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1. Retinoblastoma with and without Extraocular Tumor Extension

Author

Swathi Kaliki, MD, Vijitha S. Vempuluru, MD, Ido Didi Fabian, MD, Elhassan Abdallah, MD, Shehu U. Abdullahi, MD, Rula A. Abdulqader, MD, Aminatu A. Abdulrahaman, MD, Sherif Abouelnaga, MD, Dupe S. Ademola-Popoola, FMCOph, FWACS, Adedayo Adio, FWACS, Mahmoud A. Afifi, MD, Armin R. Afshar, MD, Priyanka Aggarwal, MD, Ada E. Aghaji, FMCOph MSc, Alia Ahmad, MRCPCH UK, Marliyanti N.R. Akib, MD, Adeseye M. Akinsete, MBBS, Lamis Al Harby, MD, Saleh A. Al Mesfer, MD, Mouroge H. Al Ani, MD, Silvia Alarcón Portabella, MD, Safaa A.F. Al-Badri, MD, Ana Patricia A. Alcasabas, MD, Saad A. Al-Dahmash, MD, Amanda Alejos, MD, Ernesto Alemany-Rubio, MD, Amadou I. Alfa Bio, MD, Yvania Alfonso Carreras, MD, Christiane E. Al-Haddad, MD, Hamoud H.Y. Al-Hussaini, MD, MSc, Amany M. Ali, MD, Donjeta B. Alia, MD, Mazin F. Al-Jadiry, MD, Usama Al-Jumaly, MD, Hind M. Alkatan, MD, Charlotta All-Eriksson, MD, PhD, Ali A.R.M. Al-Mafrachi, FIBMS, Argentino A. Almeida, MD, Khalifa M. Alsawidi, MD, Athar A.S.M. Al-Shaheen, MD, Entissar H. Al-Shammary, MD, Doreen Amankwaa-Frempong, MBChB, Primawita O. Amiruddin, MD, Inggar Armytasari, MD, Nicholas J. Astbury, FRCS, FRCOphth, Hatice T. Atalay, MD, Eda Ataseven, MD, La-ongsri Atchaneeyasakul, MD, Rose Atsiaya, OCO, Rudolf Autrata, MD, PhD, Julia Balaguer, MD, PhD, Ruhengiz Balayeva, PhD, Honorio Barranco, MD, PhD, Paulina Bartoszek, MD, Katarina Bartuma, MD, PhD, Covadonga Bascaran, MD, MSc, Nikolaos E. Bechrakis, MD, Maja Beck Popovic, MD, Ainura S. Begimkulova, MD, Sarra Benmiloud, MD, Rokia C. Berete, MD, PhD, Jesse L. Berry, MD, Anirban Bhaduri, MD, Sunil Bhat, MBBS, MD, Arpita Bhattacharyya, MD, Eva M. Biewald, MD, Elaine Binkley, MD, Sharon Blum, MD, Nadia Bobrova, MD, H. Culver Boldt, MD, Maria Teresa B.C. Bonanomi, MD, PhD, Gabrielle C. Bouda, MD, Hédi Bouguila, MD, PhD, Rachel C. Brennan, MD, Bénédicte G. Brichard, MD, PhD, Jassada Buaboonnam, MD, Aléine Budiongo, MD, Matthew Burton, FRCOphth, Patricia Calderón-Sotelo, MD, Doris A. Calle Jara, MD, Jayne E. Camuglia, FRANZCO, Miriam R. Cano, MD, MSc, Michael Capra, FRCPI, Shani Caspi, MD, Nathalie Cassoux, MD, PhD, Guilherme Castela, MD, Luis Castillo, MD, Jaume Català-Mora, MD, PhD, Isabel Caviedes, MD, Arthika Chandramohan, MD, Guillermo L. Chantada, MD, PhD, Shabana Chaudhry, MD, Bhavna Chawla, MD, Wensi Chen, MD, Faraja S. Chiwanga, MSc, Tsengelmaa Chuluunbat, MD, PhD, Krzysztof Cieslik, MD, Antony Clark, FRANZCO, Ruellyn L. Cockcroft, MB ChB , M Med Paed, Codruta Comsa, MD, Maria G. Correa Llano, MD, Timothy W. Corson, PhD, Line Couitchere, MD, Kristin E. Cowan-Lyn, MD, MBBS, Monika Csóka, MD, PhD, Wantanee Dangboon, MD, Anirban Das, MD, Pranab Das, MD, Sima Das, MS, Jacquelyn M. Davanzo, BSN, BSPH, Alan Davidson, MBChB, MPhil, Sonia De Francesco, MD, Patrick De Potter, MD, PhD, Karina Q. Delgado, MD, PhD, Hakan Demirci, MD, Laurence Desjardins, MD, Rosdali Y. Diaz Coronado, MD, Helen Dimaras, PhD, Andrew J. Dodgshun, M Phil, Carla R. Donato Macedo, MD, Monica D. Dragomir, MD, PhD, Yi Du, MD, Magritha Du Bruyn, MD, Johannes P. Du Plessis, MMed (Paed), Gagan Dudeja, MBBS, MS, Katrin Eerme, MD, I Wayan Eka Sutyawan, MD, Asmaa El Kettani, MD, Amal M. Elbahi, MD, James E. Elder, MBBS, Alaa M. Elhaddad, MD, PhD, Moawia M.A. Elhassan, MD, Mahmoud M. Elzembely, MD, Connor Ericksen, MD, Vera A. Essuman, FWACS, Ted Grimbert A. Evina, MD, Ifeoma R. Ezegwui, FMCOph, FWACS, FAEH, Zehra Fadoo, MBBS, Adriana C. Fandiño, MD, Mohammad Faranoush, MD, Oluyemi Fasina, FWACS, Delia D.P.G. Fernández, MSc, Ana Fernández-Teijeiro, MD, PhD, Allen Foster, FRCOphth, Shahar Frenkel, MD, PhD, Ligia D. Fu, MD, Soad L. Fuentes-Alabi, MD, MPH, Juan L. Garcia, MSc, David García Aldana, MD, Henry N. Garcia Pacheco, MD, Jennifer A. Geel, MBChB, MMed, Fariba Ghassemi, MD, Ana V. Girón, MD, Marco A. Goenz, MD, Aaron S. Gold, OD, Hila Golberg, MD, Glen A. Gole, MD, FRANZCO, Nir Gomel, MD, Efren Gonzalez, MD, Graciela Gonzalez Perez, MD, Liudmira González-Rodríguez, MD, Malka Gorfine, PhD, Jaime Graells, MD, Pernille A. Gregersen, MD, Nathalia D.A.K. Grigorovski, MD, Koffi M. Guedenon, MD, D Sanjeeva Gunasekera, MD, Ahmet K. Gündüz, MD, Himika Gupta, MD, Sanjiv Gupta, MS, Vineeta Gupta, MD, Theodora Hadjistilianou, MD, Patrick Hamel, MD, Syed A. Hamid, FCPS, Norhafizah Hamzah, MSc, Eric D. Hansen, MD, J William Harbour, MD, M. Elizabeth Hartnett, MD, Murat Hasanreisoglu, MD, Sadiq Hassan, MD, FWACS, Shadab Hassan, FRCS, FCPS, Wojciech Hautz, MD, Huda A. Haydar, CHD, Stanislava Hederova, MD, Laila Hessissen, MD, Hoby Lalaina, MD, Suradej Hongeng, MD, Diriba F. Hordofa, MD, G. Baker Hubbard, MD, Marlies Hummlen, MD, Kristina Husakova, MD, Allawi N. Hussein Al-Janabi, MD, Affiong A. Ibanga, MB.BCh, FMCOph, Russo Ida, MD, Vesna R. Ilic, MD, Ziyavuddin Islamov, MD, Vivekaraj Jairaj, DNB, Teyyeb A. Janjua, MD, FCPS, FRCSEd, Irfan Jeeva, FRCOphth, Xunda Ji, MD, Dong Hyun Jo, MD, PhD, Michael M. Jones, MD, PhD, FRANZCO, Theophile B. Amani Kabesha, MD, PhD, Rolande L. Kabore, MD, Abubakar Kalinaki, MD, Pius Kamsang, MD, Mehmet Kantar, MD, Noa Kapelushnik, MD, Tamar Kardava, PhD, Rejin Kebudi, MD, Jonny Keomisy, MD, Tomas Kepak, MD, Petra Ketteler, MD, Zohora J. Khan, MD, Hussain A. Khaqan, MD, Vikas Khetan, FRCS, FACS, Alireza Khodabande, MD, Zaza Khotenashvili, MD, Jonathan W. Kim, MD, Jeong Hun Kim, MD, PhD, Hayyam Kiratli, MD, Tero T. Kivelä, MD, Artur Klett, MD, PhD, Irem Koç, MD, Jess Elio Kosh Komba Palet, MD, Dalia Krivaitiene, MD, PhD, Mariana Kruger, Mmed Paed, PhD, Kittisak Kulvichit, MD, Mayasari W. Kuntorini, MD, Alice Kyara, BA, Geoffrey C. Lam, FRANZCO, Scott A. Larson, MD, Slobodanka Latinović, MD, PhD, Kelly D. Laurenti, MD, Yotam Lavi, MD, PhD, Alenka Lavric Groznik, MD, Amy A. Leverant, MD, Cairui Li, MD, Kaijun Li, MD, Ben Limbu, MD, Chun-Hsiu Liu, MD, Quah Boon Long, FRCS (Ed), MMed ( Ophth), FAMS, Juan P. López, MD, Robert M. Lukamba, MD, Sandra Luna-Fineman, MD, Delfitri Lutfi, MD, Lesia Lysytsia, MD, Shiran Madgar, MD, George N. Magrath, MD, Amita Mahajan, MD, Puja Maitra, MD, Erika Maka, MD, Emil K. Makimbetov, MD, Azza M.Y. Maktabi, MD, Carlos Maldonado, MD, Ashwin Mallipatna, MD, Rebecca Manudhane, MD, Lyazat Manzhuova, MD, Nieves Martín Begue, MD, PhD, Sidra Masud, MBBS, Ibrahim O. Matende, MD, M. Med (Oph), Clarissa C.D.S. Mattosinho, MD, Marchelo Matua, BAPH, Ismail Mayet, MD, Freddy B. Mbumba, MD, MMed Paed, John D. McKenzie, MD, Azim Mehrvar, MD, Aemero A. Mengesha, MD, Vikas Menon, MD, Gary John V.D.D. Mercado, MD, Marilyn B. Mets, MD, Edoardo Midena, MD, PhD, Audra Miller, MD, Divyansh K.C. Mishra, DNB, Furahini G. Mndeme, MD, Ahmed A. Mohamedani, FRCPath, Mona T. Mohammad, MD, FRCS, Annette C. Moll, MD, PhD, Margarita M. Montero, MD, Claude Moreira, MD, PhD, Prithvi Mruthyunjaya, MD, MHS, Mchikirwa S. Msina, MMed Ophth, Gerald Msukwa, MMed Ophth, Sangeeta S. Mudaliar, DNB Pediatric, Hassan Muhammad, MD, Kangwa I. Muma, MMed Ophth, FCOphth, Francis L. Munier, MD, Timothy G. Murray, MD, MBA, Kareem O. Musa, FWACS, FMCOphth, FICO, Asma Mushtaq, MD, Anne A. Musika, MD, Hamzah Mustak, MD, Tajudeen Mustapha, MBBS, FWACS, Okwen M. Muyen, MD, Khumo H. Myezo, Msc, Gita Naidu, MMed Paed, PhD, Natasha Naidu, MBCHB, FCS Ophthalmol, Akshay Gopinathan Nair, MD, Sundaram Natarajan, FRCS, Larisa Naumenko, MD, PhD, Paule Aïda Ndoye Roth, MD PhD, Yetty M. Nency, MD, Vladimir Neroev, MD, PhD, Yvonne Ng, MBChB ( Auckland) , FRANZCO, Marina Nikitovic, MD, PhD, Elizabeth D. Nkanga, FMCOph, Henry E. Nkumbe, MD, Marcel N. Numbi, MD, Kalle Nummi, MD, Murtuza Nuruddin, FRCS, Mutale Nyaywa, MD, MMed Ophth, FCOphth, Chinsisi Nyirenda, MD, Ghislaine Obono-Obiang, MD, Scott C.N. Oliver, MD, Joaquin Ooporto, MD, Miriam Ortega-Hernández, MD, Alexander Oscar, MD, Diego Ossandon, MD, Halimah Pagarra, MD, PhD, Vivian Paintsil, FWACP, Luisa Paiva, MD, Mahesh Shanmugam Palanivelu, FRCSED, Ruzanna Papyan, MD, Raffaele Parrozzani, MD, PhD, Claudia R. Pascual Morales, MD, Katherine E. Paton, MD, FRCSC, Jacob Pe'er, MD, Jesús Peralta Calvo, MD, Sanja Perić, MD, PhD, Chau T.M. Pham, MD, Remezo Philbert, MD, David A. Plager, MD, Pavel Pochop, MD, PhD, Rodrigo A. Polania, MD, Vladimir Polyakov, MD, Jimena Ponce, MD, Ali O. Qadir, MD, Seema Qayyum, FCPS, Jiang Qian, MD, Ardizal Rahman, MD, Purnima Rajkarnikar, MD, Rajesh Ramanjulu, MD, Aparna Ramasubramanian, MD, Marco A. Ramirez-Ortiz, MD, MPH, Jasmeen K. Randhawa, BA, Léa Raobela, MD, Riffat Rashid, MS, M. Ashwin Reddy, FRCOphth, Lorna A. Renner, FRCPCH (UK), David Reynders, MD, Dahiru Ribadu, FMCOph, Petra Ritter-Sovinz, MD, Anna Rogowska, MD, Duangnate Rojanaporn, MD, Livia Romero, MD, Soma R. Roy, DCO, Raya H. Saab, MD, Svetlana Saakyan, MD, PhD, Ahmed H. Sabhan, MD, Mandeep S. Sagoo, FRCS (Ed), Azza M.A. Said, MD, Rohit Saiju, MD, Beatriz Salas, MD, Sonsoles San Román Pacheco, MD, Gissela L. Sánchez, MD, Alma Janeth Sanchez Orozco, MD, Phayvanh Sayalith, MD, Trish A. Scanlan, MRCPI, MSc, Christoph Schwab, MD, Ahad Sedaghat, MD, Rachna Seth, DNB MNAMS, Mariana Sgroi, MD, Ankoor S. Shah, MD, PhD, Shawkat A. Shakoor, MS, Manoj K. Sharma, MD, Sadik T. Sherief, MD, Carol L. Shields, MD, David Sia, MB ChB, FRANZCO, Sorath Noorani Siddiqui, MD, Sidi Sidi cheikh, MD, PhD, Sónia Silva, MD, Arun D. Singh, MD, Usha Singh, MS, Penny Singha, MD, Rita S. Sitorus, MD, PhD, Alison H. Skalet, MD, PhD, Hendrian D. Soebagjo, MD, PhD, Tetyana Sorochynska, MD, PhD, Grace Ssali, MD, Andrew W. Stacey, MD, Sandra E. Staffieri, PhD, Erin D. Stahl, MD, David M. Steinberg, PhD, David K. Stones, MBChB, FCPaed, Caron Strahlendorf, MD, Maria Estela Coleoni Suarez, MD, Sadia Sultana, FCPS, Xiantao Sun, MD, Rosanne Superstein, MD, Eddy Supriyadi, MD, PhD, Supawan Surukrattanaskul, MD, Shigenobu Suzuki, MD, PhD, Karel Svojgr, MD, PhD, Fatoumata Sylla, MD, Gevorg Tamamyan, MD, PhD, Deborah Tan, MBBS, Alketa Tandili, MD, PhD, Jing Tang, MD, Fanny F. Tarrillo Leiva, MD, Maryam Tashvighi, MD, Bekim Tateshi, MD, PhD, Kok Hoi Teh, MD, Edi S. Tehuteru, MD, Luiz F. Teixeira, MD, Manca Tekavcic Pompe, MD, PhD, Abdullah Dahan M. Thawaba, MD, Tuyisabe Theophile, MSc, Helen Toledano, MBChB, Doan L. Trang, MD, Fousseyni Traoré, MD, Devjyoti Tripathy, MD, Samuray Tuncer, MD, Harba Tyau-Tyau, MD, Ali B. Umar, MD, FMCPath, Emel Unal, MD, Ogul E. Uner, BA, Steen F. Urbak, MD, PhD, Tatiana L. Ushakova, MD, Rustam H. Usmanov, MD, Sandra Valeina, MD, Paola Valente, MD, Milo van Hoefen Wijsard, MD, Jacqueline Karina Vasquez Anchaya, MD, Leon O. Vaughan, FRCS (Ed), Nevyana V. Veleva-Krasteva, MD, PhD, Nishant Verma, MD, Andi A. Victor, MD, PhD, Maris Viksnins, MD, Edwin G. Villacís Chafla, MD, Victor M. Villegas, MD, Victoria Vishnevskia-Dai, MD, Keith Waddell, DM, FRCP, FRCS, FRCOphth, Amina H. Wali, MD, FMCOph Nigeria, Yi-Zhuo Wang, MD, Nutsuchar Wangtiraumnuay, MD, FICO, Julie A. Wetter, MMed Rad Onc, FCRad Onc, Widiarti P. Riono, MD, Matthew W. Wilson, MD, Amelia D.C. Wime, MD, Atchareeya Wiwatwongwana, MD, Damrong Wiwatwongwana, MD, Charlotte Wolley Dod, MD, Emily S. Wong, FCOphth HK, FHKAM, Phanthipha Wongwai, MD, PhD, Si-qi Wu, MSc, Daoman Xiang, MD, PhD, Yishuang Xiao, MSc, Bing Xu, MD, Kang Xue, MD, Antonio Yaghy, MD, Jason C. Yam, FRCSEd, Huasheng Yang, MD, Jenny M. Yanga, MD, Muhammad A. Yaqub, MD, FCPS, FRCSEd, Vera A. Yarovaya, MD, Andrey A. Yarovoy, MD, PhD, Huijing Ye, MD, Roberto I. Yee, MD, Yacoub A. Yousef, MD, Putu Yuliawati, MD, Arturo M. López, MD, Ekhtelbenina Zein, MD, Yi Zhang, MD, PhD, Katsiaryna Zhilyaeva, MD, Nida Zia, MBBS, MCPS, Othman A.O. Ziko, MD, PhD, Marcia Zondervan, MBA, Sabrina Schlüter, MD, and Richard Bowman, FRCOphth

