Browsing by Author "Wasserman, Sean"
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- ItemOpen AccessBurden of pneumocystis pneumonia in HIV-infected adults in sub-Saharan Africa: a systematic review and meta-analysis(BioMed Central, 2016-09-09) Wasserman, Sean; Engel, Mark E; Griesel, Rulan; Mendelson, MarcAbstract Background Seroprevalence data and clinical studies in children suggest that the burden of pneumocystis pneumonia (PCP) in Africa may be underestimated. We performed a systematic review to determine the prevalence and attributable mortality of PCP amongst HIV-infected adults in sub-Saharan Africa. Methods We searched Pubmed, Web of Science, Africa-Wide: NiPAD and CINAHL, from Jan 1 1995 to June 1 2015, for studies that reported the prevalence, mortality or case fatality of PCP in HIV-infected adults living in sub-Saharan African countries. Prevalence data from individual studies were combined by random-effects meta-analysis according to the Mantel-Haenszel method. Data were stratified by clinical setting, diagnostic method, and study year. Results We included 48 unique study populations comprising 6884 individuals from 18 countries in sub-Saharan Africa. The pooled prevalence of PCP among 6018 patients from all clinical settings was 15 · 4 % (95 % CI 12 · 9–18 · 0), and was highest amongst inpatients, 22 · 4 % (95 % CI 17 · 2–27 · 7). More cases were identified by bronchoalveolar lavage, 21 · 0 % (15 · 0–27 · 0), compared with expectorated, 7 · 7 % (4 · 4–11 · 1), or induced sputum, 11 · 7 % (4 · 9–18 · 4). Polymerase chain reaction (PCR) was used in 14 studies (n = 1686). There was a trend of decreasing PCP prevalence amongst inpatients over time, from 28 % (21–34) in the 1990s to 9 % (8–10) after 2005. The case fatality rate was 18 · 8 % (11 · 0–26 · 5), and PCP accounted for 6 · 5 % (3 · 7–9 · 3) of study deaths. Conclusions PCP is an important opportunistic infection amongst HIV-infected adults in sub-Saharan Africa, particularly amongst patients admitted to hospital. Although prevalence appears to be decreasing, improved access to antiretroviral therapy and non-invasive diagnostics, such as PCR, are needed.
- ItemOpen AccessBurden of pneumocystis pneumonia in HIV-infected adults in sub-Saharan Africa: protocol for a systematic review(BioMed Central Ltd, 2013) Wasserman, Sean; Engel, Mark E; Mendelson, MarcBACKGROUND: Reports from Africa have suggested that pneumocystis pneumonia (PCP) is a less important cause of morbidity than in the developed world. However, more recent studies have shown high seroprevalence rates of P. jirovecii in healthy individuals with HIV as well as high rates of clinical disease in African children. This suggests that PCP may be more common in Africa than was previously recognised. Understanding the contribution of PCP to disease in HIV-infected individuals in sub-Saharan Africa (SSA) has important implications for diagnosis, management and resource allocation. We therefore propose to conduct a systematic review and meta-analysis in order to investigate the burden of PCP in this population.METHODS AND DESIGN:We plan to search electronic databases and reference lists of relevant articles published from 1995 to May 2013 using broad terms for pneumocystis, HIV/AIDS and sub-Saharan Africa. Studies will be included if they provide clear diagnostic criteria for PCP and well-defined study populations or mortality data (denominator). A novel quality score assessment tool has been developed to ensure fidelity to inclusion criteria, minimise risk of selection bias between reviewers and to assess quality of outcome ascertainment. This will be applied to eligible full-text articles. We will extract data using a standardised form and perform descriptive and quantitative analysis to assess PCP prevalence, mortality and case fatality, as well as the quality of included studies. This review protocol has been published in the PROSPERO International Prospective Register of systematic reviews, registration number CRD42013005530.DISCUSSION:Our planned review will contribute to the diagnosis and management of community-acquired pneumonia in HIV-infected individuals in SSA by systematically assessing the burden of PCP in this population. We also describe a novel quality assessment tool that may be applied to other prevalence reviews.
