Using GIS technology to identify areas of tuberculosis transmission and incidence

BACKGROUND: Currently in the U.S. it is recommended that tuberculosis screening and treatment programs be targeted at high-risk populations. While a strategy of targeted testing and treatment of persons most likely to develop tuberculosis is attractive, it is uncertain how best to accomplish this goal. In this study we seek to identify geographical areas where on-going tuberculosis transmission is occurring by linking Geographic Information Systems (GIS) technology with molecular surveillance. METHODS: This cross-sectional analysis was performed on data collected on persons newly diagnosed with culture positive tuberculosis at the Tarrant County Health Department (TCHD) between January 1, 1993 and December 31, 2000. Clinical isolates were molecularly characterized using IS6110-based RFLP analysis and spoligotyping methods to identify patients infected with the same strain. Residential addresses at the time of diagnosis of tuberculosis were geocoded and mapped according to strain characterization. Generalized estimating equations (GEE) analysis models were used to identify risk factors involved in clustering. RESULTS: Evaluation of the spatial distribution of cases within zip-code boundaries identified distinct areas of geographical distribution of same strain disease. We identified these geographical areas as having increased likelihood of on-going transmission. Based on this evidence we plan to perform geographically based screening and treatment programs. CONCLUSION: Using GIS analysis combined with molecular epidemiological surveillance may be an effective method for identifying instances of local transmission. These methods can be used to enhance targeted screening and control efforts, with the goal of interruption of disease transmission and ultimately incidence reduction

Mycobacterium tuberculosis Cluster with Developing Drug Resistance, New York, New York, USA, 2003–2009

In 2004, identification of patients infected with the same Mycobacterium tuberculosis strain in New York, New York, USA, resulted in an outbreak investigation. The investigation involved data collection and analysis, establishing links between patients, and forming transmission hypotheses. Fifty-four geographically clustered cases were identified during 2003–2009. Initially, the M. tuberculosis strain was drug susceptible. However, in 2006, isoniazid resistance emerged, resulting in isoniazid-resistant M. tuberculosis among 17 (31%) patients. Compared with patients with drug-susceptible M. tuberculosis, a greater proportion of patients with isoniazid-resistant M. tuberculosis were US born and had a history of illegal drug use. No patients named one another as contacts. We used patient photographs to identify links between patients. Three links were associated with drug use among patients infected with isoniazid-resistant M. tuberculosis. The photographic method would have been more successful if used earlier in the investigation. Name-based contact investigation might not identify all contacts, particularly when illegal drug use is involved

Long-term follow-up of persons diagnosed with multidrug-resistant TB in Chennai, India, 2013-2020

India has the largest number of multidrug-resistant TB (MDR-TB) cases, defined as Mycobacterium tuberculosis resistant to at least isoniazid (INH) and rifampicin (RIF).1 However, less than half of all persons with MDR-TB in India successfully complete treatment.1 Although initial end-of-treatment outcomes offer a standardised time point to assess the effect of treatment, these tend to underestimate the overall burden of unfavourable long-term outcomes among persons treated for TB.2,3 The long-term outcomes of persons diagnosed with MDR-TB in India, including the proportion with recurrent TB disease or mortality, are unknown. This analysis was conducted under programmatic conditions in a high-burden setting, with no regular check-ups after treatment. The results can be used to show the burden of recurrent illness and death following treatment, and can be used as a benchmark to measure improvement

Unusual Interferon Gamma Measurements with QuantiFERON-TB Gold and QuantiFERON-TB Gold In-Tube Tests

