Publications (47)232.14 Total impact
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Article: Undiagnosed tuberculosis among HIV clinic attendees: association with antiretroviral therapy and implications for intensified case finding, isoniazid preventive therapy, and infection control.
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ABSTRACT: Initiation of antiretroviral therapy (ART) and the 3I's are strategies to prevent HIV-associated tuberculosis (TB). We describe factors associated with undiagnosed TB among HIV-infected patients attending an HIV clinic in South Africa and discuss implications for the 3 Is. Convenience sample of HIV clinic attendees. HIV-infected participants were assessed for TB using a symptom screen, sputum-smear microscopy, sputum and blood mycobacterial culture, fine needle aspiration of enlarged lymph nodes, and chest radiography. Four hundred twenty-two participants were enrolled. The median age and CD4+ T-cell count were 37 years [interquartile range (IQR): 31-44 years] and 215 cells per microliter (IQR: 107-347 cells/μL). Forty-seven percent had been on ART for a median duration of 8 months (IQR: 3.3-22.8 months). Three hundred sixty-one participants (85.6%) reported TB symptoms. Twenty-seven participants (6.4%) met criteria for bacteriologically confirmed TB and 50 (11.6%) for any form of TB. Bacteriologically confirmed TB was associated with CD4+ T-cell counts ≤100 cells per microliter (odds ratio: 5.05, 95% confidence interval: 1.69 to 15.12) when compared with CD4+ T-cell counts >200 cells per microliter and hemoglobin {hemoglobin < 10 g/dL [odds ratio 3.12 (95% confidence interval: 1.26 to 7.72)]}. Undiagnosed TB among HIV-infected ambulatory patients was associated with low CD4+ T-cell counts regardless of ART status. TB screening algorithms which include CD4+ T-cell count and hemoglobin testing may be an effective way to identify HIV-infected clinic attendees at highest risk of undiagnosed TB. Isoniazid preventive therapy and TB infection control are essential for reducing occurrence of HIV-associated TB even after ART initiation.JAIDS Journal of Acquired Immune Deficiency Syndromes 06/2012; 60(2):e22-8. · 4.43 Impact Factor -
Article: A novel HIV treatment model using private practitioners in South Africa.
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ABSTRACT: The extent of the HIV epidemic in South Africa may render the public sector capacity inadequate to manage all patients requiring antiretroviral treatment (ART). Private practitioners are an underutilised resource. The authors developed a model of care using 72 private practitioners in five provinces in urban and rural areas of South Africa with centralised clinical support, training, pharmacy control and data management. The authors describe the programme, its quality control measures and patient outcomes using a cohort analysis. Between January 2005 and December 2008, 9102 individuals were started on ART, 62% female, median age 34 years, median viral load 50,655 copies/ml and median baseline CD4 count 123 cells/μl. Retention (alive and in care) after 12 months was 63% in the 2005 cohort (646 of 1026) and remained similar in the other calendar years, 58%, 68% and 64% in 2006, 2007 and 2008, respectively. After 36 months, retention was 50% and 41% for those enrolled in 2005 and 2006, respectively. The percentage virally suppressed remained similar at 6 months, 82% vs 84%, 84% and 85% from 2005, 2006, 2007 to 2008, respectively, p=0.66; but improved slightly at 12 months, 78% vs 83%, 83% and 84% from 2005 to 2008, p=0.05. At 36 months, it was 84% and 82% for the 2005 and 2006 cohorts, respectively. The results show that a well-managed private practitioner model can achieve comparable results to public services, although long-term retention needs further evaluation. This model of ART delivery can be used to expand access to ART in areas where the public sector is unable to meet the demand.Sexually transmitted infections 03/2012; 88(2):136-40. · 2.18 Impact Factor -
Article: Second-line antiretroviral therapy in a workplace and community-based treatment programme in South Africa: determinants of virological outcome.
