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2. National scientific medical meeting 1995 abstracts: Oral presentations

Author

Norris, S., Collins, C., Hegarty, J., O’Farrelly, C., Carton, J., Madrigal, L., O’Donoghue, D. P., O’Farrelly, C., Holloway, H., Fielding, J. F., Mullins, W., Hone, S. W., Donnelly, M., Powell, F., Blayney, A. W., Cahill, E. A., Daly, S. F., Turner, M. J., Sullivan, P. A., McLoughlin, M., Skelly, M. M., Mulcahy, H. E., Connell, T., O’Donoghue, D. P., Duggan, C., Duffy, M. J., Troy, A., Sheahan, K., Whelan, A., Herra, C. M., Keane, C. T., Johnson, H., Lee, B., Doherty, E., McDonnell, T., Mulherin, D., FitzGerald, O., Bresnihan, B., Hassett, H. M., Boyce, A., Greig, V., O’Herlihy, C., Smyth, P. P. A., Roche, E. F., McCormack, I., Tempany, E., Cullen, M. J., Smith, D. F., Smyth, P. P. A., McBrinn, Y., Murray, B., Freaney, R., Keating, D., McKenna, M. J., O’Hare, J. A., Alam, H., Raza, Q., Geoghegan, M., Killalea, S., Hall, M., Feely, J., Kyne, L., O’Hara, B., Cullen, M., Rea, I. M., Donnelly, J. P., Stout, R. W., Lacey, P., Donnelly, M. J., McGrath, J., Hennessy, T. P., Timon, C. V. I., Hyde, D., Xia, H. X., Keane, C. T., Buckley, M., O’Morain, C., Buckley, M., Keating, S., Xia, H., Hyde, D., O’Morain, C., McGrath, J. P., Stuart, R. C., Lawlor, P., Byrne, P. J., Walsh, T. N., Hennessy, T. P. J., Skelly, M. M., Mulcahy, H. E., Connell, T., O’Donoghue, D. P., Duggan, C., Duffy, M., Troy, A., Sheahan, K., Norris, S., Tubridy, M., Redmond, J., Hegarty, J., Holloway, H., Fielding, J. F., Mullins, W., Monahan, K., Murphy, R. P., Headon, D. R., O’Gorman, T., O’Reilly, F. M., Darby, C., Fielding, J. F., Murphy, G. M., Murphy, A., Codd, M., Powell, F., Dervan, P., Lawlor, D., Loughlin, S. O., Flanagan, N., Watson, R., Barnes, L., Flanagan, N., Watson, R., Kilgallen, C., Sweeney, E., Mynes, A., Mooney, D., Donoghue, I., Browne, O., Kirrane, J. A., Murphy, G. M., McKenna, D., Young, M., McKenna, D., Young, M., O’Toole, E., Young, M., O’Briain, S., Srinivasan, U., Feighery, C., Leonard, N., Jones, E., O’Farrelly, C., Moloney, M. A., O’Farrelly, C., Weir, D. G., Lawler, M., O’Neill, A., Gowing, H., Pamphilon, D., McCann, S. R., O’Toole, G., Orren, A., Seifer, C. M., Crowley, D. C., Sheehan, G. J., Deignan, T., Kelly, J., O’Farrelly, C., Tormey, V. J., Faul, J., Leonard, C., Burke, C. M., Poulter, L. W., Collins, C., Lynch, S., Madrigal, L., Norris, S., McEntee, G., Traynor, O., Hegarty, J., O’Farrelly, C., Barry, E., Collins, C., Costello, P., Keavney, A., O’Donoghue, D. P., O’Farrelly, C., Willoughby, R., Feighery, C., O’Donnell, C., Cahill, M., Earley, A., Eustace, P., Osborne, R., Cahill, M., Saidlear, C., Holmes, B., Early, A., Eustace, P., Moran, A. P., Neisser, A., Polt, R. J., Bernheimer, H., Kainz, M., Schwerer, B., Gallagher, L., Cahill, M., Saidlear, C., Early, A., Firth, R., Eustace, P., Kennedy, N., McGilloway, E., Redmond, J., McGilloway, E., Kennedy, N., Tubridy, N., Shields, K., Cullen, W. K., Rowan, M. J., Moore, A. R., Rowan, M., Feely, J., Coakley, D., Lawlor, B., Swanwick, G., Al-Naeemi, R., Redmond, J., Murphy, R., Feely, J., Codd, N. M., Goggins, M., Kennedy, N. P., Mallon, B. L., Kennedy, N. P., Mulherin, D., FitzGerald, O., Bresnihan, B., Mulcahy, H., Skelly, M., Donoghue, D. O., McCarthy, D., Saunders, A., Mulherin, D., Bresnihan, B., FitzGerald, O., Veale, D. J., Belch, J. J. F., Mulherin, D., Bresnihan, B., FitzGerald, O., Veale, D. J., Belch, J. J. F., Mulherin, D., FitzGerald, O., Bresnihan, B., Costello, P., Breathnach, D., Murphy, E., Mulherin, D., FitzGerald, O., Bresnihan, B., Breathnach, D., Costello, P., Mulherin, D., Bresnihan, B., FitzGerald, O., Breathnach, D., Mulherin, D., Costello, P., Bresnihan, B., FitzGerald, O., Kernohan, G., Gibson, K., Wilson, A. G., Duff, G. W., de Vries, N., van de Putte, L. B. A., Donoghue, J., O’Kelly, F., Johnson, Z., Maher, T., Kyne, L., Moran, A., Keane, C., O’Neill, D., Horgan, N., Barragry, J. M., O’Neill, D., O’Herlihy, C., Campbell, D. M., Behan, M., O’Connell, P. R., Donnelly, V. S., Crowley, D., Geary, M., Boylan, P., Geary, M., Fanagan, M., Boylan, P., Hickey, K., Teoh, T., Doyle, M., Harrison, R., Hickey, K., Lyons, D., Shenouda, Y., Coughlan, M., McKenna, P., Hickey, K., Shenouda, Y., Lyons, D., McKenna, P., Coughlan, M., Lenehan, P., Foley, M., Kelehan, P., Ravichandran, P., Kelly, M., Conroy, A., Fitzpatrick, C., Egan, D., Regan, C. L., McAdam, B. V., McParland, P., Boylan, P., FitzGerald, G. A., Fitzgerald, D. J., Sharma, S. C., Foran, K., Barry-Kinsella, C., Harrison, R. F., Gillespie, F. J., O’Mahony, P., Boyle, M., White, M. J., Donohoe, F., Birrane, Y., Naughton, M., Tempany, E., Fitzsimons, R. B., Piracha, M., McConkey, S., Griffin, E., Hayes, E., Clarke, T., Parfrey, N., Butler, K., Fitzpatrick, C., Malone, A. J., Kearney, P. J., Duggan, P. F., Lane, A., Keville, R., Turner, M., Barry, S., Sloan, D., Gallagher, S., Darby, M., Galligan, P., Stack, J., Walsh, N., O’Sullivan, M., Fitzgerald, M., O’Sullivan, M., Meagher, D., Sloan, D., Browne, S., Meagher, D., Larkin, C., Lane, A., Casey, P., O’Callaghan, E., Walsh, N., Rooney, S., Walsh, E., Morris, M., Lane, A., Burke, T., Larkin, C., O’Callaghan, E., Browne, S., Roe, M., Lane, A., Larkin, C., O’Callaghan, E., Maher, C., Wrigley, M., Gill, M., Burgess, M., Corcoran, E., Walsh, D., Gilmer, B., Johnson, H., Hayes, C. B., Thornton, L., Fogarty, J., Lyons, R., O’Connor, M., Delaney, V., Buckley, K., Johnson, Z., Johnson, Z., Lillis, D., Delany, V., Hayes, C., Dack, P., Igoe, D., Gilmer, B., O’Neill, H. J., Johnson, H., Igoe, D., Delaney, V., Johnson, Z., Kelly, P., McKeown, D., Clancy, L., Varghese, G., Hennessy, S., Codd, M., Gilmartin, J. J., Birthistle, K., Carrington, D., Maguire, H., Atkinson, P., Foley-Nolan, C., Lynch, M., Cryan, B., Whyte, D., Cryan, B., Conlon, C., Foley-Nolan, C., Johnson, Z., Hayes, C., Delany, V., Kucinskas, V., Usinskiene, U., Sakalyte, I., Johnson, Z., Hayes, C., Delaney, V., Dack, P., Gill, M., Dawson, E., Molloy, K., Goulden, N., Lawler, M., McCann, S. R., Doyle, J., Lawlor, E., Lawler, M., Harrington, M. G., El-Nageh, N., Nolan, M. -L., El-Nageh, N., Nolan, M. -L., Harrington, M. G., Lawlor, E., O’Riordan, J., McCann, S. R., Judge, G., Crotty, G., Finch, T., Borton, M., Barnes, T., Gilligan, O., Lee, G., Limmer, R., Madden, M., Whyte, D., Cryan, B., Bergin, C., O’Leary, A., Keating, S., Mulcahy, F., Wallis, F., Glennon, M., Cormican, M., NiRiain, U., Heiginbothom, M., Gannon, F., Smith, T., O’Sullivan, C., Hone, R., Orren, A., Caugant, D. A., Fijen, C. A. P., Van Schalkwyk, E. J., Coetzee, G. J., Lynch, M., Cryan, B., Riain, U. Ni, Cormican, M. G., Park, L., Flynn, J., Glennon, M., O’Connor, M., Regazzoli, V., O’Connor, M., Hayes, M., Nicholson, G., Higgins, P., NiRiain, U., Flynn, N., Corbett-Feeney, G., Conway, D. J., Sheahan, K., O’Higgins, N. J., Smyth, P. P. A., Rajendiran, S., Byrne, J., Kilfeather, E., Dingle, P., Hunter, M., Kelehan, P., Al-Ghazal, S. K., Stanley, P., Palmer, J., Hong, A., Al-Ghazal, S. K., Saxby, P., Al-Ghazal, S. K., Saxby, P., McConkey, S., Sheehan, D., Regan, I., O’Mullane, J., Chaoimh, M. Ni, Leahy, M., Heffron, J. J., Lehane, M., Keohane, C., O’Leary, N., Sheehan, M., Renny-Walsh, E., Whelton, M. J., Doyle, C. T., Webster, J., Benjamin, N., Lyons, D., FitzGerald, S., Chadha, J. S., FitzGerald, M. G., FitzGerald, G. R., Hemeryck, L., McGettigan, P., Feely, J., McGettigan, P., Feely, J., McGettigan, P., Golden, J., Feely, J., Arthur, N., Wen, S. Y., Killalea, S., Deegan, P., McGettigan, P., Feely, J., Cooke, T., Adebayo, G. I., Feely, J., Gaffney, P., Sinnot, M., O’Riordan, D., Hayes, T., O’Connor, C. M., FitzGerald, M. X., Costello, C., Finlay, G., Hayes, J., O’Connor, C., FitzGerald, M. X., McMahon, K., O’Farrelly, C., O’Connor, C., FitzGerald, M. X., Donnelly, M. J., Hone, S., Robertson, J., Coakley, R., O’Neill, S., Walsh, M., McCarthy, J., Lannon, D., Wood, A. E., Sharkey, R., Mulloy, E., Long, M., Kilgallen, I., O’Neill, S., Faul, J., Tormey, V., Leonard, C., Burke, C. M., Poulter, L. W., Horne, S., Tormey, V. J., Faul, J., Leonard, C., Burke, C. M., Feeney, T., Muiré, Ó. Ó, Gilmartin, J. J., Griffin, M. J., Hughes, D., Knaggs, A., Magee, D., Donnelly, M., McCrory, C., March, B., Hone, R., Phelan, D., White, M., Fabry, J., Lynch, M., Buggy, D., Cooney, C., Hughes, D., McCrory, C., Aziz, E., O’Herlihy, C., Kelly, J., O’Keefe, D., McShane, A. J., Boylan, J., Tobin, E., Smith, T., Motherway, C., Colreavy, F., Denish, N., Dwyer, R., Bergin, A., O’Brien, K., MacSullivan, R., Carson, K. D., Blunnie, W. P., Moriarty, D. C., Carson, K. D., Blunnie, W. P., Moriarty, D. C., Kinirons, B., Lyons, B., Cregg, N., Casey, W., Moore, K. P., Colbert, S. A., Ecoffey, C., O’Gorman, D., Fitzgerald, J., Phelan, D., Diamond, P., Codd, M. B., Sugrue, D. D., Kellett, J., Tighe, M., McKenna, C. J., Galvin, J., McCann, H. A., Sugrue, D. D., McKenna, C. J., Codd, M. B., McCann, H. A., Sugrue, D. D., Scallon, A., Buckley, M., Fraser, A., Norton, M., Tomkin, G., Graham, I., Byrne, A., Maher, M., Moran, N., Fitzgerald, D., O’Callaghan, D., Coyle, D., Nugent, A. G., McGurk, C., Johnston, G. D., McGurk, C., Nugent, A., Silke, B., Nugent, A. G., Johnston, G. D., Murphy, N., Jennings, L., Pratico, D., Doyle, C., Fitzgerald, D., Hennessy, T., McCann, H., Sugrue, D., Hennessy, T., Codd, M., Donnelly, S., Hennessy, A., Hartigan, C., McCann, H., Sugrue, D., Hennessy, T., Codd, M., Donnelly, S., Hennessy, A., Hartigan, C., McCann, H., Sugrue, D., Hennessy, T., MacDonald, D., Blake, S., McCann, H., Sugrue, D., Hennessy, T., Sugrue, D., McCann, H., Hennessy, T., McCann, H., Sugrue, D., Hennessy, T., McDonald, D., Blake, S., Dominque, D., Sugrue, D., McMechan, S. R., MacKenzie, G., Allen, J., Wright, G. T., Dempsey, G. J., Crawley, M., Anderson, J., Adgey, A. A. J., Harbinson, M. T., Campbell, N. P. S., Wilson, C. M., Ellis, P. K., McIlrath, E. M., Freaney, R., McShane, A., Keaveny, T. V., McKenna, M. J., Rabenstein, K., Scheller, F., Pfeiffer, D., Urban, C., Moser, I., Jobst, G., Manz, A., Verpoorte, S., Dempsey, F., Diamond, D., Smyth, M., Rabenstein, K., Dempsey, E., McShane, A., Keaveny, T. V., McKenna, M. J., Freaney, R., Hamilton, V., Dwyer, R., Twomey, J., Crowley, R., Fenelon, L., Walsh, F., McCann, J., McDonagh, P., White, M., McGovern, E., Luke, D., Phelan, D., McCrory, C., Crowley, K., Lyons, B., Mannion, D., Wood, A. E., Casey, W., Murphy, D., Clarkson, K., Carton, E., Higgins, P., Leonard, I., O’Toole, D., Staunton, M., Phelan, D., Srinivasan, U., Leonard, N., Jones, E., Moloney, M. A., Weir, D. G., O’Farrelly, C., Feighery, C., Griffin, M., Owens, D., Collins, P., Johnson, A., Tomkin, G. H., Herity, N. A., Allen, J. D., Silke, B., Adgey, A. A. J., O’Reilly, F. M., Darby, C., O’Moore, R., Fielding, J. F., Murphy, G. M., Crotty, G. M., Judge, G., McCann, S. R., DeArce, M., Nugent, A. G., McGurk, C., Johnston, G. D., Nikookam, K., Keenan, P., Cregan, D., Firth, R., O’Meara, N., Forman, S., Cusack, D. A., and Farrell, B.

