Browsing by Subject "Incidence"

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    Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease
    (2016) Lonn, Eva M; Bosch, Jackie; López-Jaramillo, Patricio; Zhu, Jun; Liu, Lisheng; Pais, Prem; Diaz, Rafael; Xavier, Denis; Sliwa, Karen; Dans, Antonio; Avezum, Álvaro; Piegas, Leopoldo S; Keltai, Katalin; Keltai, Matyas; Chazova, Irina; Peters, Ron JG; Held, Claes; Yusoff, Khalid; Lewis, Basil S; Jansky, Petr; Parkhomenko, Alexander; Khunti, Kamlesh; Toff, William D; Reid, Christopher M; Varigos, John; Leiter, Lawrence A; Molina, Dora I; McKelvie, Robert; Pogue, Janice; Wilkinson, Joanne; Jung, Hyejung; Dagenais, Gilles
    Antihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher, but its role in persons at intermediate risk and with lower blood pressure is unclear. In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; the second coprimary outcome additionally included resuscitated cardiac arrest, heart failure, and revascularization. The median follow-up was 5.6 years. The mean blood pressure of the participants at baseline was 138.1/81.9 mm Hg; the decrease in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in the placebo group. The first coprimary outcome occurred in 260 participants (4.1%) in the active-treatment group and in 279 (4.4%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40); the second coprimary outcome occurred in 312 participants (4.9%) and 328 participants (5.2%), respectively (hazard ratio, 0.95; 95% CI, 0.81 to 1.11; P=0.51). In one of the three prespecified hypothesis-based subgroups, participants in the subgroup for the upper third of systolic blood pressure (>143.5 mm Hg) who were in the active-treatment group had significantly lower rates of the first and second coprimary outcomes than those in the placebo group; effects were neutral in the middle and lower thirds (P=0.02 and P=0.009, respectively, for trend in the two outcomes). Therapy with candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day was not associated with a lower rate of major cardiovascular events than placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.)
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    Cervical lymph node biopsy - watch the nerves!
    (2006) Numanoglu, A; Rode, H
    Experience with the delayed diagnosis and severe consequences of accessory nerve injury following cervical gland lymph node biopsy prompted us to survey the practice of South African paediatric surgeons and to ascertain the incidence of accessory nerve injury. Cervical lymph gland biopsies are often performed for diagnostic and therapeutic purposes and although spinal accessory nerve (SAN) injury seldom occurs, it remains a significant injury. The operation is relatively minor and cervical glands are commonly biopsied/removed in South Africa by junior doctors, registrars and general practitioners. The operation is often performed as a day case under suboptimal circumstances, despite the fact that it is common knowledge that posterior triangle nodular biopsy carries the risk of iatrogenic damage to the accessory nerve.
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    The clinical features and estimated incidence of MIS-C in Cape Town, South Africa
    (2022-05-02) Butters, Claire; Abraham, Deepthi R; Stander, Raphaella; Facey-Thomas, Heidi; Abrahams, Debbie; Faleye, Ayodele; Allie, Nazneen; Soni, Khushbu; Rabie, Helena; Scott, Christiaan; Zühlke, Liesl; Webb, Kate
    Background Multisystem inflammatory syndrome is a severe manifestation of SARS-CoV-2 in children. The incidence of MIS-C after infection is poorly understood. There are very few cohorts describing MIS-C in Africa despite MIS-C being more common in Black children worldwide. Methods A cohort of children with MIS-C and healthy children was recruited from May 2020 until May 2021 from the two main paediatric hospitals in Cape Town, South Africa. Clinical and demographic data were collected, and serum was tested for SARS-CoV-2 antibodies. The incidence of MIS-C was calculated using an estimation of population exposure from seroprevalence in the healthy group. Summary data, non-parametric comparisons and logistic regression analyses were performed. Results Sixty eight children with MIS-C were recruited with a median age of 7 years (3.6, 9.9). Ninety seven healthy children were recruited with a 30% seroprevalence. The estimated incidence of MIS-C was 22/100 000 exposures in the city in this time. Black children were over-represented in the MIS-C group (62% vs 37%, p = 0.002). The most common clinical features in MIS-C were fever (100%), tachycardia (98.5%), rash (85.3%), conjunctivitis (77.9%), abdominal pain (60.3%) and hypotension (60.3%). The median haemoglobin, sodium, neutrophil count, white cell count, CRP, ferritin, cardiac (pro-BNP, trop-T) and coagulation markers (D-dimer and fibrinogen) were markedly deranged in MIS-C. Cardiac, pulmonary, central nervous and renal organ systems were involved in 71%, 29.4%, 27.9% and 27.9% respectively. Ninety four percent received intravenous immune globulin, 64.7% received methylprednisolone and 61.7% received both. Forty percent required ICU admission, 38.2% required inotropic support, 38.2% required oxygen therapy, 11.8% required invasive ventilation and 6% required peritoneal dialysis. Older age was an independent predictor for the requirement for ionotropic support (OR = 1.523, CI 1.074, 2.16, p = 0.018). The median hospital stay duration was 7 days with no deaths. Conclusion The lack of reports from Southern Africa does not reflect a lack of cases of MIS-C. MIS-C poses a significant burden to children in the region as long as the pandemic continues. MIS-C disproportionately affects black children. The clinical manifestations and outcomes of MIS-C in this region highlight the need for improved surveillance, reporting and data to inform diagnosis and treatment.
