Browsing by Author "Enarson, Donald A."
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- ItemComparing same day sputum microscopy with conventional sputum microscopy for the diagnosis of tuberculosis : Chhattisgarh, India(Public Library of Science, 2013-09-23) Nayak, Priyakanta; Kumar, Ajay M. V.; Claassens, Mareli; Enarson, Donald A.; Satyanarayana, Srinath; Kundu, Debashish; Khaparde, Kshitij; Agrawal, Tarun K.; Dapkekar, Shankar; Chandraker, Sachin; Nair, Sreenivas AchuthanBackground The World Health Organization (WHO) recommends same day sputum microscopy (spot-spot) in preference to conventional strategy (spot-morning) for the diagnosis of smear positive tuberculosis with the view that completing diagnosis on a single day may be more convenient to the patients and reduce pre-treatment losses to follow-up. Methods We conducted a cross-sectional study in seven selected district level hospitals of Chhattisgarh State, India. During October 2012 – March 2013, two sputum specimens (spot-early morning) were collected from consecutively enrolled adult (≥18 years) presumptive TB patients as per current national guidelines. In addition, a second sample was collected (one hour after the collection of first spot sample) from the same patients. All the samples were examined by ziehl-Neelsen (ZN) microscopy. McNemar’s test was used to compare statistical differences in the proportion smear positive between the two approaches (spot-spot versus spot-morning). Results Of 2551 presumptive TB patients, 69% were male. All patients provided the first spot specimen, 2361 (93%) provided the second spot specimen, and 2435 (96%) provided an early morning specimen. 72% of specimens were mucopurulent in conventional strategy as compared to 60% in same day strategy. The proportion of smear-positive patients diagnosed by same day microscopy was 14%, as compared to 17% by the conventional method (p<0.001). A total of 73 (16.9%) potential cases were missed by the same day method compared to only 2 (0.5%) by the conventional method. Conclusion Same-day microscopy method missed 17% of smear-positive cases and contrary to prior perception, did not increase the proportion of suspects providing the second sample. These findings call for an urgent need to revisit the WHO recommendation of switching to same-day diagnosis over the current policy.
- ItemComparing tuberculosis diagnostic yield in smear/culture and xpert MTB/RIF-based algorithms using a non-randomised stepped-wedge design(Public Library of Science, 2016-03) Naidoo, Pren; Dunbar, Rory; Lombard, Carl; Du Toit, Elizabeth; Caldwell, Judy; Detjen, Anne; Squire, S. Bertel; Enarson, Donald A.; Beyers, NuldaSetting Primary health services in Cape Town, South Africa. Study Aim To compare tuberculosis (TB) diagnostic yield in an existing smear/culture-based and a newly introduced Xpert MTB/RIF-based algorithm. Methods TB diagnostic yield (the proportion of presumptive TB cases with a laboratory diagnosis of TB) was assessed using a non-randomised stepped-wedge design as sites transitioned to the Xpert based algorithm. We identified the full sequence of sputum tests recorded in the electronic laboratory database for presumptive TB cases from 60 primary health sites during seven one-month time-points, six months apart. Differences in TB yield and temporal trends were estimated using a binomial regression model. Results TB yield was 20.9% (95% CI 19.9% to 22.0%) in the smear/culture-based algorithm compared to 17.9% (95%CI 16.4% to 19.5%) in the Xpert based algorithm. There was a decline in TB yield over time with a mean risk difference of -0.9% (95% CI -1.2% to -0.6%) (p<0.001) per time-point. When estimates were adjusted for the temporal trend, TB yield was 19.1% (95% CI 17.6% to 20.5%) in the smear/culture-based algorithm compared to 19.3% (95% CI 17.7% to 20.9%) in the Xpert based algorithm with a risk difference of 0.3% (95% CI -1.8% to 2.3%) (p = 0.796). Culture tests were undertaken for 35.5% of smear-negative compared to 17.9% of Xpert negative low MDR-TB risk cases and for 82.6% of smear-negative compared to 40.5% of Xpert negative high MDR-TB risk cases in respective algorithms. Conclusion Introduction of an Xpert based algorithm did not produce the expected increase in TB diagnostic yield. Studies are required to assess whether improving adherence to the Xpert negative algorithm for HIV-infected individuals will increase yield. In light of the high cost of Xpert, a review of its role as a screening test for all presumptive TB cases may be warranted.
