Influence of Spatial Resolution on Space-Time Disease Cluster Detection

Background

Utilizing highly precise spatial resolutions within disease outbreak detection, such as the patients’ address, is most desirable as this provides the actual residential location of the infected individual(s). However, this level of precision is not always readily available or only available for purchase, and when utilized, increases the risk of exposing protected health information. Aggregating data to less precise scales (e.g., ZIP code or county centroids) may mitigate this risk but at the expense of potentially masking smaller isolated high risk areas.

Methods

To experimentally examine the effect of spatial data resolution on space-time cluster detection, we extracted administrative medical claims data for 122500 viral lung episodes occurring during 2007–2010 in Tennessee. We generated 10000 spatial datasets with varying cluster location, size and intensity at the address-level. To represent spatial data aggregation (i.e., reduced resolution), we then created 10000 corresponding datasets both at the ZIP code and county level for a total of 30000 datasets. Using the space-time permutation scan statistic and the SaTScan™ cluster software, we evaluated statistical power, sensitivity and positive predictive values of outbreak detection when using exact address locations compared to ZIP code and county level aggregations.

Results

The power to detect disease outbreaks did not largely diminish when using spatially aggregated data compared to more precise address information. However, aggregations negatively impacted the ability to more accurately determine the exact spatial location of the outbreak, particularly in smaller clusters (<800 km²).

Conclusions

Spatial aggregations do not necessitate a loss of power or sensitivity; rather, the relationship is more complex and involves simultaneously considering relative risk within the cluster and cluster size. The likelihood of spatially over-estimating outbreaks by including geographical areas outside the actual disease cluster increases with aggregated data.     

Analysing spatio-temporal clustering of meningococcal meningitis outbreaks in Niger reveals opportunities for improved disease control

Background

Meningococcal meningitis is a major health problem in the “African Meningitis Belt” where recurrent epidemics occur during the hot, dry season. In Niger, a central country belonging to the Meningitis Belt, reported meningitis cases varied between 1,000 and 13,000 from 2003 to 2009, with a case-fatality rate of 5–15%.

Methodology/Principal Findings

In order to gain insight in the epidemiology of meningococcal meningitis in Niger and to improve control strategies, the emergence of the epidemics and their diffusion patterns at a fine spatial scale have been investigated. A statistical analysis of the spatio-temporal distribution of confirmed meningococcal meningitis cases was performed between 2002 and 2009, based on health centre catchment areas (HCCAs) as spatial units. Anselin''s local Moran''s I test for spatial autocorrelation and Kulldorff''s spatial scan statistic were used to identify spatial and spatio-temporal clusters of cases. Spatial clusters were detected every year and most frequently occurred within nine southern districts. Clusters most often encompassed few HCCAs within a district, without expanding to the entire district. Besides, strong intra-district heterogeneity and inter-annual variability in the spatio-temporal epidemic patterns were observed. To further investigate the benefit of using a finer spatial scale for surveillance and disease control, we compared timeliness of epidemic detection at the HCCA level versus district level and showed that a decision based on threshold estimated at the HCCA level may lead to earlier detection of outbreaks.

Conclusions/Significance

Our findings provide an evidence-based approach to improve control of meningitis in sub-Saharan Africa. First, they can assist public health authorities in Niger to better adjust allocation of resources (antibiotics, rapid diagnostic tests and medical staff). Then, this spatio-temporal analysis showed that surveillance at a finer spatial scale (HCCA) would be more efficient for public health response: outbreaks would be detected earlier and reactive vaccination would be better targeted.     

An IDEA for Short Term Outbreak Projection: Nearcasting Using the Basic Reproduction Number

Background

Communicable disease outbreaks of novel or existing pathogens threaten human health around the globe. It would be desirable to rapidly characterize such outbreaks and develop accurate projections of their duration and cumulative size even when limited preliminary data are available. Here we develop a mathematical model to aid public health authorities in tracking the expansion and contraction of outbreaks with explicit representation of factors (other than population immunity) that may slow epidemic growth.

