Browsing by Author "Cotton, M. F."
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- ItemAntiretroviral treatment for children with peripartum nevirapine exposure(2010) Palumbo, P.; Lindsey, J. C.; Hughes, M. D.; Cotton, M. F.; Bobat, R.; Meyers, T.; Bwakura-Dangarembizi, M.; Chi, B. H.; Musoke, P.; Kamthunzi, P.; Schimana, W.; Purdue, L.; Eshleman, S. H.; Abrams, E. J.; Millar, L.; Petzold, E.; Mofenson, L. M.; Jean-Philippe, P.; Violari A.Background: Single-dose nevirapine is the cornerstone of the regimen for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in resource-limited settings, but nevirapine frequently selects for resistant virus in mothers and children who become infected despite prophylaxis. The optimal antiretroviral treatment strategy for children who have had prior exposure to single-dose nevirapine is unknown. Methods: We conducted a randomized trial of initial therapy with zidovudine and lamivudine plus either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 6 to 36 months of age, in six African countries, who qualified for treatment according to World Health Organization (WHO) criteria. Results are reported for the cohort that included children exposed to single-dose nevirapine prophylaxis. The primary end point was virologic failure or discontinuation of treatment by study week 24. Enrollment in this cohort was terminated early on the recommendation of the data and safety monitoring board. Results: A total of 164 children were enrolled. The median percentage of CD4+ lymphocytes was 19%; a total of 56% of the children had WHO stage 3 or 4 disease. More children in the nevirapine group than in the ritonavir-boosted lopinavir group reached a primary end point (39.6% vs. 21.7%; weighted difference, 18.6 percentage-points; 95% confidence interval, 3.7 to 33.6; nominal P = 0.02). Baseline resistance to nevirapine was detected in 18 of 148 children (12%) and was predictive of treatment failure. No significant between-group differences were seen in the rate of adverse events. Conclusions: Among children with prior exposure to single-dose nevirapine for perinatal prevention of HIV transmission, antiretroviral treatment consisting of zidovudine and lamivudine plus ritonavir-boosted lopinavir resulted in better outcomes than did treatment with zidovudine and lamivudine plus nevirapine. Since nevirapine is used for both treatment and perinatal prevention of HIV infection in resource-limited settings, alternative strategies for the prevention of HIV transmission from mother to child, as well as for the treatment of HIV infection, are urgently required. Copyright © 2010 Massachusetts Medical Society.
- ItemBacille Calmette-Guerin (BCG) vaccine and the COVID-19 pandemic : responsible stewardship is needed(The Union, 2020) Schaaf, H. S.; Du Preez, K.; Kruger, M.; Solomons, R.; Taljaard, J. J.; Rabie, H.; Seddon, J. A.; Cotton, M. F.; Tebruegge, M.; Curtis, N.; Hesseling, A. C.We believe that responsible stewardship of the bacille Calmette-Guérin (BCG) vaccine in the context of the COVID-19 epidemic is urgently needed. Live attenuated BCG is currently the only licensed vaccine to protect against tuberculosis (TB). Neonatal BCG vaccination has proven efficacy in protecting infants and young children against life-threatening disseminated forms of TB, including TB meningitis and miliary TB.
- ItemBacteraemia in children in the south-western Cape. A hospital-based survey(Health & Medical Publishing Group, 1992-01) Cotton, M. F.; Burger, P. J.; Bodenstein, W. J. M.ENGLISH ABSTRACT: During 1989, of the 8524 children admitted to the paediatric wards of Tygerberg Hospital, 165 (1,96%) had bacteraemia. The incidence of community-acquired bacteraemias was 1,6% and that of nosocomial bacteraemias 0,5%. The most important community-acquired isolates were Streptococcus pneumoniae, Staphylococcus aureus and Neisseria meningitidis. The most important nosocomial isolates were Klebsiella and Salmonella spp. Both bacteraemia (relative risk (RR) = 2,08) and severe malnutrition (RR = 3,01) were more common in black patients. Overall, severe malnutrition was more common than mild malnutrition or a normal nutritional status in bacteraemic patients (odds radio (OR) = 3,17). Nineteen patients with bacteraemia died, there was a significantly higher case-fatality rate in patients with extreme malnutrition (P = 0,03; OR = 3,7). Gram-negative bacilli were found more commonly in patients with extreme malnutrition (OR = 5,4) and patients with nosocomial bacteraemia (OR = 4,6). Three of 39 patients (7,6%) with nosocomial bacteraemia had suppurative thrombophlebitis.