Published
1995
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4. Carriage of Haemophilus influenzae in Cape Town children

Author

Hussey, G.D., Coetzee, G, Hitchcock, J, van Schalkwyk, E, van Wyk, H, and Kibel, M

Abstract

Little is known about the epideIDiology of Haemophilus influenzae infections in South Africa. This study was designed to determine the prevalence, serotype distribution, antimicrobial susceptibility pattern and effect of age and hospitalisation on the carriage of H. influenzae in 322 Cape Town children.The overall and type b specific carriage rates in normal children (N =107) were 45,8% and 4,7% respectively. The yield following nasopharyngeal culture was twice that following throat culture (P < 0,001). Children hospitalised with tuberculosis (N =62) had significantly greater carriage rates, 66,1% and 37,1% respectively (P =0,02). Institutionalised mentally handicapped children (N =77) and children with tuberculosis attending an outpatient clinic (N =76) had lower carriage rates (P < 0,02). Antimicrobial resistance was a major problem only in children hospitalised with tuberculosis (rifampicin 100%, penicillin 43,9%, erythromycin 85,4%, co-trimoxazole 82,9%). This universal resistance to rifampicin has not been reported previously. There was no difference in the mean age of children with positive or negative cultures, with the exception of those hospitalised with tuberculosis. In this group children infected with type b were much younger (mean 19,7 months) than those with other and non-typeableinfections (32,1 months) and the non-infected(50,1 months) (P =0,04). Duration of hospitalisation or outpatient therapy in the patients with tuberculosis did not influence carriage rates.We conclude that carriage of H. influenzae in normal children is similar to that reported from other countries and that carriage, particularly of type b, in children hospitalised with tuberculosis was of significance and probably contributed to an outbreak of multi-resistant invasive H. influenzae disease in this group.

