Early Outcomes of MDR-TB Treatment in a High HIV-Prevalence Setting in Southern Africa

BACKGROUND: Little is known about treatment of multidrug-resistant tuberculosis (MDR-TB) in high HIV-prevalence settings such as sub-Saharan Africa. METHODOLOGY/PRINCIPAL FINDINGS: We did a retrospective analysis of early outcomes of the first cohort of patients registered in the Lesotho national MDR-TB program between July 21, 2007 and April 21, 2008. Seventy-six patients were included for analysis. Patient follow-up ended when an outcome was recorded, or on October 21, 2008 for those still on treatment. Fifty-six patients (74%) were infected with HIV; the median CD4 cell count was 184 cells/microl (range 5-824 cells/microl). By the end of the follow-up period, study patients had been followed for a median of 252 days (range 12-451 days). Twenty-two patients (29%) had died, and 52 patients (68%) were alive and in treatment. In patients who did not die, culture conversion was documented in 52/54 patients (96%). One patient had defaulted, and one patient had transferred out. Death occurred after a median of 66 days in treatment (range 12-374 days). CONCLUSIONS/SIGNIFICANCE: In a region where clinicians and program managers are increasingly confronted by drug-resistant tuberculosis, this report provides sobering evidence of the difficulty of MDR-TB treatment in high HIV-prevalence settings. In Lesotho, an innovative community-based treatment model that involved social and nutritional support, twice-daily directly observed treatment and early empiric use of second-line TB drugs was successful in reducing mortality of MDR-TB patients. Further research is urgently needed to improve MDR-TB treatment outcomes in high HIV-prevalence settings

Treatment outcomes of new tuberculosis patients hospitalized in Kampala, Uganda: a prospective cohort study.

BACKGROUND: In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda. METHODS AND FINDINGS: Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 - 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 - 4.01, P = 0.045). CONCLUSION: Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART

Ambulatory Multi-Drug Resistant Tuberculosis Treatment Outcomes in a Cohort of HIV-Infected Patients in a Slum Setting in Mumbai, India

Background: India carries one quarter of the global burden of multi-drug resistant TB (MDR-TB) and has an estimated 2.5 million people living with HIV. Despite this reality, provision of treatment for MDR-TB is extremely limited, particularly for HIV-infected individuals. Médecins Sans Frontières (MSF) has been treating HIV-infected MDR-TB patients in Mumbai since May 2007. This is the first report of treatment outcomes among HIV-infected MDR-TB patients in India. Methods: HIV-infected patients with suspected MDR-TB were referred to the MSF-clinic by public Antiretroviral Therapy (ART) Centers or by a network of community non-governmental organizations. Patients were initiated on either empiric or individualized second-line TB-treatment as per WHO recommendations. MDR-TB treatment was given on an ambulatory basis and under directly observed therapy using a decentralized network of providers. Patients not already receiving ART were started on treatment within two months of initiating MDR-TB treatment. Results: Between May 2007 and May 2011, 71 HIV-infected patients were suspected to have MDR-TB, and 58 were initiated on treatment. MDR-TB was confirmed in 45 (78%), of which 18 (40%) were resistant to ofloxacin. Final treatment outcomes were available for 23 patients; 11 (48%) were successfully treated, 4 (17%) died, 6 (26%) defaulted, and 2 (9%) failed treatment. Overall, among 58 patients on treatment, 13 (22%) were successfully treated, 13 (22%) died, 7 (12%) defaulted, two (3%) failed treatment, and 23 (40%) were alive and still on treatment at the end of the observation period. Twenty-six patients (45%) experienced moderate to severe adverse events, requiring modification of the regimen in 12 (20%). Overall, 20 (28%) of the 71 patients with MDR-TB died, including 7 not initiated on treatment. Conclusions: Despite high fluoroquinolone resistance and extensive prior second-line treatment, encouraging results are being achieved in an ambulatory MDR-T- program in a slum setting in India. Rapid scale-up of both ART and second-line treatment for MDR-TB is needed to ensure survival of co-infected patients and mitigate this growing epidemic.</br