- ItemBCG vaccination in South African HIV-exposed infants : risks and benefits(Health and Medical Publishing Group (HMPG), 2009-02) Hesseling, A. C.; Caldwell, J.; Cotton, M. F.; Eley, B. S.; Jaspan, H. B.; Jennings, K.; Marais, B. J.; Nuttall, J.; Rabie, H.; Roux, P.; Schaaf, H. Simon
- ItemEvaluation of tuberculosis diagnostics in children: 2. Methodological issues for conducting and reporting research evaluations of tuberculosis diagnostics for intrathoracic tuberculosis in children. Consensus from an expert panel(2012) Cuevas, L. E.; Browning, R.; Bossuyt, P.; Casenghi, M.; Cotton, M. F.; Cruz, A. T.; Dodd, L. E.; Drobniewski, F.; Gale, M.; Graham S. M.; Grzemska, M.; Heinrich, N.; Hesseling, A. C.; Huebner, R.; Jean-Philippe, P.; Kabra, S. K.; Kampmann, B.; Lewinsohn, D.; Li, M.; Lienhardt, C.; Mandalakas A. M.; Marais, B. J.; Menzies, H. J.; Montepiedra, G.; Mwansambo, C.; Oberhelman, R.; Palumbo, P.; Russek-Cohen, E.; Shapiro, D. E.; Smith, B.; Soto-Castellares, G.; Starke, J. R.; Swaminathan, S.; Wingfield, C.; Worrell, C.Confirming the diagnosis of childhood tuberculosis is a major challenge. However, research on childhood tuberculosis as it relates to better diagnostics is often neglected because of technical difficulties, such as the slow growth in culture, the difficulty of obtaining specimens, and the diverse and relatively nonspecific clinical presentation of tuberculosis in this age group. Researchers often use individually designed criteria for enrollment, diagnostic classifications, and reference standards, thereby hindering the interpretation and comparability of their findings. The development of standardized research approaches and definitions is therefore needed to strengthen the evaluation of new diagnostics for detection and confirmation of tuberculosis in children.In this article we present consensus statements on methodological issues for conducting research of Tuberculosis diagnostics among children, with a focus on intrathoracic tuberculosis. The statements are complementary to a clinical research case definition presented in an accompanying publication and suggest a phased approach to diagnostics evaluation; entry criteria for enrollment; methods for classification of disease certainty, including the rational use of culture within the case definition; age categories and comorbidities for reporting results; and the need to use standard operating procedures. Special consideration is given to the performance of microbiological culture in children and we also recommend for alternative methodological approaches to report findings in a standardized manner to overcome these limitations are made. This consensus statement is an important step toward ensuring greater rigor and comparability of pediatric tuberculosis diagnostic research, with the aim of realizing the full potential of better tests for children. © 2012 The Author.
- ItemA framework for preventing healthcare-associated infection in neonates and children in South Africa(Health & Medical Publishing Group, 2017) Dramowski, Angela; Cotton, M. F.; Whitelaw, A.Healthcare-associated infection (HAI) is a frequent and serious complication affecting 4 - 8% of hospitalised children and neonates in high-income countries. The burden of HAI in South African (SA) paediatric and neonatal wards is substantial but underappreciated, owing to a lack of HAI surveillance and reporting. Maternal and child health and infection prevention are priority areas for healthcare quality improvement in the National Core Standards programme. Despite increasing recognition in SA, infection prevention efforts targeting hospitalised children and neonates are hampered by health system, institutional and individual patient factors. To ensure safe healthcare delivery to children, a co-ordinated HAI prevention strategy should promote development of infection prevention norms and policies, education, patient safety advocacy, healthcare infrastructure, surveillance and research. We present a framework for SA to develop and expand HAI prevention in hospitalised neonates and children.