Published
2016

10. Measuring training effectiveness of laboratory biosafety program offered at African Center for Integrated Laboratory Training in 22 President's Emergency Plan for AIDS Relief supported countries (2008-2014).

Author

Shrivastava R, Stevens T, Westerman L, Bressler D, van Schalkwyk E, Bressler C, Ugwu K, Mwangi C, Opio JP, Nkodyo J, Mwangi JW, Martin MD, and Nesby-O'Dell S

Abstract

Introduction: The African Center for Integrated Laboratory Training (ACILT) in Johannesburg, South Africa offered a laboratory biosafety program to improve laboratory biosafety practices in 22 President's Emergency Plan for AIDS Relief (PEPFAR) supported countries. This manuscript evaluates the transference of newly gained knowledge and skills to the participants' place of employment for HIV and TB diagnostic laboratory programs. It also serves as a follow-on to a previously published manuscript that measured training effectiveness for all courses offered at ACILT., Methods: ACILT offered 20 Laboratory Biosafety and Infrastructure courses (2008-2014), also referred as biosafety course/course comprising of 14 core laboratory safety elements to 402 participants from 22 countries. In 2015, participants received 22 e-questions divided into four categories: (1) Safety Policies, (2) Management's Engagement, (3) Safety Programs and (4) Assessments of Safety Practices to determine retrospectively the training effectiveness of biosafety practices in their place of employment 6 months before and after attending their course. We used Kirkpatrick model to assess the transference of knowledge, skills and obstructive factors., Results: 20% (81/402) of the participants completed the e-questionnaire. The overall percentage of positive responses indicating implementation of new safety practices increased from 50% to 84%. Improvement occurred in all four categories after attending the course, with the greatest increases in Safety Policies (67-94%) and Safety Programs (43-91%). Creating a safety committee, allocating resources, and establishing a facility safety policy were important drivers for implementing and maintaining laboratory safety practices. In addition, accredited laboratories and countries with national safety regulations or policies had a higher percentage of improvements. The most reported challenges were inadequate funding and lack of management enforcement., Conclusions: PEPFAR and other partners' investments in training institutions, such as ACILT, were effective in building sustainable country ownership to strengthen biosafety practices and were leveraged to combat zoonotic diseases and COVID-19. Although support continues at the national/regional level, a standardized, coordinated and continent-wide sustainable approach to offer a biosafety program-like ACILT is missing. Continuous offerings of biosafety programs similar to ACILT could contribute to sustainable strengthening of laboratory biosafety, QMS and pandemic preparedness., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Published
2023
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11. Culture-confirmed neonatal bloodstream infections and meningitis in South Africa, 2014-19: a cross-sectional study.

Author

Mashau RC, Meiring ST, Dramowski A, Magobo RE, Quan VC, Perovic O, von Gottberg A, Cohen C, Velaphi S, van Schalkwyk E, and Govender NP

Subjects
Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Child, Cross-Sectional Studies, Gram-Negative Bacteria, Gram-Positive Bacteria, Humans, Infant, Newborn, Klebsiella pneumoniae, South Africa epidemiology, Communicable Diseases, Meningitis epidemiology, Sepsis microbiology
Abstract

Background: Few population-level estimates of invasive neonatal infections have been reported from sub-Saharan Africa. We estimated the national incidence risk, aetiology, and pathogen antimicrobial susceptibility for culture-confirmed neonatal bloodstream infections and meningitis in South Africa., Methods: We conducted a cross-sectional study of neonates (<28 days of life) admitted to neonatal or paediatric wards of 256 public sector health facilities in South Africa during 2014-19. Diagnostic pathology records from Jan 1, 2014, to Dec 31, 2019, were extracted from a national pathology data warehouse. A case was defined as a neonate with at least one positive blood or cerebrospinal fluid culture during a 14-day period. Incidence risk was calculated using annual numbers of registered livebirths. Among the causative pathogens identified, we calculated the proportion of cases attributed to each of them, as well as the rates of antibiotic susceptibility of Gram-positive and Gram-negative bacteria., Findings: Among 43 438 records of positive cultures, there were 37 631 incident cases of neonatal infection with at least one pathogen isolated. The overall incidence risk of culture-confirmed infections was 6·0 per 1000 livebirths (95% CI 6·0-6·1). The incidence risk of late-onset sepsis (days 3-27 of life) was 4·9 per 1000 livebirths (4·9-5·0) and that of early-onset sepsis (days 0-2 of life) was 1·1 per 1000 livebirths (1·1-1·1); risk ratio 4·4 (95% CI 4·3-4·5). The cause of infection differed by syndrome, timing of infection onset, facility, and province, although Klebsiella pneumoniae (26%), Acinetobacter baumannii (13%), and Staphylococcus aureus (12%) were the dominant pathogens overall. Gram-negative bacteria had declining susceptibility to most antibiotics over the study period., Interpretation: We found a high incidence risk of late-onset sepsis with provincial variations, predominance of K pneumoniae, and declining antibiotic susceptibility among Gram-negative bacteria. This national surveillance in an upper-middle-income country provides a baseline burden of neonatal infections against which the impact of future clinical and public health interventions can be measured., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests CC and AvG received grant funds from Sanofi Pasteur. AD is supported by a National Institutes of Health Emerging Global Leader Award (NIH K43 TW010682). NPG is partly supported by a National Institutes of Health grant (1R01AI118511-01A1). All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Published
2022
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12. Molecular type distribution and fluconazole susceptibility of clinical Cryptococcus gattii isolates from South African laboratory-based surveillance, 2005-2013.

Author

Naicker SD, Firacative C, van Schalkwyk E, Maphanga TG, Monroy-Nieto J, Bowers JR, Engelthaler DM, Meyer W, and Govender NP

Subjects
Fluconazole pharmacology, Genotype, Humans, Multilocus Sequence Typing, South Africa epidemiology, Cryptococcosis epidemiology, Cryptococcus gattii, Cryptococcus neoformans genetics, HIV Infections epidemiology
Abstract

As is the case globally, Cryptococcus gattii is a less frequent cause of cryptococcosis than Cryptococcus neoformans in South Africa. We performed multilocus sequence typing (MLST) and fluconazole susceptibility testing of 146 isolates randomly selected from 750 South African patients with C. gattii disease identified through enhanced laboratory surveillance, 2005 to 2013. The dominant molecular type was VGIV (101/146, 70%), followed by VGI (40/146, 27%), VGII (3/146, 2%) and VGIII (2/146, 1%). Among the 146 C. gattii isolates, 99 different sequence types (STs) were identified, with ST294 (14/146, 10%) and ST155 (10/146, 7%) being most commonly observed. The fluconazole MIC50 and MIC90 values of 105 (of 146) randomly selected C. gattii isolates were 4 μg/ml and 16 μg/ml, respectively. VGIV isolates had a lower MIC50 value compared to non-VGIV isolates, but these values were within one double-dilution of each other. HIV-seropositive patients had a ten-fold increased adjusted odds of a VGIV infection compared to HIV-seronegative patients, though with small numbers (99/136; 73% vs. 2/10; 20%), the confidence interval (CI) was wide (95% CI: 1.93-55.31, p = 0.006). Whole genome phylogeny of 98 isolates of South Africa's most prevalent molecular type, VGIV, identified that this molecular type is highly diverse, with two interesting clusters of ten and six closely related isolates being identified, respectively. One of these clusters consisted only of patients from the Mpumalanga Province in South Africa, suggesting a similar environmental source. This study contributed new insights into the global population structure of this important human pathogen., Competing Interests: The authors have declared that no competing interests exist.

Published
2022
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13. In Vitro Antifungal Resistance of Candida auris Isolates from Bloodstream Infections, South Africa.

