17 y 38 años, con una media de 27. La mayor incidencia de embarazo múltiple ocurrió entre los 25 y 34 años y fue más frecuente en multíparas. De los 46 pacientes estudiadas, 44 tuvieron embarazo gemelar, y dos, triple, obteniendo un total de 94 recién nacidos. Respecto al peso de los productos, no hubo diferencia significativa entre el primero y segundo gemelo (p = 0.05), en cambio, encontramos diferencia significativa en el peso de las masas placentarias, observando que las de mayor peso fueron las placentas dicoriales separadas, en comparación con una sola masa placentaria (monocoriales, dicoriales fusionadas), p = 0.05. Los cambios anatomopatológicos más frecuentes en este estudio fueron: inserción velamentosa de cordón en ocho casos (17,3%), anastomosis vasculares placentarias en tres casos (6,5%), y corioamniotics en seis casos (13%). Dentro de las complicaciones maternas asociadas al embarazo múltiple estuvo la anemia (HB <-10 g) en 19 casos (41,3%), trastornos hipertensivos en nueve casos (19%), y atonía uterina postparto en cuatro casos. La complicación más frecuente en los recién nacidos fue la prematurez, en 47% de los casos