- ItemHIV sero-conversion during late pregnancy - when to retest(AOSIS, 2013) Kalk, E.; Slogrove, Amy L.; Speert, D.; Bettinger, J.; Cotton, M. F.; Esser, M.The South African National Prevention of Mother-to-Child Transmission of HIV programme has resulted in significant reductions in vertical transmission, but new infant HIV infections continue to occur. We present two cases of HIV seroconversion during late pregnancy, demonstrating the limitations of the current programme. These could be mitigated by expanding the programme to include maternal testing at delivery and at immunisation clinic visits as we pursue the elimination of mother-tochild transmission.
- ItemLeadership and early strategic response to the SARS-CoV- 2 pandemic at a COVID-19 designated hospital in South Africa(Health & Medical Publishing Group, 2020-04-23) Parker, A.; Karamchand, S.; Schrueder, N.; Lahri, S.; Rabie, H.; Aucamp, A.; Abrahams, R.; Ciapparelli, P.; Erasmus, D. S.; Cotton, M. F.; Lalla, U.; Leisegang, Rory; Meintjes, J.; Mistry, R.; Moosa, M. R.; Mowlana, A.; Koegelenberg, C. F. N.; Prozesky, H.; Smith, W.; Van Schalkwyk, M.; Taljaard, J. J.While many countries are preparing to face the COVID-19 pandemic, the reported cases in Africa remain low. With a high burden of both communicable and non-communicable disease and a resource-constrained public healthcare system, sub-Saharan Africa is preparing for the coming crisis as best it can. We describe our early response as a designated COVID-19 provincial hospital in Cape Town, South Africa (SA).While the first cases reported were related to international travel, at the time of writing there was evidence of early community spread. The SA government announced a countrywide lockdown from midnight 26 March 2020 to midnight 30 April 2020 to stem the pandemic and save lives. However, many questions remain on how the COVID-19 threat will unfold in SA, given the significant informal sector overcrowding and poverty in our communities. There is no doubt that leadership and teamwork at all levels is critical in influencing outcomes.
- ItemNeoCLEAN : a multimodal strategy to enhance environmental cleaning in a resource-limited neonatal unit(BMC (part of Springer Nature), 2021-02-12) Dramowski, A.; Aucamp, M.; Bekker, A.; Pillay, S.; Moloto, K.; Whitelaw, A. C.; Cotton, M. F.; Coffin, S.Background: Contamination of the hospital environment contributes to neonatal bacterial colonization and infection. Cleaning of hospital surfaces and equipment is seldom audited in resource-limited settings. Methods: A quasi-experimental study was conducted to assess the impact of a multimodal cleaning intervention for surfaces and equipment in a 30-bed neonatal ward. The intervention included cleaning audits with feedback, cleaning checklists, in-room cleaning wipes and training of staff and mothers in cleaning methods. Cleaning adequacy was evaluated for 100 items (58 surfaces, 42 equipment) using quantitative bacterial surface cultures, adenosine triphosphate bioluminescence assays and fluorescent ultraviolet markers, performed at baseline (P1, October 2019), early intervention (P2, November 2019) and late intervention (P3, February 2020). Results: Environmental swabs (55/300; 18.3%) yielded growth of 78 potential neonatal pathogens with Enterococci, S. marcescens, K. pneumoniae, S. aureus and A. baumannii predominating. Highest aerobic colony counts were noted from moist surfaces such as sinks, milk kitchen surfaces, humidifiers and suction tubing. The proportion of surfaces and equipment exhibiting no bacterial growth increased between phases (P1 = 49%, P2 = 66%, P3 = 69%; p = 0.007). The proportion of surfaces and equipment meeting the ATP “cleanliness” threshold (< 200 relative light units) increased over time (P1 = 40%, P2 = 54%, P3 = 65%; p = 0.002), as did the UV marker removal rate (P1 = 23%, P2 = 71%, P3 = 74%; p < 0.001). Conclusion: Routine environmental cleaning of this neonatal ward was sub-optimal at baseline but improved significantly following a multimodal cleaning intervention. Involving mothers and nursing staff was key to achieving improved environmental and equipment cleaning in this resource-limited neonatal unit.
