A shortage of research on diabetes-related tuberculosis in the Middle East could hamper treatment. Diabetes triples the risk of co-morbid tuberculosis, complicates its treatment and increases the likelihood of poor outcomes for both diseases. As diabetes rates are increasing across the region, Practical Patient Care Middle East speaks to Dr Scott Heysell, who spearheaded a report on the problem of the diseases’ correlation, about where the research to beat them needs to focus, and the issues it could lead to in terms of treatment and prevention.

A problem shared – diabetes-related tuberculosis

At present, there are more than one million cases of tuberculosis (TB) in the Middle Eastern region every year; according to WHO, it could be as high as 1.2 million. Now, add to this the number of people suffering from diabetes in the region – of the ten countries with the highest age-adjusted prevalence of diabetes in the world, three are in the Middle East  – which, including North Africa, goes up to a staggering 35 million people.

Diabetes is an increasingly recognised co-morbidity that can accelerate TB and complicate its treatment. Diabetes triples the risk of developing active TB following infection compared with non-diabetic patients. In other words, they make each other a lot more difficult to treat.

The reasons for lifestyle-related diabetes prevalence being large in the Middle East are well known: the rapid transformation of traditional diets and means of living to those of ultra-modern, Western-style fast food, and sugar and salt-laden calorie-fests; and the advent of air conditioning, cars, poor urban planning and other technology that
have led to sedentary lifestyles becoming the norm.

TB or not TB

So what does this have to do with TB? Rates of the disease vary hugely in the region. Unsurprisingly, prevalence is higher in the poorer countries and generally recedes the wealthier a nation is. Yemen and Iraq have the highest levels (48 and 45 cases per 100,000 people respectively), followed by Iran (21), Turkey (20), Syria (17), Lebanon (16), Saudi Arabia (14) and Oman (11), while Israel, Jordan and the UAE have rates so low they scarcely merit a mention. But there are outliers when it comes to the wealth-TB correlation: Bahrain (18), Kuwait (24) and, in particular, Qatar at a whopping 40 cases per 100,000 people. Why does one of the richest countries in the world have such a high rate?

Kuwait’s high prevalence is most likely explained as a product of its prosperity not in terms of lifestyle changes but rather in terms of improved healthcare. The rate of TB diagnoses went up from 19 per 100,000 people in 1990 to 51 in 2010, but this rise most likely due to the improved screening and surveillance programmes established in the country.

By contrast, there’s no such explanation for Qatar. However, the country’s problems with its international migrant labour force have been documented in many parts of the media, and examples of worker abuse are not hard to find. Could this be a contributing factor? It seems that, in many parts of the Middle East, expatriate workers from countries with a high prevalence of TB contribute to the occurrence of new cases. In Saudi Arabia, for example, the incidence of TB among expatriates is double that of Saudi nationals. In Oman, the predominant strains of Mycobacterium tuberculosis, the primary organism that causes TB, are similar to those commonly found in the Indian subcontinent.

Success in treating TB in HIV has been through integration – not having programmes siloed.

Diabetes is estimated to be the cause of 15% of present TB cases, mainly because diabetes impairs a person’s immune defences in a multitude of ways. Patients with concurrent diabetes show worse TB treatment outcomes, a higher rate of relapse following TB treatment and have a higher risk of mortaility from TB than patients with TB alone. Treatment of patients affected by both diseases can be challenging, particularly in low-income settings, such as those experienced by South-Asian migrant workers.

Treated in tandem

Collaborative work on TB and diabetes has only just begun. The growing burden of TB and diabetes is changing the landscape of TB care and prevention, and it’s at this intersection that Dr Scott Heysell, co-author of a study on the research gaps in diagnosis and treatment of TB and diabetes in the Middle East, sees the best place to intervene.

“I think that there’s an increasingly recognised need to think about TB and diabetes in the way that we think about TB and HIV – that they’re very much linked,” Heysell explains. “We need to move the medical and research community to understand that the success in treating TB in HIV has been through integration – not having programmes siloed in the way they currently are for diabetes and TB.”

He believes that, in the future, the way to treat TB and diabetes will be to ‘build it in’ to the treatment of diabetes as a complementary strategy. “Diabetes is not an infectious disease and, often, TB treatment programmes are very much removed, even from other hospital systems,” Heysell says. “So I think the trend will be for further integration – and that will ultimately improve patient outcome.”