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    Drug administration errors by South African anaesthetists - a survey
    (2006) Gordon, P C; Llewellyn, R L; James, M F M
    Objectives. To investigate the incidence, nature of and factors contributing towards wrong drug administrations by South African anaesthetists. Design. A confidential, self-reporting survey was sent out to the 720 anaesthetists on the database of the South African Society of Anaesthesiologists. Results. A total of 133 questionnaires were returned for analysis (18.5% response rate). Of the respondents, 125 (94%) admitted to having inadvertently administered a wrong drug. Thirty respondents (22.6%) said they had made errors on at least four occasions. A total of 303 specific wrong drug administrations were described. Nearly 50% involved muscle relaxants. A further 43 incidents (14%) involved the erroneous administration of vasoactive drugs. Five deaths and 3 nonfatal cardiac arrests were reported. In 9.9% of incidents the anaesthetic time was prolonged by more than 30 minutes. Contributory causes identified included syringe swaps (40%), misidentification of drugs (27.1%), fatigue (14.1%), distractions (4.7%), and mislabelling of syringes (4.7%). Only 19% of respondents regularly use colour-coded syringe labels complying with the national standard. Conclusions. Most anaesthetists experienced at least one drug error. The incidence of wrong drug administrations by South African anaesthetists appears to be similar to that in Australasia and Canada. The commonest error was a ‘syringe swap’ involving muscle relaxants. Most drug errors are inconsequential. An important minority of incidents result in severe morbidity or death. The study supports efforts to improve ampoule labelling, to encourage the use of syringe labels based on the international colour code and to develop a national reporting system for such incidents.
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    HIV viral load as an independent risk factor for tuberculosis in South Africa: collaborative analysis of cohort studies
    (2017) Fenner, Lukas; Atkinson, Andrew; Boulle, Andrew; Fox, Matthew P; Prozesky, Hans; ZYrcher, Kathrin; Ballif, Marie; Furrer, Hansjakob; Zwahlen, Marcel; Davies, Mary-Ann; Egger, Matthias
    Introduction: Chronic immune activation due to ongoing HIV replication may lead to impaired immune responses against opportunistic infections such as tuberculosis (TB). We studied the role of HIV replication as a risk factor for incident TB after starting antiretroviral therapy (ART).
