First Cultivation and Characterization of Mycobacterium ulcerans from the Environment

Mycobacterium ulcerans infection, or Buruli ulcer, is the third most common mycobacteriosis of humans worldwide, after tuberculosis and leprosy. Buruli ulcer is a neglected, devastating, necrotizing disease, sometimes producing massive, disfiguring ulcers, with huge social impact. Buruli ulcer occurs predominantly in impoverished, humid, tropical, rural areas of Africa, where the incidence has been increasing, surpassing tuberculosis and leprosy in some regions. Besides being a disease of the poor, Buruli ulcer is a poverty-promoting chronic infectious disease. There is strong evidence that M. ulcerans is not transmitted person to person but is an environmental pathogen transmitted to humans from its aquatic niches. However, until now M. ulcerans has not been isolated in pure culture from environmental sources. This manuscript describes the first isolation, to our knowledge, of M. ulcerans in pure culture from an environmental source. This strain, which is highly virulent for mice, has microbiological features typical of African strains of M. ulcerans and was isolated from an aquatic insect from a Buruli ulcer–endemic area in Benin, West Africa. Our findings support the concept that M. ulcerans is a pathogen of humans with an aquatic environmental niche and will have positive consequences for the control of this neglected and socially important tropical disease

Reduction of diagnostic and treatment delays reduces rifampicin-resistant tuberculosis mortality in Rwanda

YesSETTING: In 2005, in response to the increasing prevalence of rifampicin-resistant tuberculosis (RR-TB) and poor treatment outcomes, Rwanda initiated the programmatic management of RR-TB, including expanded access to systematic rifampicin drug susceptibility testing (DST) and standardised treatment.OBJECTIVE: To describe trends in diagnostic and treatment delays and estimate their effect on RR-TB mortality.DESIGN: Retrospective analysis of individual-level data including 748 (85.4%) of 876 patients diagnosed with RR-TB notified to the World Health Organization between 1 July 2005 and 31 December 2016 in Rwanda. Logistic regression was used to estimate the effect of diagnostic and therapeutic delays on RR-TB mortality.RESULTS: Between 2006 and 2016, the median diagnostic delay significantly decreased from 88 days to 1 day, and the therapeutic delay from 76 days to 3 days. Simultaneously, RR-TB mortality significantly decreased from 30.8% in 2006 to 6.9% in 2016. Total delay in starting multidrug-resistant TB (MDR-TB) treatment of more than 100 days was associated with more than two-fold higher odds for dying. When delays were long, empirical RR-TB treatment initiation was associated with a lower mortality.CONCLUSION: The reduction of diagnostic and treatment delays reduced RR-TB mortality. We anticipate that universal testing for RR-TB, short diagnostic and therapeutic delays and effective standardised MDR-TB treatment will further decrease RR-TB mortality in Rwanda

Specific gyrA gene mutations predict poor treatment outcome in MDR-TB

YesMutations in the gyrase genes cause fluoroquinolone resistance in Mycobacterium tuberculosis. However, the predictive value of these markers for clinical outcomes in patients with MDR-TB is unknown to date. The objective of this study was to determine molecular markers and breakpoints predicting second-line treatment outcomes in M. tuberculosis patients treated with fourth-generation fluoroquinolones. We analysed treatment outcome data in relation to the gyrA and gyrB sequences and MICs of ofloxacin, gatifloxacin and moxifloxacin for pretreatment M. tuberculosis isolates from 181 MDR-TB patients in Bangladesh whose isolates were susceptible to injectable drugs. The gyrA 90Val, 94Gly and 94Ala mutations were most frequent, with the highest resistance levels for 94Gly mutants. Increased pretreatment resistance levels (>2 mg/L), related to specific mutations, were associated with lower cure percentages, with no cure in patients whose isolates were resistant to gatifloxacin at 4 mg/L. Any gyrA 94 mutation, except 94Ala, predicted a significantly lower proportion of cure compared with all other gyrA mutations taken together (all non-94 mutants + 94Ala) [OR = 4.3 (95% CI 1.4-13.0)]. The difference in treatment outcome was not explained by resistance to the other drugs. Our study suggests that gyrA mutations at position 94, other than Ala, predict high-level resistance to gatifloxacin and moxifloxacin, as well as poor treatment outcome, in MDR-TB patients in whom an injectable agent is still effective

Treating Infidelity and Comorbid Depression: A Case Study Involving Military Deployment

Sexual infidelity has a high prevalence in both representative community and treatment-seeking samples, and has been identified by experienced therapists as one of the more difficult couple problems to treat. Disclosure or discovery of infidelity triggers a broad range of adverse relationship and individual consequences, including increased risk of major depression and suicidality in either one or both partners. We describe an integrative approach for promoting recovery from infidelity, drawing on empirically supported treatments for couple distress as well as empirical literature regarding recovery from interpersonal trauma and relationship injuries. Using an exemplar case study involving military deployment, we feature three stages of intervention emphasizing containment of initial emotional trauma, understanding factors contributing to vulnerability to an affair, and strategies for helping partners to move on emotionally, either together or separately. The integrative treatment approach described here is the first treatment designed specifically to assist couples' recovery from an affair to garner empirical evidence of its efficacy

