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Background Active case finding (ACF) in household contacts of tuberculosis (TB) patients is now recommended for National TB Programs (NTP) in low- and middle-income countries. However, evidence supporting these recommendations remains limited. This study evaluates the effectiveness and cost-effectiveness of ACF for household contacts of TB cases in a large TB endemic district of Lima, Peru. Methods A pragmatic stepped-wedge cluster randomized controlled trial was conducted in 34 health centers of San Juan de Lurigancho district. Centers were stratified by TB rate and randomly allocated to initiate ACF in groups of eight or nine centers at four-month intervals. In the intervention arm, NTP providers visited households of index patients to screen contacts for active TB. The control arm was routine passive case finding (PCF) of symptomatic TB cases. The primary outcomes were the crude and adjusted active TB case rates among household contacts. Program costs were directly measured, and the cost-effectiveness of the ACF intervention was determined. Findings 3222 index TB cases and 12,566 household contacts were included in the study. ACF identified more household contact TB cases than PCF, 199.29/10,000 contacts/year vs. 132.13 (incidence rate ratio of 1.51 (95% CI 1.21–1.88)). ACF was associated with an incremental cost-effectiveness ratio of US $16,400 per disability-adjusted life year averted and not cost-effective assuming a willingness-to-pay threshold for Peru of US $6360. Conclusion ACF of TB case household contacts detected significantly more secondary TB cases than PCF alone, but was not cost-effective in this setting. In threshold analyses, ACF becomes cost-effective if associated with case detection rates 2.5 times higher than existing PCF programs.

SUMMARYWe compared the cost-effectiveness (CE) of an active case-finding (ACF) programme for household contacts of tuberculosis (TB) cases enrolled in first-line treatment to routine passive case-finding (PCF) within an established national TB programme in Peru. Decision analysis was used to model detection of TB in household contacts through: (1) self-report of symptomatic cases for evaluation (PCF), (2) a provider-initiated ACF programme, (3) addition of an Xpert MTB/RIF diagnostic test for a single sputum sample from household contacts, and (4) all strategies combined. CE was calculated as the incremental cost-effectiveness ratio (ICER) in terms of US dollars per disability-adjusted life years (DALYs) averted. Compared to PCF alone, ACF for household contacts resulted in an ICER of $2155 per DALY averted. The addition of the Xpert MTB/RIF diagnostic test resulted in an ICER of $3275 per DALY averted within a PCF programme and $3399 per DALY averted when an ACF programme was included. Provider-initiated ACF of household contacts in an urban setting of Lima, Peru can be highly cost-effective, even including costs to seek out contacts and perform an Xpert/MTB RIF test. ACF including Xpert MTB/RIF was not cost-effective if TB cases detected had high rates of default from treatment or poor outcomes.

Background/aims The use of the stepped wedge cluster randomized design is rapidly increasing. This design is commonly used to evaluate health policy and service delivery interventions. Stepped wedge cluster randomized trials have unique characteristics that complicate their ethical interpretation. The 2012 Ottawa Statement provides comprehensive guidance on the ethical design and conduct of cluster randomized trials, and the 2010 CONSORT extension for cluster randomized trials provides guidelines for reporting. Our aims were to assess the adequacy of the ethical conduct and reporting of stepped wedge trials to date, focusing on research ethics review and informed consent. Methods We conducted a systematic review of stepped wedge cluster randomized trials in health research published up to 2014 in English language journals. We extracted details of study intervention and data collection procedures, as well as reporting of research ethics review and informed consent. Two reviewers independently extracted data from each trial; discrepancies were resolved through discussion. We identified the presence of any research participants at the cluster level and the individual level. We assessed ethical conduct by tabulating reporting of research ethics review and informed consent against the presence of research participants. Results Of 32 identified stepped wedge trials, only 24 (75%) reported review by a research ethics committee, and only 16 (50%) reported informed consent from any research participants—yet, all trials included research participants at some level. In the subgroup of 20 trials with research participants at cluster level, only 4 (20%) reported informed consent from such participants; in 26 trials with individual-level research participants, only 15 (58%) reported their informed consent. Interventions (regardless of whether targeting cluster- or individual-level participants) were delivered at the group level in more than two-thirds of trials; nine trials (28%) had no identifiable data collected from any research participants. Overall, only three trials (9%) indicated that a waiver of consent had been granted by a research ethics committee. When considering the combined requirement of research ethics review and informed consent (or a waiver), only one in three studies were compliant. Conclusion The ethical conduct and reporting of key ethical protections in stepped wedge trials, namely, research ethics review and informed consent, are inadequate. We recommend that stepped wedge trials be classified as research and reviewed and approved by a research ethics committee. We also recommend that researchers appropriately identify research participants (which may include health professionals), seek informed consent or appeal to an ethics committee for a waiver of consent, and include explicit details of research ethics approval and informed consent in the trial report.