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    HIV-associated neurocognitive disorders: Antiretroviral regimen, central nervous system penetration effectiveness, and cognitive outcomes
    (2013) Cross, Helen M; Combrinck, Marc I; Joska, John A
    ABSTRACT BACKGROUND: The human immunodeficiency virus (HIV) can give rise to a spectrum of neuropsychological impairments known collectively as HIV-associated neurocognitive disorders (HAND). Although antiretroviral therapy (ART) has reduced the incidence of HIV dementia, the prevalence of milder forms of HAND has increased. It has been postulated that incomplete central nervous system (CNS) viral suppression or potential drug toxicity, both of which could be related to the CNS penetration effectiveness (CPE) of ART regimens, may contribute to this phenomenon. OBJECTIVE: This study compared cognitive outcomes in clade C-infected HIV patients in South Africa treated for 1 year with ART regimens with differing CPE scores. METHODS: We assessed 111 HIV-positive patients with varying levels of cognitive function at baseline (pre-ART) and then a year later. A neuropsychological battery was administered at both visits to derive global deficit scores. ART regimen data were collected at the follow-up visit. Some participants remained ART-naïve during this period, thus providing a non-treatment control group. RESULTS: Significantly more ART recipients maintained or improved cognitive function compared with patients not on ART (p=0.017). There was no significant difference in cognitive outcomes between higher and lower CPE regimen groups (p=0.473). CONCLUSIONS: ART preserves or improves cognition in HIV-infected patients after 1 year, irrespective of the regimen's CPE. South Africa's current low CPE-scored first-line regimen performed as well as higher CPE-scored regimens. These findings are reassuring for South Africa, but larger, longer-term studies would be more definitive.
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    Incidence of cytological abnormalities within 24 months of a normal cervical smear in Soweto, South Africa
    (2012) Adam, Yasmin; McIntyre, James Alasdair; de Bruyn, Guy
    BACKGROUND: A screening programme for cervical cancer has been implemented in South Africa (SA) with intervals of 10 years after a normal cytological result. There are no studies that evaluate repeat screening at a shorter interval in SA. OBJECTIVES: (i) To find the incidence of cytological abnormalities on a repeat test after a report of normal cytology or an inadequate Pap smear; and (ii) to explore the factors associated with an abnormal cytology on repeat testing. METHODS: This was a secondary data analysis of a randomised controlled trial of diaphragm, lubricant gel and condoms v. condoms in the prevention of HIV infection. HIV-negative women were recruited between November 2003 and December 2005, with a normal Pap smear at entry. Observation time was from the first Pap smear to the date of the repeat Pap smear. Explanatory variables used were baseline, excepting any new HIV infection. RESULTS: The incidence of cytological abnormalities was 6.48% yearly in women with a previously normal Pap smear and 11.71% yearly in women with an inadequate smear result (p=0.03). The incidence of high-grade squamous intra-epithelial lesions (HSILs) was <0.5%. Factors associated with abnormal cytology were a history of ectopic pregnancy (odds ratio (OR) 9.25; confidence interval (CI) 1.78 - 48.02; p=0.01), number of male partners (OR 1.12; CI 1.03 - 1.22; p=0.01), history of vaginal discharge (OR 13.95; CI 1.18 - 164.47; p=0.04), and incident HIV infection (OR 6.56; CI 1.14 - 38.16; p=0.04). CONCLUSION: The incidence of HSILs is low in the first 2 years after a normal or inadequate Pap smear, even in a setting with a high prevalence of cytological abnormalities.
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    Is air pollution a risk factor for rheumatoid arthritis?
    (2015) Essouma, Mickael; Noubiap, Jean Jacques N
    Rheumatoid arthritis is a chronic inflammatory debilitating disease triggered by a complex interaction involving genetic and environmental factors. Active smoking and occupational exposures such as silica increase its risk, suggesting that initial inflammation and generation of rheumatoid arthritis-related autoantibodies in the lungs may precede the clinical disease. This hypothesis paved the way to epidemiological studies investigating air pollution as a potential determinant of rheumatoid arthritis. Studies designed for epidemiology of rheumatoid arthritis found a link between traffic, a surrogate of air pollution, and this disease. Furthermore, a small case–control study recently found an association between wood smoke exposure and anticyclic citrullinated protein/peptide antibody in sera of patients presenting wood-smoke-related chronic obstructive pulmonary disease. However, reports addressing impact of specific pollutants on rheumatoid arthritis incidence and severity across populations are somewhat conflicting. In addition to the link reported between other systemic autoimmune rheumatic diseases and particulate matters/gaseous pollutants, experimental observation of exacerbated rheumatoid arthritis incidence and severity in mice models of collagen-induced arthritis after diesel exhaust particles exposure as well as hypovitaminosis D-related autoimmunity can help understand the role of air pollution in rheumatoid arthritis. All these considerations highlight the necessity to extend high quality epidemiological researches investigating different sources of atmospheric pollution across populations and particularly in low-and-middle countries, in order to further explore the biological plausibility of air pollution’s effect in the pathogenesis of rheumatoid arthritis. This should be attempted to better inform policies aiming to reduce the burden of rheumatoid arthritis.