Methodology

The Incidence Decay and Exponential Adjustment (IDEA) model is a parsimonious function that uses the basic reproduction number R₀, along with a discounting factor to project the growth of outbreaks using only basic epidemiological information (e.g., daily incidence counts).

Principal Findings

Compared to simulated data, IDEA provides highly accurate estimates of total size and duration for a given outbreak when R₀ is low or moderate, and also identifies turning points or new waves. When tested with an outbreak of pandemic influenza A (H1N1), the model generates estimated incidence at the i+1^th serial interval using data from the i^th serial interval within an average of 20% of actual incidence.

Conclusions and Significance

This model for communicable disease outbreaks provides rapid assessments of outbreak growth and public health interventions. Further evaluation in the context of real-world outbreaks will establish the utility of IDEA as a tool for front-line epidemiologists.     

Diagnostic Accuracy of the PURE-LAMP Test for Pulmonary Tuberculosis at the County-Level Laboratory in China

Background

Early and effective detection of Mycobacterium tuberculosis (MTB), particularly in smear-negative tuberculosis (TB), is a priority for global TB control. Loop-mediated isothermal amplification with a procedure for ultra rapid DNA extraction (PURE-LAMP) can detect TB in sputum samples rapidly and with high sensitivity and specificity. However, the PURE-LAMP test has not been effectively evaluated, especially in resource-limited laboratories. In this study, we evaluated the performance of the PURE-LAMP test for TB detection in TB suspects from two county-level TB dispensaries in China.

Methodology/Principal Findings

From April 2011 to February 2012, patients with suspected TB were continuously enrolled from two county-level TB laboratories in China. Three sputum samples (spot, night, and morning sputum) were collected from each recruited patient. Detection of MTB by PURE-LAMP was compared to a reference standard L-J culture. The results showed that the sensitivity of the PURE-LAMP test based on spot sputum for MTB detection was 70.67%, while the sensitivity of the PURE-LAMP test based on spot sputum for MTB detection in smear positive and culture positive patients and smear negative and culture positive patients was 92.12% and 53.81%, respectively. The specificity of PURE-LAMP based on spot sputum for MTB detection was 98.32%. The sensitivity and specificity of the PURE-LAMP test based on three sputa combination for MTB detection was 88.80% and 96.86%, respectively. The results also showed that the PURE-LAMP test had a significantly lower contamination rate than did solid culture.

Conclusions/Significance

The study suggested that, in peripheral-level TB laboratories in China, the PURE-LAMP test showed high sensitivity and specificity for TB detection in TB suspects, making it a more effective, rapid, and safe method worthy of broader use in the future.     

Combining Surveillance Systems: Effective Merging of U.S. Veteran and Military Health Data

Background

The U.S. Department of Veterans Affairs (VA) and Department of Defense (DoD) had more than 18 million healthcare beneficiaries in 2011. Both Departments conduct individual surveillance for disease events and health threats.

Methods

We performed joint and separate analyses of VA and DoD outpatient visit data from October 2006 through September 2010 to demonstrate geographic and demographic coverage, timeliness of influenza epidemic awareness, and impact on spatial cluster detection achieved from a joint VA and DoD biosurveillance platform.

Results

Although VA coverage is greater, DoD visit volume is comparable or greater. Detection of outbreaks was better in DoD data for 58% and 75% of geographic areas surveyed for seasonal and pandemic influenza, respectively, and better in VA data for 34% and 15%. The VA system tended to alert earlier with a typical H3N2 seasonal influenza affecting older patients, and the DoD performed better during the H1N1 pandemic which affected younger patients more than normal influenza seasons. Retrospective analysis of known outbreaks demonstrated clustering evidence found in separate DoD and VA runs, which persisted with combined data sets.

