Objectives We determined the performance of a sensor array (an electronic nose) made of 8 metalloporphyrins coated quartz microbalances sensors for the diagnosis and prognosis of pulmonary tuberculosis (TB) using exhaled breath samples. Methods TB cases and healthy controls were prospectively enrolled. Signals from volatile organic compounds (VOCs) in breath samples were measured at days 0, 2, 7, 14, and 30 of TB therapy and correlated with clinical and microbiological measurements. Results 51 pulmonary TB cases and 20 healthy HIV-uninfected controls were enrolled in the study. 31 (61%) of the 51 pulmonary TB cases were coinfected with HIV. At day 0 (before TB treatment initiation) the sensitivity of our device was estimated at 94.1% (95% confidence interval [CI], 83.8-98.8%) and specificity was 90.0% (95% CI, 68.3-98.8%) for distinguishing TB cases from controls. Time-dependent changes in the breath signals were identified as time on TB treatment progressed. Time-dependent signal changes were more pronounced among HIV-uninfected patients. Conclusion The identification of VOCs signals in breath samples using a sensor array achieved high sensitivity and specificity for the diagnosis of TB and allowed following signal changes during TB treatment.

Background: Dolutegravir (DTG) has recently been recommended as a preferred first-line regimen for the treatment of new and treatment experienced HIV infected patients. However, potential drug interactions between DTG and rifampicin remain a clinical and public health concern. Methods:We analyzed HIV and TB treatment outcomes of HIV-infected patients concomitantly receiving rifampicin-and DTG-based regimens under programmatic conditions in Botswana. The outcomes of interest were successful TB treatment and viral load suppression. We used multivariable logistic models to determine predictors for each outcome of interest.Results: A total of 1,225 patients were included in the analysis to evaluate predictors of successful TB outcome. Among patients on DTG and non-DTG regimens, 90.9% and 88.3% achieved favorable TB treatment outcomes, respectively. Of those who received DTG-based regimen; 44% received once-daily dosing and 53% twice-daily dosing. We found that DTG was associated with favorable TB treatment outcome (adjusted odds ratio [aOR] = 1.56; 95% confidence interval [CI] = 1.06, 2.31), after adjusting for age, gender, and CD4 cell counts. High rates of viral load suppression were found across all ART regimen categories (>92% for all). We did not find an independent association between DTG and viral suppression after adjustment of other covariates Conclusions:The use of DTG-based ART regimens in patients coinfected with TB and HIV lead to favorable TB and HIV treatment outcomes, comparable to those achieved with alternative ART regimens. Our results provide reassurance to TB and HIV programs about the overall

The association between volatile compounds (VCs) and microorganisms, as demonstrated by several studies, may offer the ground for a rapid identification of pathogens. To this regard, chemical sensors are a key enabling technology for the exploitation of this opportunity. In this study, we investigated the performance of an array of porphyrin-coated quartz microbalance gas sensors in the identification of a panel of 12 bacteria and fungi. The porphyrins were metal complexes and the free base of a functionalized tetraphenylporphyrin. Our results show that the sensor array distinguishes the VC patterns produced by microorganisms in vitro. Besides being individually identified, bacteria are also sorted into Gram-positive and Gram-negative.

During 2012–2015, 10 of 24 patients infected with matching genotypes of Mycobacterium tuberculosis received care at the same hospital in Gaborone, Botswana. Nosocomial transmission was initially suspected, but we discovered plausible sites of community transmission for 20 (95%) of 21 interviewed patients. Active case-finding at these sites could halt ongoing transmission.

T uberculosis (TB) is a global health emergency (1). The World Health Organization (WHO) End TB Strategy proposes a 90% reduction in TB incidence and 95% reduction in TB deaths by 2035 compared with 2015 (2). To reach this target, effective interventions are needed to interrupt transmission of Mycobacterium tuberculosis. Contact investigations help prevent M. tuberculosis transmission by identifying and treating persons in close contact with persons with TB disease (3). WHO recommends tuberculosis preventive treatment (TPT) for household members of bacteriologically confirmed pulmonary TB patients to prevent progression to active TB disease (4). Contact investigations are a major tenet of the End TB Strategy but remain ineffective for various reasons (2,5,6). Many TB programs in high-burden areas limit contact investigations to household members (6). Recent studies suggest that such restrictions might miss key exposures in the community (7,8). Targeted, population-based, geographic TB screening is a potential approach to augment contact investigations (9-11) but is resource and time intensive and rarely includes TPT (11,12). We used population-based, molecular epidemiologic data from Botswana to investigate potential use of a neighbor-based approach for contact investigations. The Study During August 2012-April 2016, we enrolled participants treated for TB disease at 30 healthcare facilities in Botswana for a prospective molecular epidemiologic study, Kopanyo. In brief, Kopanyo was designed to explore potential clinical, demographic, geographic, social relationships, and M. tuberculosis genotypic characteristics among persons with TB (13,14). We interviewed enrolled patients by using a standardized questionnaire and abstracted clinical data from medical records (13). We collected and processed sputum samples for culture and genotyped isolates with 24-locus mycobacterial interspersed repetitive unitsvariable-number tandem-repeats by using standard methods (15). We geocoded and validated the primary residence of each enrolled patient (Appendix, https:// wwwnc.cdc.gov/EID/article/26/5/19-1568-App1. pdf). We excluded patients without a validated primary residential geocode and those who resided in locations outside of the study area. The study area included all 11 neighborhoods in Gaborone and 3 villages in the Ghanzi District: Ghanzi, D'Kar, and Kuke. We defined index patients as the first culture-positive pulmonary TB patient identified and started on treatment in a household. We used residence plots to identify nearest neighbors, which we defined as those who lived immediately next door, and next-nearest neighbors, which we defined as those who lived 2 doors away (Figure). We enumerated all subsequent TB cases identified by bacteriologic confirmation and clinical diagnosis within the index home, nearest-neighbor homes, and next-nearest neighbor homes. We defined