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    Measles vaccination coverage in high-incidence areas of the Western Cape, following the mass vaccination campaign
    (2013) Bernhardt, G L; Cameron, N A; Willems, B; Boulle, A; Coetzee, D
    BACKGROUND: Despite significant advances in measles control, large epidemics occurred in many African countries in 2009 - 2011, including South Africa. South Africa's control strategy includes mass vaccination campaigns about every 4 years, the last of which was conducted nationally in April 2010 and coincided with the epidemic. AIM: A community survey was conducted in the Western Cape to assess measles vaccination coverage attained by routine and campaign services, in children aged 6 months to 59 months at the time of the mass campaign, from high-incidence areas. METHODS: Households were consecutively sampled in high-incidence areas identified using measles epidemic surveillance data. A caregiver history of campaign vaccination and routine vaccination status from the child's Road to Health card were collected. Pre- and post-campaign immunity was estimated by analytical methods. RESULTS: Of 8 332 households visited, there was no response at 3 435 (41.2%); 95.1% (1 711/1 800) of eligible households participated; and 91.2% (1 448/1 587; 95% confidence interval 86 - 94%) of children received a campaign vaccination. Before the campaign, 33.0% (103/312) of 9 - 17-month-olds had not received a measles vaccination, and this was reduced to 4.5% (14/312) after the campaign. Of the 1 587 children, 61.5% were estimated to have measles immunity before the campaign, and this increased to 94.0% after the campaign. DISCUSSION: Routine services had failed to achieve adequate herd immunity in areas with suspected highly mobile populations. Mass campaigns in such areas in the Western Cape significantly increased coverage. Extra vigilance is required to monitor and sustain adequate coverage in these areas.
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    Setting priorities in health research using the model proposed by the World Health Organization: development of a quantitative methodology using tuberculosis in South Africa as a worked example
    (2016) Hacking, Damian; Cleary, Susan
    BackgroundSetting priorities is important in health research given the limited resources available for research. Various guidelines exist to assist in the priority setting process; however, priority setting still faces significant challenges such as the clear ranking of identified priorities. The World Health Organization (WHO) proposed a Disability Adjusted Life Year (DALY)-based model to rank priorities by research area (basic, health systems and biomedical) by dividing the DALYs into ‘unavertable with existing interventions’, ‘avertable with improved efficiency’ and ‘avertable with existing but non-cost-effective interventions’, respectively. However, the model has conceptual flaws and no clear methodology for its construction. Therefore, the aim of this paper was to amend the model to address these flaws, and develop a clear methodology by using tuberculosis in South Africa as a worked example.MethodsAn amended model was constructed to represent total DALYs as the product of DALYs per person and absolute burden of disease. These figures were calculated for all countries from WHO datasets. The lowest figures achieved by any country were assumed to represent ‘unavertable with existing interventions’ if extrapolated to South Africa. The ratio of ‘cost per patient treated’ (adjusted for purchasing power and outcome weighted) between South Africa and the best country was used to calculate the ‘avertable with improved efficiency section’. Finally, ‘avertable with existing but non-cost-effective interventions’ was calculated using Disease Control Priorities Project efficacy data, and the ratio between the best intervention and South Africa’s current intervention, irrespective of cost.ResultsThe amended model shows that South Africa has a tuberculosis burden of 1,009,837.3 DALYs; 0.009% of DALYs are unavertable with existing interventions and 96.3% of DALYs could be averted with improvements in efficiency. Of the remaining DALYs, a further 56.9% could be averted with existing but non-cost-effective interventions.ConclusionsThe amended model was successfully constructed using limited data sources. The generalizability of the data used is the main limitation of the model. More complex formulas are required to deal with such potential confounding variables; however, the results act as starting point for development of a more robust model.Electronic supplementary materialThe online version of this article (doi:10.1186/s12961-016-0081-8) contains supplementary material, which is available to authorized users.