- ItemA comparison of multidrug-resistant tuberculosis treatment commencement times in MDRTBPlus line probe assay and XpertH MTB/RIF-based algorithms in a routine operational setting in Cape Town(PLoS, 2014-07-31) Naidoo, Pren; Du Toit, Elizabeth; Rory Dunbar, Rory; Lombard, Carl; Caldwell, Judy; Detjen, Anne; Squire, S. Bertel; Enarson, Donald A.; Beyers, NuldaBackground: Xpert MTB/RIF was introduced as a screening test for all presumptive tuberculosis cases in primary health services in Cape Town, South Africa. Study Aim: To compare multidrug-resistant tuberculosis (MDR-TB) treatment commencement times in MDRTBPlus Line Probe Assay and Xpert MTB/RIF-based algorithms in a routine operational setting. Methods: The study was undertaken in 10 of 29 high tuberculosis burden primary health facilities, selected through stratified random sampling. An observational study was undertaken as facilities transitioned to the Xpert MTB/RIF-based algorithm. MDR-TB diagnostic data were collected from electronic laboratory records and treatment data from clinical records and registers. Kaplan Meier time-to-event analysis was used to compare treatment commencement time, laboratory turnaround time and action delay between algorithms. A facility-level paired analysis was done: the median time-to-event was estimated per facility in each algorithm and mean differences between algorithms compared using a paired t-test. Cox proportional hazards regression was used to assess the effect of patient-level variables on treatment commencement time. The difference between algorithms was compared using the hazard ratio. Results: The median treatment commencement time in the Xpert MTB/RIF-based algorithm was 17 days (95% CI 13 to 22 days), with a median laboratory turnaround time (to result available in the laboratory) of <1 day (95% CI<1 to 1 day). There was a decrease of 25 days (95% CI 17 to 32 days, p<0.001) in median MDR-TB treatment commencement time in the Xpert MTB/RIF-based algorithm. We found no significant effect on treatment commencement times for the patient-level variables assessed. Conclusion: MDR-TB treatment commencement time was significantly reduced in the Xpert MTB/RIF-based algorithm. Changes in the health system may have contributed. However, an unacceptable level of delay remains. Health system and patient factors contributing to delay need to be evaluated and addressed to optimise test benefits.
- ItemDevelopment and implementation of a national programme for the management of severe and very severe pneumonia in children in Malawi(Public Library of Science -- PLOS, 2009-11) Enarson, Penelope Marjorie; Gie, Robert; Enarson, Donald A.; Mwansambo, CharlesThe reduction of child mortality by two-thirds from its 1990 level by 2015—the fourth United Nations Millennium Development Goal—is a major challenge. Pneumonia accounts for much (≥20%) of this mortality in poor countries, but standard case management (SCM) of pneumonia [1] has the potential to reduce overall child mortality. A recent meta-analysis estimated that SCM of pneumonia could reduce overall mortality in neonates, infants under 1 y old, and children aged 0–4 y, respectively, by 27%, 20%, and 24%, and pneumonia-specific mortality by 42%, 36%, and 36% in the same age groups [2]. However, even proven intervention strategies cannot function without an effective ‘‘delivery strategy’’ [3]. For, example, although the World Health Organization (WHO)/United Nations Children’s Fund has developed an Integrated Management of Childhood Illness (IMCI) strategy to reduce child mortality, of the 100+ low- and middle-income countries that introduced IMCI in the 1990s, only 48% had scaled up coverage by the end of 2002. Weak health systems were the main cause of this failure with the poorest countries doing worst [3]. We describe here the development and scaling-up of a country-wide delivery strategy of SCM for pneumonia in children in Malawi, a country where more than 200 children per thousand die before they are 5 y old.
