Browsing by Author "Ayakaka, Irene"
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Item Anybody out there? A process evaluation of SMS sent to household TB contacts in Kampala, Uganda(ResearchGate, 2018) Amanda, J. Meyer; Babirye, Diana; Armstrong-Hough, Mari; Mark, David; Ayakaka, Irene; Katamba, Achilles; Haberer, Jessica E.; Davis, J. LucianPrevious studies have reported inconsistent effectiveness of SMS (short-messaging services) for improving health outcomes, but few have examined to what degree the quality, or “fidelity”, of implementation may explain study results. Objective: We sought to determine the fidelity of a one-time SMS intervention to promote uptake of TB evaluation services among household contacts of index TB patients. Methods: From February to June 2017, we nested a process evaluation of SMS delivery within the intervention arm of a randomized controlled trial of TB contact investigation in Kampala, Uganda. Because mobile service providers in Uganda do not provide delivery confirmations, we asked household TB contacts to confirm receipt of a one-time TB-related SMS by sending an SMS reply via a toll-free “short code.” Two weeks later, a research officer followed-up by telephone to confirm receipt of the one-time SMS and administer a survey. We considered participants lost-to-follow-up after three unsuccessful call attempts on three separate days over a one-week period. Results: Of 206 consecutive household contacts, 119 had an SMS initiated from the server. Thirty-nine (33%) were children aged 5-14, including 24 (20%) girls and 15 (13%) boys. Twenty-one (18%) were adolescents or young adults, including 14 (12%) young women and seven (6%) young men. Fifty-nine (50%) were adults, including 31 (26%) women and 28 (24%) men. Of 107 (90%) participants for whom we were able to ascertain SMS receipt status, 67% (n=72) confirmed SMS receipt, including 22% (n=24) by reply SMS and 45% (n=48) during the follow-up telephone survey. There were no significant clinical or demographic differences between those who did and did not report receiving the SMS message. 52% (n=56) reported ever reading the SMS. The cumulative likelihood of an SMS reaching its target and being read and retained by a participant was 19%. Conclusions: The fidelity of a one-time SMS intervention to increase uptake of household TB contact investigation and linkage to care was extremely low, a fact only discoverable through a detailed process evaluation. Our findings suggest the need for systematic process monitoring and reporting of implementation fidelity in both research studies and programmatic interventions employing mobile communications to improve health.Item Assessing the Quality of Tuberculosis Evaluation for Children with Prolonged Cough Presenting to Routine Community Health Care Settings in Rural Uganda(PloS one, 2014) Marquez, Carina; Davis, J. Lucian; Katamba, Achilles; Haguma, Priscilla; Ochomi, Emmanuel; Ayakaka, Irene; Chamie, Gabriel; Dorsey, Grant; Kamya, Moses R.; Charlebois, Edwin; Havlir, Diane V.; Cattamanchi, AdithyaImproving childhood tuberculosis (TB) evaluation and care is a global priority, but data on performance at community health centers in TB endemic regions are sparse. Objective: To describe the current practices and quality of TB evaluation for children with cough $2 weeks’ duration presenting to community health centers in Uganda. Methods: Cross-sectional analysis of children (,15 years) receiving care at five Level IV community health centers in rural Uganda for any reason between 2009–2012. Quality of TB care was assessed using indicators derived from the International Standards of Tuberculosis Care (ISTC). Results: From 2009–2012, 1713 of 187,601 (0.9%, 95% CI: 0.4–1.4%) children presenting to community health centers had cough $ 2 weeks’ duration. Of those children, only 299 (17.5%, 95% CI: 15.7–19.3%) were referred for sputum microscopy, but 251 (84%, 95% CI: 79.8–88.1%) completed sputum examination if referred. The yield of sputum microscopy was only 3.6% (95% CI: 1.3–5.9%), and only 55.6% (95% CI: 21.2–86.3%) of children with acid-fast bacilli positive sputum were started on treatment. Children under age 5 were less likely to be referred for sputum examination and to receive care in accordance with ISTC. The proportion of children evaluated in accordance with ISTC increased over time (4.6% in 2009 to 27.9% in 2012, p = 0.03), though this did not result in increased case-detection. Conclusion: The quality of TB evaluation was poor for children with cough $2 weeks’ duration presenting for health care. Referrals for sputum smear microscopy and linkage to TB treatment were key gaps in the TB evaluation process, especially for children under the age of five.Item A cost analysis of implementing mobile health facilitated tuberculosis contact investigation in a low-income setting(PLoS ONE, 2022) Turimumahoro, Patricia; Tucker, Austin; Gupta, Amanda