Author

Maphanga TG, Naicker SD, Kwenda S, Muñoz JF, van Schalkwyk E, Wadula J, Nana T, Ismail A, Coetzee J, Govind C, Mtshali PS, Mpembe RS, and Govender NP

Subjects
Candida genetics, Drug Resistance, Fungal genetics, Fluconazole pharmacology, Humans, Microbial Sensitivity Tests, South Africa, Antifungal Agents pharmacology, Antifungal Agents therapeutic use, Candidemia drug therapy
Abstract

Candida auris is a multidrug-resistant fungal pathogen that is endemic in South African hospitals. We tested bloodstream C. auris isolates that were submitted to a reference laboratory for national laboratory-based surveillance for candidemia in 2016 and 2017. We confirmed the species identification by phenotypic/molecular methods. We tested susceptibility to amphotericin B, anidulafungin, caspofungin, micafungin, itraconazole, posaconazole, voriconazole, fluconazole, and flucytosine using broth microdilution and Etest methods. We interpreted MICs using tentative breakpoints. We sequenced the genomes of a subset of isolates and compared them to the C. auris B8441 reference strain. Of 400 C. auris isolates, 361 (90%) were resistant to at least one antifungal agent, 339 (94%) to fluconazole alone (MICs of ≥32 µg/ml), 19 (6%) to fluconazole and amphotericin B (MICs of ≥2 µg/ml), and 1 (0.3%) to amphotericin B alone. Two (0.5%) isolates from a single patient were pan-resistant (resistant to fluconazole, amphotericin B, and echinocandins). Of 92 isolates selected for whole-genome sequencing, 77 clustered in clade III, including the pan-resistant isolates, 13 in clade I, and 2 in clade IV. Eighty-four of the isolates (91%) were resistant to at least one antifungal agent; both resistant and susceptible isolates had mutations. The common substitutions identified across the different clades were VF125AL, Y132F, K177R, N335S, and E343D in ERG11 ; N647T in MRR1 ; A651P, A657V, and S195G in TAC1b ; S639P in FKS1HP1 ; and S58T in ERG3 . Most South African C. auris isolates were resistant to azoles, although resistance to polyenes and echinocandins was less common. We observed mutations in resistance genes even in phenotypically susceptible isolates.

Published
2021
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14. Genotype, Antifungal Susceptibility, and Virulence of Clinical South African Cryptococcus neoformans Strains from National Surveillance, 2005-2009.

Author

Naicker SD, Magobo RE, Maphanga TG, Firacative C, van Schalkwyk E, Monroy-Nieto J, Bowers J, Engelthaler DM, Shuping L, Meyer W, and Govender NP

Abstract

In South Africa, Cryptococcus neoformans is the most common cause of adult meningitis. We performed multi locus sequence typing and fluconazole susceptibility testing of clinical C. neoformans isolates collected from 251 South African patients with cryptococcosis through national surveillance from 2005 to 2009. We examined the association between clinical characteristics of patients and genotype, and the effect of genotype on in-hospital mortality. We performed whole genome phylogenetic analysis of fifteen C. neoformans isolates with the molecular type VNB and tested their virulence in a Galleria mellonella model. Most isolates had the molecular type VNI (206/251, 82%), followed by VNII (25/251, 10%), VNB (15/251, 6%), and VNIV (5/251, 2%); 67 sequence types were identified. There were no differences in fluconazole minimum inhibitory concentration (MIC) values among molecular types and the majority of strains had low MIC values (MIC 50 of 1 µg/mL and MIC 90 of 4 µg/mL). Males were almost twice as likely of being infected with a non-VNI genotype (adjusted odds ratio [OR]: 1.65, 95% confidence interval [CI]: 0.25-10.99; p = 0.61). Compared to patients infected with a VNI genotype, those with a non-VNI genotype had a 50% reduced adjusted odds of dying in hospital (95% CI: 0.03-7.57; p = 0.62). However, for both these analyses, our estimates had wide confidence intervals spanning 1 with large p -values. Fifteen VNB strains were not as virulent in a G. mellonella larval model as the H99 reference strain. A majority of these VNB strains belonged to the VNBII clade and were very closely related by phylogenetic analysis.

Published
2021
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15. Leveraging gains from African Center for Integrated Laboratory Training to combat HIV epidemic in sub-Saharan Africa.

Author

Shrivastava R, Poxon R, Rottinghaus E, Essop L, Sanon V, Chipeta Z, van-Schalkwyk E, Sekwadi P, Murangandi P, Nguyen S, Devos J, Nesby-Odell S, Stevens T, Umaru F, Cox A, Kim A, Yang C, Parsons LM, Malope-Kgokong B, and Nkengasong JN

Subjects
Africa South of the Sahara epidemiology, COVID-19 Testing, Clinical Laboratory Services, HIV Infections epidemiology, HIV Testing, Health Services Research, Humans, Retrospective Studies, Epidemics prevention & control, HIV Infections prevention & control, Laboratories organization & administration, Laboratory Personnel education
Abstract

Background: In sub-Saharan Africa, there is dearth of trained laboratorians and strengthened laboratory systems to provide adequate and quality laboratory services for enhanced HIV control. In response to this challenge, in 2007, the African Centre for Integrated Laboratory Training (ACILT) was established in South Africa with a mission to train staffs from countries with high burdens of diseases in skills needed to strengthen sustainable laboratory systems. This study was undertaken to assess the transference of newly gained knowledge and skills to other laboratory staff, and to identify enabling and obstructive factors to their implementation., Methods: We used Kirkpatrick model to determine training effectiveness by assessing the transference of newly gained knowledge and skills to participant's work environment, along with measuring enabling and obstructive factors. In addition to regular course evaluations at ACILT (pre and post training), in 2015 we sent e-questionnaires to 867 participants in 43 countries for course participation between 2008 and 2014. Diagnostics courses included Viral Load, and systems strengthening included strategic planning and Biosafety and Biosecurity. SAS v9.44 and Excel were used to analyze retrospective de-identified data collected at six months pre and post-training., Results: Of the 867 participants, 203 (23.4%) responded and reported average improvements in accuracy and timeliness in Viral Load programs and to systems strengthening. For Viral Load testing, frequency of corrective action for unsatisfactory proficiency scores improved from 57 to 91%, testing error rates reduced from 12.9% to 4.9%; 88% responders contributed to the first national strategic plan development and 91% developed strategies to mitigate biosafety risks in their institutions. Key enabling factors were team and management support, and key obstructive factors included insufficient resources and staff's resistance to change., Conclusions: Training at ACILT had a documented positive impact on strengthening the laboratory capacity and laboratory workforce and substantial cost savings. ACILT's investment produced a multiplier effect whereby national laboratory systems, personnel and leadership reaped training benefits. This laboratory training centre with a global clientele contributed to improve existing laboratory services, systems and networks for the HIV epidemic and is now being leveraged for COVID-19 testing that has infected 41,332,899 people globally.

Published
2021
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16. An outbreak of cutaneous abscesses caused by Panton-Valentine leukocidin-producing methicillin-susceptible Staphylococcus aureus among gold mine workers, South Africa, November 2017 to March 2018.

Author

Ismail H, Govender NP, Singh-Moodley A, van Schalkwyk E, Shuping L, Moema I, Feller G, Mogokotleng R, Strasheim W, Lowe M, Mpembe R, Naicker S, Maphanga TG, De Abreu C, Ismail F, Ismail N, Allam M, Ismail A, Singh T, Matuka O, Duba T, and Perovic O

Subjects
Adult, Bacterial Toxins metabolism, Disease Outbreaks, Electrophoresis, Gel, Pulsed-Field, Exotoxins metabolism, Female, Gold, Humans, Leukocidins metabolism, Male, Methicillin pharmacology, Middle Aged, Miners, Retrospective Studies, Skin Diseases microbiology, Soft Tissue Infections microbiology, South Africa epidemiology, Staphylococcal Infections microbiology, Staphylococcus aureus drug effects, Staphylococcus aureus genetics, Staphylococcus aureus metabolism, Abscess microbiology, Skin Diseases epidemiology, Soft Tissue Infections epidemiology, Staphylococcal Infections epidemiology, Staphylococcus aureus pathogenicity
Abstract

Background: We aimed to describe an outbreak of cutaneous abscesses caused by Panton-Valentine leukocidin (PVL)-producing methicillin-susceptible Staphylococcus aureus (MSSA) among gold mine workers., Methods: In February 2018, we retrospectively reviewed a random sample of 50 medical records from 243 cases and conducted face-to-face interviews using a structured questionnaire. Pus aspirates were sent to the National Institute for Communicable Diseases from prospectively-identified cases (November 2017-March 2018). Nasopharyngeal swabs were collected during a colonisation survey in February 2018. Staphylococcus aureus isolates were screened with a conventional PCR for lukS/F-PV. Pulsed-field gel electrophoresis (PFGE) was performed to determine the genetic relatedness among the isolates. A sample of isolates were selected for whole genome sequencing (WGS). We conducted an assessment on biological risks associated with mining activities., Results: From January 2017 to February 2018, 10% (350/3582) of mine workers sought care for cutaneous abscesses. Forty-seven medical files were available for review, 96% were male (n = 45) with a mean age of 43 years (SD = 7). About 52% (24/46) were involved in stoping and 28% (13/47) worked on a particular level. We cultured S. aureus from 79% (30/38) of cases with a submitted specimen and 14% (12/83) from colonisation swabs. All isolates were susceptible to cloxacillin. Seventy-one percent of S. aureus isolates (30/42) were PVL-PCR-positive. Six PFGE clusters were identified, 57% (21/37) were closely related. WGS analysis found nine different sequence types. PFGE and WGS analysis showed more than one cluster of S. aureus infections involving closely related isolates. Test reports for feed and product water of the mine showed that total plate counts were above the limits of 1000 cfu/ml, coliform counts > 10 cfu/100 ml and presence of faecal coliforms. Best practices were poorly implemented as some mine workers washed protective clothing with untreated water and hung them for drying at the underground surface., Conclusions: PVL-producing MSSA caused an outbreak of cutaneous abscesses among underground workers at a gold mining company. To our knowledge, no other outbreaks of PVL-producing S. aureus involving skin and soft tissue infections have been reported in mining facilities in South Africa. We recommend that worker awareness of infection prevention and control practices be strengthened.