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ABSTRACT: As antiretroviral treatment (ART) programmes in resource-limited settings mature, more patients are experiencing virological failure. Without resistance testing, deciding who should switch to second-line ART can be difficult. The consequences for second-line outcomes are unclear. In a workplace- and community-based multi-site programme, with 6-monthly virological monitoring, we describe outcomes and predictors of viral suppression on second-line, protease inhibitor-based ART. We used prospectively collected clinic data from patients commencing first-line ART between 1/1/03 and 31/12/08 to construct a study cohort of patients switched to second-line ART in the presence of a viral load (VL) ≥ 400 copies/ml. Predictors of VL<400 copies/ml within 15 months of switch were assessed using modified Poisson regression to estimate risk ratios. 205 workplace patients (91.7% male; median age 43 yrs) and 212 community patients (38.7% male; median age 36 yrs) switched regimens. At switch compared to community patients, workplace patients had a longer duration of viraemia, higher VL, lower CD4 count, and higher reported non-adherence on first-line ART. Non-adherence was the reported reason for switching in a higher proportion of workplace patients. Following switch, 48.3% (workplace) and 72.0% (community) achieved VL<400, with non-adherence (17.9% vs. 1.4%) and virological rebound (35.6% vs. 13.2% with available measures) reported more commonly in the workplace programme. In adjusted analysis of the workplace programme, lower switch VL and younger age were associated with VL<400. In the community programme, shorter duration of viraemia, higher CD4 count and transfers into programme on ART were associated with VL<400. High levels of viral suppression on second-line ART can be, but are not always, achieved in multi-site treatment programmes with both individual- and programme-level factors influencing outcomes. Strategies to support both healthcare workers and patients during this switch period need to be evaluated; sub-optimal adherence, particularly in the workplace programme must be addressed.PLoS ONE 01/2012; 7(5):e36997. · 4.09 Impact Factor -
Article: Predictive value of interferon-γ release assays for incident active tuberculosis: a systematic review and meta-analysis.
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ABSTRACT: We aimed to assess whether interferon-γ release assays (IGRAs) can predict the development of active tuberculosis and whether the predictive ability of these tests is better than that of the tuberculin skin test (TST). Longitudinal studies of the predictive value for active tuberculosis of in-house or commercial IGRAs were identified through searches of PubMed, Embase, Biosis, and Web of Science and complementary manual searches up to June 30, 2011. Eligible studies included adults or children, with or without HIV, who were free of active tuberculosis at study baseline. We summarised incidence rates in forest plots and pooled data with random-effects models when appropriate. We calculated incidence rate ratios (IRR) for rates of disease progression in IGRA-positive versus IGRA-negative individuals. 15 studies had a combined sample size of 26 680 participants. Incidence of tuberculosis during a median follow-up of 4 years (IQR 2-6), even in IGRA-positive individuals, was 4-48 cases per 1000 person-years. Seven studies with no possibility of incorporation bias and reporting baseline stratification on the basis of IGRA results showed a moderate association between positive results and subsequent tuberculosis (pooled unadjusted IRR 2·10, 95% CI 1·42-3·08). Compared with test-negative results, IGRA-positive and TST-positive results were much the same with regard to the risk of tuberculosis (pooled IRR in the five studies that used both was 2·11 [95% CI 1·29-3·46] for IGRA vs 1·60 [0·94-2·72] for TST at the 10 mm cutoff). However, the proportion of IGRA-positive individuals in seven of 11 studies that assessed both IGRAs and TST was generally lower than TST-positive individuals. Neither IGRAs nor the TST have high accuracy for the prediction of active tuberculosis, although use of IGRAs in some populations might reduce the number of people considered for preventive treatment. Until more predictive biomarkers are identified, existing tests for latent tuberculosis infection should be chosen on the basis of relative specificity in different populations, logistics, cost, and patients' preferences rather than on predictive ability alone. Special Programme for Research and Training in Tropical Diseases (WHO), Wellcome Trust, Canadian Institutes of Health Research, UK Medical Research Council, and the European and Developing Countries Clinical Trials Partnership.The Lancet Infectious Diseases 08/2011; 12(1):45-55. · 17.39 Impact Factor -
Article: Diagnostic accuracy of a urine lipoarabinomannan enzyme-linked immunosorbent assay for screening ambulatory HIV-infected persons for tuberculosis.