- ItemOpen AccessColonisation with pathogenic drug-resistant bacteria and Clostridioides difficile among residents of residential care facilities in Cape Town, South Africa(2019) September, Jason; Wasserman, SeanObjectives Residential care facilities (RCFs) act as reservoirs for multidrug-resistant organisms (MDRO). There are scarce data on colonisation with MDROs in Africa. We aimed to determine the prevalence of MDROs and C. difficile and risk factors for carriage amongst residents of RCFs in Cape Town, South Africa. Methods We performed a cross-sectional surveillance study at three RCFs. Chromogenic agar was used to screen skin swabs for methicillin-resistant Staphylococcus aureus (MRSA) and stool samples for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E). Antigen testing and PCR was used to detect Clostridiodes difficile. Risk factors for colonisation were determined with logistic regression. Results One hundred fifty-four residents were enrolled, providing 119 stool samples and 152 sets of skin swabs. Twenty-seven (22.7%) stool samples were positive for ESBL-E, and 13 (8.6%) residents had at least one skin swab positive for MRSA. Two (1.6%) stool samples tested positive for C. difficile. Poor functional status (OR 1.3 (95% CI, 1.0 – 1.6)) and incontinence (OR 2.9 (95% CI, 1.2 – 6.9)) were significant predictors for ESBL-E colonisation. There was a trend towards higher MRSA colonisation in frail care areas. Conclusion There was high prevalence of colonisation with MDROs but low C. difficile carriage, with implications for antibiotic prescribing and infection control practice.
- ItemOpen AccessColonisation with pathogenic drug-resistant bacteria and Clostridioides difficile among residents of residential care facilities in Cape Town, South Africa: a cross-sectional prevalence study(2019-11-19) September, Jason; Geffen, Leon; Manning, Kathryn; Naicker, Preneshni; Faro, Cheryl; Mendelson, Marc; Wasserman, SeanAbstract Background Residential care facilities (RCFs) act as reservoirs for multidrug-resistant organisms (MDRO). There are scarce data on colonisation with MDROs in Africa. We aimed to determine the prevalence of MDROs and C. difficile and risk factors for carriage amongst residents of RCFs in Cape Town, South Africa. Methods We performed a cross-sectional surveillance study at three RCFs. Chromogenic agar was used to screen skin swabs for methicillin-resistant S. aureus (MRSA) and stool samples for extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E). Antigen testing and PCR was used to detect Clostridiodes difficile. Risk factors for colonisation were determined with logistic regression. Results One hundred fifty-four residents were enrolled, providing 119 stool samples and 152 sets of skin swabs. Twenty-seven (22.7%) stool samples were positive for ESBL-E, and 13 (8.6%) residents had at least one skin swab positive for MRSA. Two (1.6%) stool samples tested positive for C. difficile. Poor functional status (OR 1.3 (95% CI, 1.0–1.6)) and incontinence (OR 2.9 (95% CI, 1.2–6.9)) were significant predictors for ESBL-E colonisation. MRSA colonization appeared higher in frail care areas (8/58 v 5/94, p = 0.07). Conclusions There was a relatively high prevalence of colonisation with MDROs, particularly ESBL-E, but low C. difficile carriage, with implications for antibiotic prescribing and infection control practice.
- ItemOpen AccessCommunity-based care of stroke patients in a rural african setting(2009) Wasserman, Sean; de Villiers, Linda; Bryer, AlanBackground: In order to develop a community based-model of stroke care we assessed discharge planning of stroke patients, available resources, and continuity of care between hospital and community in a remote rural setting in South Africa. We sought to determine outcomes, family participation and support needs, as well as implementation of secondary prevention strategies. Methods: Thirty consecutive stroke patients from the local hospital were assessed clinically (including Barthel Index and modified Rankin scores) at time of discharge. Patients were re-assessed three months after discharge in their homes by a trained field worker using a structured questionnaire. Results: Two thirds of all families received no stroke education before discharge. At discharge 27 (90%) were either bed or chair-bound. All the patients were discharged into family care as there was no stroke rehabilitation facility available to the community. Of 30 patients recruited, 20 (66.7%) were alive at 3 months, 9 (30%) were deceased, and 1 was lost to follow-up. At 3 months, 55% of survivors were independently mobile as compared with 10% at discharge. A total of 13 (65%) patients in our cohort were visited by home-based carers. Only 45% reported taking aspirin at 3 months. Conclusions: The 3 month mortality rate was high. Most survivors improved functionally but were left with significant disability. Measures to improve family education and the level of home-based care can be introduced in a model of stroke care attempting to reduce carer strain and improve functional disability in rural stroke patients.