Conclusion

The analyses demonstrate two complementary surveillance systems with evident benefits for the national health picture. Relative timeliness of reporting could be improved in 92% of geographic areas with access to both systems, and more information provided in areas where only one type of facility exists. Combining DoD and VA data enhances geographic cluster detection capability without loss of sensitivity to events isolated in either population and has a manageable effect on customary alert rates.     

Association between Diabetes Mellitus and Tuberculosis in United States-Born and Foreign-Born Populations in San Francisco

Setting

The impact of diabetes on tuberculosis in United States and foreign-born populations in San Francisco has not been studied.

Objective

To determine the characteristics, prevalence and temporal trends of diabetes in US and foreign-born persons attending the San Francisco Tuberculosis Clinic.

Design

We analyzed data from individuals seeking medical attention at the San Francisco Tuberculosis Clinic. We included patients with diagnosis of tuberculosis, latent infection, or not infected with Mycobacterium tuberculosis. We assessed the temporal trend and the characteristics of individuals with and without diabetes.

Result

Between 2005 and 2012, there were 4371 (19.0%) individuals without evidence of tuberculosis infection, 17,856 (77.6%) with latent tuberculosis, and 791 (3.4%) with tuberculosis. 66% were born in the United States, China, Mexico, and the Philippines. The prevalence of diabetes was the highest among individuals with tuberculosis and increased during the study period. Patients with tuberculosis and diabetes were more likely to be male, older than 45 years and born in the Philippines. There was a disproportionate association of TB and DM relative to LTBI and DM among Filipinos in individuals older than 45 years old.

Conclusions

Our data suggest that Filipinos older than 45 years old are more likely to have tuberculosis probably due to a higher prevalence of diabetes. In San Francisco, tuberculosis-screening programs in individuals with diabetes and latent tuberculosis may be beneficial in patients older than 45 years old especially from the Philippines.     

Sensitivity of the Quantiferon-Gold In-Tube Assay in Sputum Smear Positive TB Cases in Indonesia

Background

As part of a formal evaluation of the Quantiferon-Gold in-tube assay (QFT-IT) for latent TB infection we compared its sensitivity to the tuberculin skin test (TST) in confirmed adult TB cases in Indonesia. Smear-positive TB disease was used as a proxy gold standard for latent TB infection.

Methods and Findings

We compared the sensitivity of QFT-IT and TST in 98 sputum smear and chest x-ray positive TB cases and investigated risk factors for negative and discordant results in both tests. Both tests showed high sensitivity; (QFT-IT; 88.7%: TST; 94.9%), not significantly different from each other (p value 0.11). Very high sensitivity was seen when tests were combined (98.9%). There were no variables significantly associated with discordant results or with a negative TST. For QFT-IT which particular staff member collected blood was significantly associated with test positivity (p value 0.01). Study limitations include small sample size and lack of culture confirmation or HIV test results.

Conclusions

The QFT-IT has similar sensitivity in Indonesian TB cases as in other locations. However, QFT-IT, like the TST cannot distinguish active TB disease from LTBI. In countries such as Indonesia, with high background rates of LTBI, test specificity for TB disease will likely be low. While our study was not designed to evaluate the QFT-IT in the diagnosis of active TB disease in TB suspects, the data suggest that a combination of TST and QFT-IT may prove useful for ruling out TB disease. Further research is required to explore the clinical role of QFT-IT in combination with other TB diagnostic tests.     

Diagnosis of Tuberculosis in the Wild Boar (Sus scrofa): A Comparison of Methods Applicable to Hunter-Harvested Animals

Background

To obtain robust epidemiological information regarding tuberculosis (TB) in wildlife species, appropriate diagnostic methods need to be used. Wild boar (Sus scrofa) recently emerged as a major maintenance host for TB in some European countries. Nevertheless, no data is available to evaluate TB post-mortem diagnostic methods in hunter-harvested wild boar.