INTRODUCTION: Interferon gamma (IFN-γ) release assays, such as QuantiFERON®-TB Gold test (QFT-G) and QuantiFERON®-TB Gold In-Tube test (QFT-GIT) are designed to detect M. tuberculosis (Mtb) infection. Recognition of unusual IFN-γ measurements may help indicate inaccurate results. METHODS: We examined QFT-G and QFT-GIT results from subjects who had two or more tests completed. We classified unusual IFN-γ measurements as: 1) High Nil Concentration (HNC) when IFN-γ concentration in plasma from unstimulated blood exceeded 0.7 IU/mL; 2) Low Mitogen Response (LMR) when Mitogen Response was <0.5 IU/mL; 3) Very Low Mitogen Response (VLMR) when Mitogen Response was ≤-0.5 IU/mL; and 4) Very Low Antigen Response (VLAR) when the response to a Mtb antigen was ≤-0.35 IU/mL and ≤-0.5 times the IFN-γ concentration in plasma from unstimulated blood. RESULTS: Among 5,309 results from 1,728 subjects, HNC occurred in 234 (4.4%) tests for 162 subjects, LMR in 108 (2.0%) tests for 85 subjects, VLMR in 22 (0.4%) tests for 21 subjects, and VLAR in 41 (0.8%) tests for 39 subjects. QFT-GIT had fewer HNC, VLMR, and VLAR (p = 0.042, 0.004, and 0.067 respectively); QFT-G had fewer LMR (p = 0.005). Twenty-four (51.6%) of 47 subjects with positive results and HNC were negative or indeterminate by all other tests. Thirteen (61.9%) of 21 subjects with positive results and LMR were negative or indeterminate by all other tests. CONCLUSION: Unusual IFN-γ measurements including HNC, LMR, VLMR, and VLAR were encountered in small numbers, and in most instances were not seen on simultaneously or subsequently performed tests. To avoid erroneous diagnosis of Mtb infection, IGRAs with unusual IFN-γ measurements should be repeated with another blood sample and interpreted with caution if they recur

Diagnostic pathways and direct medical costs incurred by new adult pulmonary tuberculosis patients prior to anti-tuberculosis treatment - Tamil Nadu, India.

BACKGROUND: Tuberculosis (TB) patients face substantial delays prior to treatment initiation, and out of pocket (OOP) expenditures often surpass the economic productivity of the household. We evaluated the pre-diagnostic cost and health seeking behaviour of new adult pulmonary TB patients registered at Primary Health Centres (PHCs) in Vellore district, Tamil Nadu, India. METHODS: This descriptive study, part of a randomised controlled trial conducted in three rural Tuberculosis Units from Dec 2012 to Dec 2015, collected data on number of health facilities, dates of visits prior to the initiation of anti-tuberculosis treatment, and direct OOP medical costs associated with TB diagnosis. Logistic regression analysis examined the factors associated with delays in treatment initiation and OOP expenditures. RESULTS: Of 880 TB patients interviewed, 34.7% presented to public health facilities and 65% patients sought private health facilities as their first point of care. The average monthly individual income was $77.79 (SD 57.14). About 69$39.74. Overall, patients experienced a median of 6 days (3-11 IQR) of time to treatment initiation and 21 days (10-30 IQR) of health systems delay. Age ≤ 40 years (aOR: 1.73; CI: 1.22-2.44), diabetes (aOR: 1.63; CI: 1.08-2.44) and first visit to a private health facility (aOR: 17.2; CI: 11.1-26.4) were associated with higher direct OOP medical costs, while age ≤ 40 years (aOR: 0.64; CI: 0.48-0.85) and first visit to private health facility (aOR: 1.79, CI: 1.34-2.39) were associated with health systems delay. CONCLUSION: The majority of rural TB patients registering at PHCs visited private health facilities first and incurred substantial direct OOP medical costs and delays prior to diagnosis and anti-tuberculosis treatment initiation. This study highlights the need for PHCs to be made as the preferred choice for first point of contact, to combat TB more efficiently.Eunice Kennedy Shriver National Institute of Child Health and Human Developmen

Whole-Genome Sequencing to Identify Missed Rifampicin and Isoniazid Resistance Among Tuberculosis Isolates—Chennai, India, 2013–2016

India has a high burden of drug-resistant tuberculosis (DR TB) and many cases go undetected by current drug susceptibility tests (DSTs). This study was conducted to identify rifampicin (RIF) and isoniazid (INH) resistance associated genetic mutations undetected by current clinical diagnostics amongst persons with DR TB in Chennai, India. Retrospectively stored 166 DR TB isolates during 2013–2016 were retrieved and cultured in Löwenstein-Jensen medium. Whole genome sequencing (WGS) and MGIT DST for RIF and INH were performed. Discordant genotypic and phenotypic sensitivity results were repeated for confirmation and the discrepant results considered final. Further, drug resistance-conferring mutations identified through WGS were analyzed for their presence as targets in current WHO-recommended molecular diagnostics. WGS detected additional mutations for rifampicin and isoniazid resistance than WHO-endorsed line probe assays. For RIF, WGS was able to identify an additional 10% (15/146) of rpoB mutant isolates associated with borderline rifampicin resistance compared to MGIT DST. WGS could detect additional DR TB cases than commercially available and WHO-endorsed molecular DST tests. WGS results reiterate the importance of the recent WHO revised critical concentrations of current MGIT DST to detect low-level resistance to rifampicin. WGS may help inform effective treatment selection for persons at risk of, or diagnosed with, DR TB