- ItemNitazoxanide for severe cryptosporidial diarrhea in human immunodeficiency virus infected children(2008) Abraham, D. R.; Rabie, H.; Cotton, M. F.[No abstract available]
- ItemOutput from the CIHR Canadian HIV Trials Network international postdoctoral fellowship for capacity building in HIV clinical trials(Dove Medical Press, 2018) Mbuagbaw, L.; Slogrove, Amy L.; Sas, J.; Lengwe, Kunda J.; Morfaw, F.; Mukonzo, J. K.; Cao, W.; Ngomba-Kadima, G.; Zunza, Moleen; Ongolo-Zogo, P.; Nana, P. N.; Cockcroft, A.; Andersson, N.; Sewankambo, N; Cotton, M. F.; Li, T.; Young, T.; Singer, J.; Routy, J. P.; Ross, C. J. D.; Thin, K.; Thabane, L.; Anis, A. H.ENGLISH ABSTRACT: As a response to the human immunodeficiency virus (HIV) epidemic and part of Canadian Institutes for Health Research’s mandate to support international health research capacity building, the Canadian Institutes for Health Research Canadian HIV Trial Network (CTN) developed an international postdoctoral fellowship award under the CTN’s Postdoctoral Fellowship Awards Program to support and train young HIV researchers in resource-limited settings. Since 2010, the fellowship has been awarded to eight fellows in Cameroon, China, Lesotho, South Africa, Uganda and Zambia. These fellows have conducted research on a wide variety of topics and have built a strong network of collaboration and scientific productivity, with 40 peer-reviewed publications produced by six fellows during their fellowships. They delivered two workshops at international conferences and have continued to secure funding for their research, using the fellowship as a stepping stone. The CTN has been successful in building local HIV research capacity and forming a strong network of like-minded junior low- and middle-income country researchers with high levels of research productivity. They have developed into mentors, supervisors and faculty members, who, in turn, build local capacity. The sustainability of this international fellowship award relies on the recognition of its strengths and the involvement of other stakeholders for additional resources.
- ItemPaediatric ART outcomes in a decentralised model of care in Cape Town, South Africa(AOSIS Publishing, 2014-01-05) Morsheimer, M. M.; Dramowski, Angela; Rabie, H.; Cotton, M. F.Background. Although subSaharan Africa faces the world’s largest paediatric HIV epidemic, only 1 in 4 children has access to combination antiretroviral therapy (ART). A decentralised approach to HIV care is advocated, but programmes in resource-limited settings encounter many challenges to community-initiated paediatric ART implementation. Methods. A retrospective cohort analysis of 613 children receiving ART between 2004 and 2009 was performed in seven physician-run primary healthcare (PHC) clinics in Cape Town. Baseline characteristics, serial CD4+, viral load (VL) levels and status at study closure were collected. Results. Two subgroups were identified: children who were initiated on ART in a PHC clinic (n=343) and children who were down-referred from tertiary hospitals (n=270). The numbers of children initiated on ART in PHC increased sevenfold over the study period. Down-referred children were severely ill at ART initiation, with higher VLs, lower CD4+ counts and higher rates of tuberculosis co-infection (25.3% v. 16.9%; p=0.01). Median time to virological suppression was 29 weeks in PHC-ART initiates and 44 weeks in children down-referred (p<0.0001). Children down-referred to PHC either maintained or gained virological suppression. Longitudinal cohort analysis demonstrated sustained VL suppression >80%, high rates of immune reconstitution and low mortality.Conclusions. Increasing numbers of children are initiated on ART in PHC settings and achieve comparable immunological, virological and survival outcomes, suggesting successful decentralisation of paediatric HIV care. Down-referral of children with adherence-related virological failure may assist with attainment of virological suppression and sparing use of second-line medications.