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    Systematic review of the evidence for rational dosing of colistin
    (2014) Visser Kift, E; Maaartens, G; Bamford, C
    BACKGROUND: There is an alarming global increase in the incidence of nosocomial infections with multidrug-resistant Gram-negative bacteria, which are often only susceptible to colistin. Colistin was developed prior to current methods of establishing dosing using pharmacokinetic-pharmacodynamic relationships. Dosing regimens differ in package inserts from different manufacturers and in different guidelines. It is imperative to avoid under-dosing with colistin in order to limit the development of resistance, as it is the last line of defence. METHODS: We conducted a systematic review of the literature to develop guidelines for rational dosing of intravenous colistin, with a particular focus on critically ill patients. RESULTS: Colistin is administered as the inactive pro-drug colistimethate sodium. Colistin demonstrates concentration-dependent bacterial killing, suggesting that higher doses should be administered less frequently to achieve higher peak concentrations. Dose-related nephrotoxicity occurs, making it impossible to safely achieve concentrations that prevent the selection of resistant mutants or the effective eradication of bacteria with higher minimum inhibitory concentrations. Theoretically, combination therapy should be used to reduce the risk of selection of resistant bacteria. In critically ill patients, a loading dose should be given to rapidly achieve therapeutic concentrations, followed by maintenance doses of 4.5 MU 12-hourly. Maintenance dose adjustment is necessary with renal impairment. CONCLUSION: Easier access to colistin is needed in South Africa, where it is not a registered medicine. Further research is needed to better characterise colistin's pharmacokinetic-pharmacodynamic relationships in humans and to establish whether combinations of colistin with other antimicrobials result in improved clinical outcomes or a reduction in selection of resistant bacteria.
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    The burden of laboratory-confirmed pertussis in low- and middle-income countries since the inception of the Expanded Programme on Immunisation (EPI) in 1974: a systematic review and meta-analysis
    (2020-08-28) Muloiwa, Rudzani; Kagina, Benjamin M; Engel, Mark E; Hussey, Gregory D
    Abstract Background An effective vaccine against Bordetella pertussis was introduced into the Expanded Programme on Immunisation (EPI) by WHO in 1974, leading to a substantial global reduction in pertussis morbidity and mortality. In low- and middle-income countries (LMICs), however, the epidemiology of pertussis remains largely unknown. This impacts negatively on pertussis control strategies in these countries. This study aimed to systematically and comprehensively review published literature on the burden of laboratory-confirmed pertussis in LMICs over the 45 years of EPI. Methods Electronic databases were searched for relevant literature (1974 to December 2018) using common and MeSH terms for pertussis. Studies using PCR, culture or paired serology to confirm Bordetella pertussis and parapertussis in symptomatic individuals were included if they had clearly defined numerators and denominators to determine prevalence and mortality rates. Results Eighty-two studies (49,167 participants) made the inclusion criteria. All six WHO regions were represented with most of the studies published after 2010 and involving mainly upper middle-income countries (n = 63; 77%). PCR was the main diagnostic test after the year 2000. The overall median point prevalence of PCR-confirmed Bordetella pertussis was 11% (interquartile range (IQR), 5–27%), while culture-confirmed was 3% (IQR 1–9%) and paired serology a median of 17% (IQR 3–23%) over the period. On average, culture underestimated prevalence by 85% (RR = 0.15, 95% CI, 0.10–0.22) compared to PCR in the same studies. Risk of pertussis increased with HIV exposure [RR, 1.4 (95% CI, 1.0–2.0)] and infection [RR, 2.4 (95% CI, 1.1–5.1)]. HIV infection and exposure were also related to higher pertussis incidences, higher rates of hospitalisation and pertussis-related deaths. Pertussis mortality and case fatality rates were 0.8% (95% CI, 0.4–1.4%) and 6.5% (95% CI, 4.0–9.5%), respectively. Most deaths occurred in infants less than 6 months of age. Conclusions Despite the widespread use of pertussis vaccines, the prevalence of pertussis remains high in LMIC over the last three decades. There is a need to increase access to PCR-based diagnostic confirmation in order to improve surveillance. Disease control measures in LMICs must take into account the persistent significant infant mortality and increased disease burden associated with HIV infection and exposure.
