Browsing by Author "Osman, Muhammad"

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    The complex relationship between human immunodeficiency virus infection and death in adults being treated for tuberculosis in Cape Town, South Africa
    (BioMed Central, 2015) Osman, Muhammad; Seddon, James A.; Dunbar, Rory; Draper, Heather R.; Lombard, Carl; Beyers, Nulda
    Background: Despite recognised treatment strategies, mortality associated with tuberculosis (TB) remains significant. Risk factors for death during TB treatment have been described but the complex relationship between TB and HIV has not been fully understood. Methods: A retrospective analysis of all deaths occurring during TB treatment in Cape Town, South Africa between 2009 and 2012 were done to investigate risk factors associated with this outcome. The main risk factor was HIV status at the start of treatment and its interaction with age, sex and other risk factors were evaluated using a binomial regression model and thus relative risks (RR) are reported. Results: Overall in the 93,133 cases included in the study 4619 deaths (5 %) were recorded. Across all age groups HIV-positive patients were more than twice as likely to die as HIV-negative patients, RR = 2.19 (95 % CI: 2.03–2.37). However in an age specific analysis HIV-positive patients 15–24 and 25–34 years old were at an even higher risk of dying than HIV-negative patients, RR = 4.82 and RR = 3.76 respectively. Gender also modified the effect of HIV- with positive women having a higher risk of death than positive men, RR = 2.74 and RR = 1.94 respectively. Conclusion: HIV carries an increased risk of death in this study but specific high-risk groups pertaining to the impact of HIV are identified. Innovative strategies to manage these high risk groups may contribute to reduction in HIV-associated death in TB patients.
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    The epidemiology of tuberculosis in health care workers in South Africa : a systematic review
    (BioMed Central, 2016-08-20) Grobler, Liesl; Mehtar, Shaheen; Dheda, Keertan; Adams, Shahieda; Babatunde, Sanni; Van der Walt, Martie; Osman, Muhammad
    ENGLISH SUMMARY : Background: In South Africa, workplace acquired tuberculosis (TB) is a significant occupational problem among health care workers. In order to manage the problem effectively it is important to know the burden of TB in health care workers. This systematic review describes the epidemiology of TB in South African health care workers. Methods: A comprehensive search of electronic databases [MEDLINE, EMBASE, Web of Science (Social Sciences Citation Index/Science Citation Index), Cochrane Library (including CENTRAL register of Controlled Trials), CINAHL and WHO International Clinical Trials Registry Platform (ICTRP)] was conducted up to April 2015 for studies reporting on any aspect of TB epidemiology in health care workers in South Africa. Results: Of the 16 studies included in the review, ten studies reported on incidence of active TB disease in health care workers, two report on the prevalence of active TB disease, two report on the incidence of latent TB infection, three report on the prevalence of latent TB infection and four studies report on the number of TB cases in health care workers in various health care facilities in South Africa. Five studies provide information on risk factors for TB in health care workers. All of the included studies were conducted in publicly funded health care facilities; predominately located in KwaZulu-Natal and Western Cape provinces. The majority of the studies reflect a higher incidence and prevalence of active TB disease in health care workers, including drug-resistant TB, compared to the surrounding community or general population. Conclusions: There is relatively little research on the epidemiology of TB in health care workers in South Africa, despite the importance of the issue. To determine the true extent of the TB epidemic in health care workers, regular screening for TB disease should be conducted on all health care workers in all health care facilities, but future research is required to investigate the optimal approach to TB screening in health care workers in South Africa. The evidence base shows a high burden of both active and latent TB in health care workers in South Africa necessitating an urgent need to improve existing TB infection, prevention and control measures in South African.
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    The global burden of tuberculous meningitis in adults : a modelling study
    (Public Library of Science, 2021-12) Dodd, Peter J.; Osman, Muhammad; Cresswell, Fiona V.; Stadelman, Anna M.; Lan, Nguyen Huu; Thuong, Nguyen Thuy Thuong; Muzyamba, Morris; Glaser, Lisa; Dlamini, Sicelo S.; Seddon, James A.