Published
2020
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17. Screening for invasive fungal disease using non-culture-based assays among inpatients with advanced HIV disease at a large academic hospital in South Africa.

Author

van Schalkwyk E, Mhlanga M, Maphanga TG, Mpembe RS, Shillubane A, Iyaloo S, Tsotetsi E, Pieton K, Karstaedt AS, Sahid F, Menezes CN, Tsitsi M, Motau A, Wadula J, Seetharam S, van den Berg E, Sriruttan C, and Govender NP

Subjects
AIDS-Related Opportunistic Infections epidemiology, Academic Medical Centers, Adult, Antigens, Fungal blood, Antigens, Fungal urine, Cross-Sectional Studies, Cryptococcosis diagnosis, Cryptococcosis epidemiology, Female, HIV Infections microbiology, Histoplasmosis diagnosis, Histoplasmosis epidemiology, Humans, Inpatients, Invasive Fungal Infections epidemiology, Lipopolysaccharides blood, Male, Point-of-Care Systems, Prevalence, Prospective Studies, South Africa, Tuberculosis diagnosis, Tuberculosis epidemiology, AIDS-Related Opportunistic Infections diagnosis, HIV Infections complications, Invasive Fungal Infections diagnosis
Abstract

Introduction: Despite widespread access to antiretroviral therapy (ART), the burden of advanced HIV disease in South Africa is high. This translates into an increased risk of AIDS-related opportunistic infections, including invasive mycoses., Methods: Using a limited number of non-culture-based diagnostic assays, we aimed to determine the prevalence of invasive mycoses and tuberculosis among hospitalised adults with very advanced HIV (CD4 counts < 100 cells/µL) at a large academic hospital. We conducted interviews and prospective medical chart reviews. We performed point-of-care finger stick and serum cryptococcal antigen lateral flow assays; serum (1 → 3) ß-D-glucan assays; urine Histoplasma galactomannan antigen enzyme immunoassays and TB lipoarabinomannan assays., Results: We enrolled 189 participants from 5280 screened inpatients. Fifty-eight per cent were female, with median age 37 years (IQR: 30-43) and median CD4 count 32 cells/µL (IQR: 13-63). At enrolment, 60% (109/181) were receiving ART. Twenty-one participants (11%) had a diagnosis of an invasive mycosis, of whom 53% (11/21) had cryptococcal disease. Thirteen participants (7%) had tuberculosis and a concurrent invasive mycosis. ART-experienced participants were 60% less likely to have an invasive mycosis than those ART-naïve (adjusted OR: 0.4; 95% CI 0.15-1.0; P = .03). Overall in-hospital mortality was 13% (invasive mycosis: 10% [95% CI 1.2-30.7] versus other diagnoses: 13% (95% CI 8.4-19.3))., Conclusions: One in ten participants had evidence of an invasive mycosis. Diagnosis of proven invasive fungal disease and differentiation from other opportunistic infections was challenging. More fungal-specific screening and diagnostic tests should be applied to inpatients with advanced HIV disease., (© 2020 Blackwell Verlag GmbH.)

Published
2020
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18. Perceptions of mothers with preterm infants about early communication development: A scoping review.

Author

Van Schalkwyk E, Gay S, Miller J, Matthee E, and Gerber B

Subjects
Communication Disorders therapy, Culturally Competent Care, Female, Health Knowledge, Attitudes, Practice, Humans, Infant, Infant, Newborn, Infant, Premature, Mother-Child Relations, South Africa, Communication Disorders psychology, Mothers psychology
Abstract

Background: Preterm infants are at risk of communication disorders or delays, and their mothers experience various difficult emotions and realities. These communication difficulties could be effectively prevented or addressed through the provision of appropriate maternal support. Maternal perceptions regarding early communication-interaction and development in preterm population should thus be well understood by health professionals. Previous studies have focussed on parents' and patients' perceptions of medical information received from health professionals. Limited research, however, has been undertaken on maternal perceptions of early communication development in preterm infants, specifically in the South African context., Objectives: The study aims to summarise the range and the nature of available research in the fields of early communication development and intervention in preterm infants, specifically maternal perceptions thereof., Method: A scoping review methodology comprising five phases was used. Data were extracted from the final selection of 12 articles and analysed through quantitative and thematic techniques., Results: The results of the scoping review indicate that the defined research field is in a developing phase. Mothers mainly experience negative emotions and have limited knowledge regarding communication interaction with preterm infants. Furthermore, hospitalisation has been experienced as a barrier to natural communication-interaction between mother and infant., Conclusion: Based on these results, it is recommended that primary research be conducted with the mothers of preterm infants to establish the most effective strategies for communication-interaction training with this vulnerable population. A further recommendation would be to increase awareness of early communication development and intervention in the preterm population amongst both parents and health professionals.

Published
2020
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19. Federation of Infectious Diseases Societies of Southern Africa guideline: Recommendations for the detection, management and prevention of healthcare-associated Candida auris colonisation and disease in South Africa.

Author

Govender NP, Avenant T, Brink A, Chibabhai V, Cleghorn J, du Toit B, Govind C, Lewis E, Lowman W, Mahlangu H, Maslo C, Messina A, Mer M, Pieton K, Seetharam S, Sriruttan C, Swart K, and van Schalkwyk E

Abstract

Candida auris has been detected at almost 100 South African hospitals, causing large outbreaks in some facilities, and this pathogen now accounts for approximately 1 in 10 cases of candidaemia. The objective of this guideline is to provide updated, evidence-informed recommendations outlining a best-practice approach to prevent, diagnose and manage C. auris disease in public- and private-sector healthcare settings in South Africa. The 18 practical recommendations cover five focus areas: laboratory identification and antifungal susceptibility testing, surveillance and outbreak response, infection prevention and control, clinical management and antifungal stewardship., Competing Interests: All members of the guideline development group completed an International Committee of Medical Journal Editors (ICMJE) conflicts of interest form. Over the past 36 months, Adrian Brink served on speakers’ bureaus for Merck, Sharp & Dohm (MSD) South Africa and Pfizer. Warren Lowman received speaker fees from MSD South Africa, Pfizer and Astellas. Charlotte Sriruttan received a travel grant from MSD South Africa. For all other authors, no conflicts of interest were declared., (© 2019. The Authors.)

Published
2019
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20. Epidemiologic Shift in Candidemia Driven by Candida auris, South Africa, 2016-2017 1 .

Author

van Schalkwyk E, Mpembe RS, Thomas J, Shuping L, Ismail H, Lowman W, Karstaedt AS, Chibabhai V, Wadula J, Avenant T, Messina A, Govind CN, Moodley K, Dawood H, Ramjathan P, and Govender NP

Subjects
Adolescent, Adult, Aged, Antifungal Agents therapeutic use, Candidiasis drug therapy, Candidiasis microbiology, Child, Child, Preschool, Female, Humans, Incidence, Infant, Infant, Newborn, Male, Middle Aged, Risk Factors, South Africa epidemiology, Young Adult, Candida isolation & purification, Candidiasis epidemiology, Drug Resistance, Fungal
Abstract

Candida auris is an invasive healthcare-associated fungal pathogen. Cases of candidemia, defined as illness in patients with Candida cultured from blood, were detected through national laboratory-based surveillance in South Africa during 2016-2017. We identified viable isolates by using mass spectrometry and sequencing. Among 6,669 cases (5,876 with species identification) from 269 hospitals, 794 (14%) were caused by C. auris. The incidence risk for all candidemia at 133 hospitals was 83.8 (95% CI 81.2-86.4) cases/100,000 admissions. Prior systemic antifungal drug therapy was associated with a 40% increased adjusted odds of C. auris fungemia compared with bloodstream infection caused by other Candida species (adjusted odds ratio 1.4 [95% CI 0.8-2.3]). The crude in-hospital case-fatality ratio did not differ between Candida species and was 45% for C. auris candidemia, compared with 43% for non-C. auris candidemia. C. auris has caused a major epidemiologic shift in candidemia in South Africa.