- ItemOpen AccessEarly outcomes of thrombolysis for acute ischaemic stroke in a South African tertiary care centre(2012) Wasserman, Sean; Bryer, AlanStroke is an important cause of death and disability in sub-Saharan Africa. Recombinant tissue plasminogen activator (tPA) thrombolysis is effective in treating acute ischaemic stroke, but may not be a viable option in developing countries. This prospective observational study was designed to assess the short-termoutcomes and safety of tPA for the treatment of stroke at Groote Schuur Hospital.Data was collected from January 2000 to February 2012, and included patients witha clinical diagnosis of acute stroke with onset of stroke symptoms within 4.5 hours ofreceiving thrombolysis. Exclusion criteria were based on the National Institute ofNeurological Disorders and Stroke (NINDS) rt-PA trial protocol (upper age limit was 75 years). Primary outcomes were the proportion of patients achieving significant early neurological recovery defined as an improvement of 4 or more points on the National Institutes of Health stroke scale (NIHSS) score and functional independence defined as a modified Rankin score of 2 or less at discharge. The primary safety measures were the rates of symptomatic intracranial haemorrhage (SICH) and death. From January 2000 to February 2011 42 patients were thrombolysed, with a mean time to tPA infusion of 160 minutes (standard deviation (SD) 50; range 60 - 270). By discharge the median NIHSS score fell from 14 (interquartile range (IQR) 10.5 - 17) to 7.5 (IQR 1 - 15); 28 (66.7%) achieved significant neurological improvement, and 17 (40.5%) were functionally independent. Two patients (4.8%) suffered SICH and there were 3 (7.1%) deaths. Thrombolysis in routine clinical practice in a South African setting has similar safety and early efficacy outcomes to controlled trials and open-label studies in developing and developed countries.
- ItemOpen AccessImproved treatment outcomes with bedaquiline when substituted for second-line injectable agents in multidrug-resistant tuberculosis: A retrospective cohort study(2019) Zhao, Ying; Meintjes, Graeme; Wasserman, SeanBackground Bedaquiline is used as a substitute for second-line injectable (SLI) intolerance in the treatment of multidrug-resistant tuberculosis (MDR-TB), but the efficacy and safety of this strategy is unknown. Methods We performed a retrospective cohort study to evaluate treatment outcomes for MDR-TB patients who substituted bedaquiline for SLIs. Adults receiving bedaquiline substitution for MDR-TB therapy, plus a matched control group who did not receive bedaquiline, were identified from the electronic TB register in the Western Cape Province, South Africa. The primary outcome measure was the proportion of patients with death, loss to follow up, or failure to achieve sustained culture conversion at 12 months of treatment. Results Data from 162 patients who received bedaquiline substitution and 168 controls were analyzed; 70.6% were HIV-infected. Unfavorable outcomes occurred in 35/146 (23.9%) patients in the bedaquiline group versus 51/141 (36.2%) in the control group (relative risk, 0.66; 95% confidence interval [CI], 0.46 to 0.95). The number of patients with culture reversion was lower in those receiving bedaquiline (1 patient, 0.8%) compared to controls (12 patients, 10.3%; P = 0.001). Delayed initiation of bedaquiline was independently associated with failure to achieve sustained culture conversion (adjusted odds ratio, 1.5; 95% CI, 1.1 – 1.9, for every 30-day delay). Mortality was similar at 12 months (11 deaths in each group; P = 0.973). Conclusions Substituting bedaquiline for SLIs in MDR-TB treatment resulted in improved outcomes at 12 months compared with patients who remained on SLIs, supporting the use of bedaquiline for MDR-TB treatment in programmatic settings.