The role of so-called “group 5” second-line drugs as a part of antibiotic therapy for multidrug-resistant tuberculosis (MDR-TB) is widely debated. We performed an individual patient data meta-analysis to evaluate the effectiveness of several group 5 drugs including amoxicillin/clavulanic acid, thioacetazone, the macrolide antibiotics, linezolid, clofazimine and terizidone for treatment of patients with MDR-TB.Detailed individual patient data were obtained from 31 published cohort studies of MDR-TB therapy. Pooled treatment outcomes for each group 5 drug were calculated using a random effects meta-analysis. Primary analyses compared treatment success to a combined outcome of failure, relapse or death.Among 9282 included patients, 2191 received at least one group 5 drug. We found no improvement in treatment success among patients taking clofazimine, amoxicillin/clavulanic acid or macrolide antibiotics, despite applying a number of statistical approaches to control confounding. Thioacetazone was associated with increased treatment success (OR 2.6, 95% CI 1.1–6.1) when matched controls were selected from studies in which the group 5 drugs were not used at all, although this result was heavily influenced by a single study.The development of more effective antibiotics to treat drug-resistant TB remains an urgent priority.

Effective contact investigations are paramount to the success of tuberculosis (TB) control in high-risk communities in low TB prevalence countries. National and international guidelines on TB contact investigations are available and vary widely on recommendations. Because of the limitations of traditional contact tracing, new approaches are under investigation, and in some cases in use, to ensure effective TB control in those persons and communities at greatest risk. These non-traditional approaches include the use of social network analysis, geographic information systems and genomics, in addition to the widespread use of genotyping, to better understand TB transmission. Detailed guidelines for the use of these methods during TB outbreaks and in routine follow-up of TB contact investigations do not currently exist despite evidence that they may improve TB control efforts. It remains unclear as to when it is most appropriate and effective to use a network-informed approach alone, or in combination with other methodologies as well as the extent of data collection required to inform practice. TB controllers should consider developing the capacity to facilitate the systematic collection, analysis, and interpretation of contact investigation data using such novel methodologies, particularly in high-risk communities. Further investigation should focus on questionnaire development and adaptation, electronic data management and infrastructure, development of local capability and consultant expertise, and the use of coordinated approaches, including deployment strategies and evaluation.

Background Household contacts (HHCs) of TB cases are at increased risk for TB disease compared to the general population but the risk may be modified by individual or household factors. We conducted a study to determine incident TB among HHCs over two years after exposure and to identify individual and household level risk factors. Methods Adults newly diagnosed with a first episode of smear-positive pulmonary TB (index cases) between March 2010 and December 2011 in eastern Lima, were interviewed to identify their HHC and household characteristics. TB registers were reviewed for up to two years after the index case diagnosis and house visits were made to ascertain TB cases among HHC. The TB incidence rate ratio among HHCs as a function of risk factors was determined using generalized linear mixed models. Results The 1178 index cases reported 5466 HHCs. In 402/1178 (34.1 %) households, at least one HHC had experienced a TB episode ever. The TB incidence among HHCs was 1918 (95%CI 1669–2194) per 100,000 person-years overall, and was 2392 (95%CI 2005–2833) and 1435 (95%CI 1139–1787) per 100,000 person-years in the first and second year, respectively. Incident TB occurred more than six months following the index case’s TB diagnosis in 121/205 (59.0 %) HHCs. In HHCs, bacillary load and time between symptoms and treatment initiation in the index case, as well as the relationship to the index case and the sex of the HHC all had a significant association with TB incidence in HHCs. Conclusions Incidence of TB among HHCs was more than ten times higher than in the general population. Certain HHC and households were at higher risk of TB, we recommend studies to compare HHC investigation to households at highest risk versus current practice, in terms of efficiency. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1616-x) contains supplementary material, which is available to authorized users.