- ItemSurveillance of healthcare-associated infection in hospitalised South African children : Which method performs best?(Health & Medical Publishing Group, 2017) Dramowski, Angela; Cotton, M. F.; Whitelaw, A.Background. In 2012, the South African (SA) National Department of Health mandated surveillance of healthcare-associated infection (HAI), but made no recommendations of appropriate surveillance methods. Methods. Prospective clinical HAI surveillance (the reference method) was conducted at Tygerberg Children’s Hospital, Cape Town, from 1 May to 31 October 2015. Performance of three surveillance methods (point prevalence surveys (PPSs), laboratory surveillance and tracking of antimicrobial prescriptions) was compared with the reference method using surveillance evaluation guidelines. Factors associated with failure to detect HAI were identified by logistic regression analysis. Results. The reference method detected 417 HAIs among 1 347 paediatric hospitalisations (HAI incidence of 31/1000 patient days; 95% confidence interval (CI) 28.2 - 34.2). Surveillance methods had variable sensitivity (S) and positive predictive value (PPV): PPS S = 24.9% (95% CI 21 - 29.3), PPV = 100%; laboratory surveillance S = 48.4% (95% CI 43.7 - 53.2), PPV = 55.2% (95% CI 50.1 - 60.2); and antimicrobial prescriptions S = 66.4% (95% CI 61.8 - 70.8%), PPV = 88.5% (95% CI 84.5 - 91.6). Combined laboratory-antimicrobial surveillance achieved superior HAI detection (S = 84.7% (95% CI 80.9 - 87.8%), PPV = 97% (95% CI 94.6 - 98.4%)). Factors associated with failure to detect HAI included patient transfer (odds ratio (OR) 2.0), single HAI event (OR 2.8), age category 1 - 5 years (OR 2.1) and hospitalisation in a general ward (OR 2.3). Conclusions. Repeated PPSs, laboratory surveillance and/or antimicrobial prescription tracking are feasible HAI surveillance methods for low-resource settings. Combined laboratory-antimicrobial surveillance achieved the best sensitivity and PPV. SA paediatric healthcare facilities should individualise HAI surveillance, selecting a method suited to available resources and practice context.
- ItemSurveillance of transmitted resistance to antiretroviral drug classes among young children in the western cape province of SOUTH AFRICA(2010) Van Zyl, G. U.; Cotton, M. F.; Claassen, M.; Abrahams, C.; Preiser, WolfgangThere are limited data on transmitted antiretroviral resistance in young children who require antiretroviral therapy. We adapted the World Health Organization surveillance strategy, testing antiretroviral naive infants (<18 months) in the Western Cape Province of South Africa, and detecting only 3 non-nucleoside reverse transcriptase inhibitors (NNRTI) and no NRTI or protease inhibitor surveillance mutations in 49 patients. The estimated NRTI and protease inhibitor transmitted antiretroviral resistance prevalence is low (<5%), predicting good therapeutic response in Western Cape infants. Copyright © 2010 by Lippincott Williams & Wilkins.
- ItemTreatment of young children with HIV infection : using evidence to inform policymakers(Public Library of Science, 2012-07-24) Prendergast, A. J.; Penazzato, M.; Cotton, M. F.; Musoke, P.; Mulenga, V.; Abrams, E. J.; Gibb, D. M.No abstract available.
- ItemUnexplained HIV-1 infection in children : documenting cases and assessing for possible risk factors(Health and Medical Publishing Group (HMPG), 2004-03) Hiemstra, R.; Rabie, H.; Schaaf, H. Simon; Eley, B.; Cameron, N.; Mehtar, Shaheen; Janse van Rensburg, A.; Cotton, M. F.Background. In the year 2000 we reported possible horizontal transmission of HIV-1 infection between two siblings. An investigation of three families, each with an HIV-infected child but seronegative parents, permitted this finding. Sexual abuse and surrogate breast-feeding were though unlikely. The children had overlapping hospitalisation in a regional hospital. Since then several cases of unexplained HIV infection in children have been reported. A registry was established at Tygerberg Children's Hospital for collection of data on the extent of horizontal or unexplained transmission of HIV in children. Study design. Retrospective chart review. Results. Fourteen children were identified, 12 from the Western Cape and 1 each from the Eastern Cape and KwaZulu-Natal. Thirteen (92%) had been hospitalised previously. In the Western Cape, children had been hospitalised in 8 hospitals. Ten of 13 (77%) were admitted as neonates and 9 of 13 (69%0 had 2 or more admissions. Intravascular cannulation and intravenous drug administration occurred in all but 2 children before HIV diagnosis. Conclusion. We have confirmed HIV infection in a number of cases where the source of infection has been inadequately explained. Circumstantial evidence supports but does not prove nosocomial transmission. Further studies and identification of medical procedures conducive to the spread of HIV are urgently needed.