Subjects
External beam radiotherapy, Extraocular extension, Multimodal treatment, Retinoblastoma, Tumor, Ophthalmology, RE1-994
Abstract

Purpose: To study the treatment and outcomes of children with retinoblastoma (RB) with extraocular tumor extension (RB-EOE) and compare them with RB without extraocular tumor extension (RB-w/o-EOE). Design: Multicenter intercontinental collaborative prospective study from 2017 to 2020. RB-EOE cases included those with overt orbital tumor extension in treatment-naive patients. Cases with microscopic orbital extension detected postenucleation were excluded from the study. Participants: A total of 319 children with RB-EOE and 3116 children with RB-w/o-EOE. Intervention: Chemotherapy, enucleation, exenteration, radiotherapy. Main Outcome Measures: Systemic metastasis and death. Results: Of the 3435 RB patients included in this study, 309 (9%) were from low-income countries (LIC), 1448 (42%) from lower-middle income, 1012 (29%) from upper-middle income, and 666 (19%) patients from high-income countries. There was an inverse relationship between the percentage of RB-EOE and national income level, with 96 (31%) patients from LIC, 197 (6%) lower-middle income, 20 (2%) upper-middle income, and 6 (1%) patients from high-income countries (P = 0.0001). The outcomes were statistically significant for RB-EOE compared with RB-w/o-EOE: systemic metastasis (32% vs. 4% respectively; P = 0.0001) and metastasis-related death (63% vs. 6% respectively; P = 0.0001). Multimodal treatment was the most common form of treatment (n = 177; 54%) for RB-EOE, with most cases undergoing a combination of intravenous chemotherapy and enucleation (n = 97; 30%). Adjuvant external beam radiotherapy (EBRT) after surgery (enucleation/orbital exenteration) was given in only 68 (21%) cases. Kaplan–Meier analysis for systemic metastasis and metastasis-related death in RB-EOE was 28% and 57% at 1 year, 29% and 60% at 2 years, and 29% and 61% at 3 years, respectively. Cox regression analysis revealed that the risk of death from RB-EOE was greater in patients aged >4 years than

Published
2025
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2. Paediatric cerebral palsy in South Africa: Prevention and care gaps at hospital level

Author

Thembi J. Katangwe, Mariana Kruger, Ronald van Toorn, Jeanetta van Zyl, Sandile Ndlovu, Regan Solomons, and Kirsten A. Donald

Subjects
cerebral palsy, perinatal asphyxia, prematurity, care gaps, risk factors., Vocational rehabilitation. Employment of people with disabilities, HD7255-7256, Communities. Classes. Races, HT51-1595
Abstract

Background: Population-based data show high proportions of severe cases of cerebral palsy (CP) in resource-poor regions such as sub-Saharan Africa, where most children have potentially preventable risk factors (factors that may increase the likelihood of CP occurrence but can be mitigated through medical interventions). Objectives: This study aimed to describe the demographic and clinical profile of children living with CP accessing services at Tygerberg Hospital over a period of 10 years (2010–2020), identify the potential gaps in care (proportion of individuals in a country requiring but not receiving suboptimal or inadequate care), and comparison with a similar study at the same centre two decades ago. Method: This 10-year retrospective study investigated causes and morbidities in children with CP, attending a central hospital in the Western Cape, South Africa. Results: A total of 613 children with CP were identified. Perinatal causes were predominant, especially in 57.7% (n = 354) of the cohort: perinatal asphyxia (41.1%) and preterm birth (16.6%). Postnatal causes constituted 15.2% (n = 93), which included tuberculous meningitis (3.6%) and bacterial meningitis (3.6%). The most common complications were intellectual impairment (61.8%; n = 379); epilepsy (30.8%; n = 189) and visual impairment (54.7%; n = 234). A third of the cohort had severe CP, classified as Gross Motor Function Classification System IV and V (38%). Conclusion: Most of the previously documented main drivers of CP are still present and the implementation of healthcare prevention strategies remains inadequate. Contribution: This study provides longitudinal evidence to confirm that CP in a South African setting is associated with a high burden of potentially preventable causes.

Published
2024
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3. Outcome of Retinoblastoma After Implementation of National Retinoblastoma Treatment Guidelines in South Africa

Author

Mariana Kruger, Sabine L. van Elsland, Alan Davidson, David Stones, Jan du Plessis, Gita Naidu, Jennifer Geel, Janet Poole, Judy Schoeman, Clare Stannard, Hamzah Mustak, Anel van Zyl, Julie Wetter, and Karin Lecuona

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

PURPOSERetinoblastoma, a curable childhood cancer, has been identified as a tracer cancer in the WHO Global Initiative for Childhood Cancer. To document the outcomes of children with retinoblastoma in South Africa, treated as per the first prospective standard national treatment guidelines for childhood cancer in South Africa.PATIENTS AND METHODSAll children diagnosed with retinoblastoma between 2012 and 2016 in five South African pediatric oncology units were treated with a standard treatment on the basis of the International Society of Pediatric Oncology-Pediatric Oncology in Developing Countries guidelines for high-income settings. Treatment included focal therapy with/without chemotherapy, or enucleation with/without chemotherapy, and orbital radiotherapy, depending on enucleated eye histology. The end point was survival at 24 months, using Kaplan-Meier curves with log-rank (Mantel-Cox) and chi-square (χ2) tests with respective P values reported.RESULTSA total of 178 children were included in the study; 68% presented with unilateral disease. The median age was 27 months (range 0-118 months) with a male:female ratio of 1:0.75. The overall survival was 79% at 24 months with significant association with stage at diagnosis (P < .001) and older age over 2 years as opposed to younger than 2 years (P < .001). Causes of death were disease progression/relapses in 90% (34 of 38) and unknown in 2% (1 of 38), whereas treatment abandonment was 1.7% (3 of 178).CONCLUSIONEfficacy with national treatment guidelines was confirmed, and feasibility of implementing standard national childhood cancer treatment guidelines was documented, involving multidisciplinary teams in South Africa. Outcome was significantly associated with stage at diagnosis and age.

Published
2024
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5. High prevalence of long-term and late effects in a South African childhood cancer survivor cohort

Author

Anel Van Zyl, Sandile Ndlovu, Carl Lombard, Ronelle Uys, Leilah Schoonraad, Paul C. Rogers, and Mariana Kruger

Subjects
Childhood cancer survivors, Late effects, Severity, South Africa, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Purpose: We documented the prevalence of late effects in a South African childhood cancer survivor (CCS) cohort. Patients and methods: CCSs at Tygerberg Hospital, Cape Town, were evaluated for clinical abnormalities, whereafter late effects were identified, graded according to the Common Terminology Criteria for Adverse Events (CTCAE), and classified as significant or insignificant. Results: The cohort comprised 160 CCSs (median age 13 years (interquartile range 9.9 – 17.8 years); follow-up period eight years (range 5–37.2 years)). There were 89 (55.6%) hematological and 71 (44.4%) solid malignancies. Most CCSs (146/160; 91.3%) had at least one late effect; the majority were of Grade 1 CTCAE severity (73.7%). Common late effects were gastrointestinal (13.3%), metabolic (12.9%), hematological (9.2%), musculoskeletal (9.1%), and neurological (8.8%) disorders. Significant risk factors for late effects were cancer diagnosis (p = 0.005), chemotherapy (moderate intensity [incidence rate ratio (IRR) 1.84; p = 0.036]; high intensity [IRR 2.8; p = 0.001]), and radiotherapy (IRR 1.44) (p = < 0.001). Late effects severity was significantly associated with radiotherapy (IRR 1.54; p = 0.004). Solid tumor survivors were more likely to develop Grade 2 (IRR 2.4; p = < 0.001) and 3 late effects (IRR 2.8; p = 0.011). Conclusion: This is the first prospective study of a CCS cohort in South Africa. Most CCSs developed mild or moderate long-term and late effects, significantly associated with cancer diagnosis, chemotherapy intensity, and radiotherapy. It is crucial to develop long-term surveillance plans for CCSs in South Africa to ensure early detection of late effects.