Methodology/Principal Findings

Six different diagnostic methods for TB were evaluated in parallel in 167 hunter-harvested wild boar. Compared to bacteriological culture, estimates of sensitivity of histopathology was 77.8%, gross pathology 72.2%, PCR for the MPB70 gene 66.7%, detection of acid-fast bacilli (AFB) in tissue contact smears 55.6% and in histopathology slides 16.7% (estimated specificity was 96.7%, 100%, 100%, 94.4% and 100%, respectively). Combining gross pathology with stained smears in parallel increased estimated sensitivity to 94.4% (94.4% specificity). Four probable bacteriological culture false-negative animals were identified by Discriminant Function Analysis. Recalculating the parameters considering these animals as infected generated estimated values for sensitivity of bacteriology and histopathology of 81.8%, gross pathology 72.7%, PCR for the MPB70 gene 63.6%, detection of AFB in tissue contact smears 54.5% and in histopathology slides 13.6% (estimated specificity was 100% for gross pathology, PCR, bacteriology and detection of AFB in histopathology slides, 96.7% for histopathology and 94.4% for stained smears).

Conclusions/Significance

These results show that surveys for TB in wild boar based exclusively on gross pathology considerably underestimate prevalence, while combination of tests in parallel much improves sensitivity and negative predictive values. This finding should thus be considered when planning future surveys and game meat inspection schemes. Although bacteriological culture is the reference test for TB diagnosis, it can generate false-negative results and this should be considered when interpreting data.     

Use of Anti-Retroviral Therapy in Tuberculosis Patients on Second-Line Anti-TB Regimens: A Systematic Review

Introduction

Use of antiretroviral therapy (ART) during treatment of drug susceptible tuberculosis (TB) improves survival. However, data from HIV infected individuals with drug resistant TB are lacking. Second line TB drugs when combined with ART may increase drug interactions and lead to higher rates of toxicity and greater noncompliance. This systematic review sought to determine the benefit of ART in the setting of second line drug therapy for drug resistant TB.

Methods

We included individual patient data from studies that evaluated treatment of drug-resistant tuberculosis in HIV-1 infected individuals published between January 1980 and December of 2009. We evaluated the effect of ART on treatment outcomes, time to smear and culture conversion, and adverse events.

Results

Ten observational studies, including data from 217 subjects, were analyzed. Patients using ART during TB treatment had increased likelihood of cure (hazard ratio (HR) 3.4, 95% CI 1.6–7.4) and decreased likelihood of death (HR 0.4, 95% CI 0.3–0.6) during treatment for drug resistant TB. These associations remained significant in patients with a CD4 less than 200 cells/mm³ and less than 50 cells/mm³, and when correcting for drug resistance pattern.

Limitations

We identified only observational studies from which individual patient data could be drawn. Limitations in study design, and heterogeneity in a number of the outcomes of interest had the potential to introduce bias.

Discussion

While there are insufficient data to determine if ART use increases adverse drug interactions when used with second line TB drugs, ART use during treatment of drug resistant TB appears to improve cure rates and decrease risk of death. All individuals with HIV appear to benefit from ART use during treatment for TB.     

Epidemic Surveillance Using an Electronic Medical Record: An Empiric Approach to Performance Improvement

Backgrounds

Electronic medical records (EMR) form a rich repository of information that could benefit public health. We asked how structured and free-text narrative EMR data should be combined to improve epidemic surveillance for acute respiratory infections (ARI).

Methods

Eight previously characterized ARI case detection algorithms (CDA) were applied to historical EMR entries to create authentic time series of daily ARI case counts (background). An epidemic model simulated influenza cases (injection). From the time of the injection, cluster-detection statistics were applied daily on paired background+injection (combined) and background-only time series. This cycle was then repeated with the injection shifted to each week of the evaluation year. We computed: a) the time from injection to the first statistical alarm uniquely found in the combined dataset (Detection Delay); b) how often alarms originated in the background-only dataset (false-alarm rate, or FAR); and c) the number of cases found within these false alarms (Caseload). For each CDA, we plotted the Detection Delay as a function of FAR or Caseload, over a broad range of alarm thresholds.

