The many contributors to the development of the recommendations are acknowledged in the subsections below according to the evidence reviews of the intervention areas.
Funding
The consolidated WHO Guidelines for malaria, developed by the WHO Global Malaria Programme, were supported by multiple donors including the Bill & Melinda Gates Foundation, the United States Agency for International Development, and the Government of Spain.
The Malaria Vaccine Implementation Programme, the RTS,S/AS01 SAGE/MPAG Working Group, and the generation of additional evidence on the first malaria vaccine relied on financial support received from Gavi, the Vaccine Alliance, the Global Fund to Fight AIDS, Tuberculosis and Malaria, and Unitaid.
Platform contribution
WHO would like to acknowledge the MAGIC Evidence Ecosystem Foundation for its support in the consolidation of the Guidelines on the MAGICapp platform.
10.1. Guidelines for malaria vector control
The following outlines the constitution of the Guidelines Development Group, Guidelines Steering Group, and External Review Group for recommendations drafted in 2019 and in 2021. Also indicated are members of the systematic review production and management team and Grading of Recommendations Assessment, Development and Evaluation (GRADE) analysis subgroup, as well as the guidelines methodologist. Final compositions of these groups are shown as of the date of finalization of the Guidelines.
Members of the Guidelines Development Group (2019)
The WHO Technical Expert Group on Malaria Vector Control (VCTEG) served as the Guidelines Development Group and included:
Dr Constance Bart-Plange, Independent Malaria Consultant, Accra, Ghana
Professor Marc Coosemans, Department of Parasitology, Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium
Dr Camila Pinto Damasceno, FIOCRUZ Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
Dr Marcy Erskine, Senior Health Officer (Malaria), International Federation of Red Cross and Red Crescent Societies, Geneva, Switzerland
Dr Josiane Etang, Organisation de coordination pour la lutte contre les endémies en Afrique centrale, Yaoundé, Cameroon
Dr John Gimnig (Chair), Entomology Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, United States of America
Dr Jeffrey Hii, Malaria Consortium, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Dr Zhou Hong-Ning, Office of Joint Prevention and Control of Malaria/ Dengue, Yunnan Institute of Parasitic Diseases, Shanghai, People’s Republic of China
Dr Hmooda Toto Kafy, Integrated Vector Management Department Manager and Deputy Manager of National Malaria Control Programme, Federal Ministry of Health, Khartoum, Sudan
Professor Jonathan Lines, London School of Hygiene and Tropical Medicine, London, United Kingdom of Great Britain and Northern Ireland
Dr Stephen Magesa, Technical Specialist, AIRS Tanzania Project, Abt Associates Inc., Mwanza, United Republic of Tanzania
Dr Eunice Misiani, Malaria and Other Vector Borne Diseases, National Department of Health, Pretoria, South Africa
Dr Rajander Singh Sharma, Centre for Medical Entomology and Vector Control National Centre for Disease Control, Ministry of Health and Family Welfare, Delhi, India
Members of the Guidelines Steering Group (2019)
Dr Rabindra Abeyasinghe, WHO Regional Office for the Western Pacific, Manila, Philippines
Dr Birkinesh Ameneshewa, WHO Regional Office for Africa, Brazzaville, Congo
Dr Samira Al-Eryani, WHO Regional Office for the Eastern Mediterranean, Cairo, Egypt
Dr Haroldo Bezerra, WHO Regional Office for the Americas, Washington DC, United States of America
Dr Florence Fouque, Special Programme for Research and Training in Tropical Diseases, Geneva, Switzerland
Dr Jan Kolaczinski, Global Malaria Programme, World Health Organization, Geneva, Switzerland
Dr Tessa Knox, Global Malaria Programme, World Health Organization, Geneva, Switzerland
Mrs Marion Law, Prequalifications Team for Vector Control, Departments of Essential Medicines of Health Products, World Health Organization, Geneva, Switzerland
Dr Peter Olumese, Global Malaria Programme, World Health Organization, Geneva, Switzerland