Published
2023
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6. Reporting Incidences of Neuroblastoma in Various Resource Settings

Author

Jaques van Heerden, Natasha Abraham, Judy Schoeman, David Reynders, Elvira Singh, and Mariana Kruger

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

PURPOSEThe incidences of neuroblastoma (NB) differ significantly between various resource settings because of varying quality of cancer registries and underdiagnoses. This study aimed to evaluate current regional variations as reported by international cancer registries and the theoretical and reported differences in international NB incidences and to evaluate South Africa (SA) as a case for variable reporting.METHODSA comprehensive literature review on registries reporting on NB was performed to construct incidence tables. The SEER Program incidence of 10.5/million children was used to calculate the expected number of NB cases for each country. Registry data of NB cases between 2000 and 2016 were requested from The South African National Cancer registry (SA-NCR) and the South African Children's Tumour Registry (SACTR) for comparison and to perform a probabilistic linkage study.RESULTSInternationally, incidences varied between –97.1% and +80% compared with the SEER program. SA under-reported NB cases by an estimated 74.2%. Between 2000 and 2016, the SA-NCR reported between 23 and 51 cases/year, whereas the SACTR reported between 18 and 57 cases/year for the same period. The incidence reported by the SA-NCR varied between 1.5 and 2.8/million children under 15-year per year, whereas the SACTR reported 1.74-2.6 cases/million children. Both registries reported incidences less than high-income country. A probabilistic record linkage of the two registries resulted in a combined incidence of 2.9 cases/million children.CONCLUSIONAs with most low- and middle-income countries, SA has either a lower incidence or underdiagnoses of NB cases. The reasons for under-reporting are not clear, but can be due to undiagnosed NB cases with spontaneous regression, missed possible cases because of lack of autopsies, and diagnosed cases not recorded in registries.

Published
2021
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7. The Molteno Adapted Scale: A child development screening tool for healthcare settings

Author

Priscilla E. Springer, Barbara Laughton, Tonya M. Esterhuizen, Amy L. Slogrove, and Mariana Kruger

Subjects
molteno adapted scale, developmental delay, developmental screening, paediatrics, children, infants, bayley scales of infant and toddler development-3rd edition, child development, Psychology, BF1-990
Abstract

The Molteno Adapted Scale (MAS) is a developmental screening tool for children up to five years of age, used by medical practitioners in the Western Cape, South Africa. It generates subquotients for language, personal and social, fine and gross motor domains. The general quotient is the average of all four subquotients, with a score 85 indicating risk for global developmental delay. The authors aimed to determine the concurrent validity of the MAS, using the Bayley Scales of Infant and Toddler Development-3rd edition (BSID) as a comprehensive assessment reference measure. A total of 103 (55 girls) participants were enrolled from a longitudinal cohort study, of which 90 (49 girls) were assessed on both the MAS and BSID at 11–14 months, 53 (27 girls) at 30–42 months of age and 44 (21 girls) at both timepoints. The low number of developmentally delayed children precluded estimation of diagnostic accuracy of the MAS. Therefore, the authors determined Pearson correlation coefficients (r) for the MAS and BSID across similar domains at 11–14 months (n = 90) and 30–42 months (n = 53) and used the Bland–Altman analysis to detect bias between the MAS and BSID domain scores. Correlation was moderate to high between MAS and BSID domains, except for fine motor in 1-year-olds (r = 0.23), but Bland–Altman analysis found discordance especially between the MAS and BSID language and motor scores at the upper and lower performance ranges. Future studies should aim to standardise the operational procedures of the MAS, validate it across a wider age-range, and include children with varying degrees of delay.

Published
2022
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8. The outcome and cost of a capacity‐building training programme on the early recognition and referral of childhood cancer for healthcare workers in North‐West Cameroon

Author

Glenn Mbah Afungchwi, Peter Bernard Hesseling, Francine Kouya, Sam A. Enow, and Mariana Kruger

Subjects
Cameroon, capacity building, childhood cancer, early diagnosis, my child matters, Nursing, RT1-120
Abstract

Abstract Aim Early cancer diagnosis is necessary to improve survival rates. The aim of this study was to assess the outcome and cost of the childhood cancer training programme amongst healthcare workers. Design This was a prospective pre–post study design, using questionnaires for pre‐ and post‐training testing. The warning signs of childhood cancer were used as the main teaching content to improve recognition and early diagnosis. Methods Pre‐training and post‐training knowledge, as well as attitude questionnaires, was administered at the beginning and at the end of each training workshop. Paired samples t test and chi‐square were used to compare the change in knowledge and differences between groups. Results The overall percentage knowledge score increased from 51%–85% (p

Published
2020
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9. The scope of childhood cancer in South Africa: A response to ‘Childhood cancers in a section of the South African private health sector – Analysis of medicines claims data’

Author

Jaques van Heerden and Mariana Kruger

Subjects
childhood cancer, medical policy, medical aid claims, incidence, oncology, Public aspects of medicine, RA1-1270
Abstract

Childhood cancer is an under resourced medical field that is emerging as a great healthcare concern in low- and middle-income countries such as South Africa. Therefore, reporting data in this field that may inform policymakers should be representative of the subject matter. This article aims to discuss why medicines claims as an indicator for incidence, as per an article published in 2020, is not representative of childhood malignancies in the South African setting. Literature to support the commentary were sourced using Pubmed, Google scholar, and data presented by members of the South African Children’s Cancer Study Group (SACCSG). Private medical aid coverage in South Africa between 2002 and 2018 varied between 15.5% and 18.2%. Of these, 9.5% were children under 18 years and 3.5% were under the age of six. Only 13.5% of children were treated in private paediatric oncology units during 2015. The limitations in the study were the variable medical aid coverage, the disproportionate age representation, and lack of reliable indicators for measurement and calculation of incidence. Utilising one medicines claims database to evaluate the incidence of childhood cancer in South Africa is not representative and cannot inform policy. Contribution: This article highlights the importance of accurate registration of childhood cancer diagnoses, especially when data and conclusions based on these results inform policy. The study highlights the limitations of extrapolating general conclusions based on data representing only a small sector of the childhood cancer landscape in South Africa.

Published
2021
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10. Addressing challenges to rolling out COVID-19 vaccines in African countries

Author

Jean B Nachega, Nadia A Sam-Agudu, Refiloe Masekela, Marieke M van der Zalm, Sabin Nsanzimana, Jeanine Condo, Francine Ntoumi, Helena Rabie, Mariana Kruger, Charles S Wiysonge, John D Ditekemena, Raphael B Chirimwami, Mukanire Ntakwinja, Denis M Mukwege, Emilia Noormahomed, Masudah Paleker, Hassan Mahomed, Jean-Jacques Muyembe Tamfum, Alimuddin Zumla, and Fatima Suleman

Subjects
Public aspects of medicine, RA1-1270
Published
2021
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11. Inequity in paediatric oncology in South Africa – The neuroblastoma case study

Author

Jaques van Heerden, Tonya Esterhuizen, and Mariana Kruger

Subjects
paediatric oncology, equality, south africa, neuroblastoma, patient advocacy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background: The South African Constitution affords everyone the right to access healthcare services, but in children the care must ensure survival. Aim: This study aimed to determine whether there was access to equitable paediatric oncology services for the management of neuroblastoma in South Africa. Setting: Paediatric oncology services in South Africa between 2000 to 2014. Methods: A literature review was carried out, focussing on access to healthcare in South Africa for children with neuroblastoma. Services were classified in accordance with the International Society of Paediatric Oncology resource settings for neuroblastoma diagnosis. Supplementary data from a retrospective study of the management of neuroblastoma in South Africa were evaluated. Results: The neuroblastoma care services in South Africa were not uniformly resourced and accessible across the provinces. Two provinces (2/9 provinces) had excellent healthcare services that included access to transplant facilities, whilst three (3/9 provinces) had no services. Traveling distances to healthcare services pose major challenges, whilst number of medical staff providing oncology care were unequally distributed. The Constitution did not define basic healthcare for children, nor did the National Cancer Control plan acknowledge childhood cancer as a defined entity without provision until 2022. Conclusion: Children diagnosed with neuroblastoma do not have equitable access to healthcare as stated in the South African Constitution. The case of neuroblastoma highlights the inequitable access to childhood care as a whole in South Africa. As the health of children is a national priority, it is therefore necessary to sensitise policymakers to the needs of children with cancer.

Published
2021
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12. Three-dimensional visualizations from a dataset of immunohistochemical stained serial sections of human brain tissue containing tuberculosis related granulomas

Author

Stefan-Dan Zaharie, Daniel J. Franken, Martijn van der Kuip, Sabine van Elsland, Bernadette S. de Bakker, Jaco Hagoort, Sanna L. Roest, Carmen S. van Dam, Carlie Timmers, Regan Solomons, Ronald van Toorn, Mariana Kruger, and A. Marceline van Furth

Subjects
Central nervous system tuberculosis, Tuberculous meningitis, Granuloma, Rich-focus, 3D-reconstruction, Computer applications to medicine. Medical informatics, R858-859.7, Science (General), Q1-390
Abstract

This data article presents datasets associated with the research article entitled “The immunological architecture of granulomatous inflammation in central nervous system tuberculosis’’ (Zaharie et al., 2020). The morphology of tuberculosis related granulomas within the central nervous system of human patients was visualized in six different three-dimensional (3D) models. Post-mortem, formalin fixed and paraffin embedded specimens from deceased tuberculous meningitis patients were immunohistochemically stained and 800 serial histologically stained sections were acquired. Images from all sections were obtained with an Olympus BX43 light microscope and structures were identified, labeled and made three-dimensional. The interactive 3D-models allows the user to directly visualize the morphology of the granulomas and to understand the localization of the granulomas. The 3D-models can be used for multiple purposes and provide both an educational source as a gold standard for further animal studies, human research and the development of in silico models on the topic of central nervous system tuberculosis.

Published
2020
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13. An 8-year retrospective study of adult and paediatric Burkitt’s lymphoma at Tygerberg Hospital, South Africa

Author

Ernest Musekwa, Zivanai C. Chapanduka, Fatima Bassa, and Mariana Kruger

Subjects
epidemiology, burkitt lymphoma, human immunodeficiency virus, tuberculosis, children, adults, treatment, outcome, south africa, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background: Burkitt lymphoma(BL) is a high grade non-Hodgkin lymphoma, which may be underdiagnosed in South Africa, due to a high burden of infectious diseases such as HIV and TB which may present with similar clinical features. Aim: To describe demographics and clinico-pathological characteristics of patients diagnosed with BL. Setting: Tygerberg Hospital (TBH), South Africa between 2007-2014. Methods: We performed a retrospective descriptive and survival analysis of patients diagnosed with BL at TBH between 01 January 2007 and 31 December 2014 with at least 24-month follow-up. Data was collected from the Tygerberg Lymphoma Study Group database and the South African Children Cancer Study Group Tumour Registry. Results: There were 73 patients with BL, of whom 68 were admitted to TBH and whose data was further analysed. The majority of patients were adults (74%). There was a female predominance in adults and a male predominance in children (p = 0.002). Various regimens were used in adults while a single treatment protocol was used in children. The proportion of patients with HIV and advanced BL was higher in adults than in children. The 2-year overall survival of the treatment group was 45%. The outcome of patients with BL in adults (34%) was poorer than that of children (69%) (p = 0.022). HIV negative patients had a non-significant survival advantage (57%) over HIV positive patients with 41% 2-year overall survival (p = 0.2876). Conclusion: This study demonstrates a better cure rate in children treated for BL compared to adults, with HIV-infection being a risk factor for poor outcome.