Results

CDAs that combined text analyses seeking ARI symptoms in clinical notes with provider-assigned diagnostic codes in order to maximize the precision rather than the sensitivity of case-detection lowered Detection Delay at any given FAR or Caseload.

Conclusion

An empiric approach can guide the integration of EMR data into case-detection methods that improve both the timeliness and efficiency of epidemic detection.     

Treatment Default amongst Patients with Tuberculosis in Urban Morocco: Predicting and Explaining Default and Post-Default Sputum Smear and Drug Susceptibility Results

Setting

Public tuberculosis (TB) clinics in urban Morocco.

Objective

Explore risk factors for TB treatment default and develop a prediction tool. Assess consequences of default, specifically risk for transmission or development of drug resistance.

Design

Case-control study comparing patients who defaulted from TB treatment and patients who completed it using quantitative methods and open-ended questions. Results were interpreted in light of health professionals’ perspectives from a parallel study. A predictive model and simple tool to identify patients at high risk of default were developed. Sputum from cases with pulmonary TB was collected for smear and drug susceptibility testing.

Results

91 cases and 186 controls enrolled. Independent risk factors for default included current smoking, retreatment, work interference with adherence, daily directly observed therapy, side effects, quick symptom resolution, and not knowing one’s treatment duration. Age >50 years, never smoking, and having friends who knew one’s diagnosis were protective. A simple scoring tool incorporating these factors was 82.4% sensitive and 87.6% specific for predicting default in this population. Clinicians and patients described additional contributors to default and suggested locally-relevant intervention targets. Among 89 cases with pulmonary TB, 71% had sputum that was smear positive for TB. Drug resistance was rare.

Conclusion

The causes of default from TB treatment were explored through synthesis of qualitative and quantitative data from patients and health professionals. A scoring tool with high sensitivity and specificity to predict default was developed. Prospective evaluation of this tool coupled with targeted interventions based on our findings is warranted. Of note, the risk of TB transmission from patients who default treatment to others is likely to be high. The commonly-feared risk of drug resistance, though, may be low; a larger study is required to confirm these findings.     

TB Incidence in an Adolescent Cohort in South Africa

Background

Tuberculosis (TB) is a major public health problem globally. Little is known about TB incidence in adolescents who are a proposed target group for new TB vaccines. We conducted a study to determine the TB incidence rates and risk factors for TB disease in a cohort of school-going adolescents in a high TB burden area in South Africa.

Methods

We recruited adolescents aged 12 to 18 years from high schools in Worcester, South Africa. Demographic and clinical information was collected, a tuberculin skin test (TST) performed and blood drawn for a QuantiFERON TB Gold assay at baseline. Screening for TB cases occurred at follow up visits and by surveillance of registers at public sector TB clinics over a period of up to 3.8 years after enrolment.

Results

A total of 6,363 adolescents were enrolled (58% of the school population targeted). During follow up, 67 cases of bacteriologically confirmed TB were detected giving an overall incidence rate of 0.45 per 100 person years (95% confidence interval 0.29–0.72). Black or mixed race, maternal education of primary school or less or unknown, a positive baseline QuantiFERON assay and a positive baseline TST were significant predictors of TB disease on adjusted analysis.

Conclusion

The adolescent TB incidence found in a high burden setting will help TB vaccine developers plan clinical trials in this population. Latent TB infection and low socio-economic status were predictors of TB disease.     

Syndromic Surveillance for Local Outbreaks of Lower-Respiratory Infections: Would It Work?

Background

Although syndromic surveillance is increasingly used to detect unusual illness, there is a debate whether it is useful for detecting local outbreaks. We evaluated whether syndromic surveillance detects local outbreaks of lower-respiratory infections (LRIs) without swamping true signals by false alarms.