Published
2019
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21. Large Outbreaks of Fungal and Bacterial Bloodstream Infections in a Neonatal Unit, South Africa, 2012-2016.

Author

van Schalkwyk E, Iyaloo S, Naicker SD, Maphanga TG, Mpembe RS, Zulu TG, Mhlanga M, Mahlangu S, Maloba MB, Ntlemo G, Sanyane K, Mawela D, and Govender NP

Subjects
Bacteremia microbiology, Bacteremia prevention & control, Child, Female, Fungemia microbiology, Fungemia prevention & control, History, 21st Century, Humans, Infant, Newborn, Male, Public Health Surveillance, Risk Factors, South Africa epidemiology, Bacteremia epidemiology, Cross Infection, Disease Outbreaks, Fungemia epidemiology, Infant, Newborn, Diseases epidemiology, Infant, Newborn, Diseases microbiology
Abstract

Candidemia is a major cause of healthcare-associated infections. We describe a large outbreak of Candida krusei bloodstream infections among infants in Gauteng Province, South Africa, during a 4-month period; a series of candidemia and bacteremia outbreaks in the neonatal unit followed. We detected cases by using enhanced laboratory surveillance and audited hospital wards by environmental sampling and epidemiologic studies. During July-October 2014, among 589 patients, 48 unique cases of C. krusei candidemia occurred (8.2% incidence). Risk factors for candidemia on multivariable analyses were necrotizing enterocolitis, birthweight <1,500 g, receipt of parenteral nutrition, and receipt of blood transfusion. Despite initial interventions, outbreaks of bloodstream infection caused by C. krusei, rarer fungal species, and bacterial pathogens continued in the neonatal unit through July 29, 2016. Multiple factors contributed to these outbreaks; the most functional response is to fortify infection prevention and control.

Published
2018
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22. Goodness-of-fit determination of femoral knee prosthesis using computer segmentation.

Author

Van Schalkwyk EP, Scheffer C, Dillon EM, and Erasmus PJ

Subjects
Aged, Arthroplasty, Replacement, Knee, Computer Simulation, Humans, Femur surgery, Knee Prosthesis, Prosthesis Design
Abstract

35 patients undergoing Total Knee Arthroplasty (TKA) were examined with Computerized Tomography (CT). 3D computer models were created through segmentation of the CT scan data with Materialize MIMICS. Morphological dimensions of ten selected parameters were measured and then compared to two commercial femoral prosthesis design ranges. All measuring techniques were validated and the reproducibility of measuring morphological dimensions with points and planes from landmarks were investigated. The chi2 test was used as a goodness-of-fit parameter to determine which femoral component would achieve the best geometric fit for a specific patient. After establishing a database of geometric values, the method can be used to calculate the dimensions of a customized femoral knee prosthesis to achieve a perfect geometric fit for a TKA patient.

Published
2007
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23. Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, attenuates allergen-induced asthmatic reactions.

Author

van Schalkwyk E, Strydom K, Williams Z, Venter L, Leichtl S, Schmid-Wirlitsch C, Bredenbröker D, and Bardin PG

Subjects
Administration, Oral, Adult, Aminopyridines adverse effects, Asthma physiopathology, Benzamides adverse effects, Cross-Over Studies, Cyclic Nucleotide Phosphodiesterases, Type 4, Cyclopropanes adverse effects, Cyclopropanes therapeutic use, Double-Blind Method, Female, Forced Expiratory Volume drug effects, Humans, Male, 3',5'-Cyclic-AMP Phosphodiesterases antagonists & inhibitors, Allergens immunology, Aminopyridines therapeutic use, Asthma drug therapy, Benzamides therapeutic use, Phosphodiesterase Inhibitors therapeutic use
Abstract

Background: Asthma is a chronic inflammatory disease with increasing incidence worldwide. Roflumilast is an oral, once-daily inhibitor of phosphodiesterase type 4 that prevents the breakdown of cyclic adenosine monophosphate levels, leading to inhibition of proinflammatory signaling., Objective: The objective of this study was to investigate the effects of repeated doses of 250 or 500 microg of roflumilast on asthmatic airway responses to allergen., Methods: Twenty-three patients with mild asthma with an FEV1 of 70% of predicted value or greater were enrolled in a randomized, double-blind, placebo-controlled, 3-period crossover study. Patients participated in 3 treatment periods (7-10 days) separated by washout periods (2-5 weeks). Patients received 250 microg of oral roflumilast, 500 microg of roflumilast, or placebo once daily. Allergen challenge was performed at the end of each treatment period, followed by FEV1 measurements over the ensuing 24 hours., Results: Late asthmatic reactions (LARs) were reduced by 27% (P = .0110) and 43% (P = .0009) in patients treated with 250 and 500 microg of roflumilast, respectively, versus placebo. Roflumilast, 250 and 500 microg, also attenuated early asthmatic reactions by 25% (P = .0038) and 28% (P = .0046), although not to the same extent as LAR attenuation. Roflumilast was well tolerated. No serious adverse events or discontinuations caused by adverse events were reported., Conclusion: Once-daily oral roflumilast modestly attenuated early asthmatic reactions and, to a greater extent, LARs to allergen in patients with mild allergic asthma. Pronounced suppression of late responses in an allergen challenge model suggests that roflumilast might have anti-inflammatory activity, which could provide clinical efficacy in chronic inflammatory pulmonary diseases, such as asthma.

Published
2005
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24. Guideline for office spirometry in adults, 2004.

Author

van Schalkwyk EM, Schultz C, Joubert JR, and White NW

Subjects
Adult, Algorithms, Humans, Lung Diseases diagnosis, Reproducibility of Results, Respiratory Function Tests, Spirometry standards
Abstract

Objective: To provide clinical guidelines for office spirometry in South Africa., Options: More stringent guidelines are required for diagnostic laboratories and research., Outcomes: To minimise variations in standard practice and improve the quality and usefulness of spirometry in the clinical setting., Evidence: Recommendations are based on key international publications as well as research publications regarding reference values for South Africans., Benefits, Harm and Costs: The medical, social and economic benefits and costs of standardisation of office spirometry in South Africa were considered in the recommendations., Validation: The document has been reviewed and endorsed by the South African Thoracic Society., Conclusions: The indications for spirometry must be specific and clear. Spirometry equipment must meet internationally accepted performance standards and carry proof of validation. Equipment must be regularly calibrated and maintained. Individuals performing spirometry must be adequately trained and demonstrate a high level of competence. Subject preparation, testing and quality control of results must be carried out according to published guidelines. Finally, test results must be interpreted according to current diagnostic guidelines, taking into account the purpose of the test, appropriateness of reference values and the clinical evaluation.

Published
2004

25. Risk factors for near-fatal asthma--a case-control study in a Western Cape teaching hospital.

Author

de Klerk A, van Schalkwyk E, Williams Z, Lee W, and Bardin P

Subjects
Adrenal Cortex Hormones administration & dosage, Adult, Asthma classification, Asthma physiopathology, Case-Control Studies, Female, Hospitals, Teaching, Humans, Male, Respiration, Artificial, Risk Factors, Severity of Illness Index, Smoking adverse effects, South Africa, Surveys and Questionnaires, Asthma etiology
Abstract

Background and Objectives: To evaluate risk factors for asthma death such as access to health care, over-use of beta 2-agonists or under-use of inhaled corticosteroids in the Western Cape (WC) population, using near-fatal asthma (NFA) as a surrogate marker., Subjects and Methods: Patients with NFA (cases) admitted to a WC teaching hospital were compared with patients with acute asthma in a case-control study using a structured questionnaire, clinical examination, arterial blood gas measurements, chest radiograph and pulmonary function measurements., Results: Sixteen patients with NFA (cases) and 55 with acute asthma (controls) were prospectively enrolled. Duration of asthma, gender, smoking status and ethnicity were similar. Cases had significantly more previous mechanical ventilation (P < 0.05) and a trend towards more previous intensive care unit (ICU) admissions. No significant differences were found in primary health care variables., Conclusion: Our study demonstrates that patients with NFA constitute a significant number of emergency room (ER) admissions for acute asthma (30%) in our population. Similar to other studies, there was a trend for NFA toward more previous ICU admissions and mechanical ventilation. Relative under-use of beta 2-agonists the day before admission and fewer ER visits during the previous year in the NFA group, suggests an impaired perception of the severity of disease or a more rapid onset of symptoms. Negative factors such as inability to access health care or lack of medication supply were similar in both groups. The challenge remains to identify and manage high-risk patients effectively.