Aims Despite the establishment of syringe exchange programmes, syringe-sharing behaviour remains common among some injection drug users (IDU). Previous studies have identified several individual- and social network-level variables associated with syringe sharing. We examine the extent to which each of these variables is related independently to this behaviour within a diverse study population. Design, setting and participants A cross-sectional survey of 435 IDU conducted between December 2003 and September 2004 in Winnipeg, Canada. Measurements Individual and social-network variables were obtained from a survey instrument administered through a personal interview. Syringe sharing was defined as receptive syringe sharing in the last 6 months. Logistic regression analysis with generalized estimating equations was used to determine simultaneously the role of individual-level and risk network member-level variables on the odds of syringe sharing. Findings Individuals' relationship to a risk network member (sex partner, OR: 15.3 95% CI: 7.6–30.8; family member, OR: 3.4 95% CI: 1.3–9.0) and difficulty of access to syringes (OR: 3.6 95% CI: 1.3–9.9) were predictive of syringe sharing. Dyads who ‘often’ pooled resources to obtain drugs were at 4.9 times (95% CI: 2.1–11.6) the odds of syringe sharing, while those who ‘sometimes’ pooled resources were at 2.8 times (95% CI: 1.1–6.7) the odds, compared to those who ‘never’ pooled resources together. Conclusions Syringe sharing in this population depended on both the availability of clean syringes and social network relationships. Adopting interventions that take into account relationships and behaviours that shape social norms present in networks/dyads would be a necessary prevention strategy alongside the provision of clean syringes.

© 2015 Shah et al. Background: We designed a pragmatic stepped-wedge cluster randomized controlled trial in order to evaluate provider-initiated evaluation of household contacts (HCs) of smear positive tuberculosis (TB) cases within a routine TB program in Lima, Peru. Methods/Design: National TB program (NTP) officers of San Juan de Lurigancho District (Lima, Peru) and university-based researchers jointly designed a pragmatic stepped-wedge cluster randomized trial design in order to evaluate a planned active case finding (ACF) program for all HCs of smear-positive TB cases in 34 district healthcare centres. Randomization of time to intervention initiation was stratified by health centre TB case rate. The ACF intervention included provider-initiated home visits of all new sputum smear positive TB patients in order to evaluate household contacts for active TB. Active TB was diagnosed using symptom screening, sputum screening, chest x-ray and clinical evaluation. Once initiated, ACF was provided by NTP staff and integrated into the routine DOTS TB program activities. Discussion: This study protocol describes the pragmatic stepped-wedge cluster randomized trial of active household contact evaluations within an NTP. The stepped-wedge design met overlapping needs of local TB programmers and researchers to adequately evaluate the large-scale roll out of a new control program in a TB endemic setting. Multiple planning meetings were required to develop the necessary networks and in order to understand the operations, needs and goals of the NTP staff and researchers collaborating on this project. The advantages and challenges of using this study design in practice and within existing routine TB programs in a middle-income country context are discussed. Trial registration: ClinicalTrials.gov NCT02174380. Registered 24 Jun 2014

Surveillance practice is evolving rapidly: globalization of health threats, emergence of infectious diseases, and explosion of easily accessible new technologies. This fluid environment challenges the public health community, but provides it with a fertile environment to innovate and improve its practice. As surveillance is a core function of public health practice, public health practitioners need to be well equipped to achieve this function and address present and future public health challenges. We developed a training course that focused on the practical use of surveillance concepts and principles. We are sharing findings on the development of the course and learner outcomes.

© 2015 Zamudio et al. Background: Tuberculosis (TB) transmission may occur with exposure to an infectious contact often in the setting of household environments, but extra-domiciliary transmission also may happen. We evaluated if using buses and/or minibuses as public transportation was associated with acquiring TB in a high incidence urban district in Lima, Peru. Methods: Newly diagnosed TB cases with no history of previous treatment and community controls were recruited from August to December 2008 for a case-control study. Crude and adjusted odd ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression to study the association between bus/minibus use and TB risk. Results: One hundred forty TB cases and 80 controls were included. The overall use of buses/minibuses was 44.9%; 53.3% (72/135) among cases and 30.4% (24/79) among controls [OR: 3.50, (95% CI: 1.60-7.64)]. In the TB group, 25.7% (36/140) of subjects reported having had a recent household TB contact, and 13% (18/139) reported having had a workplace TB contact; corresponding figures for controls were 3.8% (3/80) and 4.1% (3/73), respectively[OR: 8.88 (95% CI: 2.64-29.92), and OR: 3.89 (95% CI: 1.10-13.70)]. In multivariate analyses, age, household income, household contact and using buses/minibuses to commute to work were independently associated with TB [OR for bus/minibus use: 11.8 (95% CI: 1.45-96.07)]. Conclusions: Bus/minibus use to commute to work is associated with TB risk in this high-incidence, urban population in Lima, Peru. Measures should be implemented to prevent TB transmission through this exposure.