Mating First, Mating More: Biological Market Fluctuation in a Wild Prosimian

In biology, economics, and politics, distributive power is the key for understanding asymmetrical relationships and it can be obtained by force (dominance) or trading (leverage). Whenever males cannot use force, they largely depend on females for breeding opportunities and the balance of power tilts in favour of females. Thus, males are expected not only to compete within their sex-class but also to exchange services with the opposite sex. Does this mating market, described for humans and apes, apply also to prosimians, the most ancestral primate group? To answer the question, we studied a scent-oriented and gregarious lemur, Propithecus verreauxi (sifaka), showing female dominance, promiscuous mating, and seasonal breeding. We collected 57 copulations involving 8 males and 4 females in the wild (Berenty Reserve, South Madagascar), and data (all occurrences) on grooming, aggressions, and marking behaviour. We performed the analyses via exact Spearman and matrix correlations. Male mating priority rank correlated with the frequency of male countermarking over female scents but not with the proportion of fights won by males over females. Thus, males competed in an olfactory tournament more than in an arena of aggressive encounters. The copulation frequency correlated neither with the proportion of fights won by males nor with the frequency of male countermarking on female scents. Male-to-female grooming correlated with female-to-male grooming only during premating. Instead, in the mating period male-to-female grooming correlated with the copulation frequency. In short, the biological market underwent seasonal fluctuations, since males bargained grooming for sex in the mating days and grooming for itself in the premating period. Top scent-releasers gained mating priority (they mated first) and top groomers ensured a higher number of renewed copulations (they mated more). In conclusion, males maximize their reproduction probability by adopting a double tactic and by following market fluctuations

Australian chiropractic sports medicine: half way there or living on a prayer?

Sports chiropractic within Australia has a chequered historical background of unorthodox individualistic displays of egocentric treatment approaches that emphasise specific technique preference and individual prowess rather than standardised evidence based management. This situation has changed in recent years with the acceptance of many within sports chiropractic to operate under an evidence informed banner and to embrace a research culture. Despite recent developments within the sports chiropractic movement, the profession is still plagued by a minority of practitioners continuing to espouse certain marginal and outlandish technique systems that beleaguer the mainstream core of sports chiropractic as a cohesive and homogeneous group. Modern chiropractic management is frequently multimodal in nature and incorporates components of passive and active care. Such management typically incorporates spinal and peripheral manipulation, mobilisation, soft tissue techniques, rehabilitation and therapeutic exercises. Externally, sports chiropractic has faced hurdles too, with a lack of recognition and acceptance by organized and orthodox sports medical groups. Whilst some arguments against the inclusion of chiropractic may be legitimate due to its historical baggage, much of the argument appears to be anti-competitive, insecure and driven by a closed-shop mentality.sequently, chiropractic as a profession still remains a pariah to the organised sports medicine world. Add to this an uncertain continuing education system, a lack of protection for the title 'sports chiropractor', a lack of a recognized specialist status and a lack of support from traditional chiropractic, the challenges for the growth and acceptance of the sports chiropractor are considerable. This article outlines the historical and current challenges, both internal and external, faced by sports chiropractic within Australia and proposes positive changes that will assist in recognition and inclusion of sports chiropractic in both chiropractic and multi-disciplinary sports medicine alike

From Social Network (Centralized vs. Decentralized) to Collective Decision-Making (Unshared vs. Shared Consensus)