Published
2002

26. Occupational respiratory diseases in South Africa--results from SORDSA, 1997-1999.

Author

Esterhuizen TM, Hnizdo E, Rees D, Lalloo UG, Kielkowski D, van Schalkwyk EM, White N, Smith FC, Hoggins B, and Curtis T

Subjects
Accidents, Occupational statistics & numerical data, Databases, Factual, Humans, Incidence, Industry statistics & numerical data, Inhalation Exposure adverse effects, Inhalation Exposure statistics & numerical data, Needs Assessment, Occupational Diseases etiology, Occupational Diseases prevention & control, Occupational Exposure adverse effects, Occupational Exposure statistics & numerical data, Occupations statistics & numerical data, Population Surveillance methods, Registries, Respiratory Tract Diseases etiology, Respiratory Tract Diseases prevention & control, Risk Factors, South Africa epidemiology, Occupational Diseases epidemiology, Respiratory Tract Diseases epidemiology
Abstract

Objectives: To describe the nature and extent of work-related respiratory diseases reported to the national Surveillance of Work-related and Occupational Respiratory Diseases in South Africa (SORDSA) reporting scheme. The causative agents and industrial categories in which they occurred are also characterised., Design: Voluntary monthly reporting of newly diagnosed cases by pulmonologists, occupational medicine practitioners and occupational health nurses., Setting: Medical and occupational health referral centres in the nine provinces of South Africa., Subjects: Cases were workers from non-mining industries or ex-miners, suffering from a newly diagnosed occupational respiratory disease, reported to SORDSA between October 1996 and December 1999., Outcome Measures: Frequencies of reported occupational respiratory disease by year, reporting source, province and sex. Frequencies of short- and long-latency diseases by industry and causative agent., Results: There was incomplete reporting coverage of the nine provinces in the first 3 years. Reporting was most comprehensive from Gauteng, KwaZulu-Natal and the Western Cape. Diseases with long latency periods made up 76.2% of the cases. Pneumoconiosis, even in non-mining industries, was the most frequently reported disease, followed by inhalation accidents. Occupational asthma was the fourth most reported disease. Apart from the prominence of pneumoconiosis, the results obtained by SORDSA are similar to those from a British occupational lung disease surveillance scheme. This study showed that newly diagnosed cases of occupational lung disease occurred in many industries and were caused by a variety of agents., Conclusion: SORDSA has contributed insight into the nature, extent and distribution of occupational respiratory diseases in South Africa. It has also highlighted important causes of occupational respiratory diseases in South Africa, as well as hazardous industries. The data indicate that South Africa has a widespread occupational lung disease problem, and provide a platform for targeted prevention strategies.

Published
2001

27. Reduced activation of peripheral blood neutrophils after late-phase asthmatic responses but not in mild stable asthma.

Author

Mattheyse FJ, van Heerden K, Mattheyse M, Williams Z, Bouic P, van Schalkwyk EM, and Bardin PG

Subjects
Adolescent, Adult, Ambulatory Care, Asthma drug therapy, Asthma physiopathology, Bronchial Provocation Tests, Female, Forced Expiratory Volume drug effects, Forced Expiratory Volume physiology, Humans, Leukocyte Count, Male, Middle Aged, Neutrophil Activation drug effects, Neutrophils drug effects, Peak Expiratory Flow Rate drug effects, Peak Expiratory Flow Rate physiology, Receptors, Adrenergic, beta-2 therapeutic use, Severity of Illness Index, Asthma blood, Neutrophil Activation physiology, Neutrophils metabolism
Abstract

Background: Asthma is a process of chronic allergic inflammation that may be worsened by the activation of neutrophils during acute exacerbations., Objective: We investigated our hypothesis that changes in cellular activation may be detectable in peripheral blood (PB) during late-phase asthma and during clinical exacerbations., Methods: Twenty-one stable asthmatics (9 on treatment with beta2-agonists only, 12 using inhaled corticosteroids) and 10 nonasthmatic volunteers were first compared using flow cytometry to measure beta2-integrin (CD11b/CD18) expression. Production of reactive oxygen species (ROS) was evaluated employing chemiluminescence. Next, 8 mild asthmatics were assessed using similar methods before and after allergen-induced late asthmatic reactions (LARs). Finally, 4 asthmatic subjects were evaluated over 3 months, and symptoms, peak expiratory flow (PEF) and ROS production were measured. Episodes of respiratory morbidity (exacerbations) were identified and their association with ROS production was examined., Results: No differences were detected in adhesion molecule expression and ROS production comparing the normal and asthmatic groups. However, after development of the LAR, significant reductions in CD11b neutrophil expression (mean fluorescence intensity; MFI) were observed [before: 994 +/- 102 MFI (mean +/- SEM) versus after: 424 +/- 81 MFI; p < 0.01]. Furthermore, strong associations were found between decreases in CD11b and the severity of the LAR (r = 0.9; p < 0.02). In the clinical study, ROS production was significantly lower during exacerbations (median 43%; p < 0.05). Again, this measurement was significantly associated with reductions in PEF (r = 0.5, p < 0.03)., Conclusions: In patients with mild stable asthma, no differences in the activation of circulating neutrophils were detectable compared to nonasthmatic individuals. During episodes of asthmatic airway obstruction, in the laboratory and in clinical disease, neutrophil activation decreased in PB, conceivably because activated cells may be preferentially sequestered in the lung., (Copyright 2001 S. Karger AG, Basel)

Published
2001
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28. Peak expiratory flow changes during experimental rhinovirus infection.

Author

Bardin PG, Fraenkel DJ, Sanderson G, van Schalkwyk EM, Holgate ST, and Johnston SL

Subjects
Adult, Asthma complications, Common Cold complications, Female, Forced Expiratory Volume, Humans, Hypersensitivity complications, Male, Middle Aged, Reference Values, Common Cold physiopathology, Peak Expiratory Flow Rate, Rhinovirus
Abstract

Rhinovirus (RV) colds are associated with asthma exacerbations and experimental infections are commonly used to investigate the mechanisms involved. However, a temporal association between experimental RV infections and falls in peak expiratory flow (PEF) have not been demonstrated. PEF was measured in 22 volunteers (11 normal, five atopic, six atopic asthmatic) who developed RV serotype 16 colds after inoculation. PEF was measured twice daily for 2 weeks prior and 6 weeks after RV infection and episodes of respiratory morbidity based on changes in PEF were defined using validated criteria. Six significant reductions in PEF were temporally related to the RV infections (in two (18%) normal, one (20%) atopic, three (50%) atopic asthmatic subjects, p=0.1) and occurred 4-9 days (median 6) after inoculation. Mean+/-SEM PEF at day 6 was 87.8+/-1.8% of the predicted value in the six subjects with reductions versus 99.4+/-1.4% pred in those without (p=0.01). Symptom scores were significantly different at day 6 in the two groups (10.6+/-1.9 versus 6.8+/-1.0, p=0.03), but no differences were noted in the viral culture scores and changes in nasal albumin. In subjects with significant PEF reduction, the decrease in the provocative concentration causing a 20% fall in the forced expiratory volume in one second (FEV1) (PC20) was 1.7+/-1.3 mg x mL(-1) versus 1.2+/-1.1 mg x mL(-1) in the negative group (p=0.06). The degree of seroconversion to RV was significantly higher in the group with reduced PEF (median change dilutions 8 versus 4, p=0.02). The results of the present study suggest that rhinovirus-associated, respiratory morbidity occurs during experimental infection in some but not all normal and asthmatic subjects and also that experimental colds are a valid model for the study of rhinovirus-associated airway symptoms and asthma exacerbations.

Published
2000
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29. Treatment of progressive pulmonary sarcoidosis with cyclosporin A. A randomized controlled trial.