Author(s): Shah, L; Choi, HW; Berrang-Ford, L; Henostroza, G; Krapp, F; Zamudio, C; Heymann, SJ; Kaufman, JS; Ciampi, A; Seas, C; Gotuzzo, E; Brewer, TF | Abstract: SettingPeru reports among the highest multidrug-resistant tuberculosis (MDR-TB) rates in the Americas, with a growing proportion in previously untreated tuberculosis (TB) cases. The identification of clusters of primary MDR-TB compared with drug-susceptible TB (DS-TB) could help prioritize interventions.ObjectiveTo examine the clustering of primary MDR-TB case residences and their proximity to high-risk locations in San Juan de Lurigancho District, Lima, Peru.DesignEnrolled primary MDR-TB and primary DS-TB cases were interviewed and their primary residence was recorded using handheld Global Positioning System devices. Kuldorff's spatial scan statistic was used for cluster detection (SaTScan(TM), v. 9.1.1). Identified clusters were visualized in Quantum Geographic Information Systems software (v1.8.0). The following cluster centers were tested: a health centre with the highest TB and MDR-TB rates (Clinic X), a hospital and two prisons. Using regression analyses, we examined predictors of primary MDR-TB cases.ResultsA statistically significant cluster of primary MDR-TB cases was identified within a 2.29 km radius around Clinic X. Proximity to Clinic X remained a significant predictor of primary MDR-TB in adjusted regression analyses.ConclusionWe identified a hotspot of primary MDR-TB cases around Clinic X in a TB-endemic area. Causes of this clustering require investigation; targeted interventions for this high-risk area should be considered.

