Sydenham, South Africa
Sydenham, South Africa

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Danaviah S.,University of KwaZulu - Natal | Sacks J.A.,Rutgers University | Kumar K.P.S.,King George v Hospital | Kumar K.P.S.,Inkosi Albert Luthuli Central Hospital | And 7 more authors.
Tuberculosis | Year: 2013

Tuberculosis (TB) is mainly a disease of the lungs, but Mycobacterium tuberculosis (Mtb) can establish infection in virtually any organ in the body. Rising rates of extrapulmonary (EP) TB have been largely associated with the HIV epidemic, as patients co-infected with HIV show a four-fold higher risk of EPTB. Spinal TB (Pott's Disease), one of the most debilitating extrapulmonary forms of disease, is difficult to diagnose and can cause deformity and/or neurological deficits. This study examined the histopathology and distribution of immune cells within spinal TB lesions and the impact of HIV on pathogenesis. The overall structure of the spinal granulomas resembled that seen in lung lesions from patients with pulmonary TB. Evidence of efficient macrophage activation and differentiation were detectable within organized structures in the spinal tissue, irrespective of HIV status. Interestingly, the granulomatous architecture and macroscopic features were similar in all samples examined, despite a reversal in the ratio of infiltrating CD4 to CD8 T cells in the lesions from HIV-infected patients. This study provides a foundation to understand the mechanism of tissue destruction and disease progression in Spinal TB, enabling the future development of novel therapeutic strategies and diagnostic approaches for this devastating disease. © 2013 Elsevier Ltd. All rights reserved.


Padayatchi N.,Center for Programme of Research in South Africa | Daftary A.,Center for Programme of Research in South Africa | Daftary A.,University of Toronto | Moodley T.,Center for Programme of Research in South Africa | And 2 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2010

BACKGROUND: Health care workers (HCWs) are at greater risk for tuberculosis (TB), including multidrugresistant TB (MDR-TB), compared to the general population. The psychosocial impact of nosocomial TB on HCWs has received little attention in the literature. METHODS: A retrospective medical record review from 1999 to 2003 found 15 HCWs who were treated for drug-resistant TB at a specialist hospital in South Africa. Five human immunodeficiency virus (HIV) negative doctors with no predisposing factors for drug resistance are included in this case series. We collectively present their clinical case histories based on medical records from 2000 to 2005, and explore the long-term psychosocial impact of TB from interviews conducted in 2009. RESULTS: Four doctors had primary MDR-TB and one had primary resistance to multiple first-line drugs. Time from symptom onset to commencement of effective treatment ranged from 8 to 39 weeks. Time for bacteriological confirmation of drug-resistant TB ranged from 6 to 24 weeks. All were cured within 3 years of initial presentation. Content analysis of follow-up interviews revealed five main themes: 1) prolonged morbidity, 2) psychological impact, 3) poor infection control, 4) weak support structures and 5) attrition from the field. CONCLUSION: Themes emergent from this case series encourage prioritisation of TB infection control education and practice to minimise HCW morbidity and prevent HCW attrition from high-burden resource-constrained settings. © 2010 The Union.


O'Donnell M.R.,Yeshiva University | O'Donnell M.R.,Center for Programme of Research in South Africa | Zelnick J.,Touro College | Werner L.,Center for Programme of Research in South Africa | And 4 more authors.
Emerging Infectious Diseases | Year: 2011

To determine whether women in KwaZulu-Natal, South Africa, with drug-resistant tuberculosis (TB) were more likely than men to have extensively drug-resistant TB, we reviewed 4,514 adults admitted during 2003-2008 for drug-resistant TB. Female sex independently predicted extensively drug-resistant TB, even after we controlled for HIV infection. This association needs further study.