Mrs Edith Patouillard, Global Malaria Programme, World Health Organization, Geneva, Switzerland
Dr Nathalie Roebbel, Department of Public Health, Environment and Social Determinants of Health, World Health Organization, Geneva, Switzerland
Dr Matt Shortus, WHO Country Office, Lao People’s Democratic Republic
Dr Raman Velayudhan, Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland
Members of the External Review Group (2019)
The WHO Malaria Policy Advisory Committee (MPAC) served as the External Review Group and included:
Professor Ahmed Adeel, Independent Consultant, United States of America
Dr Evelyn Ansah, Director, Center for Malaria Research, Institute of Health Research, University of Health and Allied Sciences, Ghana
Professor Thomas Burkot, Professor and Tropical Leader, Australian Institute of Tropical Health and Medicine, James Cook University, Australia
Professor Graham Brown, Professor Emeritus, University of Melbourne, Australia
Dr Gabriel Carrasquilla, Director of ASIESALUD, Fundación de Santa Fe de Bogota, Centre for Health Research, Colombia
Dr Maureen Coetzee, Director, Wits Research Institute for Malaria, University of Witwatersrand, South Africa
Professor Umberto d’Alessandro, Director, Medical Research Council Unit, Gambia
Dr Abdoulaye Djimde, Head, Molecular Epidemiology and Drug Resistance Unit, Malaria Research and Training Center, University of Mali, Mali
Professor Azra Ghani, Professor in Infectious Diseases, Epidemiology, Centre for Outbreak Analysis and Modelling, Imperial College, United Kingdom
Professor Brian Greenwood, Manson Professor of Clinical Tropical Medicine, London School of Hygiene and Tropical Medicine, United Kingdom
Dr Caroline Jones, Senior Social Scientist, KEMRI Wellcome Trust Research Programme, Kenya
Dr Stephen Kachur, Chief, Malaria Branch, Centers for Disease Control and Prevention, United States of America
Professor Kevin Marsh (Chair), Director, KEMRI Wellcome Trust Research Programme, Kenya
Dr Kamini Mendis, Independent Consultant in malaria and tropical medicine, Sri Lanka
Professor Gao Qi, Senior Professor, Jiangsu Institute of Parasitic Diseases and Suzhou University, People’s Republic of China
Dr Pratap Singhasivanon, Associate Professor, Department of Tropical Hygiene, Mahidol University, Thailand
Dr Larry Slutsker, Director, Malaria and Neglected Tropical Diseases, Center for Malaria Control and Elimination, PATH, United States of America
Dr Richard Steketee, Director, Malaria Control and Elimination, PATH, United States of America
Dr Neena Valecha, Director, National Institute for Malaria Research, India
Professor Dyann Wirth, Richard Pearson Strong Professor and Chair, Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, United States of America
Systematic review production and management team and GRADE analysis subgroup members (2019)
Mr Leslie Choi, Cochrane Infectious Diseases Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
Mr Joe Pryce, Cochrane Infectious Diseases Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
Ms Marty Richardson, Cochrane Infectious Diseases Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
Dr Vittoria Lutje, Cochrane Infectious Diseases Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
Dr Deirdre Walshe, Cochrane Infectious Diseases Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
Prof Paul Garner, Cochrane Infectious Diseases Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
Guidelines methodologist (2019)
Dr Joseph Okebe, Guidelines Methodologist, Disease Control and Elimination Team, Medical Research Council Unit, Gambia
Declaration of interests (2019)
Participants in the technical consultations or sessions for development of the Guidelines reported relevant interests. The declared interests, as per WHO regulations, were assessed by the WHO Secretariat, with support from the Office of Compliance, Risk Management and Ethics as needed. WHO was of the opinion that these declarations did not constitute conflicts of interest and that the considered experts could participate in the consultations on the Guidelines subject to the public disclosure of their interests, which was conducted.