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ABSTRACT: To assess the diagnostic accuracy of the urine lipoarabinomannan (LAM) test among ambulatory HIV-infected persons. Cross-sectional. HIV-infected persons consecutively presenting to the HIV Clinic at Tembisa Main Clinic in Ekhuruleni, South Africa, were screened for symptoms of tuberculosis (TB) and asked to provide sputum and blood samples for smears for acid-fast bacilli and mycobacterial culture and a urine specimen for a LAM enzyme-linked immunosorbent assay. Fine needle aspirates were obtained from participants with enlarged lymph nodes and sent for histopathology. Nonpregnant participants underwent chest x-ray. : Four hundred twenty-two HIV-infected participants were enrolled with median age 37 years (interquartile range: 31-44 years), median CD4+ T-cell count 215 cells per microliter (interquartile range: 107-347 cells/μL), and 212 (50%) receiving antiretroviral therapy. Thirty (7%) had active TB: 18 with only pulmonary TB, 5 with only extrapulmonary TB, and 7 with both pulmonary TB and extrapulmonary TB. Twenty-seven percent [95% confidence interval (CI): 12% to 48%] of TB cases were sputum acid-fast bacilli positive. The sensitivity and specificity of the urine LAM compared with the gold standard of positive bacteriology or histopathology were 32% (95% CI: 16% to 52%) and 98% (95% CI: 96% to 99%), respectively. Urine LAM had higher sensitivity in TB cases with higher bacillary burdens, though these differences were not statistically significant. The sensitivity of urine LAM testing is inadequate to replace mycobacterial culture. In contrast to prior research on the urine LAM, this study was conducted among less sick, ambulatory HIV-infected patients presenting for routine care.JAIDS Journal of Acquired Immune Deficiency Syndromes 07/2011; 58(2):219-23. · 4.43 Impact Factor -
Article: Twelve-monthly versus six-monthly radiological screening for active case-finding of tuberculosis: a randomised controlled trial.
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ABSTRACT: The incidence of tuberculosis has increased among South African gold miners despite comprehensive control programmes, including a radiological screening programme. No data are available as to the optimal frequency of screening. The aim of this study was to compare 6-monthly and 12-monthly radiological screening for active tuberculosis case-finding. Employees of a gold mining company were randomly assigned to the control arm (screening at baseline, 12 and 24 months) or the intervention arm (additional 'intervention' radiographs at 6 and 18 months after baseline). Study outcomes included proportion of tuberculosis cases detected by screening, proportion smear-positive, extent of disease and mortality. 22,634 miners were randomised. Compared with 12-monthly screening, 6-monthly screening detected more tuberculosis suspects but not more cases, partly due to greater attrition between screening and further investigation after 'intervention' compared with routine radiographs. Tuberculosis cases detected in the 6-monthly versus the 12-monthly screening arm had less extensive disease (p=0.05) and a lower tuberculosis-specific mortality (death on tuberculosis treatment) (2.1 and 2.8 per 1000 person-years respectively, HR 0.73, 95% CI 0.50 to 1.08, p=0.1), which was most marked in the first 2 months of treatment (HR 0.48, 95% CI 0.23 to 0.98, p=0.04) when death from tuberculosis is most likely. In settings with a high prevalence of HIV and tuberculosis despite standard tuberculosis control measures, more frequent case-finding may reduce the extent of disease, tuberculosis mortality and tuberculosis transmission through earlier detection of active tuberculosis cases. To be effective, however, all tuberculosis suspects identified through screening must be investigated for tuberculosis.Thorax 02/2011; 66(2):134-9. · 6.84 Impact Factor -
Article: The association between household socioeconomic position and prevalent tuberculosis in Zambia: a case-control study.
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ABSTRACT: Although historically tuberculosis (TB) has been associated with poverty, few analytical studies from developing countries have tried to: 1. assess the relative impact of poverty on TB after the emergence of HIV; 2. explore the causal mechanism underlying this association; and 3. estimate how many cases of TB could be prevented by improving household socioeconomic position (SEP). We undertook a case-control study nested within a population-based TB and HIV prevalence survey conducted in 2005-2006 in two Zambian communities. Cases were defined as persons (15+ years of age) culture positive for M. tuberculosis. Controls were randomly drawn from the TB-free participants enrolled in the prevalence survey. We developed a composite index of household SEP combining variables accounting for four different domains of household SEP. The analysis of the mediation pathway between household SEP and TB was driven by a pre-defined conceptual framework. Adjusted Population Attributable Fractions (aPAF) were estimated. Prevalent TB was significantly associated with lower household SEP [aOR = 6.2, 95%CI: 2.0-19.2 and aOR = 3.4, 95%CI: 1.8-7.6 respectively for low and medium household SEP compared to high]. Other risk factors for prevalent TB included having a diet poor in proteins [aOR = 3.1, 95%CI: 1.1-8.7], being HIV positive [aOR = 3.1, 95%CI: 1.7-5.8], not BCG vaccinated [aOR = 7.7, 95%CI: 2.8-20.8], and having a history of migration [aOR = 5.2, 95%CI: 2.7-10.2]. These associations were not confounded by household SEP. The association between household SEP and TB appeared to be mediated by inadequate consumption of protein food. Approximately the same proportion of cases could be attributed to this variable and HIV infection (aPAF = 42% and 36%, respectively). While the fight against HIV remains central for TB control, interventions addressing low household SEP and, especially food availability, may contribute to strengthen our control efforts.PLoS ONE 01/2011; 6(6):e20824. · 4.09 Impact Factor -
Article: Risk factors associated with positive QuantiFERON-TB Gold In-Tube and tuberculin skin tests results in Zambia and South Africa.
