In an era where physicians and scientists are tailoring therapies to the scale of DNA strands, why is the world’s single most lethal infectious lifeform still treated with bureaucratic rigidity?
The Government of India has audaciously claimed that India will be tuberculosis (TB)-free by 2025. Funding has increased markedly and some concrete steps have been taken. But to end TB by 2025, India needs to decrease new cases of TB by more than 10-15% every year over the next eight years. The current rate of reduction is about 1.5% per year. Old dogs will have to learn new tricks.
The newfound enthusiasm to end TB in India remains shackled by a long-standing urge to standardise diagnosis and therapy. Yet the intrinsic variability of human biology and behaviour renders the notion of uniform approaches nearly laughable. Entrapping an individual within an uncompromising therapeutic plan removes their sovereignty over their bodies, amplifying the stigma that enshrouds a diagnosis of TB.
No two patients with TB have the same disease. What works for a diabetic stockbroker in Mumbai will not work for an emaciated adivasi in rural Chhattisgarh. Differences in disease severity, antimicrobial resistance, anatomic location and concurrent illnesses in the patient, along with variability in health system infrastructure and access within the community – among other factors – demand nimble policies, strategic research and creative implementation of technology and systems. In this article, we present opportunities for India to personalise TB care.
Active case finding and early linkage to treatment are integral to controlling the epidemic. The national strategic plan for TB elimination (NSP) recognises the need to detect TB early and outlines its goals for upgrades in diagnostic technology. While vital, this is hardly enough. The NSP recognises the need for screening vulnerable populations and even performing door-to-door detection campaigns, but is short on details in its otherwise exhaustive report.
What good is a fancy test in a far-off reference laboratory to the day-labourer who doesn’t know why he has a persistent cough and can’t afford to take a day’s leave to go to a local primary health centre?
We suggest that community health worker (CHW) programs can improve such case detection and linkage to care among vulnerable populations. CHWs are quick to train and are sensitive to the needs of their localities. They can screen individuals in the privacy of their own homes, eliminating the need to miss work and incur the oft-prohibitive costs of traveling to the nearest clinic.
In India, Operation ASHA (OpASHA) has partnered with the government to improve TB diagnostics and treatment in multiple states. CHWs working with OpASHA are equipped with tablets and algorithms that enable them to deftly screen individuals and connect those who screen positive to care. More than one in six Indians who screen positive for TB never follow up in clinic.
In contrast, OpASHA, which has strong operational systems and uses sophisticated fingerprinting technology to keep patients and health workers engaged and accountable, does not allow any screened individual at risk of spreading the disease to fall through the cracks.
Further, CHWs can bring advanced TB diagnostics to the doorstep. New technologies like GeneXpert Omni allow rapid molecular tests for Mycobacterium tuberculosis DNA to move from high-end laboratories to the handbags of health workers. India should take pride in CHWs such as accredited social health activists and anganwadi workers who contribute to TB efforts, but so much more remains to be done. CHW programs in the mould of OpASHA should be expanded and implementation research should be enacted to further hone CHW programs to the needs of the geographically and socioeconomically diverse communities of India.
Once diagnosed, treatment with high quality medications at appropriate doses is critical to ensure cure. India has made progress by instituting daily dosing and using polypills to reduce the pill burden. However, we know that the standard doses of TB medicines are insufficient for young and malnourished children with TB. Among adults, TB patients with diabetes can also have lower-than-expected drug concentrations in their blood with standardised doses.
This is important because patients with inadequate drug concentrations can spread TB longer and are less likely to be cured despite completing standard therapy. The scale of the problem is massive: one in six individuals with diabetes lives in India and one in three Indian children under the age of five is malnourished.
Clearly, a one-size-fits-all approach to drug dosing will not work in India. Therapeutic drug monitoring (TDM) can help us tailor drug doses to the individual patient. This approach involves testing drug concentrations, from samples as tiny as a dried blood drop from a finger prick, and adjusting dosing to ensure optimum levels of the drug. In the US, TDM has accelerated response to therapy among TB patients with diabetes. While some implementation research may be necessary before widespread rollout, TDM is not operationally difficult to establish and can be a vital tool to improve the success of our treatments.
India has the opportunity to lead the world’s crusade against TB. We need to spend our rupees thoughtfully and creatively, with an eye to crafting diagnosis and treatment to the needs and abilities of our patients. For instance, we must fund implementation research that investigates the role of mobile phones – ubiquitous in India – which could make it easier for patients to gain awareness, seek treatment and stay engaged with care. We must also fund basic research that tries to discover molecular biomarkers of TB that improve our ability to diagnose the disease earlier and tailor the duration of therapy to the needs of the individual or even develop a vaccine that is truly preventative.
“The test of a first-rate intelligence,” wrote F. Scott Fitzgerald, “is the ability to hold two opposed ideas in mind at the same time and still retain the ability to function.” India is both teemingly dense and forlornly remote; in need of structured connectedness and individualised focus. Indian leaders must embrace the cognitive dissonance necessary to invest in systems that overcome the logistical barriers of a resource-poor country while also pioneering translational science worthy of a resource-rich country.
Some will surely shake their heads warily and advocate for the achievable, the basic, the standard. Waving aside technologies and systems that have proved effective elsewhere and prematurely writing off research avenues because they seem too expensive or too complicated for India actually belies a colonialistic double standard. To redeem our pledge of ending TB in India, we must redefine what is standard and we must start now.
Pranay Sinha is a physician in the department of Internal Medicine at Yale-New Haven Hospital. He studies the epidemiology of tuberculosis. Scott K. Heysell is a physician and associate professor of medicine, Infectious Diseases and International Health, the University of Virginia.