Methods and Findings

Using retrospective hospitalization data, we simulated prospective surveillance for LRI-elevations. Between 1999–2006, a total of 290762 LRIs were included by date of hospitalization and patients place of residence (>80% coverage, 16 million population). Two large outbreaks of Legionnaires disease in the Netherlands were used as positive controls to test whether these outbreaks could have been detected as local LRI elevations. We used a space-time permutation scan statistic to detect LRI clusters. We evaluated how many LRI-clusters were detected in 1999–2006 and assessed likely causes for the cluster-signals by looking for significantly higher proportions of specific hospital discharge diagnoses (e.g. Legionnaires disease) and overlap with regional influenza elevations. We also evaluated whether the number of space-time signals can be reduced by restricting the scan statistic in space or time. In 1999–2006 the scan-statistic detected 35 local LRI clusters, representing on average 5 clusters per year. The known Legionnaires'' disease outbreaks in 1999 and 2006 were detected as LRI-clusters, since cluster-signals were generated with an increased proportion of Legionnaires disease patients (p:<0.0001). 21 other clusters coincided with local influenza and/or respiratory syncytial virus activity, and 1 cluster appeared to be a data artifact. For 11 clusters no likely cause was defined, some possibly representing as yet undetected LRI-outbreaks. With restrictions on time and spatial windows the scan statistic still detected the Legionnaires'' disease outbreaks, without loss of timeliness and with less signals generated in time (up to 42% decline).

Conclusions

To our knowledge this is the first study that systematically evaluates the performance of space-time syndromic surveillance with nationwide high coverage data over a longer period. The results show that syndromic surveillance can detect local LRI-outbreaks in a timely manner, independent of laboratory-based outbreak detection. Furthermore, since comparatively few new clusters per year were observed that would prompt investigation, syndromic hospital-surveillance could be a valuable tool for detection of local LRI-outbreaks.     

Validation of the ALS assay in adult patients with culture confirmed pulmonary tuberculosis

Background

We have earlier shown that Bacille Calmette-Guérin (BCG) vaccine-specific IgG Antibodies in Lymphocyte Supernatant (ALS) can be used for diagnosis of active tuberculosis (TB) in adults and children.

Methodology/Principal Findings

The ALS method was validated in a larger cohort (n = 212) of patients with suspicion of pulmonary TB using multiple antigens (BCG, LAM, TB15.3, TB51A, CFP10-ESAT6-A, CFP, CW) from Mycobacterium tuberculosis. The sensitivity and specificity of the ALS assay was calculated using non-TB patients as controls. The sensitivity and the specificity were highest with BCG vaccine (90% and 88% respectively) followed by LAM (89% and 87% respectively). Simultaneous assessment of multiple antigen-specific antibodies increased sensitivity (91%) and specificity (88%). Using higher lymphocyte count in smaller volume of culture media increased detection and reduced the assay duration to ∼30 hrs. Twenty one patients with clinical findings strongly suggestive of TB finally diagnosed as non-TB patients were positive by the ALS assay, of which 9 (43%) were positive for 7 antigens and 19 (90%) for at least 3 antigens.

Conclusions/Significance

Our findings show that simultaneous detection of antigens improves the diagnostic potential of the ALS assay; the modified method increases sensitivity and can provide results in <48 hours, and enable detection of some cases of pulmonary TB that are not detectable by standard methods.     

Quantifying Spatial Disparities in Neonatal Mortality Using a Structured Additive Regression Model

Background

Neonatal mortality contributes a large proportion towards early childhood mortality in developing countries, with considerable geographical variation at small areas within countries.

