Accurate diagnosis of tuberculosis (TB) in children is a major challenge. Most commonly available TB tests are done on sputum, which many children cannot produce; and childhood TB often manifests with very few bacteria, so tests need to be extremely sensitive to detect them. The Foundation for Innovative New Diagnostics (FIND), in consultation with the National TB Program (NTP) of India, implemented a unique paediatric initiative in ten major cities in India to improve access to quality diagnosis. This initiative lasted from April 2014 until March 2018, initially focussing on demonstrating the feasibility of implementing upfront molecular diagnostics.

TB is the most deadly infectious disease in the world, with an estimated 10 million people newly infected every year. Ending the TB epidemic is a global priority targeted by SDG3.3 and reinforced by the WHO End TB Strategy. Success requires that the special challenges presented by childhood TB be addressed – which also aligns with SDG3.2. India is classified by WHO as a high-burden TB country, and the disease is a leading cause of childhood mortality there. TB is complicated to diagnose in children, because it can be difficult for them to cough hard enough to produce the sputum needed for most common diagnostics (and very young children cannot cough on demand). Furthermore, children often have disease with few bacteria, so tests need to be extremely sensitive to detect them. TB in children is usually diagnosed from samples that are obtained with invasive procedures and using methods that take weeks to provide a result and are only available in a few laboratories. Those infected find themselves isolated from family and friends, unable to go to school. Delayed diagnosis results in delayed therapy initiation, suffering and – too frequently – death. This project was conceived and conducted by FIND in collaboration with the National TB Program (NTP) of India, to tackle childhood TB through access to innovative diagnostics that enable rapid testing and linkage to treatment. By focusing on the needs of children, the initiative prioritized a population that has traditionally been neglected in national TB programmes. It also paved the way for important public–private collaboration, aiming to establish better standards of care for children with TB in India. GeneXpert is a point-of care (POC) molecular platform that has changed the landscape in TB diagnosis by providing a test result in less than 2 hours. MTB/RIF, a TB test co-developed by FIND that runs on the GeneXpert platform, is recognized by WHO as an important breakthrough, enabling not only the rapid diagnosis of TB but also whether it is a strain that is resistant to common treatments. Crucially for children, this innovative diagnostic tool can diagnose both sputum and non-sputum samples reliably. Fast diagnosis enables rapid treatment initiation, decreasing the risk of disease transmission and improving the likelihood of treatment success.

This initiative was developed by FIND in collaboration with the India NTP, funded by USAID (the US Agency for International Development) through the KNCV Tuberculosis Foundation under the Challenge TB Project.1,416 providers were engaged. Implementers included NTP officials, providers, and project staff in each of the participating sites. Hospital and laboratory attendants, NTP staff, parents and relatives of tested children were also crucial to the project by transporting the samples from the provider to the laboratory.Close to 94,500 children were tested, being the largest cohort of paediatric TB patients that has ever been evaluated in India.

Project cities were selected based on estimated TB burden, population, available TB diagnostic services as well as interventions. Multiple preparatory visits were made to assess critical pre-requisites including existing infrastructure, and to identify gaps that needed to be addressed before installation of GeneXpert equipment. Close collaboration between the project teams and district or state-level NTP managers paved the way for takeover by the NTP in later stages.The project involved significant training for all project and NTP staff, at both state and district levels. These training sessions were held at each of the participating sites, and covered the GeneXpert technology, processing of specimens and project protocols.Providers in each of the project cities were mapped using various databases. They were engaged and sensitized about the project through continuing medical education sessions, one-on-one meetings, and other advocacy interventions. Importantly, the initiative brought together both public and private healthcare providers, recognizing that many people with TB will often initially seek care in the private sector – which would usually fall outside the auspices of the NTP.Once set up was complete, the project launched in 2014, kicking off in Delhi, Chennai, Hyderabad, and Kolkata. A hub-and-spoke model was established, with one high-throughput GeneXpert laboratory situated in each of these cities. Numerous public and private facilities were linked to this laboratory through rapid specimen transportation mechanisms. GeneXpert testing was performed for all children with suspected TB, and on all types of specimens per the 2013 WHO TB recommendations. Based on the outstanding outcomes observed in these four cities over the first 2 years of the project, in 2016 the project was scaled up to include implementation in Bangalore, Guwahati, Surat, Nagpur and Visakhapatnam, and a tenth city, Indore, was added in 2017.To reach local communities, specially designed project information, education and communication materials, such as flyers and brochures, were developed in English and translated into local languages. Sensitization and advocacy interventions were also carried out. Social media platforms including WhatsApp – which are easy to use and widespread among the Indian population – were employed to circulate project-related messages.To enable a focus on speed and efficiency, the project processes were kept as simple as possible. Patient samples were collected at the hospital or clinic of the treating doctor and then rapidly transported to the GeneXpert laboratory for testing. Site-specific specimen collection and transportation plans were developed which took into consideration distances, available transportation facilities, travel time and costs.Information on treatment initiation for patients in the public-sector who tested positive for TB was obtained via telephone interview with the relevant provider, from NTP staff and from the NTP records (TB register). The treatment initiation information for patients referred through the private sector was provided by the treating provider, or the patient directly (with the provider’s consent). Free information technology tools facilitated the collection and tracking of data in a standardized format. They were also used to support the project teams in supervising the day-to-day performance of GeneXpert laboratories and other project activities remotely.