Relationships we have with our friends, family, or colleagues influence our personal decisions, as well as decisions we make together with others. As in human beings, despotism and egalitarian societies seem to also exist in animals. While studies have shown that social networks constrain many phenomena from amoebae to primates, we still do not know how consensus emerges from the properties of social networks in many biological systems. We created artificial social networks that represent the continuum from centralized to decentralized organization and used an agent-based model to make predictions about the patterns of consensus and collective movements we observed according to the social network. These theoretical results showed that different social networks and especially contrasted ones – star network vs. equal network - led to totally different patterns. Our model showed that, by moving from a centralized network to a decentralized one, the central individual seemed to lose its leadership in the collective movement's decisions. We, therefore, showed a link between the type of social network and the resulting consensus. By comparing our theoretical data with data on five groups of primates, we confirmed that this relationship between social network and consensus also appears to exist in animal societies

Assessing Tuberculosis Case Fatality Ratio: A Meta-Analysis

Background: Recently, the tuberculosis (TB) Task Force Impact Measurement acknowledged the need to review the assumptions underlying the TB mortality estimates published annually by the World Health Organization (WHO). TB mortality is indirectly measured by multiplying estimated TB incidence with estimated case fatality ratio (CFR). We conducted a meta-analysis to estimate the TB case fatality ratio in TB patients having initiated TB treatment. Methods: We searched for eligible studies in the PubMed and Embase databases through March 4(th) 2011 and by reference listing of relevant review articles. Main analyses included the estimation of the pooled percentages of: a) TB patients dying due to TB after having initiated TB treatment and b) TB patients dying during TB treatment. Pooled percentages were estimated using random effects regression models on the combined patient population from all studies. Main Results: We identified 69 relevant studies of which 22 provided data on mortality due to TB and 59 provided data on mortality during TB treatment. Among HIV infected persons the pooled percentage of TB patients dying due to TB was 9.2% (95% Confidence Interval (CI): 3.7%-14.7%) and among HIV uninfected persons 3.0% (95% CI: 21.2%-7.4%) based on the results of eight and three studies respectively providing data for this analyses. The pooled percentage of TB patients dying during TB treatment was 18.8% (95% CI: 14.8%-22.8%) among HIV infected patients and 3.5% (95% CI: 2.0%-4.92%) among HIV uninfected patients based on the results of 27 and 19 studies respectively. Conclusion: The results of the literature review are useful in generating prior distributions of CFR in countries with vital registration systems and have contributed towards revised estimates of TB mortality This literature review did not provide us with all data needed for a valid estimation of TB CFR in TB patients initiating TB treatmen

The Impact of PMSE on VLF Propagation

ABSTRACT PMSE or Polar Mesosphere Summer Echoes are a well known phenomenon in the summer northern polar regions, in which anomalous VHF/UHF radar echoes are returned from heights ~85 km. Associated phenomena at these altitudes are noctilucent clouds and electron density biteouts. The latter are electron density depletion layers of up to 90%, which may be several kms thick. Using the NOSC Modefndr code based on Wait's modal theory for subionospheric propagation, we calculate the shifts in received VLF amplitude and phase that occur as a result of electron density biteouts. The code assumes a homogeneous background ionosphere and a homogeneous biteout layer along the Great Circle Path (GCP) corridor, for transmitter receiver path lengths in the range 500-6000 km. For profiles during the 10hrs about midnight and under quiet geomagnetic conditions, where the electron density at 85 km would normally be less than 500 el/cc, it was found that received signal perturbations were significant, of the order of 1-4 dB and 5-40 degrees of phase. Perturbation amplitudes increase roughly as the square root of frequency. At short range perturbations are rather erratic, but more consistent at large ranges, readily interpretable in terms of the shifts in excitation factor, attenuation factor and v/c ratios for Wait's modes. Under these conditions such shifts should be detectable by a well constituted experiment involving multiple paths and multiple frequencies in the north polar region in summer. It is anticipated that VLF propagation could be a valuable diagnostic for biteout/PMSE when electron density at 85 km is under 500 el/cc, under which circumstances PMSE are not directly detectable by VHF/UHF radars. Keywords: 0689 Wave propagation, 2475 Polar ionosphere, 6934 Ionospheric propagation