Published
2020
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14. Neurodevelopment at 11 months after starting antiretroviral therapy within 3 weeks of life

Author

Barbara Laughton, Shalena Naidoo, Els F.M.T. Dobbels, Michael J. Boivin, Anita Janse van Rensburg, Richard H. Glashoff, Gert U. van Zyl, Mariana Kruger, and Mark F. Cotton

Subjects
hiv, infants, antiretroviral therapy, neurodevelopen, paediatricst, Public aspects of medicine, RA1-1270, Infectious and parasitic diseases, RC109-216
Abstract

Background: Antiretroviral therapy (ART) started between 7 and 12 weeks of age improves neurodevelopmental outcomes in HIV-infected (HIV+) infants, but the impact of even earlier initiation is not yet described. Objective: We assessed the early neurodevelopment of HIV+ infants who started ART within 21 days of life. Methods: Participants were enrolled from the public sector birth HIV-diagnosis program. Inclusion criteria included: birth weight 2000g, infant commencing ART 6 weeks and no infant Cytomegalovirus disease. ART included Zidovudine/Lamivudine/Nevirapine for the first 2 weeks, the latter then replaced by Lopinavir/Ritonavir. Once body weight 3kg and gestational age 44 weeks, Abacavir replaced Zidovudine. The Griffiths Mental Development Scales (GMDS) were administered at 10-12 months. Results: Of 29 infants assessed, 23 (79%) were girls. Mean birth weight was 3002 ± 501g. Twenty-four mothers (83%) received ART during pregnancy. Seven (24%) infants were diagnosed HIV+ within 48 hours of birth. Median [IQR] viral load (VL) at diagnosis was 3904 [259;16922] copies/ml, age starting ART was 6.0 [3;10] days and age at VL suppression was 19.1 [15; 36] weeks. At the GMDS assessment nine (31%) participants had detectable VL and 26 (90%) had WHO clinical stage I disease. GMDS was performed at a mean age of 11.5±0.8 months. Mean quotients were within the average range: Global Griffiths score was 103.6±10.9 and mean quotients on the subscales ranged from lowest 95.9±13.4 for Locomotor to highest 112.8±11.3 for Hearing-and-language. Conclusion: Preliminary findings in this small group suggest that early neurodevelopmental scores are within the normal range in infants with perinatal HIV-infection who started ART at a median of 6 days.

Published
2019
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15. Incidence of childhood cancer in Namibia-the need for registries in Africa

Author

Daniela Cristina Stefan, Bjorn Baadjes, and Mariana Kruger

Subjects
childhood cancer, registry, namibia, incidence, Medicine
Abstract

INTRODUCTION: Childhood cancer is rare and comprises only 1% of all cancers. The current incidence of childhood cancer in Namibia, as in many other African countries, is not known. The aim of this research was to assess the paediatric cancer incidence between 2003-2010 at Windhoek Central Hospital, the only pediatric oncology-referring centre in Namibia and to compare with the previous calculated incidence in the country 20 years ago. METHODS: A retrospective, descriptive review of the paediatric oncology cases presenting to Windhoek Central Hospital between 2003 and 2010 was undertaken, and data regarding age, sex, cancer type, area of residence were extrapolated. In this study due to the appearance of the HIV epidemic, an HIV incidence was also calculated. RESULTS: The incidence rate of all paediatric recorded cancers was 29.4 per million. Leukaemias (22.5%) and retinoblastomas (16.2%) were the most common tumours, with renal tumours, soft tissue sarcomas and lymphomas following in frequency. HIV incidence of children with malignancy was 6.8%. CONCLUSION: The incidence rates of cancers in this study are remarkably lower compared to a similar study done in the country 20 years ago. Many cancers are still not diagnosed or reported, and others are not treated in the country. The institution of a 'twinning programme' between the paediatric haematological/oncological departments in Windhoek and Tygerberg Hospital in Cape Town, South Africa, will contribute to improvement of childhood cancer cases. This twinning programme includes the formation of a cancer registry.

Published
2014
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17. Prevalence of vitamin and iron deficiencies at cancer diagnosis at two pediatric oncology units in South Africa

Author

Judy Schoeman, Ilde-Marié Kellerman, Paul C Rogers, Elena J Ladas, Carl J Lombard, Ronelle Uys, and Mariana Kruger

Subjects
Oncology, Pediatrics, Perinatology and Child Health, Hematology
Abstract

This study investigates the prevalence of vitamin and iron deficiencies at cancer diagnosis. Newly diagnosed children between October 2018 and December 2020 at two South African pediatric oncology units (POUs) were assessed for nutritional and micronutrient status (Vit A, Vit B12, Vit D, folate, and iron). A structured interview with caregivers provided information regarding hunger and poverty risks. There were 261 patients enrolled with a median age of 5.5 years and a male-to-female ratio of 1:0.8. Nearly half had iron deficiency (47.6%), while a third had either Vit A (30.6%), Vit D (32.6%), or folate (29.7%) deficiencies. Significant associations existed between moderate acute malnutrition (MAM) and low levels of Vit A (48.4%; p = .005), Vit B12 (29.6%; p < .001), and folate (47.3%; p = .003), while Vit D deficiency was associated with wasting (63.6%) (p < .001). Males had significantly lower Vit D levels (respectively, 40.9%; p = .004). Folate deficiency was significantly associated with patients born at full term (33.5%; p = .017), age older than five years (39.8%; p = .002), residing in provinces Mpumalanga (40.9%) and Gauteng (31.5%) (P = .032); as well as having food insecurity (46.3%; p < .001), or hematological malignancies (41.3%; p = .004). This study documents the high prevalence of Vit A, Vit D, Vit B12, folate, and iron deficiency in South African pediatric cancer patients, demonstrating the need to include micronutrient assessment at diagnosis to ensure optimal nutritional support for macro-and micronutrients.

Published
2023
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18. Extracranial germ cell tumours: Mature and immature (1990–2015). First report by the South African Association of Paediatric Haematology Oncology (SAAPHO).

Author

Hendricks, Marc, Cois, Annibale, Geel, Jennifer, van Heerden, Jaques, Naidu, Gita, Plessis, Jan du, van Zyl, Anel, Bassingthwaighte, Mairi, Omar, Fareed, Büchner, Ané, Rowe, Biance, Thomas, Karla, Uys, Ronelle, Mahlachana, Ngoakoana, Davidson, Alan, Frazier L., A. Lindsay, Donald, Kirsten A., and M., Mariana Kruger

Published
2024
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19. Sodium thiosulfate as cisplatin otoprotectant in children: The challenge of when to use it

Author

Penelope Brock, Annelot Meijer, Per Kogner, Marc Ansari, Michael Capra, James Geller, Marry van den Heuvel‐Eibrink, Kristin Knight, Mariana Kruger, Susan Lindemulder, Rudolf Maibach, Allison O'Neill, Vassilios Papadakis, Kaukab Rajput, Archie Bleyer, Eric Bouffet, and Michael Sullivan

Subjects
Oncology, Pediatrics, Perinatology and Child Health, Hematology
Published
2023
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20. The Incidence of Retinoblastoma in South Africa: Findings from the South African National Cancer Registry (2004–2018)

Author

Elvira Singh, Daniel Shepherd, Mariana Kruger, and Kelsey Stuart

Subjects
South Africa, Ophthalmology, Epidemiology, Incidence, Retinal Neoplasms, Retinoblastoma, Humans, Registries, Child
Abstract

To determine the frequency and incidence rate of retinoblastoma in children in South Africa from 2004 to 2018.Incident cases of histologically diagnosed retinoblastoma were identified from the South African National Cancer Registry. Crude incidence rates were calculated using national population data on children15 years and live births. Incidence rates were stratified and compared by age, sex and population group. Direct age-standardised incidence rates and comparative incidence ratios were calculated.The overall age-standardised incidence rate for children15 years was 3.3 per million or 1 per 21 641 live births. Age-specific rates for children aged 0-4, 5-9 and 10-14 years were 7.7, 0.8 and 0.2 per million, respectively. There was no difference in incidence rates by sex. White children had a significantly higher incidence rate compared to other population groups, but this finding may be due to systemic biases introduced by access to healthcare in South Africa or study methodology.This is the largest study to provide population-based, histologically confirmed national estimates of retinoblastoma incidence from an African nation to date and affirms the need for high-quality cancer registries across the African continent.

Published
2021
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21. Preface

Author

Chris Jones, Mariana Kruger, Juri van den Heever, and Anton van Niekerk

Published
2022
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23. Psychological distress of adolescent and young adult childhood cancer survivors in a South African cohort

Author

Anel Van Zyl, Mariana Kruger, Sandile Ndlovu, Sue‐Ann Meehan, and Paul C. Rogers

Subjects
Oncology, Pediatrics, Perinatology and Child Health, Hematology
Abstract

We investigated psychological distress in a South African childhood cancer survivor (CCS) cohort.Adult CCSs treated at Tygerberg Hospital, Cape Town, completed the Brief Symptom Inventory-18. Internal consistency was acceptable: Cronbach's alpha values were 0.91 (Global Severity Index (GSI)), 0.85 (depression), 0.83 (somatization), and 0.75 (anxiety). We compared results utilizing different case rules (GSI T scores of ≥50, ≥57, and ≥63) for the identification of psychological distress.Forty CCSs (median age 24 years; median follow-up period 16 years) participated. Most (58%; 23 out of 40) completed school or tertiary education, were unmarried (90%; 36 out of 40), and unemployed (59.5%; 22 out of 37). The diagnoses included hematological malignancies (65%; 26 out of 40) and solid tumors (35%; 14 out of 40). The GSI T scores of ≥63, ≥57, and ≥50 identified 10% (four out of 40), 32.5% (13 out of 40), and 45% (18 out of 40) of survivors with psychological distress, respectively. Radiotherapy (odds ratio (OR) 4.6; p = .035), presence of ≥six late effects (OR 7.5; p = .026), and severe late effects (OR 6.6; p = .024) were significant risk factors (GSI T score ≥57). Follow-up period of 11-20 years (OR 7.3; p = .034) was significant for a GSI T score ≥50.This South African CCS cohort had higher levels of psychological distress utilizing the GSI T score ≥50 and ≥57 case rules than reported in the literature. Most were unmarried or unemployed. Significant contributing factors were radiotherapy, number and severity of late effects, and follow-up period. CCSs must be screened for psychological distress.

Published
2022

24. The Critical Need for Pooled Data on Coronavirus Disease 2019 in African Children: An AFREhealth Call for Action Through Multicountry Research Collaboration

Author

Onesmus Gachuno, Michel P Hermans, Prisca Olabisi Adejumo, Oma Amadi, Jean B. Nachega, Aster Tsegaye, Mary Glenn Fowler, Rhoderick Machekano, Nancy Mongweli, Serge Zigabe, Michel Tshiasuma Pipo, Lynne M. Mofenson, Lawal Waisu Umar, Hellen Tukamuhebwa Aanyu, John O Otshudiema, Asara M Abdullahi, Alfred K Mteta, Nadia A. Sam-Agudu, Léon Tshilolo, Jean-Marie Ntumba Kayembe, Refiloe Masekela, Aishatu Mohammed Jibril, Marieke M. van der Zalm, Christian Bongo-Pasi Nswe, Evans Kofi Agbeno, Angela Dramowski, Birhanu Teshome Ayele, Emilia Virginia Noormahomed, Umar Mohammed Umar, Ameena Ebrahim Goga, Emmanuella Amoako, Andrew Redfern, Peter Nyasulu, Don Jethro Mavungu Landu, Richard J. Deckelbaum, Fatima Suleman, Liliane N. Byamungu, Nelson K. Sewankambo, Jean-Jacques Muyembe-Tamfum, Alimuddin Zumla, Abdon Mukalay, Elizabeth Agyare, Daniel Katuashi Ishoso, Adolescents, Philippa Musoke, Edward J Mills, Placide Mbala-Kingebeni, John Kinuthia, Mariana Kruger, and Helena Rabie

Subjects
Microbiology (medical), medicine.medical_specialty, Tuberculosis, business.industry, Public health, 030231 tropical medicine, Disease, medicine.disease, 03 medical and health sciences, Malnutrition, 0302 clinical medicine, Infectious Diseases, Action (philosophy), Environmental health, Epidemiology, medicine, 030212 general & internal medicine, business, Malaria, Disease burden
Abstract

Globally, there are prevailing knowledge gaps in the epidemiology, clinical manifestations, and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among children and adolescents; and these gaps are especially wide in African countries. The availability of robust age-disaggregated data is a critical first step in improving knowledge on disease burden and manifestations of coronavirus disease 2019 (COVID-19) among children. Furthermore, it is essential to improve understanding of SARS-CoV-2 interactions with comorbidities and coinfections such as human immunodeficiency virus (HIV), tuberculosis, malaria, sickle cell disease, and malnutrition, which are highly prevalent among children in sub-Saharan Africa. The African Forum for Research and Education in Health (AFREhealth) COVID-19 Research Collaboration on Children and Adolescents is conducting studies across Western, Central, Eastern, and Southern Africa to address existing knowledge gaps. This consortium is expected to generate key evidence to inform clinical practice and public health policy-making for COVID-19 while concurrently addressing other major diseases affecting children in African countries.

