TUBERCULOSIS: Tackling TB in Peru

Benjamin Thompson: 3 Nov, 2010

Up to a third of the world’s population are infected with the bacterium Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), according to the World Health Organization. The disease kills about two million people every year – more than any other single infection.
Moreover, levels of multidrug resistant (MDR) and extensively drug resistant (XDR) TB are on the rise. Peru has the highest rate of drug-resistant TB in the Americas, with levels of MDR TB doubling over the past decade.
Dr Carlton Evans has lived and worked in Peru for the last 10 years, and runs the research group IFHAD: Innovation for Health And Development, funded by the Wellcome Trust. In a recently published paper, his research group described a new method they have developed that can identify TB disease rapidly.
I spoke to Dr Evans about his group’s research and the challenges of tackling TB in Peru.
What is the burden of TB in Peru?
We know that in the shanty towns where we work approximately half the people are infected. The major problem is that TB is a very under-diagnosed disease. Research has shown that house-to-house testing of people uncovers almost twice the levels that are diagnosed in hospitals or clinics.
Why the discrepancy?
Often people have symptoms for several months before they get diagnosed, and the old fashioned way of diagnosing the disease is insensitive and can lead to false negatives. An even more important issue is the stigma attached to having TB. People would often rather not get tested for fear of getting a positive diagnosis, and those who are being treated often keep it a secret. We regularly come across tragic situations in which women are thrown out of their homes when their partner finds out they have TB.
So what are these old fashioned ways of testing for TB?
The standard test, which has been around for over a century, involves looking at stained sputum down a microscope. This is the only test that the majority of patients have access to. It only tells you whether TB is present, not whether the strain is regular, or drug-resistant, as they all look the same. This is a real problem. Modern molecular tests for MDR TB – that can often produce results within the same day – do exist but the challenge is making better tests affordable in the settings where most MDR TB occurs.
What is the method you have developed?
This research was led by two people; Eric Ramos in the lab and Samuel Schumacher who analysed the data. The question that they asked was: how can we concentrate TB from a sputum sample and identify it quickly? Normally, to concentrate a sample requires a centrifuge. These are expensive and unreliable, as well as being potentially biohazardous.
Eric’s idea was to concentrate the TB from a sputum sample not with a centrifuge, but with a filter. By sucking the sputum through a piece of filter paper he was able to concentrate the bacteria before growing them. This method is easier, quicker and safer than centrifuging, and is about as sensitive, which are real advantages in places with basic laboratory equipment.
Was this a ‘eureka’ moment?
Far from it! This method of concentrating the bacteria took years of work. A variety of different techniques were attempted, but filtration proved the best compromise between safety and efficiency.
What other benefits did your research produce?
Usually monitoring a sample to check rapidly for TB growth requires repeated microscopy to look for the characteristic bacterial colonies. M. tuberculosis grows very slowly and it takes about a month until colonies are visible to the naked eye – compared with only a week before colonies are visible down a microscope. But using the microscope takes a long time to monitor every sample for TB growth – hours every day when you have a lot of samples to check, which is difficult to manage.
After testing hundreds of chemicals, Eric developed a test using the inexpensive compound STC, which changes colour when TB grows, but doesn’t inhibit its growth. This allows lab workers to check in seconds, just with their naked eye, whether there is growth in a sample. Once a colour change is seen a quick microscope check can be used for the few samples that change colour to ensure that what has grown is TB and not a contaminant. This means that labs can test far more samples than if they had to monitor each one with a microscope.
What’s next?
The next project will involve finding a way to throw the microscope away completely! STC has never given a false negative, so we’ve never found a culture that contains TB, but doesn’t change colour. The dream is to find a compound which is specific to TB and only changes colour when TB is present, so we wouldn’t need the extra microscope step. We’re not there yet, but watch this space…
What can be done to tackle TB in Peru?
What we need moving forward is a more joined up approach. New diagnostic tools, like those outlined in this research paper, need to be integrated with improvements in case finding, infection control, treatment completion and especially in making TB care more accessible to poorer people. On their own, better diagnostic tools are not enough, just as better drugs alone won’t make a difference.
TB is a disease of poverty, of overcrowding, poor nutrition and poor access to medical services. Greater emphasis needs to be placed on the socio-economic setting in which this disease occurs. Making these changes happen and making them accessible for the people who need them most seems to be a bigger and more important challenge than developing the tools themselves.

Ramos E, Schumacher SG, Siedner M, Herrera B, Quino W, Alvarado J, Montoya R, Grandjean L, Martin L, Sherman JM, Gilman RH, & Evans CA (2010). Optimizing tuberculosis testing for basic laboratories. The American journal of tropical medicine and hygiene, 83 (4), 896-901 PMID: 20889887

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