J.; Tampi, Radhika P.; Babirye, Diana; Ochom, Emmanuel; Ggita, Joseph M.; Ayakaka, Irene; Sohn, Hojoon; Katamba, Achilles; Dowdy, David; Davis, J. LucianMobile health (mHealth) applications may improve timely access to health services and improve patient-provider communication, but the upfront costs of implementation may be prohibitive, especially in resource-limited settings. Methods We measured the costs of developing and implementing an mHealth-facilitated, homebased strategy for tuberculosis (TB) contact investigation in Kampala, Uganda, between February 2014 and July 2017. We compared routine implementation involving community health workers (CHWs) screening and referring household contacts to clinics for TB evaluation to home-based HIV testing and sputum collection and transport with test results delivered by automated short messaging services (SMS). We carried out key informant interviews with CHWs and asked them to complete time-and-motion surveys. We estimated program costs from the perspective of the Ugandan health system, using top-down and bottom- up (components-based) approaches. We estimated total costs per contact investigated and per TB-positive contact identified in 2018 US dollars, one and five years after program implementation. Results The total top-down cost was $472,327, including $358,504 (76%) for program development and $108,584 (24%) for program implementation. This corresponded to $320-$348 per household contact investigated and $8,873-$9,652 per contact diagnosed with active TB over a 5-year period. CHW time was spent primarily evaluating household contacts who returned to the clinic for evaluation (median 30 minutes per contact investigated, interquartile range [IQR]: 30–70), collecting sputum samples (median 29 minutes, IQR: 25–30) and offering HIV testing services (median 28 minutes, IQR: 17–43). Cost estimates were sensitive to infrastructural capacity needs, program reach, and the epidemiological yield of contact investigation. Conclusion Over 75% of all costs of the mHealth-facilitated TB contact investigation strategy were dedicated to establishing mHealth infrastructure and capacity. Implementing the mHealth strategy at scale and maintaining it over a longer time horizon could help decrease development costs as a proportion of total costs.Item Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV(PLoS ONE, 2018) Farr, Katherine; Ravindran, Resmi; Strnad, Luke; Chang, Emily; Chaisson, Lelia H.; Yoon, Christina; Worodria, William; Andama, Alfred; Ayakaka, Irene; Bbosa Nalwanga, Priscilla; Byanyima, Patrick; Kalema, Nelson; Kaswabuli, Sylvia; Katagira, Winceslaus; Denise Aman, Kyomugisha; Musisi, Emmanuel; Tumwine, Nuwagaba Wallen; Sanyu, Ingvar; Ssebunya, Robert; Davis, J. Lucian; Huang, Laurence; Khan, Imran H.; Cattamanchi, AdithyaApproaches to screening for active tuberculosis (TB) among people living with HIV are inadequate, leading to missed diagnoses and poor implementation of preventive therapy. Methods Consecutive HIV-infected adults hospitalized at Mulago Hospital (Kampala, Uganda) between June 2011 and July 2013 with a cough � 2 weeks were enrolled. Patients underwent extensive evaluation for pulmonary TB. Concentrations of 43 cytokines/chemokines were measured at the same time point as C-reactive protein (CRP) in banked plasma samples using commercially-available multiplex kits. Advanced classification algorithms were used to rank cytokines/chemokines for their ability to identify TB, and to model the specificity of the top-ranked cytokines/chemokines individually and in combination with sensitivity constrained to � 90% as recommended for TB screening. Results The median plasma level of 5 biomarkers (IL-6, INF-γ, MIG, CRP, IL-18) was significantly different between patients with and without TB. With sensitivity constrained to 90%, all had low specificity with IL-6 showing the highest specificity (44%; 95% CI 37.4–49.5). Biomarker panels were found to be more valuable than any biomarker alone. A panel combining IFN-γ and IL-6 had the highest specificity (50%; 95% CI 46.7–53.3). Sensitivity remained high (>85%) for all panels among sputum smear-negative TB patients. Conclusions Direct measurement of unstimulated plasma cytokines/chemokines in peripheral blood is a promising approach to TB screening. Cytokine/chemokine panels retained high sensitivity for smear-negative TB and achieved improved specificity compared to individual cytokines/ chemokines. These markers should be further evaluated in outpatient settings where most TB screening occurs and where other illnesses associated with systematic inflammation are less common.Item Drop-out from the tuberculosis contact investigation cascade in a routine public health setting in urban Uganda: A prospective, multi-center study(PLoS ONE, 2017) Armstrong-Hough, Mari; Turimumahoro, Patricia; Meyer, Amanda