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ABSTRACT: The utility of T-cell based interferon-gamma release assays for the diagnosis of latent tuberculosis infection remains unclear in settings with a high burden of tuberculosis. To determine risk factors associated with positive QuantiFERON-TB Gold In-Tube (QFT-GIT) and tuberculin skin test (TST) results and the level of agreement between the tests; to explore the hypotheses that positivity in QFT-GIT is more related to recent infection and less affected by HIV than the TST. Adult household contacts of tuberculosis patients were invited to participate in a cross-sectional study across 24 communities in Zambia and South Africa. HIV, QFT-GIT and TST tests were done. A questionnaire was used to assess risk factors. A total of 2,220 contacts were seen. 1,803 individuals had interpretable results for both tests, 1,147 (63.6%) were QFT-GIT positive while 725 (40.2%) were TST positive. Agreement between the tests was low (kappa = 0.24). QFT-GIT and TST results were associated with increasing age (adjusted OR [aOR] for each 10 year increase for QFT-GIT 1.15; 95% CI: 1.06-1.25, and for TST aOR: 1.10; 95% CI 1.01-1.20). HIV positivity was less common among those with positive results on QFT-GIT (aOR: 0.51; 95% CI: 0.39-0.67) and TST (aOR: 0.61; 95% CI: 0.46-0.82). Smear positivity of the index case was associated with QFT-GIT (aOR: 1.25; 95% CI: 0.90-1.74) and TST (aOR: 1.39; 95% CI: 0.98-1.98) results. We found little evidence in our data to support our hypotheses. QFT-GIT may not be more sensitive than the TST to detect risk factors associated with tuberculous infection. We found little evidence to support the hypotheses that positivity in QFT-GIT is more related to recent infection and less affected by HIV than the TST.PLoS ONE 01/2011; 6(4):e18206. · 4.09 Impact Factor -
Article: Cytomegalovirus viremia as a risk factor for mortality prior to antiretroviral therapy among HIV-infected gold miners in South Africa.
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ABSTRACT: Cytomegalovirus (CMV) viremia has been shown to be an independent risk factor for increased mortality among HIV-infected individuals in the developing world. While CMV infection is nearly ubiquitous in resource-poor settings, few data are available on the role of subclinical CMV reactivation on HIV. Using a cohort of mineworkers with stored plasma samples, we investigated the association between CMV DNA concentration and mortality prior to antiretroviral therapy availability. Among 1341 individuals (median CD4 count 345 cells/µl, 70% WHO stage 1 or 2, median follow-up 0.9 years), 70 (5.2%) had CMV viremia at baseline; 71 deaths occurred. In univariable analysis CMV viremia at baseline was associated with a three-fold increase in mortality (hazard ratio [HR] 3.37; 95% confidence intervals [CI] 1.60, 7.10). After adjustment for CD4 count, WHO stage and HIV viral load (N = 429 with complete data), the association was attenuated (HR 2.27; 95%CI 0.88, 5.83). Mortality increased with higher CMV viremia (≥1,000 copies/ml vs. no viremia, adjusted HR 3.65, 95%CI: 1.29, 10.41). Results were similar using time-updated CMV viremia. High copy number, subclinical CMV viremia was an independent risk factor for mortality among male HIV-infected adults in South Africa with relatively early HIV disease. Studies to determine whether anti-CMV therapy to mitigate high copy number viremia would increase lifespan are warranted.PLoS ONE 01/2011; 6(10):e25571. · 4.09 Impact Factor -
Article: Opportunities afforded by new drugs for tuberculosis.