Author

Wyser CP, van Schalkwyk EM, Alheit B, Bardin PG, and Joubert JR

Subjects
Adult, Bronchoalveolar Lavage Fluid cytology, Cyclosporine administration & dosage, Cyclosporine adverse effects, Disease Progression, Drug Therapy, Combination, Female, Glucocorticoids administration & dosage, Glucocorticoids therapeutic use, Humans, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents adverse effects, Male, Prednisone administration & dosage, Prednisone therapeutic use, Prospective Studies, Radiography, Thoracic, Recurrence, Respiratory Mechanics, Sarcoidosis, Pulmonary diagnostic imaging, Sarcoidosis, Pulmonary pathology, Sarcoidosis, Pulmonary physiopathology, Treatment Failure, Cyclosporine therapeutic use, Immunosuppressive Agents therapeutic use, Sarcoidosis, Pulmonary drug therapy
Abstract

Conventional treatment of sarcoidosis is often only partially effective. We examined the effect of cyclosporin A (CsA) combined with prednisone for the treatment of sarcoidosis. Thirty-seven patients with biopsy-proven sarcoidosis were treated with either prednisone 20 mg/d in a prospectively tapered regimen (P) or with combination therapy consisting of prednisone 20 mg/d in a prospectively tapered regimen and cyclosporin A, 5 to 7 mg/kg/d (P-CsA) for up to 18 mo in an open-label randomized controlled trial. Evaluation was done at baseline and at 3, 9, and 18 mo of the degree of dyspnea, pulmonary function, chest radiographs, bronchoalveolar lavage (BAL), and adverse events. Criteria for a good therapeutic response, improvement, treatment failure, and relapse were defined. Thirty-seven patients were treated for at least 9 mo and 18 mo. Six patients in remission were included in an intention-to-treat-analysis at 18 mo. The groups did not differ significantly with respect to therapeutic response from baseline. A significant (p < 0.05) improvement was observed in dyspnea until 9 mo (P) and 18 mo (P-CsA), and in lung function until 9 mo (P) and 3 mo (P-CsA). BAL results showed a significant decrease in lymphocyte counts at 9 mo for the P group only (p < 0.05). More side effects were observed in the P-CsA group than in the P group, including elevation of the mean serum creatinine concentration at 3 and 9 mo (p < 0.05), and a doubling of the number of infections in this group. Relapse after an initially good therapeutic response occurred in two of nine patients in the P group and five of seven patients in the P-CsA group (p < 0.07). Although CsA may have theoretical benefits in the treatment of sarcoidosis, our results do not support its use in this disease.

Published
1997
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30. Corticosteroids in the treatment of tuberculous pleurisy. A double-blind, placebo-controlled, randomized study.

Author

Wyser C, Walzl G, Smedema JP, Swart F, van Schalkwyk EM, and van de Wal BW

Subjects
Adult, Double-Blind Method, Drug Therapy, Combination, Female, Glucocorticoids adverse effects, Humans, Male, Prednisone adverse effects, Antitubercular Agents administration & dosage, Glucocorticoids therapeutic use, Prednisone therapeutic use, Tuberculosis, Pleural drug therapy
Abstract

Although several studies on tuberculous (TB) pleurisy suggest that the addition of corticosteroids to anti-TB therapy may have beneficial effects, these agents are not used routinely. To assess the effects of short-term oral prednisone therapy in TB pleurisy, 74 patients were randomly assigned in a double-blind fashion to treatment with either placebo or prednisone at a dose of 0.75 mg/kg/d for up to 4 weeks with gradual reduction over an additional 2 weeks. All subjects received a standard 3-drug anti-TB chemotherapy regimen for 6 months. TB pleurisy was diagnosed by histologic study and/or culture of pleural biopsy specimens obtained at thoracoscopy. Complete drainage of the effusion was performed simultaneously. Outcome measures were assessed periodically for 24 weeks, including indexes of morbidity and pleural thickening. After randomization, four patients were excluded from the final analysis. Of the 70 patients analyzed, 34 received prednisone and 36 received placebo. Demographic and clinical characteristics of the treatment groups were comparable at the time of hospital admission. Although a statistically significant improvement in symptoms occurred earlier in the prednisone group (8 weeks) than in the placebo group (12 weeks), between-group comparison showed no significant differences at any of the follow-up evaluations. The proportion of subjects in the prednisone group (53.1%) with residual pleural thickening at 6 months did not differ significantly from that of the placebo group (60%). Pleural effusions did not recur in any of the patients. Initial complete drainage of the effusion was associated with greater symptomatic improvement than any subsequent therapy. We conclude that standard anti-TB therapy and early complete drainage is adequate for the treatment of TB pleurisy. The addition of short-term oral prednisone therapy neither results in clinically relevant earlier symptom relief nor confers a beneficial effect on residual pleural thickening.

Published
1996
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31. Carriage of Haemophilus influenzae in Cape Town children.

Author

Hussey GD, Coetzee G, Hitchcock J, van Schalkwyk E, van Wyk H, and Kibel M

Subjects
Age Factors, Anti-Bacterial Agents therapeutic use, Child, Child, Preschool, Drug Resistance, Microbial, Haemophilus Infections complications, Haemophilus Infections drug therapy, Haemophilus influenzae isolation & purification, Hospitalization, Humans, Infant, Infant, Newborn, Prevalence, Serotyping, South Africa epidemiology, Tuberculosis complications, Haemophilus Infections epidemiology, Haemophilus influenzae drug effects
Abstract

Little is known about the epidemiology of Haemophilus influenzae infections in South Africa. This study was designed to determine the prevalence, serotype distribution, antimicrobial susceptibility pattern and effect of age and hospitalisation on the carriage of H. influenzae in 322 Cape Town children. The overall and type b specific carriage rates in normal children (N = 107) were 45.8% and 4.7% respectively. The yield following nasopharyngeal culture was twice that following throat culture (P < 0.001). Children hospitalised with tuberculosis (N = 62) had significantly greater carriage rates, 66.1% and 37.1% respectively (P = 0.02). Institutionalised mentally handicapped children (N = 77) and children with tuberculosis attending an outpatient clinic (N = 76) had lower carriage rates (P < 0.02). Antimicrobial resistance was a major problem only in children hospitalised with tuberculosis (rifampicin 100%, penicillin 43.9%, erythromycin 85.4%, co-trimoxazole 82.9%). This universal resistance to rifampicin has not been reported previously. There was no difference in the mean age of children with positive or negative cultures, with the exception of those hospitalised with tuberculosis. In this group children infected with type b were much younger (mean 19.7 months) than those with other and non-typeable infections (32.1 months) and the non-infected (50.1 months) (P = 0.04). Duration of hospitalisation or outpatient therapy in the patients with tuberculosis did not influence carriage rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Published
1994

32. Epidemiology of invasive Haemophilus influenzae infections in Cape Town, South Africa.

Author

Hussey G, Hitchcock J, Schaaf H, Coetzee G, Hanslo D, van Schalkwyk E, Pitout J, Clausen J, and van der Horst W

Subjects
Age Distribution, Arthritis epidemiology, Arthritis microbiology, Bacteremia epidemiology, Bacteremia microbiology, Child, Child, Preschool, Female, Haemophilus Infections ethnology, Haemophilus Infections microbiology, Haemophilus Infections mortality, Humans, Incidence, Infant, Length of Stay, Male, Pneumonia epidemiology, Pneumonia microbiology, Prospective Studies, Racial Groups, Seasons, Serotyping, Sex Distribution, South Africa epidemiology, Haemophilus Infections epidemiology, Haemophilus influenzae classification
Abstract

The full spectrum of invasive Haemophilus influenzae disease has not been documented previously in Africa. This 1-year prospective study was designed to determine the epidemiology of invasive Haemophilus influenzae disease in Cape Town children. During this period, 142 children with invasive disease were hospitalized; 85 (59.9%) presented with meningitis, 35 (24.6%) with pneumonia and 22 (15.5%) with other diseases. No cases of epiglottitis were seen. Sixty per cent of cases were male and 40% female. The median age of the children was 9 months, with a range of 1-144 months, and 65.5% were aged < 12 months. Neurological dysfunction was noted in 40% and 18% of children with meningitis on admission and discharge, respectively. The overall case fatality rate (95% confidence intervals) was 9.2% (4.9-15.7), and for meningitis, pneumonia and septicaemia it was 4.7% (1.2-16.4), 14.3% (4.6-31.8) and 40% (8-78.1), respectively. Serotype b accounted for 86.5% of all cases, 97.3% of cases of meningitis, 71.4% of cases of pneumonia, 50% of cases of septicaemia, all cases of arthritis and cellulitis and none of mastoiditis. The incidence rates (95% confidence intervals) for all invasive type b infections were 169 (122-198) and 47 (39-57) per 100,000 population for children < 1 and < 5 years, respectively. For meningitis the rates were 112 (84-148) and 34 (25-40) per 100,000, respectively. Rates for mixed race and white children were similar, but those for black children were more than double those rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Published
1994
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