Dick Menzies and colleagues report findings from a collaborative, individual patient-level meta-analysis of treatment outcomes among patients with multidrug-resistant tuberculosis., Background Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB. Methods and Findings Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. Study authors were contacted to solicit individual patient data including clinical characteristics, treatment given, and outcomes. Random effects multivariable logistic meta-regression was used to estimate adjusted odds of treatment success. Adequate treatment and outcome data were provided for 9,153 patients with MDR-TB from 32 observational studies. Treatment success, compared to failure/relapse, was associated with use of: later generation quinolones, (adjusted odds ratio [aOR]: 2.5 [95% CI 1.1–6.0]), ofloxacin (aOR: 2.5 [1.6–3.9]), ethionamide or prothionamide (aOR: 1.7 [1.3–2.3]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.3 [1.3–3.9]), and three or more likely effective drugs in the continuation phase (aOR: 2.7 [1.7–4.1]). Similar results were seen for the association of treatment success compared to failure/relapse or death: later generation quinolones, (aOR: 2.7 [1.7–4.3]), ofloxacin (aOR: 2.3 [1.3–3.8]), ethionamide or prothionamide (aOR: 1.7 [1.4–2.1]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.7 [1.9–3.9]), and three or more likely effective drugs in the continuation phase (aOR: 4.5 [3.4–6.0]). Conclusions In this individual patient data meta-analysis of observational data, improved MDR-TB treatment success and survival were associated with use of certain fluoroquinolones, ethionamide, or prothionamide, and greater total number of effective drugs. However, randomized trials are urgently needed to optimize MDR-TB treatment. Please see later in the article for the Editors' Summary., Editors' Summary Background In 2010, 8.8 million people developed tuberculosis—a contagious bacterial infection—and 1.4 million people died from the disease. Mycobacterium tuberculosis, the bacterium that causes tuberculosis, is spread in airborne droplets when people with the disease cough or sneeze and usually infects the lungs (pulmonary tuberculosis). The characteristic symptoms of tuberculosis are a persistent cough, weight loss, and night sweats. Tuberculosis can be cured by taking several powerful antibiotics regularly for at least 6 months. The standard treatment for tuberculosis comprises an initial intensive phase lasting 2 months during which four antibiotics are taken daily followed by a 4-month continuation phase during which two antibiotics are taken. However, global efforts to control tuberculosis are now being thwarted by the emergence of M. tuberculosis strains that are resistant to several antibiotics, including isoniazid and rifampicin, the two most powerful, first-line (standard) anti-tuberculosis drugs. Why Was This Study Done? Although multi-drug resistant tuberculosis (MDR-TB) can be cured using second-line anti-tuberculosis drugs, these are more expensive and more toxic than first-line drugs and optimal treatment regimens for MDR-TB have not been determined. Notably, there have been no randomized controlled trials of treatments for MDR-TB. Such trials, which compare outcomes (cure, treatment failure, relapse, and death) among patients who have been randomly assigned to receive different treatments, are the best way to compare different anti-tuberculosis drug regimens. It is possible, however, to get useful information about the association of various treatments for MDR-TB with outcomes from observational studies using a statistical approach called “individual patient data meta-analysis.” In observational studies, because patients are not randomly assigned to different treatments, differences in outcomes between treatment groups may not be caused by the different drugs they receive but may be due to other differences between the groups. An individual patient data meta-analysis uses statistical methods to combine original patient data from several different studies. Here, the researchers use this approach to investigate the association of specific drugs, numbers of drugs and treatment duration with the clinical outcomes of patients with pulmonary MDR-TB. What Did the Researchers Do and Find? The researchers used three recent systematic reviews (studies that use predefined criteria to identify all the research on a given topic) to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. They obtained individual patient data from the authors of these studies and estimated adjusted odds (chances) of treatment success from the treatment and outcome data of 9,153 patients with MDR-TB provided by 32 centers. The use of later generation quinolones, ofloxacin, and ethionamide/prothionamide as part of multi-drug regimens were all associated with treatment success compared to failure, relapse or death, as were the use of four or more likely effective drugs (based on drug susceptibility testing of mycobacteria isolated from study participants) during the initial intensive treatment phase and the use of three or more likely effective drugs during the continuation phase. The researchers also report that among patients who did not die or stop treatment, the chances of treatment success increased with the duration of the initial treatment phase up to 7.1–8.5 months and with the total duration of treatment up to 18.6–21.5 months. What Do These Findings Mean? These findings suggest that the use of specific drugs, the use of a greater number of effective drugs, and longer treatments may be associated with treatment success and the survival of patients with MDR-TR. However, these findings need to be interpreted with caution because of limitations in this study that may have affected the accuracy of its findings. For example, the researchers did not include all the studies they found through the systematic reviews in their meta-analysis (some authors did not respond to requests for individual patient data, for example), which may have introduced bias. Moreover, because the patients included in the meta-analysis were treated at 32 centers, there were many differences in their management, some of which may have affected the accuracy of the findings. Because of these and other limitations, the researchers note that, although their findings highlight several important questions about the treatment of MDR-TB, randomized controlled trials are urgently needed to determine the optimal treatment for MDR-TB. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001300. The World Health Organization provides information on all aspects of tuberculosis, including MDR-TB; its guidelines for the programmatic management of drug-resistant tuberculosis are available The US Centers for Disease Control and Prevention has information about tuberculosis, including information on the treatment of tuberculosis and on MDR-TB The US National Institute of Allergy and Infectious Diseases also has information on all aspects of tuberculosis, including a drug-resistant tuberculosis visual tour MedlinePlus has links to further information about tuberculosis (in English and Spanish) TB & ME, a collaborative blogging project run by patients being treated for multidrug-resistant tuberculosis and Medecins sans Frontieres, provides information about MDR-TB and patient stories about treatment for MDR-TB The Tuberculosis Survival Project, which aims to raise awareness of tuberculosis and provide support for people with tuberculosis, also provides personal stories about treatment for tuberculosis

