Data quality of drug-resistant tuberculosis and antiretroviral therapy electronic registers in South Africa.

Background: To assess the quality and completeness of treatment and outcome data in the electronic tuberculosis (TB) and antiretroviral treatment (ART) registers in drug-resistant (DR-) TB patients at three treatment facilities in South Africa.

Methods: We did a retrospective cohort study using routinely-collected data from DR-TB registers of rifampicin resistant adults (≥18 years old), on ART, initiating DR-TB treatment between January 2012 and December 2013. We linked patient information from the DR-TB register to the ART register using patient identifiers and an algorithm based on string edit distance and date of birth.

MDR-TB patients in KwaZulu-Natal, South Africa: Cost-effectiveness of 5 models of care.

Background: South Africa has a high burden of MDR-TB, and to provide accessible treatment the government has introduced different models of care. We report the most cost-effective model after comparing cost per patient successfully treated across 5 models of care: centralized hospital, district hospitals (2), and community-based care through clinics or mobile injection teams.

Methods: In an observational study five cohorts were followed prospectively.

Biomarkers for Tuberculosis Based on Secreted, Species-Specific, Bacterial Small Molecules.

Improved biomarkers are needed for tuberculosis. To develop tests based on products secreted by tubercle bacilli that are strictly associated with viability, we evaluated 3 bacterial-derived, species-specific, small molecules as biomarkers: 2 mycobactin siderophores and tuberculosinyladenosine. Using liquid chromatography-tandem mass spectrometry, we demonstrated the presence of 1 or both mycobactins and/or tuberculosinyladenosine in serum and whole lung tissues from infected mice and sputum, cerebrospinal fluid (CSF), or lymph nodes from infected patients but not uninfected controls.

Community-based care vs. centralised hospitalisation for MDR-TB patients, KwaZulu-Natal, South Africa.

Setting: KwaZulu-Natal, South Africa, a predominantly rural province with a high burden of tuberculosis (TB), multidrug-resistant TB (MDR-TB) and human immunodeficiency virus (HIV) infection.

Objective: To determine the most effective care model 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.

Revisiting Anti-tuberculosis Activity of Pyrazinamide in Mice.

The mechanism of action of pyrazinamide, a key sterilizing drug in the treatment of tuberculosis, remains elusive; pyrazinamide is a pro-drug that requires activation by a bacterial-encoded enzyme, and its activity is most apparent on non-replicating . Recently, it has been suggested that pyrazinamide might exert also some host-directed effect in addition to its antimicrobial activity. To address this possibility, three sequential experiments were conducted in immune-competent BALB/c and in immune-deficient, athymic nude mice.

Association between health systems performance and treatment outcomes in patients co-infected with MDR-TB and HIV in KwaZulu-Natal, South Africa: implications for TB programmes.

Objective: To improve the treatment of MDR-TB and HIV co-infected patients, we investigated the relationship between health system performance and patient treatment outcomes at 4 decentralised MDR-TB sites.

Methods: In this mixed methods case study which included prospective comparative data, we measured health system performance using a framework of domains comprising key health service components. Using Pearson Product Moment Correlation coefficients we quantified the direction and magnitude of the association between health system performance and MDR-TB treatment outcomes.

The treatment journey of a patient with multidrug-resistant tuberculosis in South Africa: is it patient-centred?

To improve the treatment of patients co-infected with multidrug-resistant tuberculosis (MDR-TB) and the human immunodeficiency virus, we measured the relationship between treatment outcomes and hospital performance at four decentralised MDR-TB sites in South Africa. We describe hospital performance from the patient's perspective by the use of a graphic that visually represents a patient's treatment journey. The graphic was used to report study findings to study sites and as a catalyst for a quality improvement process.

Modeling early bactericidal activity in murine tuberculosis provides insights into the activity of isoniazid and pyrazinamide.

Standard tuberculosis (TB) treatment includes an initial regimen containing drugs that are both rapidly bactericidal (isoniazid) and sterilizing (rifampin and pyrazinamide), and ethambutol to help prevent the emergence of drug resistance. Antagonism between isoniazid and pyrazinamide has been demonstrated in a TB treatment mouse model. Because isoniazid's bactericidal activity is greatest during the initial two treatment days, we hypothesized that removing isoniazid after the second day would increase the effectiveness of the standard regimen.