J.; Ochom, Emmanuel; Babirye, Diana; Ayakaka, Irene; Mark, David; Ggita, Joseph; Cattamanchi, Adithya; Dowdy, David; Mugabe, Frank; Fair, Elizabeth; Haberer, Jessica E.; Katamba, Achilles; Davis, J. LucianSeven public tuberculosis (TB) units in Kampala, Uganda, where Uganda's national TB program recently introduced household contact investigation, as recommended by 2012 guidelines from WHO. Objective To apply a cascade analysis to implementation of household contact investigation in a programmatic setting. Design Prospective, multi-center observational study. Methods We constructed a cascade for household contact investigation to describe the proportions of: 1) index patient households recruited; 2) index patient households visited; 3) contacts screened for TB; and 4) contacts completing evaluation for, and diagnosed with, active TB. Results 338 (33%) of 1022 consecutive index TB patients were eligible for contact investigation. Lay health workers scheduled home visits for 207 (61%) index patients and completed 104 (50%). Among 287 eligible contacts, they screened 256 (89%) for symptoms or risk factors for TB. 131 (51%) had an indication for further TB evaluation. These included 59 (45%) with symptoms alone, 58 (44%) children <5, and 14 (11%) with HIV. Among 131 contacts found to be symptomatic or at risk, 26 (20%) contacts completed evaluation, including five (19%) diagnosed with and treated for active TB, for an overall yield of 1.7%. The cumulative conditional probability of completing the entire cascade was 5%. Conclusion Major opportunities exist for improving the effectiveness and yield of TB contact investigation by increasing the proportion of index households completing screening visits by lay health workers and the proportion of at-risk contacts completing TB evaluation.Item Effectiveness of the standard WHO recommended retreatment regimen (Category II) for tuberculosis in Kampala, Uganda(PLoS medicine, 2011) Jones-López, Edward C.; Ayakaka, Irene; Levin, Jonathan; Reilly, Nancy; Mumbowa, Francis; Dryden-Peterson, Scott; Nyakoojo, Grace; Fennelly, Kevin; Temple, Beth; Nakubulwa, Susan; Joloba, Moses L.; Okwera, Alphonse; Eisenach, Kathleen D.; McNerney, Ruth; Elliott, Alison M.; Ellner, Jerrold J.; Smith, Peter G.; Mugerwa, Roy D.Each year, 10%–20% of patients with tuberculosis (TB) in low- and middle-income countries present with previously treated TB and are empirically started on a World Health Organization (WHO)-recommended standardized retreatment regimen. The effectiveness of this retreatment regimen has not been systematically evaluated. Methods and Findings: From July 2003 to January 2007, we enrolled smear-positive, pulmonary TB patients into a prospective cohort to study treatment outcomes and mortality during and after treatment with the standardized retreatment regimen. Median time of follow-up was 21 months (interquartile range 12–33 months). A total of 29/148 (20%) HIV-uninfected and 37/140 (26%) HIV-infected patients had an unsuccessful treatment outcome. In a multiple logistic regression analysis to adjust for confounding, factors associated with an unsuccessful treatment outcome were poor adherence (adjusted odds ratio [aOR] associated with missing half or more of scheduled doses 2.39; 95% confidence interval (CI) 1.10–5.22), HIV infection (2.16; 1.01–4.61), age (aOR for 10-year increase 1.59; 1.13–2.25), and duration of TB symptoms (aOR for 1-month increase 1.12; 1.04–1.20). All patients with multidrug-resistant TB had an unsuccessful treatment outcome. HIV-infected individuals were more likely to die than HIV-uninfected individuals (p,0.0001). Multidrug-resistant TB at enrolment was the only common risk factor for death during follow-up for both HIV-infected (adjusted hazard ratio [aHR] 17.9; 6.0–53.4) and HIV-uninfected (14.7; 4.1–52.2) individuals. Other risk factors for death during follow-up among HIVinfected patients were CD4,50 cells/ml and no antiretroviral treatment (aHR 7.4, compared to patients with CD4$200; 3.0– 18.8) and Karnofsky score ,70 (2.1; 1.1–4.1); and among HIV-uninfected patients were poor adherence (missing half or more of doses) (3.5; 1.1–10.6) and duration of TB symptoms (aHR for a 1-month increase 1.9; 1.0–3.5). Conclusions: The recommended regimen for retreatment TB in Uganda yields an unacceptable proportion of unsuccessful outcomes. There is a need to evaluate new treatment strategies in these patients.Item Experiences and intentions of Ugandan household tuberculosis contacts receiving test results via text message: an exploratory study(BMC public health, 2020) Ggita, Joseph M.; Katahoire, Anne; Meyer, Amanda J.; Nansubuga, Elizabeth; Nalugwa, Talemwa; Turimumahoro, Patricia; Ochom, Emmanuel; Ayakaka, Irene; Haberer, Jessica E.; Katamba, Achilles; Armstrong-Hough, Mari; Davis, J. LucianThe World Health Organization (WHO) recommends household contact investigation for tuberculosis (TB) in high-burden countries. However, household