The relevant declared interests are summarized as follows:
Dr T. Burkot reported several potential conflicts of interest related to consulting payments, research support and non-monetary support, as follows: 1) consulting with Intellectual Ventures Global Good Fund (IVGGF), the non-profit arm of Intellectual Ventures Laboratory. Work was conducted from October 2014 to March 2015 through James Cook University; 2) consulting with IVGGF for a secondment in 2017 to develop a vector control strategy on mosquitoproof housing and methods to age-grade mosquitoes through James Cook University; 3) consulting with the non-profit Programme for Appropriate Technology in Health (PATH) in 2017 to support grant applications to evaluate new vector control tools in Africa; 4) consulting with IVGGF from 2017 to February 2018 to provide technical support on developing guidelines for testing new vector control strategies, paid directly to Dr Burkot; 5) consulting with PATH from 2017 to February 2018 to provide technical advice on field trials for mosquito-proof housing products paid, directly to Dr Burkot; 6) research support in a supervisory role provided to James Cook University for evaluation of a new malaria diagnostic test from October 2015 to March 2017; 7) research support in a supervisory role provided to James Cook University to undertake a malaria serologic survey in the Solomon Islands until June 2018; and 8) non-monetary support to Vestergaard in a supervisory role to evaluate the impact of insecticide netting on malaria in Solomon Islands.
Dr M. Coetzee reported a potential conflict of interest related to a family member’s consulting work with AngloGold Ashanti in 2016 to carry out mosquito surveys and determine insecticide resistance in order to inform vector control strategies by gold mining companies in Africa.
Professor M. Coosemans reported receiving a grant from the Bill & Melinda Gates Foundation for studying the impact of repellents for malaria prevention in Cambodia and also reported receiving repellent products for the study from SC Johnson for work conducted in 2012–2014. He also reported receiving six grants for the evaluation of public health pesticides from WHOPES from 2007, some of which continued until 2018.
Dr J. Hii reported receiving remuneration for consulting services from WHO and from the Ministry of Health of Timor-Leste for work conducted in 2017. He reported holding a grant from SC Johnson that ceased in 2017 for the evaluation of transfluthrin, and receiving travel and accommodation support from Bayer Crop Science to attend the 4th Bayer Vector Control Expert Meeting in 2017. He reported holding a WHO/TDR research grant that focused on studying the magnitude and identifying causes for residual transmission in Thailand and Viet Nam (completed in 2018), and reported a plan to study the impact of socio-ecological systems and resilience (SESR)-based strategies on dengue vector control in schools and neighbouring household communities in Cambodia, which in November 2017 was awaiting ethical approval.
Members of the Guidelines Development Group (2021)
Dr Dorothy Achu, Programme manager, National Malaria Control Programme, Yaoundé, Cameroon, AFRO (Female – Expertise: end-user perspective, service-user, Case management & chemoprevention)
Prof Basil Brooke, Associate professor, University Witwatersrand/National Institute for Communicable Disease, Johannesburg, South Africa, AFRO (Male – Expertise: entomology, programmatic
vector control, policy)
Prof Ahmadali Enayati, Head, Medical Entomology Department, School of Public Health, Mazandaran University of Medical Sciences, Sari, Islamic Republic of Iran, EMRO (Male – Expertise: service-user, entomology)
Dr Seth Irish, Research entomologist, Centers for Disease Control and Prevention, Atlanta, United States of America, AMRO (Male – Expertise: entomology,
vector control, programme implementing partner)
Prof Fang Jing, Director, Institute for Health Sciences, Kunming Medical University, Yunnan Province, People’s Republic of China, WPRO (Female – Expertise: maternal and child health, gender, equity, ecohealth)
Dr Keziah Malm, Programme manager, National Malaria Control Programme, Accra, Ghana, AFRO (Female – Expertise: end-user perspective, service-user, public health, field epidemiology)
Dr Kui Muraya, Social scientist, KEMRI-Wellcome Trust, Nairobi, Kenya, AFRO (Female – Expertise: child health, gender and social determinants of health)