The Lancet Infectious Diseases 06/2010; 10(6):368-9. · 17.39 Impact Factor -
Article: Contrasting predictors of poor antiretroviral therapy outcomes in two South African HIV programmes: a cohort study
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ABSTRACT: Abstract Background Many national antiretroviral therapy (ART) programmes encourage providers to identify and address baseline factors associated with poor treatment outcomes, including modifiable adherence-related behaviours, before initiating ART. However, evidence on such predictors is scarce, and providers judgement may often be inaccurate. To help address this evidence gap, this observational cohort study examined baseline factors potentially predictive of poor treatment outcomes in two ART programmes in South Africa, with a particular focus on determinants of adherence. Methods Treatment-naïve patients starting ART were enrolled from a community and a workplace ART programme. Potential baseline predictors associated with poor treatment outcomes (defined as viral load > 400 copies/ml or having discontinued treatment by six months) were assessed using logistic regression. Exposure variables were organised for regression analysis using a hierarchical framework. Results 38/227 (17%) of participants in the community had poor treatment outcomes compared to 47/117 (40%) in the workplace. In the community, predictors of worse outcomes included: drinking more than 20 units of alcohol per week, having no prior experience of chronic medications, and consulting a traditional healer in the past year (adjusted odds ratio [aOR] 15.36, 95% CI 3.22-73.27; aOR 2.30, 95%CI 1.00-5.30; aOR 2.27, 95% CI 1.00-5.19 respectively). Being male and knowing someone on ART were associated with better outcomes (aOR 0.25, 95%CI 0.09-0.74; aOR 0.44, 95%CI 0.19-1.01 respectively). In the workplace, predictors of poor treatment outcomes included being uncertain about the health effects of ART and a traditional healer's ability to treat HIV (aOR 7.53, 95%CI 2.02-27.98; aOR 4.40, 95%CI 1.41-13.75 respectively). Longer pre-ART waiting time (2-12 weeks compared to <2 weeks) predicted better treatment outcomes (aOR 0.13, 95% CI 0.03-0.56). Conclusion Baseline predictors of poor treatment outcomes were largely unique to each programme, likely reflecting different populations and pathways to HIV care. In the workplace, active promotion of HIV testing may have extended ART to individuals who, without provider initiation, would not have spontaneously sought care. As provider-initiated testing makes ART available to individuals less motivated to seek care, patients may need additional adherence support, especially addressing uncertainty about the health benefits of ART.BMC Public Health. 01/2010; -
Article: Low haemoglobin predicts early mortality among adults starting antiretroviral therapy in an HIV care programme in South Africa: a cohort study
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ABSTRACT: Abstract Background Antiretroviral therapy (ART) has dramatically reduced morbidity and mortality among people with HIV infection; however, mortality after the start of ART is high in resource-limited settings. We investigated risk factors for mortality among adults starting ART in a multi-clinic community programme in South Africa. Methods Cohort of adults starting ART at 27 clinics between February 2005 and June 2006, followed to 31<sup>st </sup>March 2007. Kaplan-Meier survival estimates were used to describe overall mortality. Shared frailty Cox regression was used to identify baseline risk factors for early mortality. Results Among 1350 participants (median age 35.5 years, 60% female, median CD4 count 83/μL [interquartile range (27 - 147)], median follow-up 13.4 months), there were 185 deaths, overall mortality rate 13/100 pyrs; for 0-3, 3-9 and >9 months from ART start mortality rates were 24, 13 and 6/100 pyrs respectively. 43% of the deaths were in the first 3 months of treatment. Risk factors for mortality in univariable analysis were baseline CD4 count, viral load, haemoglobin and body mass index, in multivariable analysis adjusting for age and gender, only CD4 count and haemoglobin remained independently associated with proportional hazards not being satisfied for haemoglobin. Adjusted hazard ratios (aHR) for participants with haemoglobin 11.9(f)/12.9 (m) g/mL were 4.99, 3.05 and 0.12 respectively comparing to 10-11.9 (f)/12.9 (m)g/mL in the first 3 months of ART. aHRs for CD4 counts were 0.40, 0.38 and 0.34 for 50-99, 100-200 and >200/μL comparing to <50/μL. Conclusions The high mortality rate in the first 3 months underlines the need for earlier HIV diagnosis so that ART can be initiated earlier. Low haemoglobin and low CD4 count are both strong predictors of mortality, and could be used to identify individuals at high risk who might benefit from intensive case management.BMC Public Health. 01/2010; -
Article: Low haemoglobin predicts early mortality among adults starting antiretroviral therapy in an HIV care programme in South Africa: a cohort study.