contacts who complete evaluation for TB during contact investigation may have difficulty accessing their test results. Use of automated short-messaging services (SMS) to deliver test results could improve TB status awareness and linkage to care. We sought to explore how household contacts experience test results delivered via SMS, and how these experiences influence follow-up intentions. Methods: We conducted semi-structured interviews with household contacts who participated in a randomized controlled trial evaluating home sputum collection and delivery of TB results via SMS (Pan-African Clinical Trials Registry #201509000877140). We asked about feelings, beliefs, decisions, and behaviors in response to the SMS results. We analyzed the content and emerging themes in relation to the Theory of Planned Behavior. Results: We interviewed and achieved thematic saturation with ten household contacts. Nine received TB-negative results and one a TB-positive result. Household contacts reported relief upon receiving SMS confirming their TB status, but also said they lacked confidence in the results delivered by SMS. Some worried that negative results were incorrect until they spoke to a lay health worker (LHW). Household contacts said their long-term intentions to request help or seek care were influenced by perceived consequences of not observing the LHW’s instructions related to the SMS and follow-up procedures; beliefs about the curability of TB; anticipated support from LHWs; and perceived barriers to responding to an SMS request for further evaluation. Conclusion: Household contacts experienced relief when they received results. However, they were less confident about results delivered via SMS than results delivered by LHWs. Delivery of results by SMS should complement continued interaction with LHWs, not replace them.Item Feasibility of a short message service (SMS) intervention to deliver tuberculosis testing results in peri-urban and rural Uganda(Journal of clinical tuberculosis and other mycobacterial diseases, 2019) Babirye, Diana; Shete, Priya B.; Farr, Katherine; Nalugwa, Talemwa; Ojok, Christopher; Nantale, Mariam; Oyuku, Denis; Ayakaka, Irene; Katamba, Achilles; Davis, J. Lucian; Nadunga, Diana; Joloba, Moses; Moore, David; Cattamanchi, AdithyaPre-treatment loss to follow-up is common for patients diagnosed with tuberculosis (TB) in highburden countries. Delivering test results by Short-Messaging-Service (SMS) is increasingly being considered as a solution, but there is limited information about its feasibility as a public health tool in low resourced settings. Objective: We sought to assess the feasibility of utilizing SMS technology to deliver TB test results during routine TB diagnostic evaluation in Uganda. Methods: We conducted a single arm interventional pilot study at four community health centers in Uganda that referred sputum samples to a district hospital for GeneXpert-MTB/RIF (Xpert) testing (Cepheid, USA). Using existing GxAlert-software (SystemOne,USA), we set up an automated SMS platform to send Xpert results to patients and referring health centers. We assessed each step of the SMS delivery cascade for consecutive patients who presented to these four community health centers between December 2015 and March 2016 and underwent Xpert testing. Results: Of 233 patients enrolled, 161 (69%) had phone numbers recorded on individual Xpert referral forms. Phone numbers were entered into Xpert device software in the correct format for 152 (94%) patients. GxAlertsoftware generated an automated SMS reporting Xpert results for 151 (99%) patients and delivered it successfully to mobile phone service providers for 145/151 (96%). Of the 123 patients reached by phone to determine receipt of test results, 114 (93%) confirmed SMS receipt. SMS-based delivery of Xpert results was verified for 114/233 (49%) patients overall. In contrast, phone calls to health centers confirmed that health centers received messages for 222/233 (95%) patients. Conclusion: Reporting Xpert results via automated SMS is technically feasible and results in approximately half of patients receiving their test results immediately. Additional research should be done to address process inefficiencies in order to maximize impact of this technology and link its successful utilization to improved patient outcomes.Item Feasibility, acceptability, and adoption of fingerprint scanning during contact investigation for tuberculosis in Kampala, Uganda: A parallel-convergent, mixed-methods analysis(PeerJ Preprints, 2018) White, Elizabeth B.; Meyer, Amanda J.; Ggita, Joseph M.; Babirye, Diana; Mark, David; Ayakaka, Irene; Haberer, Jessica E.; Katamba, Achilles; Armstrong-Hough, Mari; Davis, J. LucianIn resource-constrained settings, challenges with unique patient identification may limit continuity of care, monitoring and evaluation, and data integrity. Biometrics offer an appealing but understudied potential solution. Methods We conducted a mixed-methods study to understand feasibility, acceptability, and adoption of digital fingerprinting for patient identification in a study of household TB contact investigation in Kampala, Uganda. We tested associations between demographic, clinical, and temporal characteristics and failure to capture a digital fingerprint. We used generalized estimating equations and a robust covariance estimator to account for clustering. We evaluated clustering of outcomes by household and community health worker by calculating intra-class correlation coefficients. To understand determinants of intended and actual use of fingerprinting technology, we conducted fifteen in-depth interviews with community health workers and applied a widely used conceptual framework, the Technology Acceptance Model 2. Results Digital fingerprints were captured in 74% of participants, with extensive clustering by household (ICC = 0.99) arising from hardware (XX%) and software (XX%) failures. Clinical and demographic characteristics were not significantly associated with fingerprint capture. Community health workers successfully fingerprinted all contacts in 70% of households, with modest clustering of outcomes by CHW (ICC = 0.18). Fingerprinting success at the household level declined over time (Spearman’s rho = 0.30, P < 0.001). In interviews, CHWs reported that fingerprinting non-capture events lowered their own perception of the quality of the technology, threatened their social image, and made the technology more difficult to use. Conclusions We found digital fingerprinting to be feasible and acceptable for indvidual identification, but problems implementing the hardware and software led to a high failure rate. Although CHWs found fingerprinting to be acceptable in principle, their intention to use the technology was tempered by perceptions that it was inconsistent and of questionable value. We emphasize the need for routine process evaluation of biometrics and other digital technologies during implementation in resource-constrained settings.Item “Give Me Some Time”: Facilitators of and Barriers to Uptake of Home-based HIV Testing During Household Contact Investigation for Tuberculosis in Kampala, Uganda(Journal of acquired immune deficiency syndromes, 2018) Armstrong-Hough, Mari; Ggita, Joseph; Ayakaka, Irene; Dowdy, David; Cattamanchi, Adithya; Haberer, Jessica E.; Katamba, Achilles; Davis, J. LucianIntegrating home-based HIV counseling and testing (HCT) with tuberculosis (TB) evaluation could improve uptake of HIV testing among household contacts of patients with active TB. We sought to identify the facilitators of and barriers to HCT during household contact investigation for TB in Kampala, Uganda. Methods—We nested semi-structured interviews with 28 household contacts who were offered home-based HCT in a household-randomized trial of home-based strategies for TB contact investigation. Respondents reflected on their experiences of the home visit, the social context of the household, and their decision to accept or decline HIV testing. We used content analysis to identify and evaluate facilitators and barriers to testing, then categorized the emergent themes using the Capability, Opportunity, Motivation, and Behavior (COM-B) model. Results—Facilitators included a pre-existing desire to confirm HIV status or to show support for the index TB patient; a perception that home-based services are convenient; and positive perceptions of lay health workers. Key barriers included fear of results and feeling psychologically unprepared to receive results. The social influence of other household members operated as both a facilitator and a barrier. Conclusions—Pre-existing motivation, psychological readiness to test, and the social context of the household are major contributors to the decision to test for HIV at home. Uptake might be improved by providing normalizing information about HCT prior to the visit, by offering a second HCT opportunity, by offering self-tests with follow-up counseling, or by introducing HCT using “opt-out” language.Item High Mortality Associated with Retreatment of Tuberculosis in a Clinic in Kampala, Uganda: A Retrospective Study(The American Journal of Tropical Medicine and Hygiene, 2015) Acuna-Villaorduna, Carlos; Ayakaka, Irene; Dryden-Peterson, Scott; Nakubulwa, Susan; Worodria, William; Reilly, Nancy; Hosford, Jennifer; Fennelly, Kevin P.; Okwera, Alphonse; Jones-Lopez, Edward C.The World Health Organization recommends for tuberculosis retreatment a regimen of isoniazid (H), rifampicin (R), ethambutol (E), pyrazinamide (Z), and streptomycin (S) for 2 months, followed by H, R, E, and Z for 1 month and H, R, and E for 5 months. Using data from the National Tuberculosis and Leprosy Program registry, this study determined the long-term outcome under programmatic conditions of patients who were prescribed the retreatment regimen in Kampala, Uganda, between 1997 and 2003. Patients were traced to determine their vital status; 62% (234/377) patients were found dead. Having £ 2 treatment courses and not completing retreatment were associated with mortality in adjusted analyses.Item Identifying barriers to and facilitators of tuberculosis contact investigation in Kampala, Uganda: a behavioral approach(Implementation science, 2017) Ayakaka, Irene; Ackerman, Sara; Ggita, Joseph M.; Kajubi, Phoebe; Dowdy, David; Haberer, Jessica E.; Fair, Elizabeth; Hopewell, Philip; Handley, Margaret A.; Cattamanchi, Adithya; Katamba, Achilles; Davis, J. LucianThe World Health Organization recommends routine household tuberculosis contact investigation in high-burden countries but adoption has been limited. We sought to identify barriers to and facilitators of TB contact investigation during its introduction in Kampala, Uganda. Methods: We collected cross-sectional qualitative data through focus group discussions and interviews with stakeholders, addressing three core activities of contact investigation: arranging household screening visits through index TB patients, visiting households to screen contacts and refer them to clinics, and evaluating at-risk contacts coming to clinics. We analyzed the data using a validated theory of behavior change, the Capability, Opportunity, and Motivation determine Behavior (COM-B) model, and sought to identify targeted interventions using the related Behavior Change Wheel implementation framework. Results: We led seven focus-group discussions with 61 health-care workers, two with 21 lay health workers (LHWs), and one with four household contacts of newly diagnosed TB patients. We, in addition, performed 32 interviews with household contacts from 14 households of newly diagnosed TB patients. Commonly noted barriers included stigma, limited knowledge about TB among contacts, insufficient time and space in clinics for counselling, mistrust of healthcenter staff among index patients and contacts, and high travel costs for LHWs and contacts. The most important facilitators identified were the personalized and enabling services provided by LHWs. We identified education, persuasion, enablement, modeling of health-positive behaviors, incentivization, and restructuring of the service environment as relevant intervention functions with potential to alleviate barriers to and enhance facilitators of TB contact investigation. Conclusions: The use of a behavioral theory and a validated implementation framework provided a comprehensive approach for systematically identifying barriers to and facilitators of TB contact investigation. The behavioral determinants identified here may be useful in tailoring interventions to improve implementation of contact investigation in Kampala and other similar urban settings.Item Predictors and short-term outcomes of recurrent pulmonary tuberculosis, Uganda: a cohort study(South African respiratory journal, 2017) Kalema, Nelson; Lindan, Christina; Glidden, Dave; Yoo, Samuel D.; atamba, Achilles K; Alfred, Andama; Katagira, Winceslaus; Byanyima, Patrick; Musisi, Emmanuel; Kaswabuli, Sylvia; Ingvar, Sanyu; Zawedde, Josephine; Yoon, Christina; Ayakaka, Irene; Lucian Davis, J.; Huang, Laurence; Worodria, William; Cattamanchi, AdithyaRecurrent tuberculosis (TB) occurring >2 years after completing treatment for a prior TB episode is most often due to reinfection with a new strain of M. tuberculosis. Objectives—We determined the prevalence and outcome of late recurrent TB among hospitalized patients in Kampala, Uganda. Methods—We conducted a retrospective analysis of patients admitted to Mulago Hospital who had cough of >2 weeks’ duration and completed TB treatment >2 years prior to admission. All patients had mycobacterial culture performed on two sputum specimens and vital status ascertained 2-months post-enrollment. We performed logistic regression and Cox proportional hazards modelling to identify predictors of recurrent TB and survival, respectively. Results—Among 234 patients, 84 (36%) had recurrent TB. Independent predictors included younger age (aOR=0.64, 95% CI=0.42-0.97, p=0.04), chest pain >2 weeks (aOR=3.32, 95% CI=1.38-8.02, p=0.007), severe weight loss ≥5 kilograms (aOR=4.88, 95% CI=1.66-14.29, p=0.004) and presence of ≥1 WHO danger sign of severe illness (aOR=3.55, 95% CI=1.36-9.29, p=0.01). Two-month mortality was 17.8% (95% CI=10.5-29.2%), and was higher among patients who were not initiated on TB treatment (aHR=16.67, 95% CI=1.18-200, p=0.04), those who were HIV-positive and not on antiretroviral treatment (aHR=16.99, 95% CI=1.17-246.47, p=0.04) and those with a history of smoking (aHR=1.20, 95% CI=1.03-1.40, p=0.02). Conclusion—The high prevalence of late recurrent TB likely reflects high levels of TB transmission in Kampala. Increased use of empiric TB treatment and early ART treatment initiation if HIV-positive should be considered in patients with a prior history of TB, particularly if they are young, with weight loss ≥5kgs, chest pain >2 weeks or ≥1 WHO danger sign of severe illness.Item Rate and Amplification of Drug Resistance among Previously-Treated Patients with Tuberculosis in Kampala, Uganda(Clinical infectious diseases, 2008) Temple, Beth; Ayakaka, Irene; Ogwang, Sam; Nabanjja, Helen; Kayes, Susan; Nakubulwa, Susan; Worodria, William; Levin, Jonathan; Joloba, Moses; Okwera, Alphonse; Eisenach, Kathleen D.; McNerney, Ruth; Elliott, Alison M.; Smith, Peter G.; Mugerwa, Roy D.; Ellner, Jerrold J.; Jones-Lopez, Edward C.Drug-resistant Mycobacterium tuberculosis has emerged as a global threat. In resource-constrained settings, patients with a history of tuberculosis (TB) treatment may have drug-resistant disease and may experience poor outcomes. There is a need to measure the extent of and risk factors for drug resistance in such patients. Methods. From July 2003 through November 2006, we enrolled 410 previously treated patients with TB in Kampala, Uganda. We measured the prevalence of resistance to first- and second-line drugs and analyzed risk factors associated with baseline and acquired drug resistance. Results. The prevalence of multidrug-resistant TB was 12.7% (95% confidence interval [95% CI], 9.6%–16.3%). Resistance to second-line drugs was low. Factors associated with multidrug-resistant TB at enrollment included a history of treatment failure (odds ratio, 23.6; 95% CI, 7.7–72.4), multiple previous TB episodes (odds ratio, 15.6; 95% CI, 5.0–49.1), and cavities present on chest radiograph (odds ratio, 5.9; 95% CI, 1.2–29.5). Among a cohort of 250 patients, 5.2% (95% CI, 2.8%–8.7%) were infected with M. tuberculosis that developed additional drug resistance. Amplification of drug resistance was associated with existing drug resistance at baseline (P ! .01) and delayed sputum culture conversion (P ! .01). Conclusions. The burden of drug resistance in previously treated patients with TB in Uganda is sizeable, and the risk of generating additional drug resistance is significant. There is an urgent need to improve the treatment for such patients in low-income countries.Item Sputum quality and diagnostic performance of GeneXpert MTB/RIF among smear-negative adults with presumed tuberculosis in Uganda(PLoS ONE, 2017) Meyer, Amanda J.; Atuheire, Collins; Worodria, William; Kizito, Samuel; Katamba, Achilles; Sanyu, Ingvar; Andama, Alfred; Ayakaka, Irene; Cattamanchi, Adithya; Bwanga, Freddie; Huang, Laurence; Davis, J. LucianIntroduction of GeneXpert MTB/RIF (Xpert) assay has constituted a major breakthrough for tuberculosis (TB) diagnostics. Several patient factors may influence diagnostic performance of Xpert including sputum quality. Objective We carried out a prospective, observational, cross-sectional study to determine the effect of sputum quality on diagnostic performance of Xpert among presumed TB patients in Uganda. Methods We collected clinical and demographic information and two sputum samples from participants. Staff recorded sputum quality and performed LED fluorescence microscopy and mycobacterial culture on each sample. If both smear examinations were negative, Xpert testing was performed. We calculated diagnostic yield, sensitivity, specificity, and other indicators for Xpert for each stratum of sputum quality in reference to a standard of mycobacterial culture. Results Patients with salivary sputum showed a trend towards a substantially higher proportion of samples that were Xpert-positive (54/286, 19%, 95% CI 15±24) compared with those with all other sputum sample types (221/1496, 15%, 95% CI 13±17). Blood-stained sputum produced the lowest sensitivity (28%; 95% CI 12±49) and salivary sputum the highest (66%; 95% CI 53±77). Specificity didn't vary meaningfully by sample types. Salivary sputum was significantly more sensitive than mucoid sputum (+13%, 95% CI +1 to +26), while bloodstained sputum was significantly less sensitive (-24%, 95% CI -42 to -5). Conclusions Our findings demonstrate the need to exercise caution in collecting sputum for Xpert and in interpreting results because sputum quality may impact test yield and sensitivity. In particular, it may be wise to pursue additional testing should blood-stained sputum test negative while salivary sputum should be readily accepted for Xpert testing given its higher sensitivity and potentially higher yield than other sample types. These findings challenge conventional recommendations against collecting salivary sputum for TB diagnosis and could inform new standards for sputum quality.Item Theory-Informed Interventions to Improve the Quality of Tuberculosis Evaluation at Ugandan Health Centers: A Quasi- Experimental Study(PLoS ONE, 2015) Chaisson, Lelia H.; Katamba, Achilles; Haguma, Priscilla; Ochom, Emmanuel; Ayakaka, Irene; Mugabe, Frank; Miller, Cecily; Vittinghoff, Eric; Davis, J. Lucian; Handley, Margaret A.; Cattamanchi, AdithyaTuberculosis (TB) remains under-diagnosed in many countries, in part due to poor evaluation practices at health facilities. Theory-informed strategies are needed to improve implementation of TB evaluation guidelines. We aimed to evaluate the impact of performance feedback and same-day smear microscopy on the quality of TB evaluation at 6 health centers in rural Uganda. Methods We tested components of a multi-faceted intervention to improve adherence to the International Standards for Tuberculosis Care(ISTC): performance feedback and same-day smear microscopy. The strategies were selected based on a qualitative assessment guided by the Theory of Planned Behavior and the PRECEDE model. We collected patient data 6 months before and after the introduction of each intervention component, and compared ISTC adherence in the pre- and post-intervention periods for adults with cough 2 weeks’ duration. Results The performance feedback evaluation included 1,446 adults; 838 (58%) were evaluated during the pre-intervention period and 608 (42%) during the post-intervention period. Performance feedback resulted in a 15% (95%CI +10%to +20%, p<0.001) increase in the proportion of patients receiving ISTC-adherent care. The same-day microscopy evaluation included 1,950 adults; 907 (47%) were evaluated during the pre-intervention period and 1,043 (53%) during the post-intervention period. Same-day microscopy was associated with a 14% (95%CI +10%to +18%, p<0.001) increase in the proportion of patients receiving ISTC-adherent care. Conclusions Performance feedback and same-day microscopy should be considered along with ISTC training as part of a multi-faceted intervention to improve the quality of TB evaluation in other high TB burden countries.Item Treatment Outcomes of New Tuberculosis Patients Hospitalized in Kampala, Uganda: A Prospective Cohort Study(PLoS ONE, 2014) Kirenga, Bruce J.; Levin, Jonathan; Ayakaka, Irene; Worodria, William; Reilly, Nancy; Mumbowa, Francis; Nabanjja, Helen; Nyakoojo, Grace; Fennelly, Kevin; Nakubulwa, Susan; Joloba, Moses; Okwera, Alphonse; Eisenach, Kathleen D.; McNerney, Ruth; Elliott, Alison M.; Mugerwa, Roy D.; Smith, Peter G.; Ellner, Jerrold J.; Jones-Lopez, Edward C.In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda Methods and findings: Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 – 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/mL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 – 4.01, P = 0.045). Conclusion: Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART.Item Variability of Infectious Aerosols Produced during Coughing by Patients with Pulmonary Tuberculosis(American journal of respiratory and critical care medicine, 2012) Fennelly, Kevin P.; Jones-Lopez, Edward C.; Ayakaka, Irene; Kim, Soyeon; Menyha, Harriet; Kirenga, Bruce; Muchwa, Christopher; Joloba, Moses; Dryden-Peterson, Scott; Reilly, Nancy; Okwera, Alphonse; Elliott, Alison M.; Smith, Peter G.; Mugerwa, Roy D.; Eisenach, Kathleen D.; Ellne, Jerrold J.Mycobacterium tuberculosis is transmitted by infectious aerosols, but assessing infectiousness currently relies on sputum microscopy that does not accurately predict the variability in transmission. Objectives: To evaluate the feasibility of collecting cough aerosols and the risk factors for infectious aerosol production from patients with pulmonary tuberculosis (TB) in a resource-limited setting. Methods: We enrolled subjects with suspected TB in Kampala, Uganda and collected clinical, radiographic, and microbiological data in addition to cough aerosol cultures. A subset of 38 subjects was studied on 2 or 3 consecutive days to assess reproducibility. Measurements and Main Results: M. tuberculosis was cultured from cough aerosols of 28 of 101 (27.7%; 95% confidence interval [CI], 19.9–37.1%) subjects with culture-confirmed TB, with a median 16 aerosol cfu (range, 1–701) in 10 minutes of coughing. Nearly all (96.4%) cultivable particles were 0.65 to 4.7 mm in size. Positive aerosol cultures were associated with higher Karnofsky performance scores (P ¼ 0.016), higher sputum acid-fast bacilli smear microscopy grades (P ¼ 0.007), lower days to positive in liquid culture (P ¼ 0.004), stronger cough (P ¼ 0.016), and fewer days on TB treatment (P ¼ 0.047). In multivariable analyses, cough aerosol cultures were associated with a salivary/mucosalivary (compared with purulent/ mucopurulent) appearance of sputum (odds ratio, 4.42; 95% CI, 1.23–21.43) and low days to positive (per 1-d decrease; odds ratio, 1.17;95%CI, 1.07–1.33). The within-test (kappa, 0.81; 95%CI, 0.68– 0.94) and interday test (kappa, 0.62; 95% CI, 0.43–0.82) reproducibility were high. Conclusions: A minority of patients with TB (28%) produced culturable cough aerosols. Collection of cough aerosol cultures is feasible and reproducible in a resource-limited setting.