Polymorphisms in the gene that encodes the iron transport protein ferroportin 1 influence susceptibility to tuberculosis.

Background: We studied the association between iron intake and polymorphisms in the iron transporter gene SLC40A1 and the risk of tuberculosis.

Methods: We compared iron intake, the frequency of SLC40A1 mutations, and interactions among these variables among 98 tuberculosis patients and 125 controls in Kwazulu-Natal, South Africa.

Results: Four SLC40A1 single-nucleotide polymorphisms (SNPs) were associated with an increased risk of tuberculosis and 1 SNP with reduced risk.

Comparing early treatment outcomes of MDR-TB in decentralised and centralised settings in KwaZulu-Natal, South Africa.

Setting: In KwaZulu-Natal, South Africa, a setting endemic for tuberculosis (TB) and the human immunodeficiency virus (HIV), prolonged hospitalisation for the treatment of the growing number of multidrug-resistant TB (MDR-TB) patients is neither possible nor effective.

Objective: To compare early treatment outcomes in patients with MDR-TB with and without HIV co-infection at four decentralised rural sites with a central urban referral hospital.

Design: This is an operational, prospective cohort study of patients between 1 July 2008 and 30 November 2009, where culture conversion, time to culture conversion, survival and predictors of these outcomes were analysed.

Drug-Resistant tuberculosis, KwaZulu-Natal, South Africa, 2001-2007.

In Africa, incidence and prevalence of drug-resistant tuberculosis have been assumed to be low. However, investigation after a 2005 outbreak of extensively drug-resistant tuberculosis in KwaZulu-Natal Province, South Africa, found that the incidence rate for multidrug-resistant tuberculosis in KwaZulu-Natal was among the highest globally and would be higher if case-finding efforts were intensified.

Mixed-strain Mycobacterium tuberculosis infections among patients dying in a hospital 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 prevalence and drug sensitivity of tuberculosis among patients dying in hospital in KwaZulu-Natal, South Africa: a postmortem study.

Background: Tuberculosis is the leading cause of death in South Africa by death notification, but accurate diagnosis of tuberculosis is challenging in this setting of high HIV prevalence. We conducted limited autopsies on young adults dying in a single public hospital in the province of KwaZulu-Natal between October 2008 and August 2009 in order to estimate the magnitude of deaths attributable to tuberculosis.

Methods And Findings: We studied a representative sample of 240 adult inpatients (aged 20-45 years) dying after admission to Edendale Hospital.

Tuberculosis retreatment category predicts resistance in hospitalized retreatment patients in a high HIV prevalence area.

Setting: Rates of multidrug-resistant tuberculosis (MDR-TB) are currently as high as 7.7% in retreatment cases in KwaZulu-Natal, South Africa. MDR-TB prevalence is known to be high in patients categorized as treatment failures.

The A17L gene product of vaccinia virus is exposed on the surface of IMV.

The p21 membrane protein of vaccinia virus (VV), encoded by the A17L gene, has been reported to localize on the inner of the two membranes of the intracellular mature virus (IMV). It has also been shown that p21 acts as a membrane anchor for the externally located fusion protein p14 (A27L gene). Since p14 is located on the surface of IMVs, it is hard to envision that p21 should be located only on the inner membrane.

Minimal exclusion of plasma membrane proteins during retroviral envelope formation.

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.

Localization of actin in Moloney murine leukemia virus by immunoelectron microscopy.

Immunoelectron microscopy was used to detect actin in wild-type (wt) Moloney murine leukemia virus (MoMuLV) and in virus-like particles (VLP) produced by recombinant Semliki Forest virus expressing only the MoMuLV gag polyprotein. Gold immunolabeling revealed the presence of actin on the surface of delipidized VLP and delipidized wt virus particles. Statistical evaluation of the number of colloidal gold particles per VLP revealed a large range of values and a prevalence of VLP with small numbers of gold particles.