Published
2021
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25. Recovery of HIV encephalopathy in perinatally infected children on antiretroviral therapy

Author

Steve Innes, Mark F. Cotton, Mariana Kruger, Kennedy Otwombe, Barbara Laughton, Ronald van Toorn, Afaaf Liberty, Els Dobbels, and Avy Violari

Subjects
Male, 030506 rehabilitation, Pediatrics, medicine.medical_specialty, AIDS Dementia Complex, Language delay, Developmental Disabilities, Encephalopathy, law.invention, South Africa, 03 medical and health sciences, 0302 clinical medicine, Developmental Neuroscience, Randomized controlled trial, Interquartile range, law, Outcome Assessment, Health Care, Spastic diplegia, Humans, Medicine, Child, Growth Disorders, Retrospective Studies, Movement Disorders, business.industry, Brain, Infant, Retrospective cohort study, medicine.disease, Infectious Disease Transmission, Vertical, Anti-Retroviral Agents, Case-Control Studies, Child, Preschool, Pediatrics, Perinatology and Child Health, Etiology, Female, Neurology (clinical), 0305 other medical science, business, Viral load, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

Aim To describe the trajectory of clinical signs in children who developed human immunodeficiency virus encephalopathy (HIVE) after starting early antiretroviral therapy (ART). Method This was a retrospective case-cohort description of HIVE among Cape Town participants from the Children with HIV Early AntiRetroviral treatment (CHER) trial. Criteria for HIVE diagnosis were at least two of: (1) acquired central motor deficit, (2) impaired brain growth, and (3) failure to attain or loss of developmental milestones in the absence of an alternative aetiology. Results Of 133 surviving participants who initiated ART at a median age of 9 weeks and who were followed until a median age of 6 years, 20 (12%) developed HIVE at a median age 31 months (interquartile range 19-37). In these, the first neurological deterioration was noticed at a median age of 19 months, when 16 were on ART and nine had undetectable HIV viral load for a median of 12 months. Signs of upper motor neurons were present in 18, of whom 12 resolved and four had persistent spastic diplegia; 19 had motor delay, of whom 14 resolved; 12 had language delay, of whom 11 resolved; and 16 had impaired brain growth, of whom only five recovered. For the 16 participants already on ART at HIVE diagnosis, regimens were not altered in response to diagnosis. Interpretation HIVE may occur despite early ART initiation and virological suppression and then resolve on unchanged ART, most likely as intrathecal inflammation subsides. What this paper adds Despite suppressive antiretroviral therapy, children can develop human immunodeficiency virus encephalopathy, The most common manifestations are motor deficits and impaired brain growth. Most experience improvement, with many resolving without additional intervention.

Published
2020
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26. The importance of local control management in high-risk neuroblastoma in South Africa

Author

Ronelle Uys, Jaques van Heerden, Barry Vanemmenes, Ané Büchner, Tonya M. Esterhuizen, Mariana Kruger, Jennifer Geel, Jan du Plessis, Gita Naidu, Marc Hendricks, and G. P. Hadley

Subjects
Male, medicine.medical_specialty, Multivariate analysis, Adolescent, Biopsy, medicine.medical_treatment, Nervous System Neoplasms, Disease-Free Survival, Neuroblastoma, South Africa, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Pediatric surgery, medicine, Pediatric oncology, Humans, High risk neuroblastoma, Child, Neoplasm Staging, Chemotherapy, business.industry, Incidence, Event free survival, Infant, General Medicine, medicine.disease, Combined Modality Therapy, Magnetic Resonance Imaging, Primary tumor, Surgery, Survival Rate, Radiation therapy, Child, Preschool, Pediatrics, Perinatology and Child Health, Female, 030211 gastroenterology & hepatology, Tomography, X-Ray Computed, business
Abstract

To investigate the impact of local therapies on high-risk neuroblastoma (HR-NB) outcomes in South Africa. Data from 295 patients with HR-NB from nine pediatric oncology units between 2000 and 2014 were analysed. All patients received chemotherapy. Five-year overall (OS) and event free survival (EFS) were determined for patients who had received local therapy, either surgery or radiotherapy or both. Surgery was performed in only 35.9% (n = 106/295) patients. Surgical excision was done for 34.8% (n = 85/244) of abdominal primaries, 50.0% (n = 11/22) of thoracic primaries; 22.2% (n = 2/9) neck primaries and 66.7% (n = 8/12) of the paraspinal primaries. Only 15.9% (n = 47/295) of all patients received radiotherapy. Children, who had surgery, had an improved five-year OS of 32.1% versus 5.9% without surgery (p

Published
2020
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27. Outcome of retinoblastoma treatment protocol in Cameroon as per SIOP‐PODC recommendation for a low‐income setting

Author

Mariana Kruger, Sabine L. van Elsland, Glenn M. Afungchwi, Richard Bardin, Bernard Njodzeka, Francine Kouya, Patience Nfor, Philippa Nana, Paul Wharin, and Peter B. Hesseling

Subjects
Male, Retinal Neoplasms, Retinoblastoma, Infant, Hematology, Treatment Outcome, Clinical Protocols, Oncology, Child, Preschool, Antineoplastic Combined Chemotherapy Protocols, Pediatrics, Perinatology and Child Health, Humans, Female, Cameroon, Neoplasm Recurrence, Local, Child, Developing Countries
Abstract

The International Society of Paediatric Oncology-Paediatric Oncology in Developing Countries (SIOP-PODC) group recommended graduated-intensity retinoblastoma treatment for children in low- and middle-income countries with limited local resources.The aim was to improve outcome of children with retinoblastoma by means of a treatment protocol for low-income settings as recommended by the SIOP-PODC recommendation in Cameroon.Children diagnosed with retinoblastoma between 2012 and 2016 were treated in two Baptist Mission hospitals in Cameroon, staging according to the International Retinoblastoma Staging System. Treatment included local therapy and combination chemotherapy (vincristine, cyclophosphamide, and doxorubicin) with or without surgery as per SIOP-PODC guidelines for low-income countries. Endpoint was survival at 24 months. Kaplan-Meier curves with log-rank (Mantel-Cox) chi-square (χEighty-two children were included, of whom 79.3% had unilateral disease. The majority were males (61.0%) with median age 24 months (range 1-112 months; standard deviation [SD] 19). Limited disease was diagnosed in 58.5%, metastatic disease in 35.4%, and unknown stage in 6.1%. Overall survival (OS) was 50.0% at 24 months post diagnosis, but 68.8% for limited disease. Estimated cumulative survival at 24 months was 0.528 (standard error [SE] 0.056). Causes of death included disease progression/relapses (60.5%), neutropenic sepsis (15.9%), unknown causes (18.4%), unrelated infection (2.6%), and death post surgery (2.6%). Stage was significantly associated with OS (p .001).Stage was the most significant factor for good OS and demonstrated the efficacy and feasibility of the SIOP-PODC-proposed management guidelines for retinoblastoma in a lower middle-income setting.

Published
2022
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28. Addressing challenges to rolling out COVID-19 vaccines in African countries

Author

Mariana Kruger, Helena Rabie, Jeanine Condo, Sabin Nsanzimana, Jean B. Nachega, Alimuddin Zumla, Hassan Mahomed, Emilia Virginia Noormahomed, Mukanire Ntakwinja, Francine Ntoumi, Refiloe Masekela, Jean-Jacques Muyembe Tamfum, Charles Shey Wiysonge, John Ditekemena, Masudah Paleker, Fatima Suleman, Denis Mukwege, Nadia A. Sam-Agudu, Marieke M. van der Zalm, and Raphael B Chirimwami

Subjects
2019-20 coronavirus outbreak, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), Extramural, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Comment, MEDLINE, COVID-19, General Medicine, Mass Vaccination, Environmental health, Africa, Humans, Medicine, Mass vaccination, Public aspects of medicine, RA1-1270, business
Published
2021
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29. Survey of the use of traditional and complementary medicine among children with cancer at three hospitals in Cameroon

Author

Glenn M. Afungchwi, Mariana Kruger, Peter Hesseling, Sabine van Elsland, Elena J. Ladas, and Stacey Marjerrison

Subjects
Complementary Therapies, Cross-Sectional Studies, Oncology, Child, Preschool, Neoplasms, Surveys and Questionnaires, Pediatrics, Perinatology and Child Health, Humans, Hematology, Cameroon, Prospective Studies, Child, Hospitals
Abstract

There is lack of diagnostic and treatment resources with variable access to childhood cancer treatment in low- and middle-income countries (LMIC), which may lead to subsequent poor survival. The primary aim of this study was to determine the prevalence and types of traditional and complementary medicine (TCM) used in Cameroon. Secondarily, we explored determinants of TCM use, associated costs, perceived benefits and harm, and disclosure of TCM use to medical team.A prospective, cross-sectional survey among parents and carers of children younger than 15 years of age who had a cancer diagnosis and received cancer treatment at three Baptist Mission hospitals between November 2017 and February 2019.Eighty participants completed the survey. Median patient age was 8.1 years (IQR4.1-11.1). There was significant availability (90%) and use (67.5%) of TCM, whereas 24% thought TCM would be good for cancer treatment. Common TCM remedies included herbs and other plant remedies or teas taken by mouth, prayer for healing purposes and skin cutting. Living more than five hours away from the treatment center (P = 0.030), anticipated costs (0.028), and a habit of consulting a traditional healer when sick (P = 0.006) were associated with the use of TCM. TCM was mostly paid for in cash (53.7%) or provided free of charge (29.6%). Of importance was the fact that nearly half (44%) did not want to disclose the use of TM to their doctor.Pediatric oncology patients used TCM before and during treatment but were unlikely to disclose its use to the child's health care team.

Published
2022

30. Malignant Extracranial Germ Cell Tumours: A First Report by the South African Children’s Cancer Study Group

Author

Marc Hendricks, Annibale Cois, Jennifer Geel, Jan du Plessis, Mairi Bassingthwaighte, Gita Naidu, Biance Rowe, Ane Buchner, Fareed Omar, Karla Thomas, Ronelle Uys, Anel van Zyl, Jaques van Heerden, Ngoakoana Mahlachana, Johani Vermeulen, Alan Davidson, Lindsay Frazier, Kirsty Donald, and Mariana Kruger

Abstract

OBJECTIVE To determine the overall survival (OS) and prognostic factors influencing outcomes in children and adolescents with malignant extracranial germ cell tumours (MEGCTs) in preparation for the development of a harmonised national treatment protocol.METHODS A retrospective folder review was undertaken at nine South African paediatric oncology units to document patient profiles, tumour and treatment-related data and outcomes for all children with biopsy proven MEGCTs from birth up to and including 16 years of age. RESULTS Between 1 January 2000 and 31 December 2015, 218 patients were diagnosed with MEGCTs. Female sex (HR 0.284 p=0.037) and higher socio-economic status (SES) (HR 0.071; p=0.039) were associated with a significantly lower risk of death. Advanced clinical stage at diagnosis significantly affected 5-year OS: stage I -96%; stage II - 94.3%; stage III -75.5%; (p=0.017) and stage IV (60.1%; pCONCLUSIONS The cohort demonstrated a 5-year OS of 80.3% with an EFS of 75.3%. Stage, the use of chemotherapy and an elevated serum AFP level of more than 33,000ng/ml were independently predictive of outcome. The relationship between SES and outcome is important as the implementation of the new national protocol hopes to standardise care across the socio-economic divide.

Published
2021
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31. Malignant extracranial germ cell tumours: A first national report by the South African Children's Cancer Study Group

Author

Marc Hendricks, Annibale Cois, Jennifer Geel, Johan du Plessis, Mairi Bassingthwaighte, Gita Naidu, Biance Rowe, Ané Büchner, Fareed Omar, Karla Thomas, Ronelle Uys, Anel Zyl, Jaques Heerden, Ngoakoana Mahlachana, Johani Vermeulen, Alan Davidson, A. Lindsay Frazier, Kirsty Donald, and Mariana Kruger

Subjects
Male, Adolescent, Hematology, Neoplasms, Germ Cell and Embryonal, Prognosis, South Africa, Oncology, Testicular Neoplasms, Pediatrics, Perinatology and Child Health, Antineoplastic Combined Chemotherapy Protocols, Humans, Female, Human medicine, alpha-Fetoproteins, Child, Neoplasm Staging, Retrospective Studies
Abstract

Objective To determine the overall survival (OS) and prognostic factors influencing outcomes in children and adolescents with malignant extracranial germ cell tumours (MEGCTs) in preparation for the development of a harmonised national treatment protocol. Methods A retrospective folder review was undertaken at nine South African paediatric oncology units to document patient profiles, tumour and treatment-related data and outcomes for all children with biopsy-proven MEGCTs from birth up to and including 16 years of age. Results Between 1 January 2000 and 31 December 2015, 218 patients were diagnosed with MEGCTs. Female sex (hazard ratio [HR] 0.284, p = .037) and higher socio-economic status (SES) (HR 0.071, p = .039) were associated with a significantly lower risk of death. Advanced clinical stage at diagnosis significantly affected 5-year OS: stage I: 96%; stage II: 94.3%; stage III: 75.5% (p = .017) and stage IV (60.1%; p < .001). There was a significant association between earlier stage at presentation and higher SES (p = .03). Patients with a serum alpha-fetoprotein (AFP) level of more than 33,000 ng/ml at diagnosis had significantly poorer outcomes (p = .002). The use of chemotherapy significantly improved survival, irrespective of the regimen used (p < .001). Conclusions The cohort demonstrated a 5-year OS of 80.3% with an event-free survival (EFS) of 75.3%. Stage, the use of chemotherapy and an elevated serum AFP level of more than 33,000 ng/ml were independently predictive of outcome. The relationship between SES and outcome is important as the implementation of the new national protocol hopes to standardise care across the socio-economic divide.