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ABSTRACT: Antiretroviral therapy (ART) has dramatically reduced morbidity and mortality among people with HIV infection; however, mortality after the start of ART is high in resource-limited settings. We investigated risk factors for mortality among adults starting ART in a multi-clinic community programme in South Africa. Cohort of adults starting ART at 27 clinics between February 2005 and June 2006, followed to 31st March 2007. Kaplan-Meier survival estimates were used to describe overall mortality. Shared frailty Cox regression was used to identify baseline risk factors for early mortality. Among 1350 participants (median age 35.5 years, 60% female, median CD4 count 83/microL [interquartile range (27-147)], median follow-up 13.4 months), there were 185 deaths, overall mortality rate 13/100 pyrs; for 0-3, 3-9 and >9 months from ART start mortality rates were 24, 13 and 6/100 pyrs respectively. 43% of the deaths were in the first 3 months of treatment. Risk factors for mortality in univariable analysis were baseline CD4 count, viral load, haemoglobin and body mass index, in multivariable analysis adjusting for age and gender, only CD4 count and haemoglobin remained independently associated with proportional hazards not being satisfied for haemoglobin. Adjusted hazard ratios (aHR) for participants with haemoglobin <8, 8.1-9.9, >11.9(f)/12.9 (m) g/mL were 4.99, 3.05 and 0.12 respectively comparing to 10-11.9 (f)/12.9 (m)g/mL in the first 3 months of ART. aHRs for CD4 counts were 0.40, 0.38 and 0.34 for 50-99, 100-200 and >200/microL comparing to <50/microL. The high mortality rate in the first 3 months underlines the need for earlier HIV diagnosis so that ART can be initiated earlier. Low haemoglobin and low CD4 count are both strong predictors of mortality, and could be used to identify individuals at high risk who might benefit from intensive case management.BMC Public Health 01/2010; 10:433. · 2.00 Impact Factor -
Article: Host genetic factors and vaccine-induced immunity to HBV infection: haplotype analysis.
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ABSTRACT: Hepatitis B virus (HBV) infection remains a significant health burden world-wide, although vaccines help decrease this problem. We previously identified associations of single nucleotide polymorphisms in several candidate genes with vaccine-induced peak antibody level (anti-HBs), which is predictive of long-term vaccine efficacy and protection against infection and persistent carriage; here we report on a haplotype-based analysis. A total of 688 SNPs from 117 genes were examined for a two, three and four sliding window haplotype analysis in a Gambian cohort. Analysis was performed on 197 unrelated individuals, 454 individuals from 174 families, and the combined sample (N = 651). Global and individual haplotype association tests were carried out (adjusted for covariates), employing peak anti-HBs level as outcome. Five genes (CD44, CD58, CDC42, IL19 and IL1R1) had at least one significant haplotype in the unrelated or family analysis as well as the combined analysis. Previous single locus results were confirmed for CD44 (combined global p = 9.1x10(-5) for rs353644-rs353630-rs7937602) and CD58 (combined global p = 0.008 for rs1414275-rs11588376-rs1016140). Haplotypes in CDC42, IL19 and IL1R1 also associated with peak anti-HBs level. We have identified strong haplotype effects on HBV vaccine-induced antibody level in five genes, three of which, CDC42, IL19 and IL1R1, did not show evidence of association in a single SNP analyses and corroborated the majority of these effects in two datasets. The haplotype analysis identified associations with HBV vaccine-induced immunity in several new genes.PLoS ONE 01/2010; 5(8):e12273. · 4.09 Impact Factor -
Article: The risk and timing of tuberculosis diagnosed in smear-negative TB suspects: a 12 month cohort study in Harare, Zimbabwe.
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ABSTRACT: Cases of smear-negative TB have increased dramatically in high prevalence HIV settings and pose considerable diagnostic and management challenges. Between February 2006 and July 2007, a cohort study nested within a cluster-randomised trial of community-based case finding strategies for TB in Harare, Zimbabwe was undertaken. Participants who had negative sputum smears and remained symptomatic of TB were follow-up for one year with standardised investigations including HIV testing, repeat sputum smears, TB culture and chest radiography. Defaulters were actively traced to the community. The objectives were to investigate the incidence and risk factors for TB. TB was diagnosed in 218 (18.2%) participants, of which 39.4% was bacteriologically confirmed. Most cases (84.2%) were diagnosed within 3 months, but TB incidence remained high thereafter (111.3 per 1000 person-years, 95% CI: 86.6 to 146.3). HIV prevalence was 63.3%, and HIV-infected individuals had a 3.5-fold higher risk of tuberculosis than HIV-negative individuals. We found that diagnosis of TB was insensitive and slow, even with early radiography and culture. Until more sensitive and rapid diagnostic tests become widely available, a much more proactive and integrated approach towards prompt initiation of ART, ideally from within TB clinics and without waiting for TB to be excluded, is needed to minimise the risk and consequences of diagnostic delay.PLoS ONE 01/2010; 5(7):e11849. · 4.09 Impact Factor -
Article: Evaluation of the prognostic value of IFN-gamma release assay and tuberculin skin test in household contacts of infectious tuberculosis cases in Senegal.
