Recent research in India found that providing food baskets to people with TB and their households went a long way to preventing and mitigating the disease, and scientists say that similar action, and launching a form of social benefit to South Africans with the disease, could be an effective strategy to reduce statistics.
Yogan Pillay and Madhukar Pai write in The Conversation that we have long known – in fact for centuries – that TB is a social disease, that it thrives on poverty and social factors like malnutrition, poor housing, overcrowding, unsafe work environments and stigma.
Globally in 2021, an estimated 2.2m cases of TB were attributable to undernourishment, 0.86m to HIV infection, 0.74m to alcohol use disorders, 0.69m to smoking and 0.37m to diabetes.
But knowledge about social determinants alone does not always translate into tangible action and progress.
A recent trial in India, called RATIONS, aimed to determine the effect of nutritional supplementation on new cases of tuberculosis in households of adults with pulmonary TB.
The research found that providing food baskets to people with TB and their households could go a long way to prevent and mitigate the disease.
No easy silver bullets
The TB community has typically looked for biomedical solutions, or “silver bullets”, for a social pathology, and we are struggling to make progress.
Since the pandemic, TB mortality and incidence have increased globally, putting TB back on top as the single, most deadly infectious killer of humankind.
In 2021, 1.6m people died of TB. In Africa, TB incidence is high (212 per 100 000 population) with a high case fatality rate because of the HIV epidemic.
Under-nutrition is the most important cause of TB. This has been shown in studies in many countries, including South Africa, where researchers found poor levels of nutrition in patients admitted to a specialised TB hospital.
Malnutrition refers to all forms of deficiencies in nutrition, including over-nutrition and obesity. Under-nutrition refers more specifically to a deficiency of nutrients.
While we know that many patients with TB have poor nutrition, the latest evidence is that under-nutrition also plays a key role in TB within households.
The results of the Reducing Activation of Tuberculosis by Improvement of Nutritional Status (RATIONS) trial (published in The Lancet) show that improved nutrition in families of patients with lung TB reduced all forms of TB by nearly 40%, and infectious TB by nearly 50%.
This trial recruited 10 345 household members of 2 800 patients with lung TB.
All TB patients received a monthly 10kg food basket (rice, pulses, milk powder, oil) and multivitamins for six months.
In one group, a family received 5kg rice and 1.5kg pulses per person per month, while the other group of families did not get food baskets.
Food worked like a vaccine in this trial, cutting the risk of households developing TB.
Nutrition could also protect against other conditions such as anaemia, diarrhoea and respiratory infections, but these were not the main focus of the trial.
An accompanying paper, based on the results of the RATIONS trial, showed that severe under-nutrition was present in nearly half of all patients.
An early weight gain in the first two months was associated with 60% lower risk of TB mortality. The other benefits were higher treatment success and better weight gain. During the six-month follow-up period, a remarkable treatment success rate of 94% was achieved.
Getting food to patients
How expensive was the intervention? The cost of a food basket was US$13 per TB patient per month and US$4 per household member per month, and could be delivered, even in rural areas, using field staff.
Even before the RATIONS trial, the Indian Government had recognised the need for nutrition support for people with TB, and in 2018 launched “Nikshay Poshan Yojana”, a direct benefit transfer scheme.
Under this scheme, each TB patient receives a financial incentive of US$6 per month for the duration of the anti-TB treatment (typically, six months for people with drug-sensitive TB).
Emerging data suggest that while the scheme improves the treatment completion rates among patients with TB in India, they often receive their payments late. There is a need to improve the efficiency and provide timely payments.
The RATIONS trial indicates that directly providing food baskets may be another effective strategy.
Many countries, including India, have other social security programmes, including public distribution systems to provide food grains at subsidised prices. Using existing channels to provide extra food rations to people with TB, and expanding the menu to include proteins such as pulses and millets, is a strategy worth exploring.
This could also have positive effects on other diseases such as diabetes.
Implications for South Africa
South Africa is one of the countries labelled by the WHO as a “high TB burden country”.
What does this latest research mean for South Africa? Statistics South Africa reported that in 2021 2.6m people had inadequate access to food and 1.1m had “severe” inadequate access to food. More than 683 000 children under five experienced hunger.