Published
2021

32. Survey of the Use of Traditional and Complementary Medicine (T&CM) Among Children with Cancer at three hospitals in Cameroon

Author

Glenn Afungchwi, Mariana Kruger, Peter Hesseling, Sabine van Elsland, Elena Ladas, and Stacey Marjerrison

Abstract

Introduction There is lack of diagnostic and treatment resources with variable access to childhood cancer treatment in low- and middle-income countries (LMIC), which may lead to subsequent poor survival. The primary aim of this study is to determine the prevalence and types of T&CM used in Cameroon. Secondarily, we explored determinants of T&CM use, associated costs, perceived benefits and harm, and disclosure of T&CM use to medical team. Method A prospective, cross-sectional survey amongst parents and carers of children younger than 15 years of age who had a cancer diagnosis and received cancer treatment at three Baptist Mission hospitals between November 2017 and February 2019. Results Eighty participants completed the survey. Median patient age was 8.1 years (IQR4.1 – 11.1). There was significant availability (90%) and use (67.5%) of T&CM, while 24% thought T&CM would be good for cancer treatment. Common T&CM remedies included herbs and other plant remedies or teas taken by mouth, prayer for healing purposes and skin cutting. Living more than 5 hours away from the treatment center (p=0.030), anticipated costs (0.028), and a habit of consulting a traditional healer when sick (p=0.006) were associated with the use of T&CM. T&CM was mostly paid for in cash (36.3%) or provided free of charge (20%). Of importance was the fact that nearly half (44%) did not want to disclose the use of TM to their doctor. Conclusion Pediatric oncology patients used T&CM before and during treatment but would be unlikely to disclose to the child’s health care team.

Published
2021
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33. Recommendations for Age-Appropriate Testing, Timing, and Frequency of Audiologic Monitoring during Childhood Cancer Treatment

Author

Bruce Carleton, Richard J. Cohn, Stefan Rutkowski, Eric Bouffet, Wendy Landier, Mariana Kruger, David R. Freyer, Vassilios Papadakis, Gabriele Calaminus, Antoinette am Zehnhoff-Dinnesen, Lillian Sung, Marry M. van den Heuvel-Eibrink, James I. Geller, Kaukab Rajput, Claudia Blattmann, Kay W. Chang, Jennifer H Foster, Kristin Knight, Alexander E Hoetink, A Meijer, Hiske W Helleman, Beth Brooks, Penelope Brock, Godelieve A.M. Tytgat, Lisa L. Hunter, Martine van Grotel, Rachael Windsor, Bruce Morland, A. Lindsay Frazier, and Barbara Hero

Subjects
Cancer Research, medicine.medical_specialty, Hearing loss, Psychological intervention, Context (language use), Disease, Medical Oncology, Ototoxicity, SDG 3 - Good Health and Well-being, Neoplasms, medicine, Humans, Child, Hearing Loss, Intensive care medicine, medicine.diagnostic_test, business.industry, Cancer, medicine.disease, Oncology, Cisplatin, Cranial Irradiation, medicine.symptom, Audiometry, business, Tinnitus
Abstract

Importance Ototoxicity is an irreversible direct and late effect of certain childhood cancer treatments. Audiologic surveillance during therapy as part of the supportive care pathway enables early detection of hearing loss, decision-making about ongoing cancer treatment, and, when applicable, the timely use of audiologic interventions. Pediatric oncologic clinical practice and treatment trials have tended to be driven by tumor type and tumor-specific working groups. Internationally accepted standardized recommendations for monitoring hearing during treatment have not previously been agreed on. Objective To provide standard recommendations on hearing loss monitoring during childhood cancer therapy for clinical practice. Methods An Ototoxicity Task Force was formed under the umbrella of the International Society of Paediatric Oncology, consisting of international audiologists, otolaryngologists, and leaders in the field of relevant pediatric oncology tumor groups. Consensus meetings conducted by experts were organized, aimed at providing standardized recommendations on age-directed testing, timing, and frequency of monitoring during cancer treatment based on literature and consensus. Consensus statements were prepared by the core group, adapted following several videoconferences, and finally agreed on by the expert panel. Findings The consensus reached was that children who receive ototoxic cancer treatment (platinum agents, cranial irradiation, and/or brain surgery) require a baseline case history, monitoring of their middle ear and inner ear function, and assessment of tinnitus at each audiologic follow-up. As a minimum, age-appropriate testing should be performed before and at the end of treatment. Ideally, audiometry with counseling before each cisplatin cycle should be considered in the context of the individual patient, specific disease, feasibility, and available resources. Conclusions and Relevance This is an international multidisciplinary consensus report providing standardized supportive care recommendations on hearing monitoring in children undergoing potentially ototoxic cancer treatment. The recommendations are intended to improve the care of children with cancer and facilitate comparative research on the timing and development of hearing loss caused by different cancer treatment regimens.

Published
2021
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35. Value of the Goodenough Drawing Test as a research tool to detect developmental delay in South African preschool children

Author

Barbara Laughton, Mariana Kruger, Maxwell Chirehwa, Chrisma Pretorius, Emma Kalk, M. F. Cotton, and Priscilla Springer

Subjects
Preschool child, 05 social sciences, 050109 social psychology, Developmental psychology, Test (assessment), 03 medical and health sciences, 0302 clinical medicine, Simple (abstract algebra), Fine Motor Delay, 0501 psychology and cognitive sciences, 030212 general & internal medicine, Psychology, Value (mathematics), General Psychology
Abstract

There is a need for simple, cost-effective research tools to detect developmental delay in preschool children in low- and middle-income countries where insufficient resources are often a barrier to detection and management. The Goodenough Draw-a-Person test is freely available, easily administered, and requires limited language ability and equipment; it is thus potentially useful in resource-constrained settings. We aimed to determine the diagnostic accuracy of the Draw-a-Person test to identify developmental delay in 5-year-old preschool children using the Griffiths Mental Developmental Scales-Extended Revised eye-hand coordination subquotient as the gold standard. This was a cross-sectional analysis of drawings by South African preschool children from low-income families, whose Griffiths Mental Developmental Scales-Extended Revised assessments included a human figure drawing. Draw-a-Person test quotients were estimated independently by a developmental paediatrician and two medical officers to calculate inter-rater agreement. The paediatrician’s scores were used to determine the diagnostic accuracy of the Draw-a-Person test quotient (

Published
2019
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36. The Association of Clinical Characteristics and Tumour Markers With Image-Defined Risk Factors in the Management of Neuroblastoma in South Africa

Author

J. Van Heerden, Mariana Kruger, Saccsg Neuroblastoma Workgroup, Tonya M. Esterhuizen, Janet Poole, J. du Plessis, Ané Büchner, E Mathews, B. van Emmenes, Gita Naidu, Marc Hendricks, A. Van Zyl, and SACCSG Neuroblastoma Workgroup

Subjects
Oncology, medicine.medical_specialty, Neuroblastoma, South Africa, Risk Factors, Internal medicine, Ascites, medicine, Biomarkers, Tumor, Humans, Radiology, Nuclear Medicine and imaging, Pathological, Neoplasm Staging, Retrospective Studies, business.industry, Retrospective cohort study, Airway obstruction, medicine.disease, Prognosis, Pleural Effusion, Human medicine, medicine.symptom, business, Tomography, X-Ray Computed
Abstract

Aims: Image-defined risk factors (IDRFs) in neuroblastoma predict surgical complications and management outcomes. As there is a lack of data regarding the association of IDRFs with clinical and pathological factors, this study evaluated the prognostic value of IDRFs to predict neuroblastoma survival outcomes. Materials and methods: This was a retrospective study including 345 patients and reviewed diagnostic imaging for 20 IDRFs, pleural effusions and ascites. The IDRFs were grouped into five `primary IDRFs' cohorts with vascular encasement, involvement of multiple body compartments, organ infiltration, airway obstruction and intraspinal extension. The association between clinical, histopathological and biological characteristics of neuroblastoma and management was evaluated. Results: More patients without IDRFs had operations compared with patients with IDRFs, with a trend towards significance (64.4% versus 35.6%, P = 0.082). Patients with multiple compartment tumour involvement (P = 0.003) and organ infiltration (P < 0.001) had a higher risk of surgical complications. The 5-year overall survival of the group with more than one IDRF was 0.0% and those with pleural effusions or ascites 6.7%, associated with the worst outcome (P = 0.005). The total number of IDRFs was not predictive of the metastatic remission rate (P = 0.585) or overall survival (P = 0.142), with no conclusive association found between IDRF groups and clinical or biological markers. Conclusions: Patients with more than one IDRF had the shortest survival time, whereas those with pleural effusions and ascites at diagnosis had a poor outcome. Standardised reporting of IDRFs is crucial for predicting prognosis. (C) 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Published
2021

37. Cisplatin Ototoxicity in Children

Author

Marry M. van den Heuvel-Eibrink, Lindsey Edwards, Philippa Simpkin, Alex E. Hoetink, Kaukab Rajput, Mariana Kruger, A Meijer, Michael J. Sullivan, and Penelope Brock

Subjects
medicine.medical_specialty, Side effect, Hearing loss, medicine.medical_treatment, InformationSystems_INFORMATIONSTORAGEANDRETRIEVAL, Audiology, 03 medical and health sciences, 0302 clinical medicine, Ototoxicity, Vertigo, otorhinolaryngologic diseases, medicine, 030223 otorhinolaryngology, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Chemotherapy, biology, Cumulative dose, business.industry, biology.organism_classification, medicine.disease, 3. Good health, 030220 oncology & carcinogenesis, Hearing range, medicine.symptom, business, Tinnitus
Abstract

Cisplatin is a highly effective chemotherapy medicine used in the treatment of many childhood cancers. Like all medications, cisplatin has many side effects and as always the treatment of cancer in children is a balance between the risks of the medications used and their potential benefits. While many side effects of cisplatin chemotherapy are reversible, one major side effect is permanent and irreversible hearing loss (ototoxicity) in both ears which may worsen with time. The severity of cisplatin-related ototoxicity is associated with age and the cumulative dose received: the younger the child and the higher the total dose, the more severe the hearing loss may be. The spectrum of hearing loss varies from mild to moderate high tone hearing loss, to profound loss across the hearing range and permanent deafness. In addition to hearing loss, some children, especially adolescents, also experience tinnitus and vertigo. Cisplatin ototoxicity is one of most important of the many long-term effects experienced by children who are cured of their cancer. The burden of this toxicity may be compounded by other long-term health issues that emerge with time. This chapter will focus on cisplatin-induced hearing loss, its mechanisms, its health impact on the young person and ways to mitigate or reduce the severity of ototoxicity. This chapter has been written by a multi-disciplinary team including paediatric oncologists, audiologists, a psychologist, a health scientist and a parent of a child growing up with high frequency hearing loss.

Published
2021
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38. Two decades of childhood cancer care in Cameroon: 2000–2020

Author

Mariana Kruger, Peter McCormick, Pius M. Tih, Angele-Hermine Pondy-Ongotsoyi, Glenn M. Afungchwi, Peter B. Hesseling, and Francine Kouya

Subjects
medicine.medical_specialty, Palliative care, Population, 03 medical and health sciences, 0302 clinical medicine, Clinical Protocols, Neoplasms, Health care, Epidemiology, medicine, Humans, Cameroon, Child, education, Government, education.field_of_study, business.industry, Cancer, Capacity building, Hematology, medicine.disease, Malnutrition, Oncology, 030220 oncology & carcinogenesis, Family medicine, Pediatrics, Perinatology and Child Health, business, 030215 immunology
Abstract

Background Before the year 2000, there was no dedicated childhood cancer service in Cameroon. The aim of this study was to investigate the progress made with pediatric oncology care in Cameroon from 2000 to 2020. Method A literature search was conducted for published articles on childhood cancer in Cameroon and relevant documents, and conference abstracts were reviewed. The articles were analyzed under the themes: awareness, diagnosis, epidemiology, treatment, outcome, advocacy, partnerships, traditional and complementary medicine, palliative care, and capacity building. Results Low awareness on childhood cancer was addressed with education activities targeting the general population and health care professionals. Cancer diagnosis was achieved with cytology, histology, and simple imaging. Management for common and curable cancers was implemented with use of modified treatment regimens for low- and middle-income settings. Nutritional support was shown to mitigate the effects of malnutrition on treatment toxicity, and support was provided for transportation and accommodation. There was good collaboration between the pediatric oncology professionals nationally and twinning with international partners. Capacity building activities led to the availability of three pediatric oncologists and pediatric oncology-trained nurses. Advocacy nationally led to the support of the Ministry of Health with pediatric oncology-specific priority actions in the latest national cancer control plan. Conclusion Childhood cancer should receive the necessary attention of health care policymakers in Cameroon. With continued commitment of government, nongovernmental organizations, charities, childhood cancer specialists, patient and parent groups, there should be an improved future for children with cancer in Cameroon.