Methods

A geo-additive logistic regression model is proposed for quantifying small-scale geographical variation in neonatal mortality, and to estimate risk factors of neonatal mortality. Random effects are introduced to capture spatial correlation and heterogeneity. The spatial correlation can be modelled using the Markov random fields (MRF) when data is aggregated, while the two dimensional P-splines apply when exact locations are available, whereas the unstructured spatial effects are assigned an independent Gaussian prior. Socio-economic and bio-demographic factors which may affect the risk of neonatal mortality are simultaneously estimated as fixed effects and as nonlinear effects for continuous covariates. The smooth effects of continuous covariates are modelled by second-order random walk priors. Modelling and inference use the empirical Bayesian approach via penalized likelihood technique. The methodology is applied to analyse the likelihood of neonatal deaths, using data from the 2000 Malawi demographic and health survey. The spatial effects are quantified through MRF and two dimensional P-splines priors.

Results

Findings indicate that both fixed and spatial effects are associated with neonatal mortality.

Conclusions

Our study, therefore, suggests that the challenge to reduce neonatal mortality goes beyond addressing individual factors, but also require to understanding unmeasured covariates for potential effective interventions.     

Market Assessment of Tuberculosis Diagnostics in Brazil in 2012

Background

Improved diagnostics for the diagnosis of tuberculosis (TB) are urgently needed. However, test developers and investors require market size data to support new product development. This study assessed the served available market for TB diagnostics in Brazil in 2012 and the market segmentation in the public and private sectors.

Methods

Data were collected on test volumes done in the public and private sectors for the diagnosis of latent and active TB, drug susceptibility testing and treatment follow-up. Tests included were tuberculin skin tests, interferon-gamma releases assays, smear microscopy, solid and liquid cultures, nucleic acid amplification tests and phenotypic drug susceptibility tests. The data were collected by means of an electronic survey via the Brazilian State laboratories and from sales information provided by manufacturers. Test costs for the public sector were calculated using a components approach, while costs for the private sector were based on prices paid by patients. The overall market value (expenditure) for the entire country was calculated using the public sector test costs.

Results

During 2012, an estimated total of 2.4 million TB diagnostic tests were done in Brazil, resulting in an estimated overall market value of USD 17.2 million. The public sector accounted for 91% of the test volumes and 88% of the market value. Smear microscopy was the most commonly test (n = 1.3 million; 55% of total) at an estimated value of USD 3.7 million. Culture overall (n = 302,761) represented 13% of test volumes and 40% (USD 6.9 million) of the market value. On average, USD 208 was spent on TB diagnostics for every notified TB patient in Brazil, in 2012.

Conclusion

The TB diagnostics market value in Brazil in 2012 was over USD 17 million. These study results will help test developers to understand the current and potential market for replacement or add-on diagnostic technologies.     

Diagnostic Performance of Interferon-Gamma Releasing Assay in HIV-Infected Patients in China

Background

Active tuberculosis infection represents a very common and significant threat to HIV-infected patients. But measures to accurately detect it are limited.

Objective

To compare and analyze the diagnostic efficacy of T-SPOT.TB alone and in combination with TST in HIV-infected patients in China.

Method

TST (tuberculin skin test) and T-SPOT.TB were performed on 131 HIV-infected patients admitted in Beijing You’an Hospital and Beijing Ditan Hospital between Oct, 2010 and Jul, 2012, who were initially diagnosed as suspected ATB (active TB). The patients were further categorized into ATB and Not ATB based on clinical and cultural evidences. The performance of TST and T-SPOT.TB were analyzed and compared.

Results

The sensitivity and specificity of T-SPOT.TB were 41.3% and 94.6%, respectively, both higher than TST (12.9% and 91.8%). By combining T-SPOT.TB and TST, the sensitivity did not increase, but specificity was elevated to 100%. TST, T-SPOT.TB and their combinations all performed better in patients with extra-pulmonary diseases than with pulmonary disorders. False-positive T-SPOT.TB results were found to be associated with history of prior TB. In addition, concomitant bacterial infections and low CD4 counts were associated with increased ATB risk.