Evaluation of tuberculosis control by periodic or routine susceptibility testing in previously treated cases

SETTING: A national tuberculosis control programme (NTP) disposing of baseline drug resistance rates and using 2EHRZ/6TH in the treatment of new cases. OBJECTIVE: To estimate the extent of drug resistance created by the NTP. DESIGN: Resistance rates in 2EHRZ/6TH failure and relapse cases were compared to baseline, and resistance profiles of repeat isolates were checked. Numbers of observed resistant failures were compared to numbers expected due to pre-existing resistance. Trends of resistance in combined new and previously treated cases were extrapolated. RESULTS: High drug resistance rates were observed. Changes in resistance to streptomycin, the virtual absence of documented acquired resistance and a close match of observed with expected resistant failures all indicated accumulation of primary drug resistance as the main mechanism. Resistance in relapse/failure cases showed a significantly declining trend, and estimated combined drug resistance decreased rapidly. CONCLUSIONS: Drug resistance in previously treated cases seems to consist of passed-on primary rather than true acquired resistance. A one-time survey is thus confusing, but continuous routine testing may constitute the best drug resistance monitoring method. Cases previously treated with short-course chemotherapy may show drug resistance much more frequently than generally assumed, and all should receive a re-treatment regimen. The 2EHRZ/6TH regimen proved very safe under field conditions, causing no 'amplification' towards multidrug resistance and almost no acquired isoniazid resistance. Implementation of this regimen, together with a standardised re-treatment regimen, seemed to rapidly reduce isoniazid as well as multidrug resistance levels, despite the fact that directly observed treatment was not strictly applied

Rifampicin mono-resistant Mycobacterium tuberculosis in Bujumbura, Burundi; results of a drug resistance survey

SETTING: Bujumbura, Burundi. OBJECTIVES: To determine resistance levels of Mycobacterium tuberculosis (TB) to the main anti-tuberculosis drugs after 11 years of a DOTS programme using a WHO-recommended partially intermittent 6-month rifampicin (RMP) first-line regimen and fixed-dose drug combinations (FDCs). DESIGN: Drug susceptibility testing of systematic samples of M. tuberculosis isolated from newly registered sputum smear-positive cases in the capital during a 15-month period (2002-2003). RESULTS: Of 496 strains from new cases, 16.1% showed resistance to any drug, 6.3% to isoniazid (INH), 2.0% to RMP (1.4% multidrug-resistant TB [MDR-TB]), 13.3% to streptomycin and 1.6% to ethambutol. Among 69 strains from previously treated cases, the prevalence of resistance was 30%, 19%, 15% (12% MDR-TB strains), 25% and 6%, respectively. CONCLUSION: Levels of drug resistance in Bujumbura are higher than average for Africa, despite long-term use of the DOTS strategy with FDCs and a ban on sales of TB drugs. Most worrying is the appearance of MDR-TB and RMP-resistant, INH-susceptible strains in new cases. Although a survey cannot prove that high HIV prevalence, elevated levels of resistance to some other drugs and irregular intake allowed acquisition of drug resistance, the effectiveness and safety of 6-month regimens with (partially) intermittent RMP throughout under such conditions should be investigated

Endogenous reactivation and true treatment failure as causes of recurrent tuberculosis in a high incidence setting with a low HIV infection

The definitive version is available at www3.interscience.wiley.comThe definitive version is available at www3.interscience.wiley.comOBJECTIVE: To determine the relative frequencies of reinfection vs. reactivation or treatment failure in patients from a high tuberculosis incidence setting with a low prevalence of HIV infection. METHOD: We performed DNA fingerprinting on serial isolates from one and multiple TB episodes from 97 retreatment patients; 35 patients had been previously cured, whereas 62 had not. RESULTS: DNA fingerprinting patterns of recurrence Mycobacterium tuberculosis isolates of 5 of the 35 previously cured patients did not match with those of the corresponding initial isolates, indicating reinfection. We did not document reinfection during treatment. Isolates from each of the remaining 30 previously cured patients had identical DNA fingerprinting results, indicating reactivation. DNA fingerprinting patterns of isolates from the 62 patients with persistently positive sputum smears were identical, suggesting treatment failure. CONCLUSION: These findings suggest that reinfection is not a common cause of relapse and treatment failure in this rural predominantly HIV-free population despite the high incidence of TB

AS01-adjuvanted vaccine induces a transient innate immune response in ă humans

International Congress of Immunology (ICI), Melbourne, AUSTRALIA, AUG ă 21-26, 2016International audienceno abstrac