Tuberculosis-Learning the Impact of Nutrition (TB LION): protocol for an interventional study to decrease TB risk in household contacts.

BACKGROUND: Comorbidities such as undernutrition and parasitic infections are widespread in India and other tuberculosis (TB)-endemic countries. This study examines how these conditions as well as food supplementation and parasite treatment might alter immune responses to Mycobacterium tuberculosis (Mtb) infection and risk of progression to TB disease. METHODS: This is a 5-year prospective clinical trial at Jawaharlal Institute of Post Graduate Medical Education and Research in Puducherry, Tamil Nadu, India. We aim to enroll 760 household contacts (HHC) of adults with active TB in order to identify 120 who are followed prospectively for 2 years: Thirty QuantiFERON-TB Gold Plus (QFT-Plus) positive HHCs ≥ 18 years of age in four proposed groups: (1) undernourished (body mass index [BMI] < 18.5 kg/m2); (2) participants with a BMI ≥ 18.5 kg/m2 who have a parasitic infection (3) undernourished participants with a parasitic infection and (4) controls-participants with BMI ≥ 18.5 kg/m2 and without parasitic infection. We assess immune response at baseline and after food supplementation (for participants with BMI < 18.5 kg/m2) and parasite treatment (for participants with parasites). Detailed nutritional assessments, anthropometry, and parasite testing through polymerase chain reaction (PCR) and microscopy are performed. In addition, at serial time points, these samples will be further analyzed using flow cytometry and whole blood transcriptomics to elucidate the immune mechanisms involved in disease progression. CONCLUSIONS: This study will help determine whether undernutrition and parasite infection are associated with gene signatures that predict risk of TB and whether providing nutritional supplementation and/or treating parasitic infections improves immune response towards this infection. This study transcends individual level care and presents the opportunity to benefit the population at large by analyzing factors that affect disease progression potentially reducing the overall burden of people who progress to TB disease. Trial registration ClinicalTrials.gov; NCT03598842; Registered on July 26, 2018; https://clinicaltrials.gov/ct2/show/NCT03598842.

Containing HIV/AIDS in India: the unfinished agenda.

India's HIV epidemic is not yet contained and prevention in populations most at risk (high-risk groups) needs to be enhanced and expanded. HIV prevalence as measured through surveillance of antenatal and sexually transmitted disease clinics is the chief source of information on HIV in India, but these data cannot provide real insight into where transmission is occurring or guide programme strategy. The factors that influence the Indian epidemic are the size, behaviours, and disease burdens of high-risk groups, their interaction with bridge populations and general population sexual networks, and migration and mobility of both bridge populations and high-risk groups. The interplay of these forces has resulted in substantial epidemics in several pockets of many Indian states that could potentially ignite subepidemics in other, currently low prevalence, parts of the country. The growth of HIV, unless contained, could have serious consequences for India's development. India's national response to HIV began in 1992 and has shown early success in some states. The priority is to build on those successes by increasing prevention coverage of high-risk groups to saturation level, enhancing access and uptake of care and treatment services, ensuring systems and capacity for evidence-based programming, and building in-country technical and managerial capacity.

Rolling out new biomedical HIV prevention tools: what can be learned from Avahan, the India AIDS initiative?

More than 30 years after HIV was first identified as a disease, with disastrous consequences for many subpopulations in most countries and for entire populations in some African countries, it continues to occupy centre stage among the world's many global health challenges. Prevention still remains the primary long-term focus. New biomedical tools such as pre-exposure propyhlaxis (PrEP) and treatment hold great promise for select groups such as key populations (KPs) who are critical to transmission dynamics, and serodiscordant couples. Programs delivering these new tools will need to layer them over existing services, with potential modifications for increased and sustained engagement between health services and beneficiaries owing to the nature of the interventions. Avahan, an HIV prevention intervention for KPs in six states in India, achieved population-level impact with conventional prevention programming, which, however, required high program-beneficiary engagement. Avahan's implementation strategy included articulating clear service definitions and denominator-based targets; establishing routine data systems with regular, multilevel supervision that allowed for cross-learning across the program; and developing a cadre of frontline workers through KP peer outreach workers who addressed structural issues and provided viable and sustainable mechanisms for sustained interaction between health services and KPs. This basic prevention implementation infrastructure was used to expand clinical services over time. Many of the lessons from programs such as Avahan can be applied to KP programs that are expanding service scope, including PrEP and treatment.

Learning about scale, measurement and community mobilisation: reflections on the implementation of the Avahan HIV/AIDS initiative in India.

Debates have raged in development for decades about the appropriateness of participatory approaches and the degree to which they can be managed, scaled and measured. The Avahan programme confronted these issues over the last 7 years and concludes that it is advantageous to manage scaled community mobilisation processes so that participation evolves and programming on the ground is shaped by what is learnt through implementation. The donor (Bill & Melinda Gates Foundation) and its partners determined a standard set of programme activities that were implemented programme-wide but evolved with input from communities on the ground. Difficulties faced in monitoring and measurement in Avahan may be characteristic of similar efforts to measure community mobilisation in a scaled programme, and ultimately these challenges informed methods that were useful. The approach the programme undertook for learning and changing, the activities it built into the HIV prevention programme, and its logic model and measurement tools, may be relevant in other public health settings seeking to integrate community mobilisation.

Evaluation design for large-scale HIV prevention programmes: the case of Avahan, the India AIDS initiative.

BACKGROUND: Closing the HIV prevention gap to prevent HIV infections requires rapid, worldwide rollout of large-scale national programmes. Evaluating such programmes is challenging and complex, requiring clarity of evaluation purpose and evidential approaches substantively different to those employed for pilots and small programmes. OBJECTIVES: This paper describes the evaluation design for the implementation phase of Avahan, the India AIDS initiative, a large HIV prevention programme funded by the Bill and Melinda Gates Foundation. Avahan, which began in December 2003, has a 10-year charter to impact the Indian epidemic and its response by implementing an HIV prevention programme targeting core and bridge groups in 83 districts of six Indian states, transferring the programme to the Government of India, and disseminating programme learning. METHODS: The foundation commissioned an external process to design Avahan's evaluation framework. An independent advisory group oversees and guides course corrections in the execution of this framework. RESULTS: Avahan's evaluation framework comprises: trend and synthetic analysis of data from core, bridge and household biobehavioural surveys in a subset of intervention districts, denominator estimates and programme monitoring from all intervention districts, and government's antenatal surveillance (two sites per district in all districts); bespoke transmission dynamics modelling to estimate infections averted (subset of districts); cost effectiveness studies (subset of districts). In addition, there are other knowledge-building and quality-monitoring activities. CONCLUSION: Rather than a small set of monofocal outcome measures, scaled programmes require nuanced evaluations that approximate programmatic scale by collecting data with different levels of geographical scope, synthesize multiple data and methods to arrive at a composite picture, and can cope with continuous environmental and programme evolution.