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author:("Moyo, isizulu")
1.  Predictors of knowledge about tuberculosis: results from SANHANES I, a national, cross-sectional household survey in South Africa 
BMC Public Health  2016;16:276.
Background
South Africa is one of the 22 high tuberculosis burden countries that contribute 80 % of the global tuberculosis cases. Tuberculosis is infectious and due to its rapid and easy transmission route poses a threat to population health. Considering the importance of social and psychological factors in influencing health outcomes, appraising knowledge and awareness of tuberculosis, remain vital for effective tuberculosis control. The main aim of this study was to investigate the factors that predict knowledge about tuberculosis among 18–64 year old adults in South Africa.
Methods
A cross-sectional survey method was used. Multi-stage disproportionate, stratified cluster sampling was used to select households within enumeration areas stratified by province and locality type. Based on the Human Sciences Research Council 2007 master sample, 500 Enumerator Areas representative of the socio-demographic profile of South Africa were identified and a random sample of 20 households was randomly selected from each Enumerator Area, yielding an overall sample of 10 000 households. The tuberculosis module contained in the South African National Health And Nutrition Examination Survey I was the only module that examined the social determinants of an infectious disease. This module was questionnaire-based with no biomarkers obtained to screen for the presence of tuberculosis disease among the participants. Data was collected by administering a researcher developed individual level questionnaire. Simple and multiple linear regression was used to determine the independent variables associated with tuberculosis knowledge.
Results
Half the sample (52.6 %) was female and the majority of the respondents were black African (76.5 %). More than two thirds (68.0 %) resided in urban areas, 56.9 % did not complete high school and half were not in formal employment. Significant predictors of tuberculosis knowledge were race, sex, completion of high school, being in employment, having a diagnosis of the disease in ones’ life-time and learning about tuberculosis from television, brochures, health workers, and teachers.
Conclusions
To reduce the burden of tuberculosis in South Africa, media campaigns targeting both rural and urban communities should include conveying accurate information about the disease. Policy makers should also address structural barriers that vulnerable communities face.
Electronic supplementary material
The online version of this article (doi:10.1186/s12889-016-2951-y) contains supplementary material, which is available to authorized users.
doi:10.1186/s12889-016-2951-y
PMCID: PMC4797251  PMID: 26987759
Cross-sectional national survey; Adult participants 18–64 years old; Tuberculosis (TB) knowledge; Social determinants of TB; TB/HIV co-existence; High burden country
2.  Time to Symptom Resolution in Young Children Treated for Pulmonary Tuberculosis 
Background
Response to treatment may be useful for diagnostic confirmation of childhood tuberculosis (TB). We aimed to evaluate time to symptom resolution in children treated for pulmonary TB.
Methods
We compared pulmonary TB cases and non-cases, classified by a published diagnostic algorithm, in South African children younger than two years of age. TB treatment was prescribed independently on clinical grounds. We analyzed independent determinants of baseline symptom resolution by Cox regression.
Results
191 symptomatic children, median age 12 months, were prescribed TB treatment. Chest radiograph features of TB were associated with longer time to resolution of cough (adjusted hazard ratio, AHR 0.31), wheeze (AHR 0.26) and failure to thrive (FTT) (AHR 0.41), (all p<0.05). However, median duration of baseline cough (63 vs. 70 days, p=0.98), wheeze (62 vs. 68 days, p=0.87) and FTT (76 vs. 66 days, p=0.59) did not differ in TB cases (n=48) vs. non-cases (n=46).
Conclusions
Baseline symptoms take longer than 60 days to resolve in the majority of young children after starting TB treatment. Further, since time to resolution does not differentiate TB cases from non-cases, clinical response to treatment is not an appropriate diagnostic criterion for pediatric trials of TB diagnostics, drugs and vaccines.
doi:10.1097/INF.0000000000000523
PMCID: PMC4229401  PMID: 25144794
Resolution; tuberculosis; children; symptoms; treatment
3.  Time to ART Initiation among Patients Treated for Rifampicin-Resistant Tuberculosis in Khayelitsha, South Africa: Impact on Mortality and Treatment Success 
PLoS ONE  2015;10(11):e0142873.
Setting
Khayelitsha, South Africa, with high burdens of rifampicin-resistant tuberculosis (RR-TB) and HIV co-infection.
Objective
To describe time to antiretroviral treatment (ART) initiation among HIV-infected RR-TB patients initiating RR-TB treatment and to assess the association between time to ART initiation and treatment outcomes.