Objective: Healthcare facilities are a well-known high-risk environment for transmission of M. tuberculosis, the etiologic agent of tuberculosis (TB) disease. However, the link between M. tuberculosis transmission in healthcare facilities and its role in the general TB epidemic is unknown. We estimated the proportion of overall TB transmission in the general population attributable to healthcare facilities. Methods: We combined data from a prospective, population-based molecular epidemiologic study with a universal electronic medical record (EMR) covering all healthcare facilities in Botswana to identify biologically plausible transmission events occurring at the healthcare facility. Patients with M. tuberculosis isolates of the same genotype visiting the same facility concurrently were considered an overlapping event. We then used TB diagnosis and treatment data to categorize overlapping events into biologically plausible definitions. We calculated the proportion of overall TB cases in the cohort that could be attributable to healthcare facilities. Results: In total, 1,881 participants had TB genotypic and EMR data suitable for analysis, resulting in 46,853 clinical encounters at 338 healthcare facilities. We identified 326 unique overlapping events involving 370 individual patients; 91 (5%) had biologic plausibility for transmission occurring at a healthcare facility. A sensitivity analysis estimated that 3%–8% of transmission may be attributable to healthcare facilities. Conclusions: Although effective interventions are critical in reducing individual risk for healthcare workers and patients at healthcare facilities, our findings suggest that development of targeted interventions aimed at community transmission may have a larger impact in reducing TB.

Identifying host factors that influence infectious disease transmission is an important step toward developing interventions to reduce disease incidence. Recent advances in methods for reconstructing infectious disease transmission events using pathogen genomic and epidemiological data open the door for investigation of host factors that affect onward transmission. While most transmission reconstruction methods are designed to work with densely sampled outbreaks, these methods are making their way into surveillance studies, where the fraction of sampled cases with sequenced pathogens could be relatively low. Surveillance studies that use transmission event reconstruction then use the reconstructed events as response variables (i.e., infection source status of each sampled case) and use host characteristics as predictors (e.g., presence of HIV infection) in regression models. We use simulations to study estimation of the effect of a host factor on probability of being an infection source via this multi-step inferential procedure. Using TransPhylo - a widely-used method for Bayesian estimation of infectious disease transmission events - and logistic regression, we find that low sensitivity of identifying infection sources leads to dilution of the signal, biasing logistic regression coefficients toward zero. We show that increasing the proportion of sampled cases improves sensitivity and estimation of logistic regression coefficients. Application of these approaches to real world data from a population-based TB study in Botswana fails to detect an association between HIV infection and probability of being a TB infection source. We conclude that application of a pipeline, where one first uses TransPhylo and sparsely sampled surveillance data to infer transmission events and then estimates effects of host characteristics on probabilities of these events, should be accompanied by a realistic simulation study to better understand biases stemming from imprecise transmission event inference.

Committee (GHIC) is an inter-academic committee of faculty and students. It is the premier point of engagement on global health issues. The GHIC is building a student-to-student social media campaign to provide educational messages to students in the diaspora and the countries affected by Ebola. Students manage the social media network with faculty oversight. The network collaborates with key stakeholder organizations to identify and propagate important public health information. Program Period: From crises through recovery phases of the Ebola epidemic. Why: The program looks to capitalize on the social media capabilities of students as a methodology to disseminate key information and form support groups locally and globally. Aim: To disseminate information regarding Ebola from crises to recovery phase in readily understood messages, in the appropriate language or signage, at the appropriate educational level, both locally and globally. Structure/Method/Design: Desired Outcomes: To inform students in effected areas about Ebola and to inform and support them through recovery Participants: An inter-professional team of Jefferson students and faculty volunteered to develop the outreach and social media campaign. Hesperian Foundation, famous for health resources such as Where there is No Doctor, is assisting in creating the messages. We are collaborating with nonprofit and faith-based organizations and ambassadors from Sierra Leone and Guinea. Sustainability: The plan is to address each phase of the emergency from crisis to recovery with appropriately targeted messages.Outcomes & Evaluation: To date: The GHIC coordinated a symposium with key stakeholders, including ambassadors from three West African countries, that was broadcast to universities in West Africa. The GHIC developed an inter-professional team of student volunteers and faculty advisors who identified key stakeholders at nonprofit and faithbased organizations both in the diaspora and effected countries to help build the social media campaign. The GHIC continues to act as a liaison with key embassies in effected countries and has begun collaborating with the Hesperian Foundation to help craft messages that can be translated and/or disseminated in a myriad of languages through a variety of social media. M & E: The GHIC will monitor the number of messages and the number of times each message is propagated as an indicator of success. Going Forward: Ongoing challenges? Maintaining a constant stream of effective educational messages using pragmatic social media venues in a multitude of languages from crisis to recovery phases with a student volunteer team that will change with the semesters. Unmet goals? Future program activities change? Future program activities will change as the current Ebola crises moves to recovery.