Prof Martha Quiñones, Professor, Universidad Nacional de Colombia, Bogotá, Colombia, AMOR (Female – Expertise: service-user, entomology,
insecticide resistance)
Dr Christina Rundi, Health director, Sabah Health Department, Ministry of Health, Sabah, Malaysia, WPRO (Female – Expertise: end-user perspective, health programme delivery)
Dr Tanya Russell, Research fellow, James Cook University, Cairns, Australia, WPRO (Female – Expertise: Entomology,
vector control)
Dr Lucy Tusting, Assistant professor, Faculty of Infectious Tropical Disease, LSHTM, London, United Kingdom, EURO (Female – Expertise: housing interventions for
malaria control &
larval source management)
Dr Josh Yukich, Associate professor, Department of Tropical Medicine Tulane University School of Public Health and Tropical Medicine, New Orleans, United States of America, PAHO (Male – Expertise: epidemiology, mathematical modelling, economics,
vector control)
Members of the Guidelines Steering Group (2021)
Dr Samira Al-Eryani, WHO Regional Office for the Eastern Mediterranean, Cairo, Egypt
Dr Haroldo Bezerra, WHO Regional Office for the Americas, Washington DC, United States of America
Dr Maurice Bucagu, Family, Women, Children and Adolescents, World Health Organization, Geneva, Switzerland
Dr Emmanual Chanda, WHO Regional Office for Africa, Brazzaville, Congo
Dr Florence Fouque, Special Programme for Research and Training in Tropical Diseases, Geneva, Switzerland
Dr Riffat Hossain, Programme for Health and Migration, World Health Organization, Geneva, Switzerland
Dr Tessa Knox, WHO Country Office, Vanuatu
Dr Jan Kolaczinski, Global Malaria Programme, World Health Organization, Geneva, Switzerland
Mrs Marion Law, Prequalification Team for Vector Control, Departments of Essential Medicines of Health Products, World Health Organization, Geneva, Switzerland
Dr Kim Lindblade, Global Malaria Programme, World Health Organization, Geneva, Switzerland
Dr Katherine Littler, Department of Research for Health, World Health Organization, Geneva, Switzerland
Dr Ramona Ludolph, Environment, Climate Change and Health, World Health Organization, Geneva, Switzerland
Dr Edith Patouillard, Global Malaria Programme, World Health Organization, Geneva, Switzerland
Dr Matt Shortus, WHO Country Office, Lao People’s Democratic Republic
Dr Jennifer Stevenson, Global Malaria Programme, World Health Organization, Geneva, Switzerland
Dr Raman Velayudhan, Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland
Members of the External Review Group (2021)
Dr Jenifer Armistead, Malaria Division, United States Agency for International Development (USAID), Unites States of America
Prof Maureen Coetzee, University of the Witwatersrand, South Africa
Professor Umberto d’Alessandro, Director, Medical Research Council Unit, Gambia
Dr Scott Filler, Global Fund to Fight AIDS, Tuberculosis and Malaria, Geneva, Switzerland
Dr Caroline Jones, Senior Social Scientist, KEMRI Wellcome Trust Research Programme, Kenya
Prof Neil Lobo, University of Notre Dame, United States of America
Dr Melanie Renshaw, African Leaders Malaria Alliance
Systematic review team members (2021)
Prof Paul Garner, Cochrane Infectious Diseases Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
Dr Jo Leonardi-Bee, University of Nottingham, United Kingdom
Prof Jo Lines, London School of Hygiene and Tropical Medicine, London, United Kingdom
Dr Elisa Martello, University of Nottingham, United Kingdom
Dr Lucy Paintain, London School of Hygiene and Tropical Medicine, London, United Kingdom
Dr Rebecca Thomas, Cochrane Infectious Diseases Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
Dr Gowsika Yogeswaran, University of Nottingham, United Kingdom
Guidelines methodologist and co-chair (2021)
Elie Akl, American University of Beirut, Lebanon
Declaration of interests (2021)
Members of the GDG and ExRG were requested to declare any interests related to the topic of the meeting. The declared interests, as per WHO regulations, were assessed by the WHO Secretariat with support from the Office of Compliance, Risk Management and Ethics as needed.
The relevant declared interests for the GDG are summarized as follows:
Lucy Tusting: It was determined that Dr Tusting could participate in all parts of the meeting except for decision-making with respect to recommendations related to housing improvements.