Design
A retrospective cohort study of patients with RR-TB and HIV co-infection not on ART at RR-TB treatment initiation.
Results
Of the 696 RR-TB and HIV-infected patients initiated on RR-TB treatment between 2009 and 2013, 303 (44%) were not on ART when RR-TB treatment was initiated. The median CD4 cell count was 126 cells/mm3. Overall 257 (85%) patients started ART during RR-TB treatment, 33 (11%) within 2 weeks, 152 (50%) between 2–8 weeks and 72 (24%) after 8 weeks. Of the 46 (15%) who never started ART, 10 (21%) died or stopped RR-TB treatment within 4 weeks and 16 (37%) had at least 4 months of RR-TB treatment. Treatment success and mortality during treatment did not vary by time to ART initiation: treatment success was 41%, 43%, and 50% among patients who started ART within 2 weeks, between 2–8 weeks, and after 8 weeks (p = 0.62), while mortality was 21%, 13% and 15% respectively (p = 0.57). Mortality was associated with never receiving ART (adjusted hazard ratio (aHR) 6.0, CI 2.1–18.1), CD4 count ≤100 (aHR 2.1, CI 1.0–4.5), and multidrug-resistant tuberculosis (MDR-TB) with second-line resistance (aHR 2.5, CI 1.1–5.4).
Conclusions
Despite wide variation in time to ART initiation among RR-TB patients, no differences in mortality or treatment success were observed. However, a significant proportion of patients did not initiate ART despite receiving >4 months of RR-TB treatment. Programmatic priorities should focus on ensuring all patients with RR-TB/HIV co-infection initiate ART regardless of CD4 count, with special attention for patients with CD4 counts ≤ 100 to initiate ART as soon as possible after RR-TB treatment initiation.
doi:10.1371/journal.pone.0142873
PMCID: PMC4640533  PMID: 26555134
4.  Loss from Treatment for Drug Resistant Tuberculosis: Risk Factors and Patient Outcomes in a Community-Based Program in Khayelitsha, South Africa 
PLoS ONE  2015;10(3):e0118919.
Background
A community based drug resistant tuberculosis (DR-TB) program has been incrementally implemented in Khayelitsha, a high HIV and TB burden community in South Africa. We investigated loss from treatment (LFT), and post treatment outcomes of DR-TB patients in this setting.
Methodology
LFT, defined as interruption of treatment for ≥2 consecutive months was assessed among patients initiating DR-TB treatment for the first time between January 2009 and July 2011. Patients were traced through routine data sources to identify those who subsequently restarted treatment and those who died. Additional information on patient status and survival after LTF was obtained from community DR-TB counselors and from the national death registry. Post treatment outcomes were observed until July 2013.
Results
Among 452 patients initiating treatment for the first time within the given period, 30% (136) were LFT, with 67% retention at 18 months. Treatment was restarted in 27 (20%) patients, with additional resistance recorded in 2/25 (8%), excluding two with presumed DR-TB. Overall, 34 (25%) patients died, including 11 who restarted treatment. Males and those in the age category 15-25 years had a greater hazard of LFT; HR 1.93 (95% CI 1.35-2.75), and 2.43 (95% CI 1.52-3.88) respectively. Older age (>35 years) was associated with a greater hazard of death; HR 3.74 (1.13- 12.37) post treatment. Overall two-year survival was 62%. It was lower (45%) in older patients, and was 92% among those who received >12 months treatment.
Conclusion
LFT was high, occurred throughout the treatment period and was particularly high among males and those aged 15-25 years. Overall long term survival was poor. High rates of LFT should however not preclude scale up of community based care given its impact in increasing access to treatment. Further research is needed to support retention of DR-TB patients on treatment, even within community based treatment programs.
doi:10.1371/journal.pone.0118919
PMCID: PMC4364980  PMID: 25785451
5.  Impact of Decentralized Care and the Xpert MTB/RIF Test on Rifampicin-Resistant Tuberculosis Treatment Initiation in Khayelitsha, South Africa 
Open Forum Infectious Diseases  2015;2(1):ofv014.
Decentralization of treatment for rifampicin-resistant tuberculosis was associated with high treatment initiation and resulted in reduced time to treatment initiation. Xpert for TB diagnosis resulted in a significant further reduction in time to treatment.