    Tuberculous meningitis (TBM) is the most lethal form of tuberculosis. The incidence and mortality of TBM is unknown due to diagnostic challenges and limited disaggregated reporting of treated TBM by existing surveillance systems. We aimed to estimate the incidence and mortality of TBM in adults (15+ years) globally. Using national surveillance data from Brazil, South Africa, the United Kingdom, the United States of America, and Vietnam, we estimated the fraction of reported tuberculosis that is TBM, and the case fatality ratios for treated TBM in each of these countries. We adjusted these estimates according to findings from a systematic review and meta-analysis and applied them to World Health Organization tuberculosis notifications and estimates to model the global TBM incidence and mortality. Assuming the case detection ratio (CDR) for TBM was the same as all TB, we estimated that in 2019, 164,000 (95% UI; 129,000–199,000) adults developed TBM globally; 23% were among people living with HIV. Almost 60% of incident TBM occurred in males and 20% were in adults 25–34 years old. 70% of global TBM incidence occurred in Southeast Asia and Africa. We estimated that 78,200 (95% UI; 52,300–104,000) adults died of TBM in 2019, representing 48% of incident TBM. TBM case fatality in those treated was on average 27%. Sensitivity analysis assuming improved detection of TBM compared to other forms of TB (CDR odds ratio of 2) reduced estimated global mortality to 54,900 (95% UI; 32,200–77,700); assuming instead worse detection for TBM (CDR odds ratio of 0.5) increased estimated mortality to 125,000 (95% UI; 88,800–161,000). Our results highlight the need for improved routine TBM monitoring, especially in high burden countries. Reducing TBM incidence and mortality will be necessary to achieve the End TB Strategy targets.
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    Health system determinants of tuberculosis mortality in South Africa : a causal loop model
    (BMC (part of Springer Nature), 2021-04-26) Osman, Muhammad; Karat, Aaron S.; Khan, Munira; Meehan, Sue-Ann; Von Delft, Arne; Brey, Zameer; Charalambous, Salome; Hesseling, Anneke C.; Naidoo, Pren; Loveday, Marian
    Background: Tuberculosis (TB) is a major public health concern in South Africa and TB-related mortality remains unacceptably high. Numerous clinical studies have examined the direct causes of TB-related mortality, but its wider, systemic drivers are less well understood. Applying systems thinking, we aimed to identify factors underlying TB mortality in South Africa and describe their relationships. At a meeting organised by the ‘Optimising TB Treatment Outcomes’ task team of the National TB Think Tank, we drew on the wide expertise of attendees to identify factors underlying TB mortality in South Africa. We generated a causal loop diagram to illustrate how these factors relate to each other. Results: Meeting attendees identified nine key variables: three ‘drivers’ (adequacy & availability of tools, implementation of guidelines, and the burden of bureaucracy); three ‘links’ (integration of health services, integration of data systems, and utilisation of prevention strategies); and three ‘outcomes’ (accessibility of services, patient empowerment, and socioeconomic status). Through the development and refinement of the causal loop diagram, additional explanatory and linking variables were added and three important reinforcing loops identified. Loop 1, ‘Leadership and management for outcomes’ illustrated that poor leadership led to increased bureaucracy and reduced the accessibility of TB services, which increased TBrelated mortality and reinforced poor leadership through patient empowerment. Loop 2, ‘Prevention and structural determinants’ describes the complex reinforcing loop between socio-economic status, patient empowerment, the poor uptake of TB and HIV prevention strategies and increasing TB mortality. Loop 3, ‘System capacity’ describes how fragmented leadership and limited resources compromise the workforce and the performance and accessibility of TB services, and how this negatively affects the demand for higher levels of stewardship. Conclusions: Strengthening leadership, reducing bureaucracy, improving integration across all levels of the system, increasing health care worker support, and using windows of opportunity to target points of leverage within the South African health system are needed to both strengthen the system and reduce TB mortality. Further refinement of this model may allow for the identification of additional areas of intervention.
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    Levofloxacin versus placebo for the prevention of tuberculosis disease in child contacts of multidrug-resistant tuberculosis : study protocol for a phase III cluster randomised controlled trial (TB-CHAMP)
    (BMC (part of Springer Nature), 2018-12-20) Seddon, James A.; Garcia-Prats, Anthony J.; Purchase, Susan E.; Osman, Muhammad; Demers, Anne-Marie; Hoddinott, Graeme; Crook, Angela M.; Owen-Powell, Ellen; Thomason, Margaret J.; Turkova, Anna; Gibb, Diana M.; Fairlie, Lee; Martinson, Neil; Schaaf, H. Simon; Hesseling, Anneke C.