This toxic mix requires prevention of TB by nutritional support, drugs to prevent TB infections and early diagnosis with molecular tests and treatment.
With high levels of food insecurity and under-nutrition in South Africa, fuelled by the highest levels of inequality, it is critical the country includes social benefits for people with TB and those in their households to reduce the prevalence of TB and to meet the Sustainable Development Goals for 2030.
Regardless of how social benefits are distributed, action must be based on evidence. We need better tests, cures and vaccines for TB, but they alone cannot end the epidemic.
TB patients must be provided with the social benefits that they need and deserve, as a basic human right.
Study 1 details
Nutritional supplementation to prevent tuberculosis incidence in household contacts of patients with pulmonary tuberculosis in India (RATIONS): a field-based, open-label, cluster-randomised, controlled trial
Anurag Bhargava, Madhavi Bhargava, Ajay Meher, Andrea Benedetti, Banurekha Velayutham, G Sai Teja, et al.
Published in The Lancet on 8 August 2023
Summary
Background
In India, tuberculosis and under-nutrition are syndemics with a high burden of tuberculosis coexisting with a high burden of under-nutrition in patients and in the population. The aim of this study was to determine the effect of nutritional supplementation on tuberculosis incidence in household contacts of adults with microbiologically confirmed pulmonary tuberculosis.
Methods
In this field-based, open-label, cluster-randomised controlled trial, we enrolled household contacts of 2800 patients with microbiologically confirmed pulmonary tuberculosis across 28 tuberculosis units of the National Tuberculosis Elimination Programme in four districts of Jharkhand, India. The tuberculosis units were randomly allocated 1:1 by block randomisation to the control group or the intervention group, by a statistician using computer-generated random numbers. Although microbiologically confirmed pulmonary tuberculosis patients in both groups received food rations (1200 kcal, 52 grams of protein per day with micronutrients) for 6 months, only household contacts in the intervention group received monthly food rations and micronutrients (750 kcal, 23 grams of protein per day with micronutrients). After screening all household contacts for co-prevalent tuberculosis at baseline, all participants were followed up actively until July 31, 2022, for the primary outcome of incident tuberculosis (all forms). The ascertainment of the outcome was by independent medical staff in health services. We used Cox proportional hazards model and Poisson regression via the generalised estimating equation approach to estimate unadjusted hazard ratios, adjusted hazard ratios (aHRs), and incidence rate ratios (IRRs).
Findings
Between Aug 16, 2019, and Jan 31, 2021, there were 10 345 household contacts, of whom 5328 (94·8%) of 5621 household contacts in the intervention group and 4283 (90·7%) of 4724 household contacts in the control group completed the primary outcome assessment. Almost two-thirds of the population belonged to Indigenous communities and 34% (3543 of 10 345) had under-nutrition. We detected 31 (0·3%) of 10 345 household contact patients with co-prevalent tuberculosis disease in both groups at baseline and 218 (2·1%) people were diagnosed with incident tuberculosis (all forms) over 21 869 person-years of follow-up, with 122 of 218 incident cases in the control group (2·6% [122 of 4712 contacts at risk], 95% CI 2·2–3·1; incidence rate 1·27 per 100 person-years) and 96 incident cases in the intervention group (1·7% [96 of 5602], 1·4–2·1; 0·78 per 100 person-years), of whom 152 (69·7%) of 218 were patients with microbiologically confirmed pulmonary tuberculosis. Tuberculosis incidence (all forms) in the intervention group had an adjusted IRR of 0·61 (95% CI 0·43–0·85; aHR 0·59 [0·42–0·83]), with an even greater decline in incidence of microbiologically confirmed pulmonary tuberculosis (0·52 [0·35–0·79]; 0·51 [0·34–0·78]). This translates into a relative reduction of tuberculosis incidence of 39% (all forms) to 48% (microbiologically confirmed pulmonary tuberculosis) in the intervention group. An estimated 30 households (111 household contacts) would need to be provided nutritional supplementation to prevent one incident tuberculosis.