- ItemOperational challenges in managing Isoniazid Preventive Therapy in child contacts : a high-burden setting perspective(2011-07-08) Van Wyk, Susan S.; Reid, Anthony J.; Mandalakas, Anna M.; Enarson, Donald A.; Beyers, Nulda; Morrison, Julie; Hesseling, Anneke C.Abstract Background The study was conducted at a high TB-HIV burden primary health community clinic in Cape Town, South Africa. We describe the management of children under five years of age in household contact with a smear and/or culture-positive adult TB case. Methods This study was a record review of routinely-collected programme data. Results A total of 1094 adult TB case folders were reviewed. From all identified contacts, 149 children should have received IPT based on local guidelines; in only 2/149 IPT was initiated. Management of child contacts of sputum smear and/or culture-positive compared to sputum-negative TB patients were similar. Conclusions IPT delivery to children remains an operational challenge, especially in high TB-HIV burden communities. A tool to improve IPT management and targeting sputum smear and/or culture-positive TB child contacts may overcome some of these challenges and should be developed and piloted in such settings.
- ItemPotentially modifiable factors associated with death of infants and children with severe pneumonia routinely managed in district hospitals in Malawi(Public Library of Science, 2015) Enarson, Penelope M.; Gie, Robert P.; Mwansambo, Charles C.; Chalira, Alfred E.; Lufesi, Norman N.; Maganga, Ellubey R.; Enarson, Donald A.; Cameron, Neil A.; Graham, Stephen M.Objective: To investigate recognised co-morbidities and clinical management associated with inpatient pneumonia mortality in Malawian district hospitals. Methods: Prospective cohort study, of patient records, carried out in Malawi between 1st October 2000 and 30th June 2003. The study included all children aged 0-59 months admitted to the paediatric wards in sixteen district hospitals throughout Malawi with severe and very severe pneumonia. We compared individual factors between those that survived (n = 14 076) and those that died (n = 1 633). Results: From logistic regression analysis, predictors of death in hospital, adjusted for age, sex and severity grade included comorbid conditions of meningitis (OR =2.49, 95% CI 1.50-4.15), malnutrition (OR =2.37, 95% CI 1.94-2.88) and severe anaemia (OR =1.41, 95% CI 1.03-1.92). Requiring supplementary oxygen (OR =2.16, 95% CI 1.85-2.51) and intravenous fluids (OR =3.02, 95% CI 2.13-4.28) were associated with death while blood transfusion was no longer significant (OR =1.10, 95% CI 0.77-1.57) when the model included severe anaemia. Conclusions: This study identified a number of challenges to improve outcome for Malawian infants and children hospitalised with pneumonia. These included improved assessment of co-morbidities and more rigorous application of standard case management.
- ItemThe rate of sputum smear-positive tuberculosis after treatment default in a high-burden setting : a retrospective cohort study(PLoS, 2012-09) Marx, Florian M.; Dunbar, Rory; Enarson, Donald A.; Beyers, NuldaRationale: High rates of recurrent tuberculosis after successful treatment have been reported from different high burden settings in Sub-Saharan Africa. However, little is known about the rate of smear-positive tuberculosis after treatment default. In particular, it is not known whether or not treatment defaulters continue to be or become again smear-positive and thus pose a potential for transmission of infection to others. Objective: To investigate, in a high tuberculosis burden setting, the rate of re-treatment for smear-positive tuberculosis among cases defaulting from standardized treatment compared to successfully treated cases. Methods: Retrospective cohort study among smear-positive tuberculosis cases treated between 1996 and 2008 in two urban communities in Cape Town, South Africa. Episodes of re-treatment for smear-positive tuberculosis were ascertained via probabilistic record linkage. Survival analysis and Poisson regression were used to compare the rate of smear-positive tuberculosis after treatment default to that after successful treatment. Results: A total of 2,136 smear-positive tuberculosis cases were included in the study. After treatment default, the rate of retreatment for smear-positive tuberculosis was 6.86 (95% confidence interval [CI]: 5.59–8.41) per 100 person-years compared to 2.09 (95% CI: 1.81–2.41) after cure (adjusted Hazard Ratio [aHR]: 3.97; 95% CI: 3.00–5.26). Among defaulters, the rate was inversely associated with treatment duration and sputum conversion prior to defaulting. Smear grade at start of the index treatment episode (Smear3+: aHR 1.61; 95%CI 1.11–2.33) was independently associated with smear-positive tuberculosis retreatment, regardless of treatment outcome. Conclusions: In this high-burden setting, there is a high rate of subsequent smear-positive tuberculosis after treatment default. Treatment defaulters are therefore likely to contribute to the pool of infectious source cases in the community. Our findings underscore the importance of preventing treatment default, as a means of successful tuberculosis control in highburden settings.
