Extensively drug-resistant tuberculosis: epidemiology and management.

The advent of antibiotics for the treatment of tuberculosis (TB) represented a major breakthrough in the fight against the disease. However, since its first use, antibiotic therapy has been associated with the emergence of resistance to drugs. The incorrect use of anti-TB drugs, either due to prescription errors, low patient compliance, or poor quality of drugs, led to the widespread emergence of Mycobacterium tuberculosis strains with an expanding spectrum of resistance. The spread of multidrug-resistant (MDR) strains (ie, strains resistant to both isoniazid and rifampicin) has represented a major threat to TB control since the 1990s. In 2006, the first cases of MDR strains with further resistance to fluoroquinolone and injectable drugs were described and named extensively drug-resistant TB (XDR-TB). The emergence of XDR-TB strains is a result of mismanagement of MDR cases, and treatment relies on drugs that are less potent and more toxic than those used to treat drug-susceptible or MDR strains. Furthermore, treatment success is lower and mortality higher than achieved in MDR-TB cases, and the number of drugs necessary in the intensive phase of treatment may be higher than the four drugs recommended for MDR-TB. Linezolid may represent a valuable drug to treat cases of XDR-TB. Delamanid, bedaquiline, and PA-824 are new anti-TB agents in the development pipeline that have the potential to enhance the cure rate of XDR-TB. The best measures to prevent new cases of XDR-TB are the correct management of MDR-TB patients, early detection, and proper treatment of existing patients with XDR-TB.

Travel-associated sexually transmitted infections: an observational cross-sectional study of the GeoSentinel surveillance database.

BACKGROUND: Travel is thought to be a risk factor for the acquisition of sexually transmitted infections (STIs), but no multicentre analyses have been done. We aimed to describe the range of diseases and the demographic and geographical factors associated with the acquisition of travel-related STIs through analysis of the data gathered by GeoSentinel travel medicine clinics worldwide. METHODS: We gathered data from ill travellers visiting GeoSentinel clinics worldwide between June 1, 1996, and Nov 30, 2010, and analysed them to identify STIs in three clinical settings: after travel, during travel, or immigration travel. We calculated proportionate morbidity for each of the three traveller groups and did logistic regression to assess the association between STIs and demographic, geographical, and travel variables. FINDINGS: Our final analysis was of 112 180 ill travellers-64 335 patients seen after travel, 38 287 patients seen during travel, and 9558 immigrant patients. 974 patients (0·9%) had diagnoses of STIs, and 1001 STIs were diagnosed. The proportionate STI morbidities were 6·6, 10·2, and 16·8 per 1000 travellers in the three groups, respectively. STIs varied substantially according to the traveller category. The most common STI diagnoses were non-gonococcal or unspecified urethritis (30·2%) and acute HIV infection (27·6%) in patients seen after travel; non-gonococcal or unspecified urethritis (21·1%), epididymitis (15·2%), and cervicitis (12·3%) in patients seen during travel; and syphilis in immigrant travellers (67·8%). In ill travellers seen after travel, significant associations were noted between diagnosis of STIs and male sex, travelling to visit friends or relatives, travel duration of less than 1 month, and not having pretravel health consultations. INTERPRETATION: The range of STIs varies substantially according to traveller category. STI preventive strategies should be particularly targeted at men and travellers visiting friends or relatives. Our data suggest target groups for pretravel interventions and should assist in post-travel screening and decision making. FUNDING: US Centers for Disease Control and Prevention, and International Society of Travel Medicine.

TMC207: the first compound of a new class of potent anti-tuberculosis drugs.

Disease caused by Mycobacterium tuberculosis continues as a global epidemic: over 2 billion people harbor latent TB infection, and more than 9 million new TB cases, of whom 500,000 are multidrug-resistant (MDR), and nearly 2 million deaths are estimated to occur each year. New drugs are required to shorten treatment duration of drug-sensitive TB and for the treatment of MDR-TB. TMC207 is a first-in-class diarylquinoline compound with a novel mechanism of action, the inhibition of bacterial ATP synthase, and potent activity against drug-sensitive and drug-resistant TB. It has bactericidal and sterilizing activity against M. tuberculosis and other mycobacterial species, but little activity against other bacteria. In a Phase II efficacy study conducted in patients with MDR-TB taking TMC207 plus a standard background regimen, the drug appeared to be safe and well tolerated, and showed significant efficacy after 2 months of treatment with conversion rates of sputum culture of 48% (vs 9% in the placebo group). Given the product development partnership between Tibotec and the TB Alliance, the strategies of using TMC207 in shorter first-line regimens or using it in second-line regimens for drug-resistant M. tuberculosis infections are both being pursued. No clinical data of TMC207 in TB patients with HIV coinfection have been published; drug-drug interaction studies with antiretrovirals are being conducted. Finally, the remarkable sterilizing capacity of TMC207 also makes it an attractive drug in the strategy of TB elimination. Current and future studies will determine the role of TMC207 in a shortened treatment regimen for drug-sensitive TB, a more effective and better-tolerated regimen for MDR-TB, the treatment of latent TB infection, and intermittent-TB treatment regimens.