- ItemOpen AccessRadiological predictors of PCP in HIV-positive adults in South Africa: a matched case-control study(2024) Wills, Nicola; Wasserman, SeanBackground Definition of chest X-ray (CXR) features associated with laboratory-confirmed pneumocystis pneumonia (PCP) among HIV-positive adults is needed to improve diagnosis in high-burden settings. Methods We conducted a case-control study involving HIV-positive adults with laboratory-confirmed PCP and a matched cohort with non-PCP respiratory presentations at regional hospitals in Cape Town, South Africa (2012 - 2020). The primary objective was to identify CXR features associated with confirmed PCP diagnosis and severe PCP (defined by hypoxia, ICU referral/admission, and/or in-hospital death). We explored the performance of logistic regression models, incorporating selected clinical and CXR predictors, for PCP diagnosis and severe PCP. Results Records from 104 adults (52 PCP cases and 52 non-PCP controls) were included. Diffuse versus patchy ground glass opacification was associated with increased odds of PCP diagnosis (adjusted odd's ratio (aOR) 6.2, 95% confidence interval (CI) 1.6 - 28.9, p = 0.01) and severe PCP (aOR 4.5, 95%CI 1.6 - 14.4, p = 0.008). Consolidation was associated with severe PCP (aOR 3.3, 95%CI 1.2 - 11.0, p =0.03) as was increasing ground glass zone involvement (aOR 2.1 for each one-unit increase in involved zone; 95% CI, 1.4 - 3.2, p = 0.0004). Models incorporating hypoxia (hypoxia model) or tachypnoea (respiratory rate model) with diffuse ground glass opacities, absence of pleural effusion or reticular/reticulonodular changes on CXR performed well in predicting PCP (area under the receiver operating characteristic curve 0.828 (hypoxia model) and 0.857 (respiratory rate model)). Conclusions CXR evaluation alongside bedside clinical information offers good accuracy for discriminating definite PCP from other HIV-associated respiratory diseases
- ItemOpen AccessRadiological predictors of PCP in HIV-positive adults in South Africa: a matched case-control study(2025) Wills, Nicola; Wasserman, SeanDefinition of chest X-ray (CXR) features associated with laboratory-confirmed pneumocystis pneumonia (PCP) among HIV-positive adults is needed to improve diagnosis in high-burden settings. Methods: We conducted a case-control study involving HIV-positive adults with laboratory-confirmed PCP and a matched cohort with non-PCP respiratory presentations at regional hospitals in Cape Town, South Africa (2012 – 2020). The primary objective was to identify CXR features associated with confirmed PCP diagnosis and severe PCP (defined by hypoxia, ICU referral/admission, and/or in-hospital death). We explored the performance of logistic regression models, incorporating selected clinical and CXR predictors, for PCP diagnosis and severe PCP. Results: Records from 104 adults (52 PCP cases and 52 non-PCP controls) were included. Diffuse versus patchy ground glass opacification was associated with increased odds of PCP diagnosis (adjusted odd's ratio (aOR) 6.2, 95% confidence interval (CI) 1.6 – 28.9, p =0.01) and severe PCP (aOR 4.5, 95%CI 1.6 – 14.4, p =0.008). Consolidation was associated with severe PCP (aOR 3.3, 95%CI 1.2 –11.0, p =0.03) as was increasing ground glass zone involvement (aOR 2.1 for each one-unit increase in involved zone; 95% CI, 1.4 – 3.2, p = 0.0004). Models incorporating hypoxia (hypoxia model) or tachypnoea (respiratory rate model) with diffuse ground glass opacities, absence of pleural effusion or reticular/reticulonodular changes on CXR performed well in predicting PCP (area under the receiver operating characteristic curve 0.828 (hypoxia model) and 0.857 (respiratory rate model). Conclusions: CXR evaluation alongside bedside clinical information offers good accuracy for discriminating definite PCP from other HIV-associated respiratory diseases.