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ABSTRACT: Chemoprophylaxis of contacts of infectious tuberculosis (TB) cases is recommended for TB control, particularly in endemic countries, but is hampered by the difficulty to diagnose latent TB infection (LTBI), classically assessed through response to the Tuberculin Skin Test (TST). Interferon-gamma release assays (IGRA) are proposed new tools to diagnose LTBI, but there are limited data on their ability to predict the development of active TB disease. To address this, we investigated the response to TST and IGRA in household contacts of infectious TB cases in a TB high-burden country and the potential correlation with development of TB. Prospective household contacts study conducted in two health centres in Dakar, Senegal. A total of 2679 household contacts of 206 newly detected smear and/or culture positive index TB cases aged 18 years or greater were identified A TST was performed in each contact and an ESAT6/CFP10 ELISPOT assay performed in a random sample of those. Contacts were followed-up for 24 months. TB was diagnosed in 52 contacts, an incidence rate of 9.27/1000 person-years. In univariable analysis, the presence of positive TST (> or = 10 mm) and ELISPOT (>32 SFC/million PBMC) responses at baseline were associated with active TB during follow-up: Rate Ratio [RR] = 2.32 (95%CI:1.12-4.84) and RR = 2.09 (95%CI:0.83-5.31), respectively. After adjustment for age, sex and proximity to index case, adjusted RRs were 1.51 (95%CI:0.71-3.19) and 1.98 (95%CI:0.77-5.09), respectively. Restricting analysis to the 40 microbiologically confirmed cases, the adjusted RR for positive ELISPOT was 3.61 (95%CI:1.03-12.65). The median ELISPOT response in contacts who developed TB was 5-fold greater than in those who did not develop TB (p = 0.02). TST and IGRAs are markers of a contact of the immune system with tubercle bacilli. In a TB endemic area, a high ELISPOT response may reflect increased bacterial replication that may subsequently be associated with development of TB disease and may have a prognostic value. Further longitudinal data are needed to assess whether IGRAs are reliable markers to be used for targeting chemoprophylaxis.PLoS ONE 01/2010; 5(5):e10508. · 4.09 Impact Factor -
Article: Tuberculosis infection in Zambia: the association with relative wealth.
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ABSTRACT: This study aimed to assess the association between household socioeconomic position and tuberculosis (TB) infection in two communities of Zambia. For this purpose we implemented a cross-sectional investigation, nested within a larger case control study. Infection was assessed using Quantiferon-TB Gold. A socioeconomic position index was constructed through principal component analysis combining data on human resources, food availability, housing quality, and access to services and infrastructures. In this study, higher socioeconomic position, rather than lower, was associated with significantly higher risk of TB infection. None of the traditional risk factors for TB infection mediated this association, suggesting that in these two communities TB transmission may occur through exposure to as yet undefined risk factors that are associated with higher socioeconomic position. Although further studies are needed, these results suggest emerging new patterns of TB transmission and a role of socioeconomic position on the risk of TB infection opposite to that expected.The American journal of tropical medicine and hygiene 07/2009; 80(6):1004-11. · 2.59 Impact Factor -
Article: HIV suppression with stavudine 30 mg versus 40 mg in adults over 60 kg on antiretroviral therapy in South Africa.
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ABSTRACT: In 2007, the WHO recommended a maximum stavudine dose of 30 mg. We compared virologic suppression among patients weighing more than 60 kg and receiving stavudine 30 mg (n = 110) versus 40 mg (n = 508) in community HIV clinics in South Africa, before and after guidelines changed. At 6 months, HIV RNA less than 400 copies/ml was achieved in 79% and 81% receiving 30 and 40 mg stavudine, respectively (chi2, P = 0.6). In regression modeling, including baseline HIV RNA and nonnucleoside reverse transcriptase inhibitor agent, stavudine dose remained unassociated with suppression.AIDS (London, England) 07/2009; 23(13):1784-6. · 4.91 Impact Factor -
Article: Discussing matters of sexual health with children: what issues relating to disclosure of parental HIV status reveal.
