Generations of doctors, politicians, and public health officials have struggled to defeat tuberculosis. But, after years of success, TB is making a comeback. The increase in TB in the developed world since 1992 was initially attributed to HIV. However, over time, other factors behind the growing number of cases, such as immigration and a particular type of drug-resistant TB, have emerged.
The World Health Organization has developed a strategy to fight TB’s return, including a standardized therapy that specifies appropriate drugs, doses, and timing of therapy. Unfortunately, multi-drug resistant tuberculosis (MDR-TB), which is any TB resistant to the traditional treatments of isoniazid and rifampicin, represents a serious challenge: because standard treatment is less effective in curing it, its transmission continues.
Moreover, any inadequately treated TB becomes multi-drug resistant, so that treatment failure can be either cause or consequence of MDR-TB. This underscores the need for a determined regimen to treat TB today, as well as a more complex strategy to control the disease, one which cures as many cases as possible, prevents acquired drug resistance and decreases the transmission of infection. The WHO recommends what it calls a “Directly Observed Therapy Strategy” (DOTS) and has set diagnostic thresholds of at least 70% of infectious cases, and curative thresholds of 85%.
We conducted a systematic review of published reports to identify the factors that cause unsuccessful TB treatment in Europe. Twenty-six papers were included in the review, covering 13 countries (the former USSR, the Czech Republic, Poland, and Romania in Eastern Europe, and Denmark, France, Germany, Italy, the Netherlands, Northern Ireland, Spain, Sweden, and Switzerland in Western Europe) in the period from 1988-2001.
On average, the studies found that 74.4% of the curative outcomes were “successful,” falling short of the WHO’s 85% target. Patients were treated “unsuccessfully” 12.3% of the time, and 6.8% of treated patients died.
MDR-TB was inversely associated with successful treatments. We found that populations with at least 10% MDR-TB showed a notable reduction in successful outcomes. Surprisingly, no relationship was found between TB treatment outcomes and immigrant status in these studies, perhaps because all immigrants were combined, regardless of country of origin.
These results suggest the following clinical and public health implications:
· since successful TB treatment outcomes are below the 85% threshold, an enhancement of national TB control programs is needed in most European countries;
· MDR is the most important obstacle to controlling TB in Europe;
· analyzing immigrants by specific country of origin, timing of immigration, and previous treatment can help define the risk of MDR-TB associated with immigrants;
· treatment characteristics need to be reported more consistently in order to identify and correct the factors related to inadequate treatment of TB in Europe.
Although some characteristics of TB therapy, such as interruption of treatment, are well known predictors of multi-drug resistance, other aspects of treatment that reflect the health-care system, such as the drugs used and the length of therapy, must be studied to help improve control programmes. For example, one of the studies that we reviewed found that no standard therapy in the initial or secondary phase of treatment was associated with an unsuccessful outcome or death. Moreover, some aspects of patient management emerged as risk factors for not completing therapy, which suggests difficulties in access to health services for TB patients.
Structural barriers do not represent the only problems of access to treatment in the health care system. Foreign-born patients may interrupt treatment due to lack of confidence in diagnosis and care, or they may ignore the more minor symptoms of the illness. Patients who feel better after the initial treatment may also fail to complete therapy.
Social factors other than birthplace should be studied to evaluate what causes primary multi-drug resistance. Treatment interruption has been associated with asylum seekers and refugees in Switzerland. Interruption was also associated with homelessness, intravenous drug use, and alcohol dependence in Hamburg. In Spain, homelessness was a risk factor for interruption and HIV positivity, and intravenous drug use was a risk factor for unsuccessful treatment.
I also believe that there is a relationship between the need for therapy and the political choices that countries make. The DOTS strategy is not implemented in all European countries, owing in part to disagreement about whether treatment is a duty or a right. Public health workers argue that therapy should be imposed upon patients who are at risk of failing to complete it – a policy that others claim would violate individual liberty.
Unless we act to step up the fight against TB, many health-care systems may find themselves facing a less abstract problem: securing the economic resources and organizational capacity to ensure treatment for the growing number of patients who want and need it.