Background. Globally, case detection and treatment access are poor for rifampicin-resistant tuberculosis (RR-TB). The Xpert MTB/RIF test has the potential to increase detection and reduce time to treatment (TTT). However, these benefits are dependent on health system capacity to provide treatment.
Methods. We retrospectively assessed the impact of Xpert on treatment initiation and TTT in the context of decentralized RR-TB care in Khayelitsha, Cape Town, using routine programmatic data. Community-based treatment was introduced progressively from 2008. Before 2007, diagnosis relied on phenotypic resistance (culture). During 2007–2008, the line probe assay (LPA) was introduced, followed by Xpert in 2012.
Results. Before decentralization (2003–2006), median TTT was 71 days (interquartile range [IQR], 49–134; n = 158). The LPA introduction during 2007–2008 was associated with reduced median TTT from 76 to 50 days (P < .0001, n = 257). Between January 2009 and June 2013, 938 RR-TB cases were diagnosed (74% human immunodeficiency virus [HIV]-infected). Decentralization during 2008–2011 was associated with declining TTT (P < .0001, test for trend), a decline to 28 days in 2011 (IQR, 16–40; n = 173). Xpert was associated with a further reduction to 8 days in 2013 (IQR, 5–25; n = 89; P < .0001). Treatment initiation remained unchanged with Xpert and was lower among HIV-infected (2010–2013); 87.9% (445 of 506) compared with 96.9% (188 of 194) for HIV-uninfected (P < .0001) patients.
Conclusions. Improved case detection and rapid treatment initiation are required to interrupt transmission and reduce mortality. In this setting, decentralization was associated with high treatment initiation and reduced TTT. Xpert implementation significantly enhanced the reduction in TTT and has the potential to reduce transmission.
doi:10.1093/ofid/ofv014
PMCID: PMC4438894  PMID: 26034764
delay; MDR-TB; RR-TB; treatment; Xpert
6.  A Phase IIa Trial of the New Tuberculosis Vaccine, MVA85A, in HIV- and/or Mycobacterium tuberculosis–infected Adults 
Rationale: Novel tuberculosis (TB) vaccines should be safe and effective in populations infected with Mycobacterium tuberculosis (M.tb) and/or HIV for effective TB control.
Objective: To determine the safety and immunogenicity of MVA85A, a novel TB vaccine, among M.tb- and/or HIV-infected persons in a setting where TB and HIV are endemic.
Methods: An open-label, phase IIa trial was conducted in 48 adults with M.tb and/or HIV infection. Safety and immunogenicity were analyzed up to 52 weeks after intradermal vaccination with 5 × 107 plaque-forming units of MVA85A. Specific T-cell responses were characterized by IFN-γ enzyme-linked immunospot and whole blood intracellular cytokine staining assays.
Measurements and Main Results: MVA85A was well tolerated and no vaccine-related serious adverse events were recorded. MVA85A induced robust and durable response of mostly polyfunctional CD4+ T cells, coexpressing IFN-γ, tumor necrosis factor-α, and IL-2. Magnitudes of pre- and postvaccination T-cell responses were lower in HIV-infected, compared with HIV-uninfected, vaccinees. No significant effect of antiretroviral therapy on immunogenicity of MVA85A was observed.
Conclusions: MVA85A was safe and immunogenic in persons with HIV and/or M.tb infection. These results support further evaluation of safety and efficacy of this vaccine for prevention of TB in these target populations.
doi:10.1164/rccm.201108-1548OC
PMCID: PMC3326425  PMID: 22281831
tuberculosis; HIV-1; vaccine; MVA85A; clinical trial
7.  MVA85A, a novel TB vaccine, is safe in adolescents and children, and induces complex subsets of polyfunctional CD4+ T cells 
European journal of immunology  2010;40(1):279-290.
Summary
MVA85A is a new tuberculosis vaccine aimed at enhancing immunity induced by BCG. We investigated the safety and immunogenicity of MVA85A in healthy adolescents and children from a tuberculosis endemic region, who received BCG at birth.
Twelve adolescents and 24 children were vaccinated and followed up for 12 or 6 months, respectively. Adverse events were documented and vaccine-induced immune responses assessed by IFN-γ ELISpot and intracellular cytokine staining.
