Setting KwaZulu-Natal, South Africa a predominantly rural province with high burdens of TB, MDR-TB and HIV infection. Objective To determine the most effective model of care by comparing MDR-TB treatment outcomes at community-based sites with traditional care at a central, specialised hospital. Design A non-randomised observational prospective cohort study comparing community-based and centralised care. Patients at community-based sites were closer to home, had easier access to care and home-based care was available from treatment initiation. Results Four community-based sites treated 736 patients, while 813 were treated at the centralised hospital (a total of 1549 patients). Overall, 75% were HIV co-infected (community: 76% vs. hospitalised: 73%, p=0.45) and 86% received antiretroviral therapy (community: 91% vs. hospitalised: 82%, p=0.22). In multivariate analysis MDR-TB patients were more likely to have a successful treatment outcome if they were treated at a community-based site (adjusted OR=1.43, p=0.01). However, there was heterogeneity in outcomes at the four community-based sites, with Site 1 demonstrating that home-based care was associated with increased treatment success of 72% compared with success of between 52 - 60% at the other three sites. Conclusion Community-based care for patients with MDR-TB was more effective than care in a central, specialised hospital. Home-based care further increased treatment success.

A postmortem study by Ted Cohen and colleagues reveals a huge toll of tuberculosis among patients dying in hospitals in KwaZulu-Natal, South Africa.

We performed spoligotyping and 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing on M. tuberculosis culture-positive biopsy specimens collected from adults dying in a hospital in KwaZulu-Natal. Of 56 culture-positive samples genotyped, we detected mixed strains in five (9%) and clonal heterogeneity in an additional four (7%).The application of molecular approaches for detecting variation among Mycobacterium tuberculosis isolates has generated new appreciation for the diversity present within this relatively genetically conserved bacterial species (4, 17). Genotyping methods, such as insertion sequence typing (IS6110), spacer oligonucleotide typing (spoligotyping), and mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing, have been used to identify transmission chains (1,10,18,26), to classify strains into families and lineages (2,5,9,18,27,29), to identify episodes of exogenous reinfection (3,20,25,31), and, most recently, to detect the presence of within-host genetic heterogeneity (11,19,24,33).Genetic heterogeneity of M. tuberculosis within a host may arise by one of two mechanisms: (i) within-host diversification following a single infection event or (ii) reinfection resulting in a mixed infection with more than one strain (12, 16). The clinical consequences of within-host diversity are most obvious when manifesting as subpopulations of bacteria with resistance to tuberculosis (TB) antibiotics, either reflecting acquired drug resistance (mechanism 1) or transmitted drug resistance (mechanism 2). Furthermore, because individuals can be simultaneously infected by strains with different phenotypic characteristics (e.g., growth rates, drug resistance), the withinhost competition between strains may influence the clinical outcomes for coinfected patients (30) and may affect the population dynamics of the pathogen in the community (6,8).While within-host M. tuberculosis genetic diversity has been documented in many settings, systematic efforts to measure the prevalence of these complex infections have rarely been attempted. In this study, we report the results of a genotyping analysis on isolates collected from young adults dying in a hospital in KwaZulu-Natal, South Africa.We conducted limited autopsies on adults aged 20 to 45 years who died after admission to Edendale Hospital in KwaZulu-Natal, South Africa, between October 2008 and August 2009. The incidence of tuberculosis in KwaZulu-Natal is 1,094 cases/100,000 persons per year, and the HIV prevalence among women in antenatal clinical settings is 39% (14, 21). Our primary aim was to investigate the burden of tuberculosis as a contributing cause of death in this highly vulnerable community. Of the 240 decedents enrolled in the study, 94% were HIV seropositive. Fifty-eight percent of those on treatment for tuberculosis at the time of death were still infected with viable M. tuberculosis, while 42% of those not receiving treatment for TB also had positive M. tuberculosis cul...

Setting In KwaZulu-Natal, South Africa, a TB and HIV endemic setting, prolonged hospitalisation for the treatment of the growing number of MDR-TB patients is not possible or effective. Objective We compared early treatment outcomes in patients with MDR-TB, with and without HIV co infection, at a central, urban, referral hospital with four decentralised rural sites. Design This is an operational, prospective cohort study of patients between 1 July 2008 to 30 November 2009, where culture conversion, time-to-culture-conversion, survival and predictors of these outcomes were analysed. Results Of the 860 patients with MDR-TB, 419 were at the decentralised sites and 441 at the central hospital. Overall, 71% were HIV co-infected. In the 17 month study period, there was a higher proportion of culture conversion at the decentralised sites compared with the centralised hospital (54% vs. 24%; P<0.001; Odds Ratio 3.76, 95% CI 2.81 – 5.03). The median time to treatment initiation was significantly shorter at the decentralised sites compared with the centralised hospital (72 vs 93 days; p<0.001). There was no significant difference in survival following treatment initiation. Conclusion This study shows that early treatment outcomes suggest that decentralised care for MDR-TB patients is superior to that in a centralised setting.

The retrovirus forms its envelope by budding at the plasma membrane (PM). This process is primarily driven by its cytoplasmic core-precursor protein, Gag, as shown by the efficient formation of virus-like Gag particles in the absence of its envelope protein, Env. Most interestingly, several studies have demonstrated incorporation of various PM proteins into retrovirus, but the underlying mechanism of this phenomenon has remained elusive. We have purified Moloney murine leukemia virus Gag particles by sedimentation in an iodixanol gradient and donor PMs by flotation in a sucrose gradient and compared their protein compositions at equal lipid basis. We found that most PM proteins are present at similar density in both membranes. The inclusion of PM proteins was unaffected by incorporation of Env protein into the envelope of the Gag particles and whether these were produced at high or low level in the cells. These findings indicate that most PM proteins become incorporated into the retrovirus envelope without significant sorting. This feature of retrovirus assembly should be considered when studying retrovirus functions and developing retrovirus vectors.A ccording to a prevailing model, virus-specific membrane proteins are incorporated into the viral envelope by means of specific interactions with the viral core, whereas host membrane proteins, lacking possibilities to undergo such interactions, will be excluded (1). Although, experimental results support the validity of this model for some viruses-e.g., the alphaviruses (2)-it is not applicable to others-e.g., the retroviruses. In particular, several studies with HIV-1 suggest that many plasma membrane (PM) proteins of the host become incorporated into the viral envelope. These proteins include cell adhesion molecules such as CD44, LFA-1, and ICAM-1 and the antigen presenters . Similarly, studies with several different retroviruses show that they can be pseudotyped with envelope proteins of nonrelated viruses if the latter are expressed at the PM of the host cell (reviewed in refs. 4 and 5). These phenomenon may be related to the fact that retrovirus budding is not, like that of alphavirus, dependent on core-envelope protein (Env) interactions but depend on interactions of core proteins alone (reviewed in ref. 5). Thus, expression of the gag gene-i.e., the gene encoding the internal core protein (the Gag precursor)-in the absence of other viral genes results in formation of retrovirus-like Gag particles (reviewed in ref. 6). This Env-independent budding might favor host protein incorporation into the retrovirus envelope. However, the exact mechanism for the incorporation is still unclear. In particular, it is not known whether only certain or most PM proteins are incorporated into the retrovirus envelope and whether that incorporation occurs passively. To characterize this process it is necessary to compare the densities of PM proteins in the donor PM of the host cell and in the envelope of the retrovirus. Here we present such a study with Moloney murine leukemia ...