Interpretation
To our knowledge, this is the first randomised trial looking at the effect of nutritional support on tuberculosis incidence in household contacts, whereby the nutritional intervention was associated with substantial (39%–48%) reduction in tuberculosis incidence in the household during 2 years of follow-up. This biosocial intervention can accelerate reduction in tuberculosis incidence in countries or communities with a tuberculosis and under-nutrition syndemic.
Study 2 details
Nutritional support for adult patients with microbiologically confirmed pulmonary tuberculosis: outcomes in a programmatic cohort nested within the RATIONS trial in Jharkhand, India
Anurag Bhargava, Madhavi Bhargava, Ajay Meher, G Sai Teja, Banurekha Velayutham, Basilea Watson, et al.
Published in The Lancet on 8 August 2021
Summary
Background
Undernutrition is a common comorbidity of tuberculosis in countries with a high tuberculosis burden, such as India. RATIONS is a field-based, cluster-randomised controlled trial evaluating the effect of providing nutritional support to household contacts of adult patients with microbiologically confirmed pulmonary tuberculosis in Jharkhand, India, on tuberculosis incidence. The patient cohort in both groups of the trial was provided with nutritional support. In this study, we assessed the effects of nutritional support on tuberculosis mortality, treatment success, and other outcomes in the RATIONS patient cohort.
Methods
We enrolled patients (aged 18 years or older) with microbiologically confirmed pulmonary tuberculosis across 28 tuberculosis units. Patients received nutritional support in the form of food rations (1200 kcal and 52 g of protein per day) and micronutrient pills. Nutritional support was for 6 months for drug-susceptible tuberculosis and 12 months for multidrug-resistant tuberculosis; patients with drug-susceptible tuberculosis could receive an extension of up to 6 months if their BMI was less than 18·5 kg/m2 at the end of treatment. We recorded BMI, diabetes status, and modified Eastern Cooperative Oncology Group (ECOG) performance status at baseline. Clinical outcomes (treatment success, tuberculosis mortality, loss to follow-up, and change in performance status) and weight gain were recorded at 6 months. We assessed the predictors of tuberculosis mortality with Poisson and Cox regression using adjusted incidence rate ratios (IRRs) and adjusted hazard ratios (HRs).
(CTRI/2019/08/020490).
Findings
Between Aug 16, 2019, and Jan 31, 2021, 2800 patients (mean age 41·5 years [SD 14·5]; 1979 [70·7%] men and 821 [29·3%] women) were enrolled. At enrolment, 2291 (82·4%) patients were underweight (BMI <18·5 kg/m2), and 480 (17·3%) had a BMI of less than 14 kg/m2. The mean weight and BMI were 42·6 kg (SD 7·8) and 16·4 kg/m2 (2·6) in men and 36·1 kg (7·3) and 16·2 kg/m2 (2·9) in women. During the 6-month follow-up, treatment was successful in 2623 (93·7%) patients, 108 (3·9%) tuberculosis deaths occurred, 28 (1·0%) patients were lost to follow-up, and treatment failure was experienced by five (0·2%) patients. The median weight gain was 4·6 kg (IQR 2·8–6·8), but 1441 (54·8%) of 2630 patients remained underweight. At 2 months, 1444 (54·0%) of 2676 patients gained at least 5% of baseline weight. Baseline weight (adjusted IRR 0·95, 95% CI 0·90–0·99), BMI (0·88, 0·76–1·01), poor performance status (ECOG categories 3–4; 5·33, 2·90–9·79), diabetes (3·30, 1·65–6·72), and haemoglobin (0·85, 0·71–1·00) were predictors of tuberculosis mortality. A reduced hazard of death (adjusted HR 0·39, 95% CI 0·18–0·86) was associated with a 5% weight gain at 2 months.
Interpretation
In this study, nutritional support was provided to a cohort with a high prevalence of severe undernutrition. Weight gain, particularly in the first 2 months, was associated with a substantially decreased hazard of tuberculosis mortality. Nutritional support needs to be an integral component of patient-centred care to improve treatment outcomes in such settings.
Yogan Pillay, Extraordinary Professor in the Division of Health Systems and Public Health, Stellenbosch University
Madhukar Pai, Director of Global Health & Professor, McGill University
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