Drug Resistance

TB : Coming Back Hard

Elizabeth Blunt

Tuberculosis control programmes are among the oldest public health campaigns (dating back 125 years) but are not nearly as successful as they should be. Despite effective drugs having been available for over 50 years, TB still kills a million people a year, making it the world's single deadliest infectious disease after AIDS.

When those who work in the field of TB want to be cheerful they stress that TB is no longer the killer that it used to be; there has been a drop in mortality of 45% in the last 25 years. But actually that is not very good. It is certainly nowhere near good enough to meet the World Health Organization's (WHO) own target - to reduce by 2035 the incidence of the disease to the kind of levels seen, for instance, in North America. "It's not going to happen," admits Suvanand Sahu, deputy executive secretary of the Stop TB Partnership, "not in our lifetime nor in our children's lifetime. Business as usual will not get us there."

Even more discouragingly, it is by no means clear that the 45% reduction is the result of national and international TB control programmes. TB had already ceased to be a threat in most of Europe and North America by the 1960s before the development of effective drugs. When people are better housed, better fed, and generally enjoy a more satisfactory standard of living, TB tends to fade away. A new report by the Economist Intelligence Unit (EIU) points out that the reduction in TB correlates far more closely with a country's score on the Human Development Index than it does with the intensity of the effort it puts into disease control.

The report puts its finger on whal it calls a lack of focus by those working on the disease. Part of the problem, it says, is a tendency to think of TB as a kind of "background noise", something which is always there and attracts no particular sense of urgency. There has also been a failure to understand the way in which the disease is concentrated in certain vulnerable populations, and to act accordingly. Encouraging national figures for the incidence of TB can conceal pockets of much higher infection rates.

David Moore, professor of infectious diseases at the London School of Hygiene and Tropical Medicine, told a meeting in London to launch the report that even the UK's own low national rates conceal much higher levels in the capital. "And even within London, rates are not uniform," he told his listeners. "There are some boroughs of London where the incidence of TB is between 70 and 150 per 100,000 of the population per year, which is about the rate of TB in Sudan.

So one message of the report is that it is no use just creating TB clinics and waiting for people to turn up. You have to go out into those high-incidence pockets—which may be among migrants or prisoners, or the homeless or indigenous people—and actively seek out cases. The people most likely to be infected are those least likely to come looking for health care. It is estimated that a third of cases of active TB are never diagnosed or treated. A pioneering "cough monitor" project in Kenya's Rift Valley, where rates are high, has been testing around 2,000 people a year: 16% tested positive for TB. Using village health workers in Ethiopia to test people with persistent coughs doubled the detection rate for the disease.

Detection rates among children are even lower. Their disease is harder to diagnose by the most common testing methods, and workers with a public health focus tend to overlook children, assuming that they are less likely to be a source of infection. Scientists at the University of Sheffield have done some complicated analysis of the data, and reckon that high-burden countries only detect one third of the children with active TB.

Their report suggests that childhood TB could be greatly reduced if you gave preventative therapy with isoniazid, one of the most basic of TB drugs, to all children under the age of 15 who are living with an actively infectious patient (as estimated 15 million children worldwide).

The lead author, Peter Dodd, says getting good figures is also important in its own right. "Quantifying the burden of TB in children is important," he says, "because without good numbers, there can be no targets for improvement, no monitoring of trends and there is a lack of evidence to encourage industry to invest in developing medicines or diagnostics that are more appropriate for children than those available today."

TB is not an easy disease to treat, and is unforgiving of mistakes. Courses of treatment are long and many of the drugs have side effects. Because of this, because they move away or because the drugs are not always available, patients often fail to complete their treatment. According to the author of the EIU report, Paul Kielstra, "with any infectious disease, if you make some progress but not a lot of progress, the disease will fight back. With TB, if you don't keep a lid on it, it will come back and it will come back hard."

Now multi-drug resistant (MDR) and extensively drug resistant (XDR) tuberculosis are ruthlessly exposing the inadequacies of TB control programmes, "Every single one of those cases,'' says Moore, "is the story of a failure somewhere along the line." Some patients with MDRTB find that their disease has become resistant to basic drugs because of failures in treatment. A far greater number contract MDRTB directly from someone who has the resistant strain but where this has not been identified, so that he or she is not recovering and is still walking round infecting others.

Most of the EIU's recommendations are about using existing tools and systems more effectively. After all, despite the spread of resistant strains, 85% of TB cases are still curable with basic, first line drugs.

But the London meeting also heard about prospects for new and better tools. High-tech diagnostic tests, like Gene-Xpert, are already in use, but are expensive. They can be cost-effective if they are deployed in health facilities with a high burden of TB, or perhaps in mobile units so they can target at-risk communities. Again, a more accurate focus is crucial.

And there are a few new drugs in the pipeline, although not too many. The furthest ahead are Bedaquiline and Delaminid, both of which are now undergoing Phase III trials. But it is a slow process, especially if you are comparing them with the existing WHO recommended, two-year regimen. Andrew Nunn, from the clinical trials unit of the UK's Medical Research Council, told IRIN that testing TB drugs was not like testing antibiotics against most other infections, where you can see whether or not they work more or less straight away.

"Every patient will need to be treated for 4-6 months, and then the follow-up period is the time when, having apparently successfully treated someone, you see whether they relapse afterwards or not. And you need a minimum of 12 months after the last patient being treated, to see whether or not those patients are going to relapse and therefore have an unfavourable outcome. Are there dormant organisms which are going to raise their head? So it's a real challenge, TB is more challenging than many other areas."                    —TWNF

Vol. 47, No. 17, Nov 2 - 8, 2014