Published
2021
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39. Inequity in paediatric oncology in South Africa – The neuroblastoma case study

Author

Mariana Kruger, Jaques van Heerden, and Tonya M. Esterhuizen

Subjects
Supplementary data, south africa, medicine.medical_specialty, Medical staff, Paediatric oncology, Constitution, business.industry, media_common.quotation_subject, Childhood cancer, Retrospective cohort study, patient advocacy, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Patient advocacy, lcsh:RC254-282, neuroblastoma, paediatric oncology, Political science, Family medicine, Health care, medicine, equality, business, media_common
Abstract

Background: The South African Constitution affords everyone the right to access healthcare services, but in children the care must ensure survival. Aim: This study aimed to determine whether there was access to equitable paediatric oncology services for the management of neuroblastoma in South Africa. Setting: Paediatric oncology services in South Africa between 2000 to 2014. Methods: A literature review was carried out, focussing on access to healthcare in South Africa for children with neuroblastoma. Services were classified in accordance with the International Society of Paediatric Oncology resource settings for neuroblastoma diagnosis. Supplementary data from a retrospective study of the management of neuroblastoma in South Africa were evaluated. Results: The neuroblastoma care services in South Africa were not uniformly resourced and accessible across the provinces. Two provinces (2/9 provinces) had excellent healthcare services that included access to transplant facilities, whilst three (3/9 provinces) had no services. Traveling distances to healthcare services pose major challenges, whilst number of medical staff providing oncology care were unequally distributed. The Constitution did not define basic healthcare for children, nor did the National Cancer Control plan acknowledge childhood cancer as a defined entity without provision until 2022. Conclusion: Children diagnosed with neuroblastoma do not have equitable access to healthcare as stated in the South African Constitution. The case of neuroblastoma highlights the inequitable access to childhood care as a whole in South Africa. As the health of children is a national priority, it is therefore necessary to sensitise policymakers to the needs of children with cancer.

Published
2021

40. Burkitt lymphoma: Age Specific Fertility Rate in 113 long-term female survivors after treatment with cyclophosphamide

Author

Peter B Hesseling PhD, Glenn M Afungchwi MSc, Vera Njamshi Dip. Nursing, Mariana Kruger PhD, Comfort Kimbi Dip Nursing, Patience Nfor BSc, Paul Wharin MD, Heather Draper MSc, and Francine Kouya MD

Subjects
Adult, Pediatrics, medicine.medical_specialty, Cyclophosphamide, Adolescent, Total fertility rate, media_common.quotation_subject, Fertility, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Pregnancy, medicine, Humans, Cameroon, Survivors, Birth Rate, Child, media_common, 030203 arthritis & rheumatology, business.industry, Incidence (epidemiology), medicine.disease, Burkitt Lymphoma, Lymphoma, Log-rank test, Infectious Diseases, 030220 oncology & carcinogenesis, Child, Preschool, Pediatrics, Perinatology and Child Health, Menarche, Female, business, After treatment, medicine.drug
Abstract

Introduction Reduced fertility risk is a risk in females treated with a high cumulative cyclophosphamide (CPM) dose. Objectives The objective of this study is to establish the age at menarche, record all pregnancies, calculate age-specific fertility rate (ASFR) in female BL survivors, treated in Cameroon, in the age groups 15–19 and 20–24 years, and association with an increasing cumulative CPM dose. Methods Data collection included personal data and telephone interviews for female survivors, aged ≥12 years with regards to menarche age, their mothers’ menarche age, incidence and outcome of all pregnancies. The cumulative CPM/m2 dose was categorized as low (10 635 mg/m2). Results The median age at first treatment for 113 patients was 8 years (range 3–17 years), with median current age 17 years (range 12–26 years); the median duration of follow-up was 9 years (range 1.2–13.3 years). The median age of patients at menarche (n = 109; 4 unknown) was 14 years (range 10–17 years, SD 1.19) and that of their mothers (n = 68; 45 unknown) 15 years (range 10–17 years, SD 1.53). The median time to first pregnancy following menarche (the fertility time) was 3.04 years (n = 10) with low-dose CPM, 6.09 years with medium-dose CPM (n = 81) and 6.04 years with high-dose CPM (n = 32) (log rank difference p = 0.420). The ASFR in the age group 15–19 years was 82.19 (n = 73) and in the age group 20–24 years was 863.6 (n = 22), with significantly lower ASFR (p > 0.001) in children treated before the age of 10 years. Conclusion Fertility rates of girls treated for BL with CPM were normal but reduced in patients who commenced treatment before the age of 10 years.

Published
2021

41. Sex cord stromal tumors in children and adolescents : a first report by The South African Children's Cancer Study Group (1990-2015)

Author

Karla Thomas, Anel van Zyl, Mariana Kruger, Jaques van Heerden, Marc Hendricks, Ane Bϋchner, Ngoakoane Mahlachana, Johani Vermeulen, Alan Davidson, Ronelle Uys, Gita Naidu, Kirsty Donald, Annibale Cois, Biance Rowe, Jennifer Geel, Jan du Plessis, Mairi Bassingthwaighte, and Fareed Omar

Subjects
Male, Pediatrics, medicine.medical_specialty, Stromal cell, Gonadal cord, Adolescent, medicine.medical_treatment, Renal function, Antineoplastic Agents, Kaplan-Meier Estimate, 03 medical and health sciences, 0302 clinical medicine, Thecoma, Testicular Neoplasms, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Sex Cord-Gonadal Stromal Tumors, Stage (cooking), Child, Africa South of the Sahara, Retrospective Studies, Ovarian Neoplasms, Chemotherapy, business.industry, Infant, Cancer, Hematology, Prognosis, medicine.disease, Oncology, Child, Preschool, 030220 oncology & carcinogenesis, Pediatrics, Perinatology and Child Health, Cohort, Female, Human medicine, Cisplatin, business, 030215 immunology
Abstract

Objectives: Pediatric sex cord stromal tumors (SCSTs) are extremely rare and there are no reported data from Africa. The authors evaluated the outcomes of children and adolescents with biopsy-proven SCSTs in preparation for the introduction of a national protocol. Materials and Methods: Retrospective data were collated from 9 South African pediatric oncology units from January 1990 to December 2015. Kaplan-Meier analysis was performed to estimate overall survival (OS) and event-free survival. Results: Twenty-three patients were diagnosed with SCSTs, 3 male and 20 female individuals, during the study period. Histologies included 1 thecoma, 9 Sertoli-Leydig cell tumors, and 13 juvenile granulosa cell tumors. Stage I tumors predominated (n=14; 60.9%), with 2 stage II (8.7%), 5 stage III (21.7%), and 2 stage IV tumors (8.7%). The upfront resection rate was 91.3% with no reported surgical morbidity or mortality and an OS of 82.1%. Chemotherapy approaches were not standardized. Most children (81.8%), except 2, had recognized platinum-based regimens. Chemotherapy-related toxicity was minimal and acceptable. Assessment of glomerular filtration rate and audiology assessments were infrequent and not standardized. Three patients were lost to follow-up. Conclusions: Although the numbers in this cohort are small, this study represents the first national cohort in Africa. The 5-year OS of 82.1% was encouraging. Standardized management of rare tumors like SCSTs is critical to improve ensure OS and address potential long-term sequelae.

Published
2021

42. The need for resource-linked translational oncology in the management of neuroblastoma and other childhood malignancies in low- and middle-income countries

Author

Jaques van Heerden and Mariana Kruger

Subjects
medicine.medical_specialty, Resource (biology), Translational oncology, business.industry, MEDLINE, Hematology, Medical Oncology, medicine.disease, Neuroblastoma, Oncology, Low and middle income countries, Neoplasms, Family medicine, Pediatrics, Perinatology and Child Health, Income, Humans, Medicine, Human medicine, Child, business, Developing Countries, Translational Science, Biomedical
Published
2021

43. The implementation of a national paediatric oncology protocol for neuroblastoma in South Africa

Author

Jan du Plessis, Anel van Zyl, Jaques van Heerden, Biance Rowe, G. P. Hadley, D Harrison, Johani Johani, Janet Poole, Mariana Kruger, Barry van Emmenes, Ané Büchner, Ronelle Uys, Mairi Bassingthwaighte, Gita Naidu, Nicolene Moonsamy, Marc Hendricks, and SACCSG Neuroblastoma Workgroup

Subjects
Male, Cancer Research, medicine.medical_specialty, National Health Programs, Consolidated Framework for Implementation Research, National protocols, South Africa, Neuroblastoma, 03 medical and health sciences, 0302 clinical medicine, Resource (project management), Intervention (counseling), Health care, medicine, Humans, 030212 general & internal medicine, Child, Children, Protocol (science), Original Paper, Research ethics, business.industry, Public health, Antineoplastic Protocols, Infant, Patient Outcome Assessment, Clinical trial, Oncology, Child, Preschool, 030220 oncology & carcinogenesis, Family medicine, Female, Implementation research, Human medicine, business, Delivery of Health Care
Abstract

Purpose The aim of the World Health Organization-International Paediatric Oncology Society is to improve childhood cancer survival in low- and middle-income countries to 60% by 2030. This can be achieved using standardised evidence-based national treatment protocols for common childhood cancers. The aim of the study was to describe the development and implementation of the SACCSG NB-2017 neuroblastoma (NB) treatment protocol as part of the treatment harmonisation process of the South African Children’s Cancer Study Group. Methods The Consolidated Framework for Implementation Research was used to identify factors that could influence the implementation of the national NB protocol as a health care intervention. The evaluation was done according to five interactive domains for implementation: intervention characteristics, inner setting, outer setting, individual or team characteristics and the implementation process. Results The protocol was developed over 26 months by 26 physicians involved in childhood cancer management. The process included an organisational phase, a resource identification phase, a development phase and a research ethics approval phase. Challenges included nationalised inertia, variable research ethical approval procedures with delays and uncoordinated clinical trial implementation. Conclusion The implementation of the national NB protocol demonstrated the complexity of the implementation of a national childhood cancer treatment protocol. However, standardised paediatric cancer treatment protocols based on local expertise and resources in limited settings are feasible. Supplementary Information The online version contains supplementary material available at 10.1007/s10552-021-01424-2.

Published
2021

44. The association between tumour markers and meta-iodobenzylguanidine scans in South African children with high-risk neuroblastoma

Author

Ronelle Uys, Mariana Kruger, M. Janse van Vuuren, G. Engelbrecht, S. More, B. van Emmenes, N. Nyakale, J. du Plessis, Adrian Brink, C. Burger, J. Van Heerden, Tonya M. Esterhuizen, and Marc Hendricks

Subjects
Oncology, medicine.medical_specialty, Meta iodobenzylguanidine, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, chemistry.chemical_compound, Neuroblastoma, 0302 clinical medicine, Lactate dehydrogenase, Internal medicine, Disease patterns, medicine, Overall survival, Biomarkers, Tumor, Humans, Radiology, Nuclear Medicine and imaging, High risk neuroblastoma, Child, Radionuclide Imaging, biology, business.industry, Resource constraints, Reproducibility of Results, medicine.disease, Ferritin, 3-Iodobenzylguanidine, chemistry, 030220 oncology & carcinogenesis, biology.protein, Human medicine, business
Abstract

Aims: Diagnostic and post-induction I-123-meta-iodobenzylguanidine (I-123-mIBG) scans have prognostic significance in the treatment of neuroblastoma, but data from low-and middle-income countries are limited due to resource constraints. The aim of this study was to determine the association between neuroblastoma-associated tumour markers (lactate dehydrogenase [LDH], ferritin and MYCN amplification) and I-123-mIBG scans (modified Curie scores and metastatic disease patterns) in predicting complete metastatic response rates (mCR) and overall survival. Materials and methods: Two hundred and ninety patients diagnosed with high-risk neuroblastoma in South Africa between January 2000 and May 2018 and a subanalysis of 78 patients with diagnostic I-123-mIBG scans were included. Data collection included LDH, ferritin and MYCN amplification at diagnosis. Two nuclear physicians independently determined the modified Curie scores and pattern of distribution for each diagnostic and post-induction I-123-mIBG scans with high inter-rater agreement (r = 0.952) and reliability (K = 0.805). The cut-off values for the diagnostic and post-induction modified Curie scores of >= 7.0 (P = 0.026) and 3 (P = 0.009), respectively, were generated. The association between the tumour markers and the modified Curie score of the I-123-mIBG scans was determined using post-induction mCR and 2-year overall survival. Results: Diagnostic LDH (P < 0.001), ferritin (P < 0.001) and the diagnostic modified Curie scores (P = 0.019) significantly predicted mCR. Only ferritin correlated with diagnostic modified Curie scores (P = 0.003) but had a low correlation coefficient of 0.353. On multivariable analysis, the only significant covariate for 2 year overall survival at diagnosis was LDH 3.0 (P = 0.484). Conclusion: LDH, ferritin and the diagnostic I-123-mIBG scans significantly predicted mCR, but only LDH predicted 2-year overall survival. Ferritin and the modified Curie scores correlated with each other. MYCN amplification neither correlated with any aspect of the I-123-mIBG scans nor significantly predicted mCR or 2-year overall survival. LDH and ferritin are therefore appropriate neuroblastoma tumour markers to be used in low-and middle-income countries with limited or no access to mIBG scans and/or MYCN amplification studies. (C) 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Published
2021

