Mike: Hello, I'm Mike Clarke, podcast editor for the Cochrane Library. There are many Cochrane Reviews relevant to the diagnosis and treatment of tuberculosis. These were added to in June 2024 by a new review of prognosis, specifically to look at the impact of undernutrition. Here are two of the authors, Juan Franco and Brenda Bongaerts from the Institute of General Practice, Medical Faculty of the Heinrich-Heine-University Düsseldorf in Germany, to tell us more.

Juan: Worldwide, tuberculosis or TB caused an estimated 1.6 million deaths in 2022, with about 10.6 million new cases diagnosed in that year.
Undernutrition is one of the important risk factors and, each year, the WHO provides a statistic, called the "population attributable fraction" (PAF) as an estimate of how much TB is due to undernutrition. This reported in the WHO TB Report, which is a comprehensive and up-to-date overview of TB and progress made on strategies to try and end the disease.
The population attributable fraction helps us understand what percentage of cases of a disease, in this case, TB, can be attributed to a specific risk factor, in this case, undernutrition. It tells us how much of the TB burden could be avoided if undernutrition were eliminated. It's based on the latest data on the prevalence of TB and estimates for the risk posed by undernutrition. And that is where our own work comes into play. So, I'll hand over to Brenda, to summarise what we did for our Cochrane Review.

Brenda: Thanks Juan. In our review, we aimed to determine the prognostic value of undernutrition in predicting TB in both children and adults and across all settings.
We searched for both retrospective and prospective cohort studies in which adults, adolescents, and children from diverse settings were characterised by many baseline characteristics, including undernutrition. This is defined as wasting, stunting, or being underweight. Our primary outcome of interest was the incidence of TB disease.

Juan: So, for context, people can be infected with TB (and not have any symptoms), or they can present with symptoms. Symptoms that alert a physician to suspect TB include persistent cough, which may be bloody, weight loss, fever, and night sweats. After the diagnosis is made, this is called TB disease. And we were interested in the association between this outcome and undernutrition.

Brenda: To do this, used data from a total of 51 cohort studies with over 27 million participants. We used standard Cochrane methodology and a tool called QUIPS to assess risk of bias in the studies, before performing a random-effects meta-analysis.
Our main analysis indicated that being underweight doubles the risk of TB disease. Or more precisely in statistical terms, the hazard ratio for developing TB disease was 2.23 times higher in people being underweight compared to people not being underweight, based on data from about half the included studies.
A few of the studies in our review presented their data in a different way, using the odds ratio or risk ratio for the development of TB. We pooled these studies separately, and they also showed results similar to the hazard ratios, with a pooled odds ratio of 1.56 and a pooled risk ratio of 1.95.
It is important to add that most of the included studies had less than ten years of follow-up. However, the very few studies that had longer follow-up signalled an even higher risk for TB disease, but these results are uncertain.

Juan: Thanks for summarising the numbers so clearly, Brenda. These estimates will inform future WHO Global TB Reports, which deliver state-of-the-art, annual updates on the TB epidemic and progress in TB prevention, diagnosis and treatment worldwide.
These reports also update on the milestones achieved by the World End TB Strategy. This comprehensive global framework, launched in 2014, aims to eliminate TB-related deaths, TB incidence, and catastrophic costs for families affected by TB. So, all in all, the Global TB Report is a vital tool for tracking the epidemic, guiding policies, and promoting research and innovation.
With that in mind, Brenda would you like to conclude by saying a little about how systematic reviews like ours on undernutrition as a risk factor for TB might help the End TB Strategy?

Brenda: In general, systematic reviews are crucial for policy makers. They provide valuable insights into prognosis, diagnosis, treatment and even prevention strategies. Concerning the End TB Strategy, systematic reviews may facilitate the design and implementation of effective TB control programs and, thereby, ease the enormous burden of TB.
In the case of our Cochrane Review, the prognostic information we provide allows the prediction of the proportion of TB cases that are attributable to undernutrition. This in turn, may raise overall awareness on the importance of nutrition in preventing TB. It may inform health systems to design targeted interventions for populations at high risk of both TB and undernutrition, such as children and people living with HIV. And it could support the careful planning and prioritisation of resources as part of TB control efforts.
Finally, Juan, if people would like to read our review, how can they get hold of it?

Juan: It's available free online at Cochrane Library dot com. A search for "undernutrition and tuberculosis" will show it near the top of the list.