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ABSTRACT: Little is published about the disclosure of parents' own HIV status to their children in Africa. Research shows that keeping family secrets from children, including those related to a parent's HIV status, can be detrimental to their psychological well-being and to the structure of the family. Further, children with HIV-positive parents have been shown to be more vulnerable to poorer reproductive health outcomes. This qualitative study in Botswana conducted in-depth interviews among 21 HIV-positive parents on antiretroviral therapy. The data revealed that parents found discussing the issue of HIV with children difficult, including disclosing their own HIV status to them. Reasons for disclosing included: children being HIV positive, the rest of the family knowing, or the parent becoming very sick. Reasons for not disclosing included: believing the child to be too young, not knowing how to address the issue of HIV, that it would be "too painful" for the child/ren. Concern that other people might find out about their status or fear of children experiencing stigmatising behaviour. Interviews elucidated the difficulty that parents have in discussing their own HIV status and more general sexual health issues with their children. Parents and other guardians require support in managing age-appropriate disclosure to their children. This may further enable access to forums that can help children cope with their fears about the future and develop life skills in preparation for dealing with relationships of a sexual nature and sexual health as children move into adulthood. In developing such support mechanisms, changing family roles in Botswana need to be taken into consideration and the role of other family members in the upbringing of children in Tswana society need to be recognised and utilised.AIDS Care 04/2009; 21(3):389-95. · 1.60 Impact Factor -
Article: Effect of rifampicin-based antitubercular therapy and the cytochrome P450 2B6 516G>T polymorphism on efavirenz concentrations in adults in South Africa.
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ABSTRACT: Rifampicin induces expression of the cytochrome P450 isoenzyme 2B6 (CYP2B6), which metabolizes efavirenz. The CYP2B6 516G>T polymorphism impairs efavirenz metabolism and occurs more commonly in Africans than in Caucasians. We explored the effect of rifampicin-based antitubercular therapy and the 516G>T polymorphism on efavirenz concentrations in HIV-infected patients in South Africa. Between-patient and within-patient comparisons were made of mid-dosing interval efavirenz plasma concentrations in adults on antiretroviral therapy including efavirenz 600 mg daily, with and without antitubercular therapy. There were 142 participants (40 were on antitubercular therapy and 102 were controls), the mean weight was 66 kg. Median efavirenz concentration was 2.4 mg/l (interquartile range [IQR] 1.3-3.1) and 1.8 mg/l (IQR 1.4-4.4) in participants on antitubercular therapy and controls, respectively (P=0.734). Paired efavirenz concentrations during and after antitubercular therapy in 17 participants were also similar (P=0.113). Genotyping results were 60 (49%) G/G homozygotes, 46 (38%) G/T heterozygotes and 16 (13%) T/T homozygotes. In a multivariate logistic regression model adjusted for sex, weight and concomitant antitubercular therapy, the 516G>T polymorphism was strongly associated with high (>4 mg/l) efavirenz concentrations: odds ratio (OR) 4.4 (95% confidence interval [CI] 1.3-14.9) for G/T versus G/G and 31.1 (95% CI 6.6-146.6) for T/T versus G/G. High efavirenz concentrations were associated with severe sleep disturbance (P=0.048). Low (<1 mg/l) efavirenz concentrations were associated with virological failure (OR 12.5, 95% CI 2.7-57.3). Efavirenz can be used together with rifampicin-based antitubercular therapy without dose adjustment in this population. The 516G>T polymorphism occurred commonly and was associated with high efavirenz concentrations.Antiviral therapy 01/2009; 14(5):687-95. · 3.16 Impact Factor
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Institutions
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2002–2012
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London School of Hygiene and Tropical Medicine
- Department of Clinical Research
London, ENG, United Kingdom -
Medical Research Council Unit, The Gambia Unit
Bakau, City of Banjul, Gambia
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2011
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Johns Hopkins University
- Department of Medicine
Baltimore, MD, USA
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2007–2011
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The Aurum Institute
Johannesburg, Gauteng, South Africa
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2004
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Université Libre de Bruxelles
Brussels, BRU, Belgium
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2003–2004
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University of Oxford
- Wellcome Trust Centre for Human Genetics
Oxford, ENG, United Kingdom
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