45. Neuroblastoma: The basis for cure in limited-resource settings

Author

Jaques van Heerden, Tonya M. Esterhuizen, Wim Pinxten, and Mariana Kruger

Subjects
medicine.medical_specialty, Poor prognosis, Disease, Medical Oncology, 03 medical and health sciences, Neuroblastoma, 0302 clinical medicine, International congress, Surveys and Questionnaires, medicine, Humans, Developing Countries, Poverty, Income.status, Descriptive statistics, business.industry, Paediatric oncology, Disease spectrum, Hematology, Oncology, 030220 oncology & carcinogenesis, Family medicine, Pediatrics, Perinatology and Child Health, Human medicine, business, Limited resources, 030215 immunology
Abstract

BACKGROUND Neuroblastoma (NB) contributes the most to the mortality of childhood malignancies worldwide. The disease spectrum is heterogenous and the management complex and costly, especially in advanced disease or disease with adverse biology. In low- and middle-income countries (LMICs) the majority of NB presents in advanced stages. Therefore, with limited resources and poor prognosis the treatment of NB is often not a priority. The aim of the study was to evaluate the research activities and perceptions of the management of NB that determine the research and treatment approaches in LMICs. METHODS Data were sourced from https://www.clinicaltrials.gov/ identifying NB trials open to LMIC. Abstracts on NB research presented at the International Society for Paediatric Oncology (SIOP) Congresses between 2014 and 2020 were evaluated according to income status. An online survey evaluating medical views on NB in LMICs and the effect on the management was conducted. Descriptive analysis was done. Where appropriate categorical association between covariates was assessed using the Pearson chi-square (χ2 ) test or Fishers exact test. RESULTS There were 15/562 (2.7%) trials open to LMIC. Only six of 138 (4.3%) LMIC participated in NB trials. Of the 688 abstracts presented between 2014 and 2020 at the SIOP International Congress on NB as primary subject, 297 (42.7%) were from LMICs. Only two were from low-income countries (LICs). Sixty-one countries responded to the NB survey. Positive views towards NB management were present when treatment was based on a national protocol, the availability of trimodal or advanced treatment options were present, and when a balance of metastatic or local disease were treated. CONCLUSION Management of NB in LMICs should include increased advocacy and research as well as implementation of national management strategies.

Published
2020

46. The immunological architecture of granulomatous inflammation in central nervous system tuberculosis

Author

A. Marceline van Furth, Mariana Kruger, Sabine L van Elsland, Ronald van Toorn, Carmen S. van Dam, Sanna L. Roest, Jaco Hagoort, Daniel J. Franken, Regan Solomons, Bernadette S. de Bakker, Carlie Timmers, Martijn van der Kuip, Stefan-Dan Zaharie, Pediatric surgery, AII - Infectious diseases, Internal medicine, Amsterdam Reproduction & Development (AR&D), Medical Biology, Amsterdam Cardiovascular Sciences, and ACS - Heart failure & arrhythmias

Subjects
0301 basic medicine, Microbiology (medical), Adult, Male, Pathology, medicine.medical_specialty, Tuberculosis, Adolescent, 030106 microbiology, Immunology, Central nervous system, Microbiology, Tuberculous meningitis, 03 medical and health sciences, Young Adult, Cerebrospinal fluid, medicine, Humans, Child, Neuroinflammation, Central nervous system tuberculosis, Aged, Retrospective Studies, Inflammation, Immunity, Cellular, Rich focus, Granuloma, 3D-reconstruction, business.industry, Leptomeninges, Infant, Mycobacterium tuberculosis, Middle Aged, Tuberculosis, Central Nervous System, medicine.disease, Immunohistochemistry, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, Child, Preschool, Female, business
Abstract

Of all tuberculosis (TB) cases, 1% affects the central nervous system (CNS), with a mortality rate of up to 60%. Our aim is to fill the 'key gap' in TBM research by analyzing brain specimens in a unique historical cohort of 84 patients, focusing on granuloma formation. We describe three different types: non-necrotizing, necrotizing gummatous, and necrotizing abscess type granuloma. Our hypothesis is that these different types of granuloma are developmental stages of the same pathological process. All types were present in each patient and were mainly localized in the leptomeninges. Intra-parenchymal granulomas were less abundant than the leptomeningeal ones and mainly located close to the cerebrospinal fluid (subpial and subependymal). We found that most of the intraparenchymal granulomas are an extension of leptomeningeal lesions which is the opposite of the classical Rich focus theory. We present a 3D-model to facilitate further understanding of the topographic relation of granulomas with leptomeninges, brain parenchyma and blood vessels. We describe innate and adaptive immune responses during granuloma formation including the cytokine profiles. We emphasize the presence of leptomeningeal B-cell aggregates as tertiary lymphoid structures. Our study forms a basis for further research in neuroinflammation and infectious diseases of the CNS, especially TB.

Published
2020
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47. Two decades of childhood cancer care in Cameroon: 2000 – 2020

Author

Francine Kouya, Peter Hesseling, Mariana Kruger, Glenn M. Afungchwi, Pius M. Tih, Angele Pondy, and Peter McCormick

Subjects
Government, medicine.medical_specialty, Treatment regimen, business.industry, Childhood cancer, Cancer, medicine.disease, Cancer control, Family medicine, medicine, Pediatric oncology, Program development, Christian ministry, business
Abstract

BACKGROUND The aim of this study was to investigate the progress made with pediatric oncology care in Cameroon from 2000 to 2020. METHOD A literature search was conducted for published articles on childhood cancer in Cameroon and relevant documents and conference abstracts were reviewed. The articles were analysed under eight themes: covering detection, diagnosis, management and program development. RESULTS Forty publications were analysed. Cancer diagnosis was achieved with cytology, histology and simple imaging. Management for common and curable cancers was with use of modified treatment regimens for low- and middle- income settings. There was good collaboration between the pediatric oncology professionals nationally and international partners. Advocacy led to the support of the Ministry of Health with pediatric oncology specific priority actions in the latest national cancer control plan. CONCLUSION Commitment of childhood cancer specialists, non-governmental organizations, and the government can lead to successful childhood cancer management in a low-income country.

Published
2020
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48. The Evolution of a Hospital-Based Cancer Registry in Northwest Cameroon from 2004 to 2015

Author

P. Wharin, Richard Bardin, Glenn M. Afungchwi, Francine Kouya, Mariana Kruger, and Peter B. Hesseling

Subjects
Male, Pediatrics, medicine.medical_specialty, Developing country, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Rhabdomyosarcoma, medicine, Humans, 030212 general & internal medicine, Cameroon, Registries, Radiation treatment planning, Child, business.industry, Retinoblastoma, Incidence, Cancer, medicine.disease, Pediatric cancer, Burkitt Lymphoma, Hospitals, Cancer registry, Infectious Diseases, 030220 oncology & carcinogenesis, Pediatrics, Perinatology and Child Health, Female, Sarcoma, business
Abstract

Effective cancer registration is required for the development of cancer management policies, but is often deficient in the developing world. In 2008 cancer registration was set up Banso Baptist Hospital and Mbingo Baptist Hospital in the Northwest region of Cameroon, using the Pediatric Oncology Networked Database (POND). The objective of this study was to analyze the POND registry data for patients with cancer aged 0–15 years for the period 2004–15. A total of 1029 malignancies were recorded in children 0–15 years in the study period. The male-to-female ratio was 1.4:1. The median age at diagnosis was 7.22 years. The most common malignancies were lymphomas followed by nephroblastoma, retinoblastoma, rhabdomyosarcoma and Kaposi sarcoma. There were more Burkitt lymphomas cases between 2004 and 2009 than between 2010 and 2015, while the number of cases rose for other diagnoses like retinoblastoma and nephroblastoma. This report has demonstrated how pediatric oncology registration can be implemented, improved and sustained in a low- and middle-income country setting with limited resources. Using the data, these hospitals can improve their treatment planning and ensure the availability of essential chemotherapy for childhood cancers.

Published
2020

49. Bacille Calmette-Guérin (BCG) vaccine and the COVID-19 pandemic: responsible stewardship is needed

Author

Marc Tebruegge, K du Preez, Jantjie Taljaard, James A Seddon, Mark F. Cotton, Anneke C. Hesseling, Nigel Curtis, Helena Rabie, H S Schaaf, Regan Solomons, and Mariana Kruger

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, Tuberculosis, Coronavirus disease 2019 (COVID-19), Pneumonia, Viral, Bacille Calmette Guerin, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, Immunogenicity, Vaccine, Pandemic, Medicine, Humans, Pandemics, business.industry, SARS-CoV-2, COVID-19, medicine.disease, Virology, Immunity, Innate, 030104 developmental biology, Infectious Diseases, Lung disease, BCG Vaccine, Stewardship, business, Tuberculosis vaccines, Coronavirus Infections, BCG vaccine, Immunologic Memory, 030217 neurology & neurosurgery
Abstract

CITATION: Schaaf, H. S. et al. 2020. Bacille Calmette-Guerin (BCG) vaccine and the COVID-19 pandemic : responsible stewardship is needed. International Journal of Tuberculosis and Lung Disease, 4(7):732-734, doi:10.5588/ijtld.20.0267.

Published
2020

50. Age at diagnosis as a prognostic factor in South African children with neuroblastoma

Author

Mariana Kruger, Jaques van Heerden, Tonya M. Esterhuizen, Ané Büchner, G. P. Hadley, Gita Naidu, Ronelle Uys, Jan du Plessis, Marc Hendricks, Janet Poole, and Barry van Emmenes

Subjects
Male, medicine.medical_specialty, Age at diagnosis, Cohort Studies, 03 medical and health sciences, Neuroblastoma, South Africa, 0302 clinical medicine, Positive predicative value, Internal medicine, medicine, Humans, Child, Receiver operating characteristic, business.industry, Area under the curve, Age Factors, Infant, Hematology, medicine.disease, Prognosis, Survival Analysis, Confidence interval, Oncology, 030220 oncology & carcinogenesis, Relative risk, Child, Preschool, Pediatrics, Perinatology and Child Health, Cohort, Female, Human medicine, business, 030215 immunology
Abstract

Purpose Low- and middle-income countries (LMICs) reported a higher median age at diagnosis of neuroblastoma (NB) compared to high-income countries. The aim was to determine if the optimal age at diagnosis, which maximizes the difference in overall survival between younger versus older patients in the South African population was similar to the internationally validated 18 months age cut-point. Methods Four hundred sixty NB patients diagnosed between 2000 and 2016 were included. Receiver operating characteristic (ROC) curves were used to predict potential age cut-point values for overall survival in all risk group classifications. Risk ratios, sensitivity, specificity, and positive and negative predictive values at the specific cut-points were estimated with 95% confidence intervals, and time to mortality by age at the specific cut-points was shown with Kaplan-Meier curves and compared using log-rank tests. Results The median age at diagnosis for the total cohort was 31.9 months (range 0.2-204.7). For high-risk (HR), intermediate-risk, low-risk, and very low-risk patients, the median age at diagnosis was, respectively, 36 months (range 0.4-204.7), 16.8 months (range 0.7-145.1), 14.2 months (range 2.0-143.5), and 8.7 months (range 0.2-75.6). The ROC curves for the total NB cohort (area under the curve [AUC] 0.696; P < .001) and HR (AUC 0.682; P < .001) were analyzed further. The optimal cut-point value for the total cohort was at 19.1 months (sensitivity 59%; specificity 78%). The HR cohort had potential cut-point values identified at 18.4 months age at diagnosis (sensitivity 45%; specificity 87%) and 31.1 months (sensitivity 67%; specificity 62%). The 19.1 months cut-point value in the total cohort and the 18.4 months cut-point value in HR were as useful in predicting overall survival as 18 months age at diagnosis. Conclusion The 18 months cut-point value appears to be the appropriate age for prognostic determination, despite the higher median age at diagnosis in South Africa.

Published
2020

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