The vaccine was well tolerated and there were no vaccine-related serious adverse events. MVA85A induced potent and durable T cell responses. Multiple CD4+ T cell subsets, based on expression of IFN-γ, TNF-α, IL-2, IL-17 and GM-CSF, were induced. Polyfunctional CD4+ T cells co-expressing IFN-γ, TNF-α and IL-2 dominated the response in both age groups. A novel CD4+ cell subset co-expressing these three Th1 cytokines and IL-17 was induced in adolescents, while a novel CD4+ T cell subset co-expressing Th1 cytokines and GM-CSF was induced in children. Antigen-specific CD8+ T cells were not detected.
We conclude that in adolescents and children MVA85A safely induces the type of immunity thought to be important in protection against tuberculosis. This includes induction of novel Th1 cell populations which have not been previously described in humans.
doi:10.1002/eji.200939754
PMCID: PMC3044835  PMID: 20017188
MVA85A; tuberculosis; vaccine; polyfunctional; IL-17
8.  Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in healthy adults in South Africa1 
The Journal of infectious diseases  2008;198(4):544-552.
BACKGROUND
The efficacy of BCG may be enhanced by heterologous vaccination strategies that boost the BCG-primed immune response. One leading booster vaccine, MVA85A, has shown promising safety and immunogenicity in UK human trials. We investigated the safety and immunogenicity of MVA85A in mycobacteria-exposed, but Mycobacterium tuberculosis-uninfected, healthy adults from a TB-endemic region of South Africa.
METHODS
Twenty-four adults were vaccinated with MVA85A. All subjects were followed up for one year for adverse events and for immunological assessment.
RESULTS
MVA85A vaccination was well tolerated and induced potent T cell responses, measured by IFN-γ ELISPOT assay, which exceeded pre-vaccination levels up to 364 days after vaccination. BCG-specific CD4+ T cells boosted by MVA85A comprised of multiple populations expressing combinations of IFN-γ, TNF-α, IL-2 and IL-17, as measured by polychromatic flow cytometry. IFN-γ expressing and polyfunctional IFN-γ+TNF-α+IL-2+ CD4+ T cells were boosted during the peak BCG-specific response 7 days post-vaccination.
CONCLUSION
The excellent safety profile and quantitative and qualitative immunogenicity data strongly support further trials to assess the efficacy of MVA85A as a boosting vaccine in TB endemic countries.
doi:10.1086/590185
PMCID: PMC2822902  PMID: 18582195
Vaccination; tuberculosis; T cells; MVA85A; South Africa
9.  Isolation of Non-Tuberculous Mycobacteria in Children Investigated for Pulmonary Tuberculosis 
PLoS ONE  2006;1(1):e21.
Objective
To evaluate the frequency and clinical significance of non-tuberculous mycobacteria (NTM) isolates among children investigated for pulmonary tuberculosis in a rural South African community.
Methods
Children were investigated for pulmonary tuberculosis as part of a tuberculosis vaccine surveillance program (2001–2005). The clinical features of children in whom NTM were isolated, from induced sputum or gastric lavage, were compared to those with culture-proven M. tuberculosis.
Results
Mycobacterial culture demonstrated 114 NTM isolates from 109 of the 1,732 children investigated, a crude yield of 6% (95% CI 5–7). The comparative yield of positive NTM cultures from gastric lavage was 40% (95% CI 31–50), compared to 67% (95% CI 58–76) from induced sputum. 95% of children with NTM isolates were symptomatic. Two children were HIV-infected. By contrast, M. tuberculosis was isolated in 187 children, a crude yield of 11% (95% CI 9–12). Compared to those with culture-proven M. tuberculosis, children with NTM isolates were less likely to demonstrate acid-fast bacilli on direct smear microscopy (OR 0.19; 95% 0.0–0.76). Children with NTM were older (p<0.0001), and more likely to demonstrate constitutional symptoms (p = 0.001), including fever (p = 0.003) and loss of weight or failure to gain weight (p = 0.04), but less likely to demonstrate a strongly positive tuberculin skin test (p<0.0001) or radiological features consistent with pulmonary tuberculosis (p = 0.04).
Discussion
NTM were isolated in 6% of all children investigated for pulmonary tuberculosis and in more than one third of those with a positive mycobacterial culture. NTM may complicate the diagnosis of PTB in regions that lack capacity for mycobacterial species identification. The association of NTM isolates with constitutional symptoms suggestive of host recognition requires further investigation.
doi:10.1371/journal.pone.0000021
PMCID: PMC1762386  PMID: 17183648

Results 1-9 (9)