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    The burden of pertussis in low- and middle-income countries since the inception of the Expanded Programme on Immunization (EPI) in 1974: a systematic review protocol
    (2015-05-01) Muloiwa, Rudzani; Kagina, Benjamin M; Engel, Mark E; Hussey, Gregory D
    Abstract Background Vaccine against pertussis has been in use for several decades. Despite the widespread use of pertussis vaccine, evidence shows resurgence of pertussis in high-income countries. Pertussis surveillance data is largely missing from low- and middle-income countries (LMICs). Without data on trends of pertussis, it is difficult to review and amend pertussis control policies in any country. We propose conducting a systematic review to evaluate the burden and trends of pertussis in LMICs since 1974. Methods/design Common and medical subject heading (MeSH) terms for pertussis and LMICs will be used to search electronic databases for the relevant literature published between 1974 and December 2014. Only studies from LMICs that fulfils World Health Organisation (WHO) or CDC pertussis case definitions will be included. The studies must have a clear numerator and denominator in a well-defined population. Risk of bias will be evaluated by assessing all qualifying full-text articles for quality and eligibility using a modified quality score assessment tool. Standardised data extraction will be carried out after which descriptions of trends in the prevalence, incidence, as well as mortality rate and case fatality rate, will be done. Where sufficient data is available, the results will be stratified by age group, geography, location, vaccination and HIV status. Discussion The systematic review proposed by this protocol seeks to address the knowledge gap in the epidemiology of pertussis in LMICs for the first time. It is anticipated that the background epidemiological trends of pertussis in LMICs that our study will provide could be used in the planning for the control of pertussis. Systematic review registration PROSPERO CRD42015015159
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    The Clostridium difficile problem: A South African tertiary institution's prospective perspective
    (2013) Rajabally, N M; Pentecost, M; Pretorius, G; Whitelaw, A; Mendelson, M; Watermeyer, G
    BACKGROUND AND OBJECTIVES: The aim of this study is to report the incidence of Clostridium difficile-associated disease (CDAD) in a tertiary-care hospital in South Africa and to identify risk factors, assess patient outcomes and determine the impact of the hypervirulent strain of the organism referred to as North American pulsed-field type 1 (NAP1). METHODS: Adults who presented with diarrhoea over a period of 15 months were prospectively evaluated for CDAD using stool toxin enzyme immunoassay (EIA). Positive specimens were evaluated by PCR. Patient demographics, laboratory parameters and outcomes were analysed. RESULTS: CDAD was diagnosed in 59 (9.2%) of 643 patients (median age 39 years, IQR 30 - 55). Thirty-four (58%) were female. Recent antibiotic exposure was reported in 39 (66%), 27 (46%) had been hospitalised within 3 months, and 14 (24%) had concomitant inflammatory bowel disease (IBD). Nineteen (32%) had community-acquired CDAD (CA-CDAD). The annual incidence of hospital-acquired CDAD (HA-CDAD) was 8.7 cases/10 000 hospitalisations. Two cases of the hypervirulent strain NAP1 were identified. Seven (12%) patients underwent colectomy (OR 6.83; 95% CI 2.41 - 19.3). On logistic regression, only antibiotic exposure independently predicted for CDAD (OR 2.9; 95% CI 1.6 - 5.1). Three (16%) cases of CA-CDAD reported antibiotic exposure (v. 90% of HA-CDAD, p<0.0001). Twelve (86%) patients had concomitant IBD (p<0.0001 v. HA-CDAD). CA-CDAD was significantly associated with antibiotic exposure (OR 0.04, 95% CI 0.01 - 0.24) and IBD (OR 9.6, 95% CI 1.15 - 79.8). CONCLUSION: The incidence of HA-CDAD in the South African setting is far lower than that reported in the West. While antibiotic use was a major risk factor for HA-CDAD, CA-CDAD was not associated with antibiotic therapy. Concurrent IBD was a predictor of CA-CDAD.
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    The epidemiology of tuberculosis in health care workers in South Africa: a systematic review
    (2016) Grobler, Liesl; Mehtar, Shaheen; Sabur, Natasha F; Adams, Shahieda; Babatunde, Sanni; van der Walt, Martie; Osman, Muhammad
    Abstract 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 health care facilities.