- ItemOpen AccessSevere Neurotoxicity Associated with supra-therapeutic Efavirenz concentrations: a retrospective cohort study(2023) Arnab, Priyadarshini; Wasserman, Sean; Cohen KarenIntroduction Efavirenz, still used for first line antiretroviral therapy, is associated with neuropsychiatric symptoms, often occurring early in therapy. Severe neurotoxicity has been reported but the clinical phenotype and risk factors are poorly defined. Methods We retrospectively identified adults with supratherapeutic efavirenz concentrations (> 4 mg/L) obtained as part of routine clinical care at five hospitals in Cape Town, South Africa. Clinical and laboratory data at the time of efavirenz quantification were extracted from medical records. Logistic regression was performed to identify associations with neuropsychiatric symptoms, and with severe neurotoxicity (defined as Division of Allergy and Infectious Diseases altered mental status or ataxia ≥ Grade 3). Results and Discussion 81 patients were included; 28 (34.6%) were male and 49 (60.5%) had concomitant isoniazid exposure. Median efavirenz concentration was 12.1 mg/L (interquartile range (IQR) 6.6-20.0). The most frequent neuropsychiatric manifestations were ataxia in 20 patients and psychomotor slowing in 24. The presence of any neuropsychiatric symptoms were associated with: longer duration, per 180 days, of efavirenz therapy (aOR 1.3; 95% CI, 1.0-1.7); increasing efavirenz concentrations per 1 mg/L increase (aOR 1.2; 95% CI, 1.1-1.4); higher efavirenz concentrations per 1 mg/L increase (aOR 1.2; 95% CI, 1.0- 1.4); and isoniazid exposure (aOR 8.2; 95% CI, 2.5-26.7). Severe neuropsychiatric symptoms occurred in 47 (75%) patients at a median of 5.9 months (IQR 2.1-40.8) after efavirenz initiation. Odds of having severe symptoms compared with mild symptoms were 1.2-fold higher (95% CI, 1.1-1.4) for every 1 mg/L increase in efavirenz concentration. Among patients with severe neurotoxicity, symptoms resolved completely within 1 month in the 29 (94%) who discontinued efavirenz. Conclusion We describe a distinct clinical phenotype and factors. There were duration- and concentration dependent effects, and higher risk with concomitant INH exposure and those with lower CD4 count. Despite most patients with severe neurotoxicity having symptom resolution within 1 month after stopping EFV, the overall 3-month mortality was high in this population.
- ItemOpen AccessThe management and outcomes of Staphylococcus aureus Bacteraemia at a South African referral hospital: A prospective observational study(2018) Steinhaus, Nicola; Wasserman, Sean; Davies, Mary-AnnStaphylococcus aureus is a major human pathogen found worldwide, causing a wide variety of clinical infections. This ranges from skin and soft tissue infections to lifethreatening invasive disease, such as S. aureus bacteraemia (SAB). Despite being a common cause of both community-acquired and hospital-acquired infections, limited evidence exists on the management and outcomes of Staphylococcus aureus bacteraemia (SAB) in resource-limited settings. The aim of this study was to describe a cohort of South African patients with SAB, and explore the factors associated with complicated infection and death. A prospective observational study was performed of patients over the age of 13 years admitted to a South African referral hospital with SAB. Data were analysed using Kaplan Meier survival models and linear regression models. One hundred consecutive SAB infection episodes in 98 patients were included. SAB was healthcare-associated in 68.4%, with 57.6% of these linked to drip site infection; 24.0% of all cases were caused by methicillin-resistant S. aureus (MRSA). Ninety-day mortality was 47.0%, with 83.3% of deaths attributable to SAB. Predictors of 90-day mortality were MRSA (odds ratio (OR) 1.28; 95% confidence interval (CI) 1.0 to 15.1) and the presence of co-morbidities (OR 4.1; 95% CI 1.0 to 21.6). The risk of complicated infection was higher with suboptimal antibiotic therapy (OR 8.5; 95% CI 1.8 to 52.4), female sex (OR 3.8; 95% CI 1.1 to 16.3) and community-acquired infection (OR 7.4; 95% CI 2.0 to 33.1). Definitive antibiotic therapy was suboptimal in 22.6% of all cases. Overall, SAB-related mortality was high. A large proportion of SAB episodes may be preventable, and there is a need for improved antibiotic management in this setting. Part A. The study protocol, as submitted for departmental and ethical approval, is presented here. It includes the background, rationale and methodology of the research done for this mini-dissertation. Part B. A structured literature review is presented of articles pertaining to SAB epidemiology and treatment, with the aim to place this research study in context and identify gaps in research. Part C. A journal-ready manuscript according to the requirements of the International Journal of Infectious Diseases. Appendix. All additional documentation necessary as addendums in the presentation of this mini-dissertation.