Does directly observed therapy (DOT) reduce drug resistant tuberculosis?

<p>Abstract</p> <p>Background</p> <p>Directly observed therapy (DOT) is a widely recommended and promoted strategy to manage tuberculosis (TB), however, there is still disagreement about the role of DOT in TB control and the impact it has on reducing the acquisition and transmission of drug resistant TB. This study compares the portion of drug resistant genotype clusters, representing recent transmission, within and between communities implementing programs differing only in their directly observed therapy (DOT) practices.</p> <p>Methods</p> <p>Genotype clusters were defined as 2 or more patient members with matching IS<it>6110 </it>restriction fragment length polymorphism (RFLP) and spoligotype patterns from all culture-positive tuberculosis cases diagnosed between January 1, 1995 and December 31, 2001. Logistic regression was used to compute maximum-likelihood estimates of odds ratios (ORs) and 95% confidence intervals (CIs) comparing cluster members with and without drug resistant isolates. In the universal DOT county, all patients received doses under direct observation of health department staff; whereas in selective DOT county, the majority of received patients doses under direct observation of health department staff, while some were able to self-administer doses.</p> <p>Results</p> <p>Isolates from 1,706 persons collected during 1,721 episodes of tuberculosis were genotyped. Cluster members from the selective DOT county were more than twice as likely than cluster members from the universal DOT county to have at least one isolate resistant to isoniazid, rifampin, and/or ethambutol (OR = 2.3, 95% CI: 1.7, 3.1). Selective DOT county isolates were nearly 5 times more likely than universal DOT county isolates to belong to clusters with at least 2 resistant isolates having identical resistance patterns (OR = 4.7, 95% CI: 2.9, 7.6).</p> <p>Conclusions</p> <p>Universal DOT for tuberculosis is associated with a decrease in the acquisition and transmission of resistant tuberculosis.</p

Mind the gap:TB trends in the USA and the UK, 2000-2011

BACKGROUND: TB remains a major public health concern, even in low-incidence countries like the USA and the UK. Over the last two decades, cases of TB reported in the USA have declined, while they have increased substantially in the UK. We examined factors associated with this divergence in TB trends between the two countries. METHODS: We analysed all cases of TB reported to the US and UK national TB surveillance systems from 1 January 2000 through 31 December 2011. Negative binominal regression was used to assess potential demographic, clinical and risk factor variables associated with differences in observed trends. FINDINGS: A total of 259 609 cases were reported. From 2000 to 2011, annual TB incidence rates declined from 5.8 to 3.4 cases per 100 000 in the USA, whereas in the UK, TB incidence increased from 11.4 to 14.4 cases per 100 000. The majority of cases in both the USA (56%) and the UK (64%) were among foreign-born persons. The number of foreign-born cases reported in the USA declined by 15% (7731 in 2000 to 6564 in 2011) while native-born cases fell by 54% (8442 in 2000 to 3883 in 2011). In contrast, the number of foreign-born cases reported in the UK increased by 80% (3380 in 2000 to 6088 in 2011), while the number of native-born cases remained largely unchanged (2158 in 2000 to 2137 in 2011). In an adjusted negative binomial regression model, significant differences in trend were associated with sex, age, race/ethnicity, site of disease, HIV status and previous history of TB (p<0.01). Among the foreign-born, significant differences in trend were also associated with time since UK or US entry (p<0.01). INTERPRETATION: To achieve TB elimination in the UK, a re-evaluation of current TB control policies and practices with a focus on foreign-born are needed. In the USA, maintaining and strengthening control practices are necessary to sustain the progress made over the last 20 years

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability