Implementation Science

Tuberculosis Epidemiologic Studies Consortium III

This CDC funded research study is being implemented by UCSF at North East Medical Services, a Federally Qualified Health Center in the San Francisco Bay Area.   The project is a collaboration with the California Department of Public Health and the San Francisco TB program.  The overall objective is to  evaluate the impact of interventions implemented to increase the proportion of non-US born individuals with latent tuberculosis infection who are diagnosed and treated. Using implementation science approaches, the study will prioritize the barriers/facilitators to target and then evaluate the effectiveness of the intervention on closing the gaps in the LTBI cascade of care. The impact of this work will be to identify scalable interventions that will reduce the burden of latent TB among immigrant communities, currently the population most at risk for active TB in the United States. 

Sponsor: CDC

PI: Priya Shete, MD


PREVENT TB Mozambique: Using mobile technologies and community health workers to find and support TB contacts in Beira, Mozambique

The PREVENT TB mobile health (mHealth) application developed by the WHO is a tool that allows Community Health Workers to register TB index cases and contacts, perform screening for active TB, refer contacts for further evaluation at health facilities and monitor test results and treatment initiation.  In this project, the PREVENT TB app was adapted from the generic version, translated into Portuguese, and implemented into a system of TB case finding to develop strong, systematic approaches to finding, informing, and keeping vulnerable patients on TB treatment in Beira, Mozambique.

Source: UCSF Resource Allocation Program (RAP) Grant; WHO

Elizabeth Fair, PhD, MPH; Mariana Velleca, MS 


Simplified Isoniazid Preventative Therapy (SPIRIT) Strategy to Reduce TB Burden

Given the existence of both country guidelines recommending isoniazid prevantitive therapy (IPT), as well as simple clinical algorithms to identify IPT eligible persons, a remaining critical requirement for scale-up is strengthening the link - mediated by middle management in most health systems - between health ministry policy and clinics. In Uganda, District Health Officers (DHOs) serve as key middle managers working at the nexus between policy and implementation.This is an implementation research study where we study whether a multicomponent intervention (SPIRIT) that assists DHOs in Uganda can overcome barriers to latent TB infection treatment scale up.

Sponsor: NIH, NIAID

PI: Diane Havlir, MD


Options for Delivering Isoniazid-Rifapentine (3HP) for TB Prevention Trial (3HP Options Trial)

This is a hybrid effectiveness-implementation trial of three strategies for delivering short-course TB preventive therapy in the context of routine HIV/AIDS care in Kampala, Uganda. The overall objective is to identify a patient-centered delivery strategy that will facilitate acceptance and completion of 3HP (a three-month, 12-dose regimen of weekly rifapentine and isoniazid). Participants will be randomized to one of three delivery strategies: 1) Facilitated directly-observed therapy (DOT); 2) Facilitated Self Administered Therapy (SAT) using a Medication Event Reminder Monitor (MERM) device; and 3) Patient choicebetween Facilitated SAT and Facilitated DOT using a decision aid. Facilitation in all arms will include standardized patient counseling, streamlined clinic visits for DOT or medication refills, and reimbursement of costs associated with completing DOT or refill visits. Our central hypothesis is that offering PLHIV an informed choice between DOT and SAT delivery strategies that are optimized to overcome key barriers to treatment adherence will result in greater acceptance and completion of 3HP. Embedded mixed methods and health economic studies will evaluate the implementation of each delivery strategy and compare their cost-effectiveness

Sponsor: NIH/NHLBI

PI: Adithya Cattamanchi, MD


From DOT to DAT: Scale-up of 99DOTS in Uganda

Our initial Wave 6 project demonstrated that 99DOTS, a digital adherence monitoring solution, was feasible to implement in Uganda and improved short-term treatment outcomes among adults with drug susceptible TB (target 1890 patients) at 18 DTUs. This project will scale-up 99DOTS to 6000 patients at 30 DTUs in Uganda (representing approximately 10% of TB patients in the country) and conduct an interrupted time series analysis to assess impact on treatment outcomes.

TB treatment success rates are well below the 90% target in Uganda. In our current Wave 6 project, we first used a human centered design approach to adapt 99DOTS by 1) re-designing the packaging to reduce stigma, improve literacy and incorporate motivational imagery; 2) providing educational/motivational messages when patients call to confirm dosing; and 3) adding task lists and refill logs to enable providers to focus attention on patients who require additional support (this was unable to be implemented during the current Wave 6 project). Results to date show improved persistence on treatment (89.6% vs. 76.1%, p<0.001) and high levels of enthusiasm from patients, health workers and NTLP staff. Building on the successes and lessons learned, we now propose to further refine and scale-up 99DOTS. Specifically, we plan to 1) fully develop and implement the task lists and refill logs; 2) task shift adherence monitoring and patient follow-up to CHWs to enable more consistent support for non-adherent patients; and 3) involve District TB supervisors in regular meetings with health center staff to strengthen NTP oversight. In addition, to support further scale-up, we will establish local printing of 99DOTS envelopes and a 99DOTS user-support help desk. We anticipate 6000 patients across 30 DTUSs will undergo treatment during the Wave 6 scale-up period, and 900 additional patients will experience treatment success. Our project team has a long history of collaboration with the Uganda NTLP, is involved in implementation research addressing programmatic priorities in >30 districts across Uganda and has expertise in delivering health worker trainings.

Sponsor: Government of Canada, the Bill & Melinda Gates Foundation, and the United States Agency for International Development.

PI: Adithya Cattamanchi, MD


XPEL-TB trial

In high burden countries, many patients with tuberculosis (TB) who present to community health centers are lost to follow-up before TB can be diagnosed or treated, leading to ongoing transmission. A primary reason is that the standard approach of collecting sputum specimens over multiple days for microscopic examination is not only insensitive but also inconvenient and costly for patients. Xpert MTB/RIF (Xpert) is a semi-automated molecular test that identifies 90% of TB cases within 2 hours. Xpert is now recommended as the initial diagnostic test for pulmonary TB but cannot be deployed at community health centers because of cost and infrastructure requirements. To achieve access, utilization and impact on health outcomes, strategies for successful referrals from community health centers to facilities in which Xpert is being deployed are essential. Our overall objective s to assess the effectiveness, implementation and impact of a streamlined, single- sample (SIMPLE) TB diagnostic evaluation strategy. The SIMPLE TB strategy was developed after a theory-informed assessment of provider- and patient-level barriers to TB diagnostic evaluation and through a process of stakeholder engagement. Its components include: 1) Single-sample LED fluorescence microscopy (analysis and reporting of smear results from the initial specimen within two hours); 2) Daily transport of smear-negative sputum samples to Xpert testing sites; 3) SMS-based reporting of Xpert test results to patients and health centers; and 4) Routine feedback of TB evaluation metrics to health center staff. Our central hypothesis is that the SIMPLE TB strategy will increase the number of patients with active TB for whom treatment is initiated. To test this hypothesis, we will conduct a cluster-randomized trial at 20 community health centers in Uganda to determine whether the SIMPLE TB strategy improves TB diagnosis and treatment initiation rates relative to the prevailing standard-of-care (Aim 1). Routine data collected on adults undergoing TB diagnostic evaluation at intervention and control health centers will be used to assess trial outcomes. Concurrently with the clinical trial, we will employ a mixed methods approach to evaluate in detail the process of implementation (Aim 2), focusing on factors that influence the adoption and maintenance of intervention components and faithfulness to our conceptual model. Last, we will perform economic and epidemic modeling to estimate the cost-effectiveness and epidemiological impact (i.e., future TB incidence) of the SIMPLE TB strategy (Aim 3). Relying solely on novel diagnostic technologies without also supporting health system interventions to facilitate their uptake and use is unlikely to result in sustained and meaningful progress in the ongoing fight against TB. The comprehensive research plan will generate the high-quality evidence needed to guide TB policy makers in deciding whether to adopt the SIMPLE TB strategy, and on how best to implement it at other health centers. This research will also lead to a better understanding of the factors and types of interventions associated with successful implementation of novel TB diagnostics in low- income, high TB burden countries.

Source: National Heart, Lung, and Blood Institute

PI: Adithya Cattamanchi, MD


Feasibility and acceptability of a peer-led strategy to improve community tuberculosis case finding among non-household contacts in Zambia

Systematic screening for tuberculosis (TB) in high-risk populations, including people living with HIV and all persons living in high TB prevalence settings is recommended by the World Health Organization as an important strategy to improve TB control. While community-wide TB screening in high burden settings is unlikely to be sustainable, community-based systematic TB screening among non-household contacts of newly diagnosed TB patients (contact tracing) using trained peers (recent TB patients) may represent an efficient and effective implementation strategy that compliments existing strategies and is sustainable. The proposed research will develop and pilot a theory-informed, peer-led, multicomponent implementation strategy to improve TB contact tracing among non-household contacts of HIV-positive and HIV-negative adults in Lusaka, Zambia.

Sponsor: NIH, National Institute of Allergy and Infectious Diseases

PI: Andrew Kerkhoff, MD, PhD


Digital adherence technologies to facilitate completion of short-course tuberculosis preventive therapy among people living with HIV

Although tuberculosis (TB) – the leading cause of death among people living with HIV (PLHIV) – can be prevented with only 12 weekly doses of isoniazid and rifapentine (3HP), implementation studies in sub-Saharan Africa have shown low rates of completion. The proposed studies will explore how two low-cost digital adherence technologies (DAT) can be adapted to address barriers to 3HP completion and conduct pilot studies to evaluate their acceptability, feasibility and preliminary effectiveness. The results will inform a future trial comparing the effectiveness and cost-effectiveness of contextually adapted DATs vs. routine care to support scale-up of 3HP or other novel, short-course regimens for TB prevention among PLHIV.

Sponsor: NIH, National Heart, Lung, and Blood Institute

PI: Christopher Berger, MD