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 between these variables among 98 TB patients and 125 controls in Kwazulu-Natal, South Africa. Results: Four SLC40A1 SNPs were associated with an increased risk of tuberculosis and one with reduced risk. We also found a gene-environment interaction for four non-exonic SNPs and iron intake. Conclusions: This pilot study demonstrated an association between polymorphisms in SLC40A1 and tuberculosis and provided evidence for an interaction between dietary iron and SLC40A1.Organismic and Evolutionary Biolog

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

Comparing early treatment outcomes of MDR-TB in a decentralised setting with a centralised setting in KwaZulu-Natal, South Africa.

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

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

CAPRISA, 2015.Abstract available in pdf

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

CAPRISA, 2018.Abstract available in pdf

The Prevalence and Drug Sensitivity of Tuberculosis among Patients Dying in Hospital in KwaZulu-Natal, South Africa: A Postmortem Study

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

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.

CAPRISA, 2014.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. Qualitative data from participant observation and interviews analysed using systematic text condensation (STC) complemented our quantitative findings. Findings: We found significant differences in treatment outcomes across the sites with successful outcomes varying from 72% at Site 1 to 52% at Site 4 (p<0.01). Health systems performance scores also varied considerably across the sites. Our findings suggest there is a correlation between treatment outcomes and overall health system performance which is significant (r = 0.99, p<0.01), with Site 1 having the highest number of successful treatment outcomes and the highest health system performance. Although the 'integration' domain, which measured integration of MDR-TB services into existing services appeared to have the strongest association with successful treatment outcomes (r = 0.99, p<0.01), qualitative data indicated that the 'context' domain influenced the other domains. Conclusion: We suggest that there is an association between treatment outcomes and health system performance. The chance of treatment success is greater if decentralised MDR-TB services are integrated into existing services. To optimise successful treatment outcomes, regular monitoring and support are needed at a district, facility and individual level to ensure the local context is supportive of new programmes and implementation is according to guidelines

Envelopment of retrovirus and vaccinia virus

This thesis describes envelopment of retrovirus and vaccinia virus. Retrovirus envelopment, i.e. budding, occurs from the plasma membrane (PM) of infected cells in an environment that is abundant with cellular proteins. In general, the viral budding process has been assumed to displace cellular membrane proteins with viral proteins, thus producing viral particles that are free from cellular components. Although this appears to be true for tightly organised viruses such as alphavirus, a number of host proteins have been reported to be incorporated in retroviral particles. Our aim was to study host protein incorporation on a general basis in Moloney- Murine Leukaemia virus Gag particles. Therefore, we developed a method by which it was possible to directly and quantitatively compare the protein composition of the PM used for budding, with the viral envelope. Our results demonstrated that most cellular proteins present in PM were recovered in the retrovirus membrane in almost similar concentrations. This indicated that the lateral associations of Gag proteins, while forming the internal shell, did not exclude any significant amount of host proteins. Since the presence of host proteins in retrovirus particles was never studied in depth until now, the presence of a certain host protein in the particles was thought to be specific. Our results demonstrated that there is no specific sorting of host proteins during budding. In fact, retroviruses randomly included host proteins that were located in the area of budding. Structural studies of the matrix protein of Gag revealed a lattice of loosely packaged hexameric rings. This structure appears to give plenty of room to accommodate foreign proteins, as long as they do not exert significant sterical hindrance for the formation of the Gag shell. We have also demonstrated an interaction in vivo between the Gag and Env protein, since the Env protein was five times more concentrated in viral particles, when compared to the PM. This amount was the same for the wild type retroviral particles. The Env-Gag interaction had no effect on the incorporation of host proteins in the viral particles. One of the host proteins present in the Gag particles was identified by immunolabeling to be actin. By studying Gag particles in immunoelectron microscopy, we found that actin was located underneath the membrane, on top of the Gag-shell. We do not think that actin is a structural component of the particles, but rather we hypothesise that actin is an accidental stowaway from scissioning and release of Gag particles from the PM. Intracellular mature virus (IMV) of Vaccinia virus (VV) is thought to be wrapped by a double membrane derived from the intermediate compartment between ER and Golgi. The membranes are modified by the insertion of VV membrane proteins to form two tightly apposed membranes, which line up as rigid crescents around the virosome. The virosome contains material, which is engulfed by the membrane crescents forming a spherical, immature virus, which matures into the brick-shaped IMV. The IMV membrane protein p21 (gene product of A17L) is essential for formation of the viral crescents, since in its absence, the precursor membranes do not form the rigid crescents. By using immuno-electron microscopy and biochemical methods, we demonstrated that p21 is located on the surface of IMV in the outer membrane, in addition to the internal membrane. Its localisation and topology makes it possible for p21 to form disulphide-linked homodimers between both leaflets of the double membrane. Thus, p21 might function as the merging force to flatten the compartment membranes and form the tightly apposed double membrane of IM

Salivary IgA reactions to cell-surface antigens of oral streptococci.

BACKGROUND: In the immunoblot technique, using whole bacteria cell extracts as antigens, both intra- and extracellular antigens are de-tected, which gives a large number of immunoglobulin A (IgA) reac-tions (immunoblot bands) when incubated with saliva. It is important to distinguish which immunoblot bands represent bacterial cell-surface antigens, since these antigens could be involved in adhesion mecha-nisms and be available for blocking in vivo. METHODS: Bacterial ex-tracts of Streptococcus mutans, Streptococcus sobrinus, Streptococcus parasanguis and the streptococcal antigen I/II were separated using SDS-PAGE. The antigens were detected with saliva in Western blot. Untreated saliva and saliva in which cell-surface reactive IgA had been absorbed with whole bacteria cells were analyzed. RESULTS: Ap-proximately half the number of the bands were absent for saliva ab-sorbed with homologous cells, compared to untreated saliva. The ab-sorption pattern was almost identical for S. mutans and S. sobrinus but not for S. parasanguis. Salivary IgA reactive against streptococcal antigen I/II was absorbed by S. mutans cells, to a lesser extent by S. sobrinus cells, and not at all by S. parasanguis cells. CONCLUSION: It is likely that the bands that were absent after absorption represented cell-surface antigens. For S. mutans and S. sobrinus, these bands were probably the streptococcal antigen I/II. Copyright Blackwell Munks-gaard, 2004