Conclusions

T-SPOT.TB is superior in screening ATB in HIV-infected patients in China over traditional TST. Additional TST would help to confirm a positive T-SPOT.TB result. Both tests work better for patients with extra-pulmonary conditions.     

Results from the First 12 Months of the National Surveillance of Healthcare Associated Outbreaks in Germany, 2011/2012

Background

In August 2011, the German Protection against Infection Act was amended, mandating the reporting of healthcare associated infection (HAI) outbreak notifications by all healthcare workers in Germany via local public health authorities and federal states to the Robert Koch Institute (RKI).

Objective

To describe the reported HAI-outbreaks and the surveillance system’s structure and capabilities.

Methods

Information on each outbreak was collected using standard paper forms and notified to RKI. Notifications were screened daily and regularly analysed.

Results

Between November 2011 and November 2012, 1,326 paper forms notified 578 HAI-outbreaks, between 7 and 116 outbreaks per month. The main causative agent was norovirus (n = 414/578; 72%). Among the 108 outbreaks caused by bacteria, the most frequent pathogens were Clostridium difficile (25%) Klebsiella spp. (19%) and Staphylococcus spp. (19%). Multidrug-resistant bacteria were responsible for 54/108 (50%) bacterial outbreaks. Hospitals were affected most frequently (485/578; 84%). Hospital outbreaks due to bacteria were mostly reported from intensive care units (ICUs) (45%), followed by internal medicine wards (16%).

Conclusion

The mandatory HAI-outbreak surveillance system describes common outbreaks. Pathogens with a particular high potential to cause large or severe outbreaks may be identified, enabling us to further focus research and preventive measures. Increasing the sensitivity and reliability of the data collection further will facilitate identification of outbreaks able to increase in size and severity, and guide specific control measures to interrupt their propagation.     

Cost Analysis of a Nucleic Acid Amplification Test in the Diagnosis of Pulmonary Tuberculosis at an Urban Hospital with a High Prevalence of TB/HIV

Introduction

The Centers for Disease Control and Prevention has recommended using a nucleic acid amplification test (NAAT) for diagnosing pulmonary tuberculosis (TB) but there is a lack of data on NAAT cost-effectiveness.

Methods

We conducted a prospective cohort study that included all patients with an AFB smear-positive respiratory specimen at Grady Memorial Hospital in Atlanta, GA, USA between January 2002 and June 2008. We determined the sensitivity, specificity, and positive and negative predictive value of a commercially available and FDA-approved NAAT (amplified MTD, Gen-Probe) compared to the gold standard of culture. A cost analysis was performed and included costs related to laboratory tests, hospital charges, anti-TB medications, and contact investigations. Average cost per patient was calculated under two conditions: (1) using a NAAT on all AFB smear-postive respiratory specimens and (2) not using a NAAT. One-way sensitivity analyses were conducted to determine sensitivity of cost difference to reasonable ranges of model inputs.

Results

During a 6 1/2 year study period, there were 1,009 patients with an AFB smear-positive respiratory specimen at our public urban hospital. We found the NAAT to be highly sensitive (99.6%) and specific (99.1%) on AFB smear-positive specimens compared to culture. Overall, the positive predictive value (PPV) of an AFB smear-positive respiratory specimen for culture-confirmed TB was 27%. The PPV of an AFB smear-positive respiratory specimen for culture-confirmed TB was significantly higher for HIV-uninfected persons compared to those who were HIV-seropositive (152/271 [56%] vs. 85/445 [19%]; RR = 2.94, 95% CI 2.36–3.65, p<0.001). The cost savings of using the NAAT was $2,003 per AFB smear-positive case.

Conclusions

Routine use of the NAAT on AFB smear-positive respiratory specimens was highly cost-saving in our setting at a U.S. urban public hospital with a high prevalence of TB and HIV because of the low PPV of an AFB smear for culture-confirmed TB.