Shenoi S.V.,Yale University | Brooks R.P.,Philanjalo Care Center | Barbour R.,Yale University | Altice F.L.,Yale University | And 5 more authors.
PLoS ONE | Year: 2012

Background: Drug-resistant tuberculosis (TB) is a major threat to global public health. Patients with extensively drug-resistant TB (XDR-TB), particularly those with HIV-coinfection, experience high and accelerated mortality with limited available interventions. To determine modifiable factors associated with survival, we evaluated XDR-TB patients from a community-based hospital in rural South Africa where a large number of XDR-TB cases were first detected. Methodology/Principal Findings: A retrospective case control study was conducted of XDR-TB patients diagnosed from 2005-2008. Survivors, those alive at 180 days from diagnostic sputum collection date, were compared with controls who died within 180 days. Clinical, laboratory and microbiological correlates of survival were assessed in 69 survivors (median survival 565 days [IQR 384-774] and 73 non-survivors (median survival 34 days [IQR 18-90]). Among 129 HIV+ patients, multivariate analyses of modifiable factors demonstrated that negative AFB smear (AOR 8.4, CI 1.84-38.21), a lower laboratory index of routine laboratory findings (AOR 0.48, CI 0.22-1.02), CD4>200 cells/mm 3 (AOR 11.53, 1.1-119.32), and receipt of antiretroviral therapy (AOR 20.9, CI 1.16-376.83) were independently associated with survival from XDR-TB. Conclusions/Significance: Survival from XDR-TB with HIV-coinfection is associated with less advanced stages of both diseases at time of diagnosis, absence of laboratory markers indicative of multiorgan dysfunction, and provision of antiretroviral therapy. Survival can be increased by addressing these modifiable risk factors through policy changes and improved clinical management. Health planners and clinicians should develop programmes focusing on earlier case finding and integration of HIV and drug-resistant TB diagnostic, therapeutic, and preventive activities. © 2012 Shenoi et al.


Brust J.C.M.,Yeshiva University | Gandhi N.R.,Yeshiva University | Carrara H.,Center for the Programme of Research in South Africa | Osburn G.,King George V Hospital | Padayatchi N.,Center for the Programme of Research in South Africa
International Journal of Tuberculosis and Lung Disease | Year: 2010

SETTING: Multidrug-resistant tuberculosis (MDR-TB) has emerged as a significant public health threat in South Africa. OBJECTIVE: To describe treatment outcomes and determine risk factors associated with unfavorable outcomes among MDR-TB patients admitted to the provincial TB referral hospital in KwaZulu-Natal Province, South Africa. DESIGN: Retrospective observational study of MDR-TB patients admitted from 2000 to 2003. RESULTS: Of 1209 MDR-TB patients with documented treatment outcomes, 491 (41%) were cured, 35 (3%) completed treatment, 208 (17%) failed treatment, 223 (18%) died and 252 (21%) defaulted. Of the total number of patients with known human immunodeficiency virus (HIV) status, 52% were HIV-infected. Treatment failure, death and default each differed in their risk factors. Greater baseline resistance (aOR 2.3-3.0), prior TB (aOR 1.7), and diagnosis in 2001, 2002 or 2003 (aOR 1.9-2.3) were independent risk factors for treatment failure. HIV co-infection was a risk factor for death (aOR 5.6), and both HIV (aOR 2.0) and male sex (aOR 1.9) were risk factors for treatment default. CONCLUSION: MDR-TB treatment outcomes in KwaZulu-Natal were substantially worse than those published from other MDR-TB cohorts. Interventions such as concurrent antiretroviral therapy and decentralized MDR-TB treatment should be considered to improve MDR-TB outcomes in this high HIV prevalence setting. © 2010 The Union.