Objective Quantify and describe Acanthamoeba keratitis (AK) cases in British Columbia (BC). Design A comparison of annual incidence rates confirms the presence of an outbreak. A case series describes characteristics of the outbreak. Participants All laboratory-confirmed AK cases (persons) in BC (1988–2011; n=68) were included in the incidence rate comparison. Of the 42 cases (persons) between 2003 and 2007, 32 were selected to interview (laboratory confirmed, 2005–2007), and the 23 who completed interviews form the case series. Methods A comparison of standardized annual incidence rates in historic to outbreak periods is performed by z -score test. A telephone interview and descriptive analysis detailing demographics, risk factors, and contact lens (CL) wearing habits was completed for 23 cases. Main Outcome Measures We measure number of laboratory confirmed cases in BC. In addition, risk factors and potential exposures of these cases are reported. Results The annual incidence of AK increased significantly from 0.029 to 0.200 per 100 000 population between historic years (1988–2002) and outbreak years (2003–2007; P = 0.022). The annual incidence of AK has since returned to near historic levels (0.056/100 000 population). The case series identified multiple risk factors, including the use of a specific recalled solution (60.9%), daily soft CL wear (95.7%), all-in-one solutions (95.7%), showering while wearing CL (65.2%), and generally poor CL hygiene. Conclusions A significant increase in annual AK incidence occurred between 2003 and 2007 in BC. After 2007, the incidence of AK returned to near historic levels. The recalled solution was associated with many cases; however, other risk factors were also identified, including being unaware of the recall and poor CL hygiene practices, highlighting the need for improved education about the severity of AK and consequences of improper CL hygiene. Financial Disclosure(s) The authors have no proprietary or commercial interest in any of the materials discussed in this article.

An outbreak of tuberculosis occurred over a 3-year period in a medium-size community in British Columbia, Canada. The results of mycobacterial interspersed repetitive unit-variable-number tandem-repeat (MIRU-VNTR) genotyping suggested the outbreak was clonal. Traditional contact tracing did not identify a source. We used whole-genome sequencing and social-network analysis in an effort to describe the outbreak dynamics at a higher resolution.We sequenced the complete genomes of 32 Mycobacterium tuberculosis outbreak isolates and 4 historical isolates (from the same region but sampled before the outbreak) with matching genotypes, using short-read sequencing. Epidemiologic and genomic data were overlaid on a social network constructed by means of interviews with patients to determine the origins and transmission dynamics of the outbreak.Whole-genome data revealed two genetically distinct lineages of M. tuberculosis with identical MIRU-VNTR genotypes, suggesting two concomitant outbreaks. Integration of social-network and phylogenetic analyses revealed several transmission events, including those involving "superspreaders." Both lineages descended from a common ancestor and had been detected in the community before the outbreak, suggesting a social, rather than genetic, trigger. Further epidemiologic investigation revealed that the onset of the outbreak coincided with a recorded increase in crack cocaine use in the community.Through integration of large-scale bacterial whole-genome sequencing and social-network analysis, we show that a socioenvironmental factor--most likely increased crack cocaine use--triggered the simultaneous expansion of two extant lineages of M. tuberculosis that was sustained by key members of a high-risk social network. Genotyping and contact tracing alone did not capture the true dynamics of the outbreak. (Funded by Genome British Columbia and others.).

Author(s): Brewer, Timothy F; Choi, Howard W; Seas, Carlos; Krapp, Fiorella; Zamudio, Carlos; Shah, Lena; Ciampi, Antonio; Heymann, S Jody; Gotuzzo, Eduardo | Abstract: BackgroundMultiple drug-resistance in new tuberculosis (TB) cases accounts for the majority of all multiple drug-resistant TB (MDR-TB) worldwide. Effective control requires determining which new TB patients should be tested for MDR disease, yet the effectiveness of global screening recommendations of high-risk groups is unknown.MethodsSixty MDR-TB cases with no history of previous TB treatment, 80 drug-sensitive TB and 80 community-based controls were recruited in Lima, Peru between August and December, 2008 to investigate whether recommended screening practices identify individuals presenting with MDR-TB. Odd ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression to study the association of potential risk factors with case/control variables.ResultsMDR-TB cases did not differ from drug-sensitive TB and community controls in rates of human immunodeficiency virus infection, reported hospital or prison visits in the 3 years prior to diagnosis. MDR-TB cases were more likely than drug-sensitive TB controls to have had a recent MDR-TB household contact (OR 4.66, (95% CI 1.56-13.87)); however, only 15 cases (28.3%) reported this exposure. In multivariate modeling, recent TB household contact, but not contact with an MDR-TB case, remained predictive of MDR-TB, OR 7.47, (95% CI 1.91-29.3). Living with a partner rather than parents was associated with a lower risk of MDR-TB, OR 0.15, (95% CI 0.04-0.51).ConclusionTargeted drug susceptibility testing (DST) linked to reported MDR-TB contact or other high-risk exposures does not identify the majority of new TB cases with MDR disease in Lima where it is endemic. All new TB cases should be screened with DST to identify MDR patients. These findings are likely applicable to other regions with endemic MDR-TB.