    Background: Multidrug-resistant (MDR) tuberculosis (TB) presents a challenge for global TB control. Treating individuals with MDR-TB infection to prevent progression to disease could be an effective public health strategy. Young children are at high risk of developing TB disease following infection and are commonly infected by an adult in their household. Identifying young children with household exposure to MDR-TB and providing them with MDR-TB preventive therapy could reduce the risk of disease progression. To date, no trials of MDR-TB preventive therapy have been completed and World Health Organization guidelines suggest close observation with no active treatment. Methods: The tuberculosis child multidrug-resistant preventive therapy (TB-CHAMP) trial is a phase III cluster randomised placebo-controlled trial to assess the efficacy of levofloxacin in young child contacts of MDR-TB cases. The trial is taking place at three sites in South Africa where adults with MDR-TB are identified. If a child aged < 5 years lives in their household, we assess the adult index case, screen all household members for TB disease and evaluate any child aged < 5 years for trial eligibility. Eligible children are randomised by household to receive daily levofloxacin (15–20 mg/kg) or matching placebo for six months. Children are closely monitored for disease development, drug tolerability and adverse events. The primary endpoint is incident TB disease or TB death by one year after recruitment. We will enrol 1556 children from approximately 778 households with an average of two eligible children per household. Recruitment will run for 18–24 months with all children followed for 18 months after treatment. Qualitative and health economic evaluations are embedded in the trial. Discussion: If the TB-CHAMP trial demonstrates that levofloxacin is effective in preventing TB disease in young children who have been exposed to MDR-TB and that it is safe, well tolerated, acceptable and cost-effective, we would expect that that this intervention would rapidly transfer into policy.
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    Morbidity and mortality up to 5 years post tuberculosis treatment in South Africa : a pilot study
    (Elsevier, 2019) Osman, Muhammad; Welte, Alex; Dunbar, Rory; Brown, Rosemary; Hoddinott, Graeme; Hesseling, Anneke C.; Marx, Florian M.
    Background: A high risk of tuberculosis (TB), chronic lung disease, and mortality have been reported among people with a history of previous TB treatment, but data from high-incidence settings remain limited. The aim of this study was to characterize general morbidity and mortality among adults who had successfully completed TB treatment in the past 5 years in a high-incidence setting in South Africa. Methods: Adults ( 18 years) who had completed treatment for pulmonary TB between 2013 and 2017 were randomly selected from TB treatment registers. Household visits were conducted to locate and interview former TB (FTB) patients, and bacteriological testing for TB was offered. Additional data sources were used to ascertain the vitality status of FTB patients who could not be located. Results: Addresses were located for 200 of the 223 FTB patients sampled and 89 FTB patients were contacted of whom 51 agreed to be interviewed. Approximately half reported persistent respiratory symptoms, such as shortness of breath and wheezing, and repeated lung infections. One (3.6%) of 28 patients who provided a sputum sample had culture-positive TB and another two were currently on re-treatment for TB. Fifteen deaths post treatment were ascertained, resulting in a standardized mortality ratio of 3.8 (95% confidence interval 2.3–6.3) after successful TB treatment relative to the general population. Conclusions: In this high-incidence setting, locating and interviewing FTB patients was challenging. The study findings are consistent with a high rate of respiratory disease, including recurrent TB, and substantially elevated mortality among FTB patients.
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    Mortality during tuberculosis treatment in South Africa using an 8-year analysis of the national tuberculosis treatment register
    (Nature, 2021-08) Osman, Muhammad; Van Schalkwyk, Cari; Naidoo, Pren; Seddon, James A.; Dunbare, Rory; Dlamini, Sicelo S.; Welte, Alex; Hesseling, Anneke C.; Claassens, Mareli M.