O'Donnell M.R.,Yeshiva University | O'Donnell M.R.,Center for Programme of Research in South Africa | Padayatchi N.,Center for Programme of Research in South Africa | Padayatchi N.,Boston University | And 5 more authors.
Emerging Infectious Diseases | Year: 2013

High mortality rates have been reported for patients co-infected with extensively drug-resistant tuberculosis (XDR-TB) and HIV, but treatment outcomes have not been reported. We report treatment outcomes for adult XDR TB patients in KwaZulu-Natal Province, South Africa. Initial data were obtained retrospectively, and outcomes were obtained prospectively during 24 months of treatment. A total of 114 XDR TB patients were treated (median 6 drugs, range 3-9 drugs) 82 (73%) were HIV positive and 50 (61%) were receiving antiretroviral therapy. After receiving treatment for 24 months, 48 (42%) of 114 patients died, 25 (22%) were cured or successfully completed treatment, 19 (17%) withdrew from the study, and 22 (19%) showed treatment failure. A higher number of deaths occurred among HIV-positive patients not receiving antiretroviral therapy and among patients who did not show sputum culture conversion. Culture conversion was a major predictor of survival but was poorly predictive (51%) of successful treatment outcome.


Thomas T.A.,Tugela Ferry Care and Research Collaboration | Thomas T.A.,Yale University | Thomas T.A.,University of Virginia | Shenoi S.V.,Tugela Ferry Care and Research Collaboration | And 13 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2010

SETTING: Extensively drug-resistant tuberculosis (XDRTB) has been documented worldwide, but reports of XDR-TB in children are extremely limited. OBJECTIVE: To report the characteristics of pediatric XDR-TB patients in rural South Africa. DESIGN: We retrospectively reviewed children with sputum culture-confirmed XDR-TB from Tugela Ferry, South Africa, from January 2006 to December 2007. Demographic, clinical and microbiologic data were abstracted from medical records. RESULTS: Four children aged 6-8 years with XDR-TB were reviewed. Two had previous histories of TB. All were human immunodeficiency virus (HIV) infected orphans; three received highly active antiretroviral therapy (HAART) before XDR-TB diagnosis. All had clinical and radiographic improvement and sputum culture conversion while on standardized XDR-TB treatment and HAART. Two tolerated concomitant XDR-TB and HIV treatment well. Two experienced neuropsychiatric side effects related to cycloserine. All have survived >24 months and all were cured. Prior to XDR-TB diagnosis, the children had resided in the hospital's pediatric ward for a median of 8 months (range 5-17), including a 3-month overlapping period. CONCLUSIONS: XDR-TB is a microbiologic diagnosis that, even with HIV co-infection, can be successfully identified. Concurrent XDR-TB and HIV therapy is feasible and effective in children, although more research is needed into potential overlapping toxicities. Nosocomial transmission is suggested, calling for infection control policies in pediatric wards. © 2010 The Union.


Heller T.,Hlabisa Hospital | Lessells R.J.,University of KwaZulu - Natal | Wallrauch C.G.,University of KwaZulu - Natal | Barnighausen T.,University of KwaZulu - Natal | And 8 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2010

SETTING: Hlabisa health sub-district, KwaZulu-Natal, South Africa. OBJECTIVE: To describe the establishment of a community-based multidrug-resistant tuberculosis (MDR-TB) treatment programme embedded in the district TB control programme and to evaluate whether early outcomes are comparable to those in the traditional hospital-based model of care. DESIGN: Cases who initiated community-based MDRTB treatment (CM) between March and December 2008 were compared with patients who initiated MDR-TB treatment under the traditional hospital-based model of care (TM) between January 2001 and February 2008. Time to initiation of treatment and time to sputum smear and culture conversion were compared for the two groups in Kaplan-Meier survival curves using the Mantel-Cox log-rank test. RESULTS: Overall, 50 CM cases and 57 TM cases were included; 39 of the 50 CM cases (78.0%) were human immunodeficiency virus positive. The median time to initiation of treatment was 84 days for CM and 106.5 days for TM (P = 0.002). Median time to sputum smear conversion was shorter for CM than TM (59 vs. 92 days, P = 0.055), as was time to sputum culture conversion (85 vs. 119 days, P = 0.002). CONCLUSION: Community-based treatment for MDRTB can be implemented within the existing TB control programme in rural South Africa and should be scaled up where resources allow. © 2010 The Union.

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