- ItemReducing deaths from severe pneumonia in children in Malawi by improving delivery of pneumonia case management(PLoS, 2014-07-22) Enarson, Penelope M.; Gie, Robert P.; Mwansambo, Charles C.; Maganga, Ellubey R.; Lombard, Carl J.; Enarson, Donald A.; Graham, Stephen M.Objective: To evaluate the pneumonia specific case fatality rate over time following the implementation of a Child Lung Health Programme (CLHP) within the existing government health services in Malawi to improve delivery of pneumonia case management. Methods: A prospective, nationwide public health intervention was studied to evaluate the impact on pneumonia specific case fatality rate (CFR) in infants and young children (0 to 59 months of age) following the implementation of the CLHP. The implementation was step-wise from October 1st 2000 until 31st December 2005 within paediatric inpatient wards in 24 of 25 district hospitals in Malawi. Data analysis compared recorded outcomes in the first three months of the intervention (the control period) to the period after that, looking at trend over time and variation by calendar month, age group, severity of disease and region of the country. The analysis was repeated standardizing the follow-up period by using only the first 15 months after implementation at each district hospital. Findings: Following implementation, 47,228 children were admitted to hospital for severe/very severe pneumonia with an overall CFR of 9•8%. In both analyses, the highest CFR was in the children 2 to 11 months, and those with very severe pneumonia. The majority (64%) of cases, 2–59 months, had severe pneumonia. In this group there was a significant effect of the intervention Odds Ratio (OR) 0•70 (95%CI: 0•50–0•98); p = 0•036), while in the same age group children treated for very severe pneumonia there was no interventional benefit (OR 0•97 (95%CI: 0•72–1•30); p = 0•8). No benefit was observed for neonates (OR 0•83 (95%CI: 0•56–1•22); p = 0•335). Conclusions: The nationwide implementation of the CLHP significantly reduced CFR in Malawian infants and children (2–59 months) treated for severe pneumonia. Reasons for the lack of benefit for neonates, infants and children with very severe pneumonia requires further research.
- ItemTuberculosis in healthcare workers and infections control measures at primary healthcare facilities in South Africa(Public Library of Science, 2013-10-02) Claassens, Mareli; Van Schalkwyk, Cari; Du Toit, Elizabeth; Roest, Eline; Lombard, Carl J.; Enarson, Donald A.; Beyers, Nulda; Borgdorff, Martien W.Background Challenges exist regarding TB infection control and TB in hospital-based healthcare workers in South Africa. However, few studies report on TB in non-hospital based healthcare workers such as primary or community healthcare workers. Our objectives were to investigate the implementation of TB infection control measures at primary healthcare facilities, the smear positive TB incidence rate amongst primary healthcare workers and the association between TB infection control measures and all types of TB in healthcare workers. Methods One hundred and thirty three primary healthcare facilities were visited in five provinces of South Africa in 2009. At each facility, a TB infection control audit and facility questionnaire were completed. The number of healthcare workers who had had TB during the past three years was obtained. Results The standardised incidence ratio of smear positive TB in primary healthcare workers indicated an incidence rate of more than double that of the general population. In a univariable logistic regression, the infection control audit score was significantly associated with reported cases of TB in healthcare workers (OR=1.04, 95%CI 1.01-1.08, p=0.02) as was the number of staff (OR=3.78, 95%CI 1.77-8.08). In the multivariable analysis, the number of staff remained significantly associated with TB in healthcare workers (OR=3.33, 95%CI 1.37-8.08). Conclusion The high rate of TB in healthcare workers suggests a substantial nosocomial transmission risk, but the infection control audit tool which was used did not perform adequately as a measure of this risk. Infection control measures should be monitored by validated tools developed and tested locally. Different strategies, such as routine surveillance systems, could be used to evaluate the burden of TB in healthcare workers in order to calculate TB incidence, monitor trends and implement interventions to decrease occupational TB.