Problems with Current Tuberculosis Treatment

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Problems with Current Tuberculosis Treatment

    One-thirdof the world population is infected with Mycobacterium tuberculosis (MTB) andhence at risk of developing active tuberculosis (TB). Each year, 8.8 millionpatients are newly diagnosed with active TB and 1.6 million patients die of TB.

   There are several major problems associated with the currently availableTB treatment. First, the duration and complexity of treatment result innon-adherence to treatment. This leads to suboptimal response (failure andrelapse), the emergence of resistance, and continuous spread of the disease.

   Second, adverse events in response to anti-TB drugs are common andcontribute to the problem of nonadherence.

   Third, the increasing incidence of multidrug-resistant and extensivelydrug-resistant TB is a serious concern. Resistant TB occurs in the presence ofpartially suppressive drug concentrations that enable replication of bacteria,the formation of mutants, and overgrowth of wild-type strains by mutants (selectivepressure). Second-line drugs for drug-resistant TB are not available everywhereand are less effective, more toxic, and require longer use than first-linedrugs.

   Fourth, co-infection of TB and HIV is a problem by itself. Combinedtreatment of TB and HIV involves a high pill count with associated adherenceproblems, overlapping toxicity profiles of the anti-retroviral and anti-TBdrugs, drug interactions between rifampin and the anti-retroviral proteaseinhibitors, and the risk of immune reconstitution syndrome.

   Fifth, prophylactic therapy of latent TB (TB infection without symptoms)with isoniazid is also associated with problems of nonadherence. Attempts toshorten treatment with alternative drugs resulted in severe adverse events.

   Clearly, there is an urgent need to improve treatment by eitherenhancing the application of existing agents or introducing new drugs.