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    The timing of tuberculosis after isoniazid preventive therapy among gold miners in South Africa: a prospective cohort study
    (2016) Hermans, Sabine M; Grant, Alison D; Chihota, Violet; Lewis, James J; Vynnycky, Emilia; Churchyard, Gavin J; Fielding, Katherine L
    BackgroundThe durability of isoniazid preventive therapy (IPT) in preventing tuberculosis (TB) is limited in high-prevalence settings. The underlying mechanism (reactivation of persistent latent TB or reinfection) is not known. We aimed to investigate the timing of TB incidence during and after IPT and associated risk factors in a very high TB and HIV-prevalence setting, and to compare the observed rate with a modelled estimate of TB incidence rate after IPT due to reinfection.MethodsIn a post-hoc analysis of a cluster-randomized trial of community-wide IPT among South African gold miners, all intervention arm participants that were dispensed IPT for at least one of the intended 9months were included. An incident TB case was defined as any participant with a positive sputum smear or culture, or with a clinical TB diagnosis assigned by a senior study clinician. Crude TB incidence rates were calculated during and after IPT, overall and by follow-up time. HIV status was not available. Multivariable Cox regression was used to analyse risk factors by follow-up time after IPT. Estimates from a published mathematical model of trial data were used to calculate the average reinfection TB incidence in the first year after IPT.ResultsAmong 18,520 participants (96% male, mean age 41years, median follow-up 2.1years), 708 developed TB. The TB incidence rate during the intended IPT period was 1.3/100 person-years (pyrs; 95% confidence interval (CI), 1.0–1.6) and afterwards 2.3/100 pyrs (95% CI, 1.9–2.7). TB incidence increased within 6months followed by a stable rate over time. There was no evidence for changing risk factors for TB disease over time after miners stopped IPT. The average TB incidence rate attributable to reinfection in the first year was estimated at 1.3/100 pyrs, compared to an observed rate of 2.2/100 pyrs (95% CI, 1.8–2.7).ConclusionsThe durability of protection by IPT was lost within 6–12 months in this setting with a high HIV prevalence and a high annual risk of M. tuberculosis infection. The observed rate was higher than the modelled rate, suggesting that reactivation of persistent latent infection played a role in the rapid return to baseline TB incidence.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0589-3) contains supplementary material, which is available to authorized users.
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    Tuberculosis preventive therapy: An underutilised strategy to reduce individual risk of TB and contribute to TB control
    (2014) Churchyard, Gavin J; Chaisson, Richard E; Maartens, Gary; Getahun, Haileyesus
    Tuberculosis (TB) remains a global health problem, and South Africa (SA) has one of the world's worst TB epidemics. The World Health Organization (WHO) estimated in 1999 that one-third of the world's population was latently infected with TB. In SA up to 88% of HIV-uninfected young adults (31 - 35 years) are latently infected with TB. In the most recent meta-analysis, 6 - 12 months of isoniazid preventive therapy (IPT) was associated with a lower incidence of active TB than placebo (relative risk (RR) 0.68; 95% confidence interval (CI) 0.54 - 0.85), with the greatest benefit among individuals with a positive tuberculin skin test (TST) (RR 0.38; 95% CI 0.25 - 0.57). A clinical trial of IPT given with antiretroviral therapy (ART) for 12 months reduced TB incidence by 37% compared with ART alone (hazard ratio (HR) 0.63; 95% CI 0.41 - 0.94). The effect of IPT is limited in high-burden countries. IPT for 36 months v. 6 months reduced TB incidence among HIV-positive, TST-positive participants by 74% (HR 0.26; 95% CI 0.09 - 0.80). A study of more than 24 000 goldminers confirmed that IPT is safe, with only 0.5% experiencing adverse events. A meta-analysis of studies of IPT since 1951 did not show an increased risk of developing resistance. Alternative TB preventive therapy regimens, including high-dose isoniazid and rifapentine given weekly for 3 months, have been shown to have similar efficacy to IPT. Mathematical modelling suggests that scaling up continuous IPT targeted to HIV-positive persons, when used in combination with other treatment and prevention strategies, may substantially improve TB control.