    In 2011, the South African HIV treatment eligibility criteria were expanded to allow all tuberculosis (TB) patients lifelong ART. The impact of this change on TB mortality in South Africa is not known. We evaluated mortality in all adults (≥ 15 years old) treated for drug-susceptible TB in South Africa between 2009 and 2016. Using a Cox regression model, we quantified risk factors for mortality during TB treatment and present standardised mortality ratios (SMR) stratified by year, age, sex, and HIV status. During the study period, 8.6% (219,618/2,551,058) of adults on TB treatment died. Older age, male sex, previous TB treatment and HIV infection (with or without the use of ART) were associated with increased hazard of mortality. There was a 19% reduction in hazard of mortality amongst all TB patients between 2009 and 2016 (adjusted hazard ratio: 0.81 95%CI 0.80–0.83). The highest SMR was in 15–24-year-old women, more than double that of men (42.3 in 2016). Between 2009 and 2016, the SMR for HIV-positive TB patients increased, from 9.0 to 19.6 in women, and 7.0 to 10.6 in men. In South Africa, case fatality during TB treatment is decreasing and further interventions to address specific risk factors for TB mortality are required. Young women (15–24-year-olds) with TB experience a disproportionate burden of mortality and interventions targeting this age-group are needed.
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    Tuberculosis-associated mortality in South Africa: longitudinal trends and the impact of health system interventions
    (Stellenbosch : Stellenbosch University, 2021-03) Osman, Muhammad; Hesseling, Anneke Catharina; Naidoo, Prenavum; Welte, Alex; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health.
    ENGLISH ABSTRACT: Tuberculosis (TB) is estimated to have infected a quarter of the world’s population. In 2019, it was estimated that 10 million people developed TB globally and that the treatment coverage was 71%. In South Africa, approximately 360,000 people developed TB in 2019 with an estimated treatment coverage of 58%. Human immunodeficiency virus (HIV) is one of the most important drivers of TB, especially in sub-Saharan Africa. Of the estimated 38 million people living with HIV globally, 7.5 million (20%) were in South Africa. People living with HIV are more likely to develop TB disease and TB is one of the leading causes of death among people living with HIV. Among the estimated 1.4 million TB deaths in 2019; 59,000 occurred in South Africa. This estimate of mortality includes any death, regardless of the cause, occurring before or during antituberculosis treatment, and does not include TB-related deaths that occurred after the successful completion of treatment. TB reporting in South Africa is based on data captured in TB treatment registers and there are no routine estimates for TB-associated mortality before or after TB treatment. I used the onion model and the TB care cascade frameworks, to evaluate TB-associated mortality during, before and after TB treatment. Through a series of four interlinked studies, I investigated TB-associated mortality during TB treatment for adults and in children. I showed that mortality in South Africa decreased from 11% in 2009 to 8% in 2016 in adults, and from 3.3% in 2007 to 1.9% in 2016 in children and adolescents. I demonstrated that young children, older adolescents, the oldest adults, males, and people living with HIV (especially those with the lowest CD4 counts) were at highest risk of mortality during TB treatment whilst antiretroviral therapy (ART) had a protective effect. I also showed how this differs by HIV status and demonstrated that in people living with HIV, younger adult females have the greatest risk of mortality. I collected data for two studies to evaluate mortality before TB treatment. In the first, I reported a TB prevalence of 8% in people who died suddenly and unexpectedly; more than 90% had undiagnosed TB. I demonstrated multiple missed opportunities for TB screening and testing in these individuals. Sentinel surveillance for TB in this group could be an important indicator of TB control efforts. In the second study, I reported initial loss to follow up (ILTFU) of 20% in TB patients in 2 sub-districts of Cape Town among whom 17% had died. Although hospitals accounted for 25% of TB diagnoses, they contributed to 55% of patients with ILTFU and to 85% of the mortality in this group. This study demonstrates the need for earlier case-finding to reduce mortality and the value of including hospitals in routine TB reporting. Given the exclusion of mortality after TB treatment from the current definition of TB- deaths and the recognition of the burden of post-TB lung health, I conducted a study in Cape Town to assess TB patients who had successfully completed TB treatment. I showed the complexity of tracing these individuals. In the sample of adults located, I reported a high burden of respiratory symptoms and 6% had recurrent TB. The mortality rate following the successful completion of TB treatment was 2.5 deaths per 100 person years with a standardised mortality ratio of 4 compared to the general population. This highlights the need for ongoing care, post TB treatment completion. In this dissertation I documented the key health system changes in the public sector in South Africa and the changes in TB-associated mortality over time. Finally, I attempted to collate the findings of TB-associated mortality during, before and after TB treatment in the context of losses along the TB care cascade. This dissertation provides novel insights into TB-associated mortality in South Africa. I propose additional strategies to improve mortality estimates and to reduce TB-associated mortality in South Africa.