An association between leukoencephalopathy, a disease of the white matter of the brain, and smoking heroin is well recognized. This paper describes 27 cases of leukoencephalopathy identified in two cities in British Columbia, Canada 2001-2006; the largest number of geographically and temporally defined reported cases in North America. Twenty cases of leukoencephalopathy were identified in and around Vancouver with onset dates December 2001 to July 2003; seven further cases were identified in Victoria September 2005-August 2006. Twenty (74%) of all cases were male, two couples were reported and eleven cases (55%) had Asian ethnicity. One case reported smoking heroin on a single occasion and developed mild symptoms; all other cases were hospitalized. Thirteen (48%) cases died; all had smoked heroin for a minimum of 3 years. Testing of one available heroin sample identified no substance other than common cutting agents. Although a specific etiology was not identified our study supports the theory of an intermittent exposure to a toxic agent added to the heroin or a combustion by-product. It also suggests a dose response effect rather than genetic predisposition. Collaboration with public health, health professionals, law enforcement and persons who use illegal drugs, will facilitate the early identification of cases to enable timely and complete follow-up including obtaining samples. Testing of implicated heroin samples may allow identification of the contaminant and therefore prevent further cases. It is therefore important to ensure key stakeholders are aware of our findings.

Objectives. We used cluster analysis to subdivide a population of injection drug users and identify previously unknown behavioral heterogeneity within that population. Methods. We applied cluster analysis techniques to data collected in a cross-sectional survey of injection drug users in Winnipeg, Manitoba. The clustering variables we used were based on receptive syringe sharing, ethnicity, and types of drugs injected. Results. Seven clusters were identified for both male and female injection drug users. Some relationships previously revealed in our study setting, such as the known relationship between Talwin (pentazocine) and Ritalin (methylphenidate) use, injection in hotels, and hepatitis C virus prevalence, were confirmed through our cluster analysis approach. Also, relationships between drug use and infection risk not previously observed in our study setting were identified, an example being a cluster of female crystal methamphetamine users who exhibited high-risk behaviors but an absence or low prevalence of blood-borne pathogens. Conclusions. Cluster analysis was useful in both confirming relationships previously identified and identifying new ones relevant to public health research and interventions.

Background Previous studies have used social network variables to improve our understanding of HIV transmission. Similar analytic approaches have not been undertaken for hepatitis C (HCV) or B (HBV), nor used to conduct comparative studies on these pathogens within a single setting. Methods A cross-sectional survey consisting of a questionnaire and blood sample was conducted on injection drug users in Winnipeg between December 2003 and September 2004. Logistic regression analyses were used to correlate respondent and personal network data with HCV, HBV and HIV prevalence. Results At the multivariate level, pathogen prevalence was correlated with both respondent and IDU risk network variables. Pathogen transmission was associated with several distinct types of high-risk networks formed around specific venues (shooting galleries, hotels) or within users who are linked by their drug use preferences. Smaller, isolated pockets of IDUs also appear to exist within the larger population where behavioural patterns pose a lesser risk, unless or until, a given pathogen enters those networks. Conclusion The findings suggest that consideration of both respondent and personal network variables can assist in understanding the transmission patterns of HCV, HBV, and HIV. It is important to assess these effects for multiple pathogens within one setting as the associations identified and the direction of those associations can differ between pathogens.

Using social network analysis, we investigated how communal meeting places can link injection drug user (IDU) populations and create opportunities for the transmission of bloodborne pathogens. In our locale, specific hotels played a key role in the injection drug scene. Within this hotel network some IDU injected at only one hotel while others injected at multiple hotels; this latter group potentially acted as spatial bridges linking relatively distinct hotel networks. Pathogen prevalence showed a gradation with the highest prevalence occurring at the centre of the network. Consistent with pathogen prevalence, people most central to the network were more likely to engage in risky injection practices. Incorporating geographic place into analyses involving IDU can contribute to an understanding of pathogen transmission patterns in an area and assist public health efforts to develop targeted intervention programs.