Heysell is based at the University of Virginia and, together with two Middle Eastern-based co-authors, recently wrote a report on how to best treat the region’s growing problem of TB and diabetes.

“I’m an infectious disease physician,” he explains. “My clinical research activities are primarily in TB, principally in pharmacokinetics – so understanding drug exposure in relation to clinical outcomes, different drug dosages and combinations. We work in drug-resistant TB but also in the diseases that lead people to be predisposed to a poor outcome in TB. Those include co-morbidities of HIV, for instance, as well as diabetes.”

Their report is one of just a handful on the subject. “There hasn’t been a significant amount of research in the Middle East, in particular with regard to TB and diabetes,” he says. In some Middle Eastern countries, Heysell points out, there’s been absolutely no research at all.

“Diabetes has been increasingly recognised as a risk factor for development of active TB, so someone who has been latently infected [with TB] has a higher chance of it progressing to active infection, but those with diabetes also have a slower time to respond to TB treatments.”

“Therefore, they also have a prolonged period of infectiousness, but then they have worse outcomes overall – so a higher risk of death after being diagnosed and treated for TB compared with a patient without diabetes.”

Middle Eastern problem

But why the Middle East? Why is this region specifically showing such alarming rates of TB and diabetes? Heysell believes there are several intertwining factors that can help explain. 

“I think that there’s a convergence of cultural changes,” he says, referring to the Middle East’s rapid urbanisation and immigrant-heavy populations. “This is in addition to the types of movements of people within these regions of change.

“I think the Middle East is certainly a region of change; you have incredible wealth and development in many areas, and then you also have areas of extreme poverty – the condition of TB has always been a quintessential disease of poverty.

“What we found with diabetes, and what I think is happening in places like the Middle East – and South-East Asia is another very keen example of this – is you have dietary and cultural changes that predispose a person to the development of type 2 diabetes principally, and then that just happens to be in a population that has an endemic rate of tuberculosis infection.”

Heysell points out that, even despite the paucity of empirical research, the causes appear to be strikingly obvious.

“Places like the Middle East and South-East Asia are good examples of poverty and cultural changes merging, and there are certain pockets where the epidemiology is even more drastically different.”

Academic research has not yet specified whether the huge immigrant populations from countries like India are fuelling this rise in Gulf State countries such as Qatar or Bahrain, but Heysell believes it is likely to be a factor.

“In general, in most countries of wealth, there are much higher rates of TB in foreign-born patients. In the Gulf States, these often include those that are migrating principally for work, and that’s been observed in many places; even in the US, 75% or so of our TB patients in my home state of Virginia, and the country as a whole as well, are foreign born, so that’s the principal trend in countries of wealth.”

This explanation makes sense – TB prevalence is highest in the poorest countries, and diabetes highest in the countries of rapid wealth growth and cultural change. When those two things mix, it’s a recipe for disaster.

The study Hasell was involved in primarily focused on the lack of research in this area, but he does see places where policy or healthcare initiatives could be effective in terms of treatment.

TB prevalence is highest in the poorest countries, and diabetes highest in the countries of rapid wealth growth and cultural change. When those two things mix, it’s a recipe for disaster.

“I think there’s a huge reservoir for latent TB infection, and countries that have the resources to treat TB – particularly TB and diabetes – will be able to do so with high efficacy in patients at high risk for conversion to active disease, so that will include diabetics.”

He already sees signs of this two-pronged treatment pattern as being viable, in some locations at least: “For instance, in a diabetic clinic in Saudi Arabia, they may be able to screen all their patents for TB and treat all those with a latent infection. So I think there’s a lot of research that can be done on bidirectional screening, and that would include screening diabetic patients for TB and then screening all TB patients for diabetes, and being able to principally treat both.

“We have a developing programme in Saudi Arabia that looks at the pharmacokinetics of TB treatments in diabetic patients specifically, and whether we need to adjust drug dosages or monitor their drug exposure differently than we do for non-diabetic patients.” Taken together, this type of research and the use of bidirectional screening could be enough to identify the diseases and ensure effective treatment.

However, the priority must be recognition and prevention of the two diseases’ initial development, and improving treatment of their separate, as well as a combined, effects – something that could take many more years and a lot more effort to solve.