Over 10,000 providers were approached and sensitized as part of the project, and 1,416 were subsequently engaged (61% of whom were from the private sector). Uptake of services across the project cities continually increased during the time-span of the project. In the first 2 years, the TB detection rate in the target cities increased by 300% compared with conventional microscopy. Overall, almost 94,500 children with suspected TB were provided with upfront GeneXpert testing, across the ten cities, from April 2014 to March 2018. This is the largest cohort of paediatric TB patients that has ever been evaluated in India. Of those tested, 6,270 (6.6%) cases of paediatric TB were diagnosed. A total of 545 of those cases (8.7%) were found to be resistant to the common TB treatment rifampicin. A key achievement of the project was the rapid sample transportation from the referring facility to the GeneXpert laboratory in the intervention cities. Same-day turnaround for GeneXpert testing including specimen transportation, testing, and reporting was achieved in 90% of cases. Diagnostic results were also found to be very reliable, with 99.7% test validity. Of 103,045 specimens tested, 51,133 (49.6%) were non-sputum samples: this was the first time that a large proportion of extra-pulmonary specimens from children with suspected TB were routinely tested under the NTP. More than half (51.2%) of the cases of rifampicin resistant TB were identified from non-sputum specimens, demonstrating the critical importance of diagnostic tools that can process these samples. The majority of those who tested positive for TB (5,563; 88.7%) initiated treatment. Among those with rifampicin resistant TB, treatment was initiated in 467 (85.7%) patients.

TB diagnostics have been slow to reach the countries where they are most needed, often because of limited national TB programme budgets. Our project was launched with financial support from USAID under the Challenge TB Project and benefited from USAID fast-track funding approval. Funding enabled GeneXpert MTB/Rif testing to be performed free of charge. The project was a marriage of technology and process innovation. It exploited the potential of the GeneXpert molecular diagnostic technology – still quite new when the project first started. FIND’s familiarity with the technology and its potential (as a co-developer of the MTB/Rif assay), coupled with our expertise in TB diagnostics overall and strong relationships with the NTP in India and other stakeholders, enabled us to design and implement a robust project that would help to address a critical unmet need.

Global health initiatives must be supported by political will to be sustainably implemented in countries, and the support of the Indian government was critical to this project’s success. Indeed, data from the project has contributed to development of a national policy on the use of GeneXpert for the diagnosis of TB in children. Moreover, India is now rolling out a national programme aimed at speedily spotting cases of TB and drug resistance in all suspected cases. India is aiming to make GeneXpert a first-line diagnostic tool for TB. Some 639 machines are now in use throughout the country, due in part to this initiative. Today, processes in place are similar, if not identical, to those instigated for this initiative: when a child presents with suspected TB, a sample is transported to a government facility with specialized laboratories dedicated to paediatric TB. Staff members inform the health provider of the test results via text message or email within 24 hours, enabling the doctor to immediately start the child on treatment, therefore greatly reducing the delay in diagnosis and the risk of transmission and mortality. The initiative has therefore demonstrated the success of a very simple and uncomplicated operational service delivery model, which can certainly be leveraged in other countries with a high disease burden. The project has also shown the value of bringing public and private healthcare providers together – and in so doing has established a trusted network of local doctors working in both public and private facilities to aid and expedite diagnosis and treatment.

Introducing innovative technology and rethinking the TB diagnostic process in India has enabled three times as many children to be diagnosed with TB than in the past. Same-day delivery of test results in 90% of cases enabled children to be linked to care quickly, limiting their potential for disease transmission in their families and communities, and providing the best chance of a positive treatment outcome. Open communication channels and local partnerships ensured that challenges could be identified and overcome as quickly and simply as possible. While the project was implemented in a relatively small geography of only 10 cities, it provided a major contribution to the evidence base that led to the NTP taking positive steps in the nationwide identification and management of paediatric TB. Upfront testing with GeneXpert is now part of India’s national implementation policy, as well as being an integral part of the revised diagnostic algorithm. The number of GeneXpert machines has increased from 639 to over a thousand deployed across India and all districts now have at least one GeneXpert machine. The project focused on access to diagnosis, which is too often the missing element in the healthcare cascade. However specific needs of paediatric TB are now firmly on the agenda in India: multiple innovative e-based adherence tools have since been rolled out by the NTP to ensure that affected children complete the treatment regimen prescribed and mandatory notification of TB cases is being enforced throughout the country. Crucially, the paediatric TB guidelines are also being revised, demonstrating that the project has had a significant impact on improving the standards of paediatric TB care in India. On 7 December 2018, this project was awarded the prestigious Public Health Initiative prize at the India Health & Wellness Summit and Awards.

News stories: FIND awarded for expanding paediatric TB diagnosis in India: https://www.finddx.org/news/find-awarded-expanding-paediatric-tb-diagnosis-india. Sabir’s long road to TB diagnosis: https://www.finddx.org/news/sabirs-tb-diagnosis/. Articles: GeneXpert: transforming the diagnosis of pediatric TB in India / U.S. Agency for International Development – September 2017. Drug-resistant TB higher among children than expected: report / Hindu, Delhi – July 2017. India rolls out new TB diagnosis aimed at catching child cases / Devex – September 2017
National Paediatric TB Project has increased detection by 300% / The Times of India – July 2016. Scientific papers: Ref: Piloting Upfront GeneXpert MTB/RIF Testing on Various Specimens under Programmatic Conditions for Diagnosis of TB & DR-TB in Paediatric Population / PLOS One – October 2015. Ref: Accelerating access to quality TB care for paediatric TB cases through better diagnostic strategy in four major cities of India / PLOS One – February 2018. Ref: Upfront GeneXpert MTB/RIF testing on various specimen types for presumptive infant TB cases for early and appropriate treatment initiation / PLOS One – August 2018. Ref: Catalysing progressive uptake of newer diagnostics by health care providers through outreach and education in four major cities of India / PLOS One March 2018. Ref: Before GeneXpert , I only had my expertise: A qualitative study on the utilization and effects of GeneXpert technology among paediatricians in 4 Indian cities / PLOS One – March 2018.