The relevant declared interests for the ExRG are summarized as follows:
Umberto d’Allessandro: the declared interests regarding the remuneration for acting on the advisory board, travel and the value of the donated drugs were considered financially significant, however the subjects of these interests were not related to the topics of the review. The projects associated with housing modifications or improvements (2 to 4) were related to the subject of discussion. However, as the remit of the ExRG was limited to identifying factual errors, providing clarity and commenting on implications for implementation not changing the recommendations formulated by the GDG it was concluded that his contributions would be valuable given his vast field experience.
Jennifer Armistead: The declared interests were considered financially significant. Projects 1 and 2 were not related to the subject of the review. The fourth project was evaluating larviciding, which, although part of larval source management, was not an intervention for which revisions were being made in the vector control guidelines. The project associated with housing modifications (3) was related to the subject of discussion. However, as reviewers were not being asked to change the meaning of the recommendations themselves, it was concluded that her contributions would be valuable particularly in commenting on uptake of the recommendations given her vast field implementation experience.
Maureen Coetzee: The declared interests regarding the funding provided were considered financially significant. Project 3 investigated housing characteristics that were associated with the risk of mosquito biting but did not evaluate the impact of housing modifications on malaria. Given her vast field experience, it was concluded that her review of the vector control guidelines would be valuable especially in commenting on implications for implementation.
Caroline Jones: Endectocides and vaccines were not topics of discussion for this review and so these projects were not considered a potential conflict of interest. The second project above aimed to investigate the factors limiting the efficacy of current tools to prevent malaria, largely insecticide-treated nets, and to identify the most cost effective, complementary interventions that would drive malaria transmission towards zero. Although this project could consider interventions under discussion by the ExRG, it did not seek to systematically evaluate a particular tool. The third project was linked to one of the subjects being discussed as part of the review. As with Prof D’Alessandro and Prof Coetzee, because the review was limited to identifying factual errors and commenting on clarity and implementation of the recommendations, it was felt that Dr Jones could provide useful insight on factors to be considered associated with gender and social determinants, equity, and human rights.
Neil Lobo: The declared interests regarding the funding provided and provision of research materials were considered financially significant. None of the projects where companies had provided support were deemed to be related to the subject of the review. Only the topic of research project 7, ‘Screening mosquito entry points into houses with novel long lasting insecticidal netting to reduce indoor vector densities and mitigate pyrethroid resistance’ was considered to be related to the subject of the review. As the ExRG was not being asked to comment on the recommendations themselves, but rather to ensure the wording was clear, accurate and supporting uptake by end-users, it was felt that Prof Lobo could provide a useful review given his vast experience working with national programmes.
Melanie Renshaw: While the amount received was deemed significant, the nature of her work did not address the specific topics under review and so did not represent a conflict of interest.
10.2. Malaria vaccine recommendation
The following outlines the constitution of MPAG, SAGE, the RTS,S/AS01 MPAG/SAGE Working Group, and the External Review Group for the recommendations drafted in 2021. Also indicated are members of the systematic review production and management team and GRADE analysis subgroup, as well as the guidelines methodologists. Final compositions of these groups are shown as of the date of finalization of the Guidelines.
Members of MPAG
Dr Samira Abdelrahman, Professor of Community Medicine, Faculty of Medicine, University of Gezira, Sudan
Professor Ahmed Adeel, Professor of Medical Parasitology, College of Medicine, King Saud University, Saudi Arabia
Emeritus Professor Graham Brown, University of Melbourne, Australia
Professor Tom Burkot, Professor and Tropical Leader, Australian Institute for Topical Health and Medicine, James Cook University, Cairns, Australia
Dr Gabriel Carrasquilla, Director of ASIESALUD for consultancy and research in epidemiology and public health
Professor Maureen Coetzee, Professor and Director, Wits Research Institute for Malaria, University of the Witwatersrand, Johannesburg, South Africa
Professor Umberto d’Alessandro, Director, Medical Research Council Unit, Gambia
Professor Abdoulaye Djimde, Head, Molecular Epidemiology and Drug Resistance Unit, Faculty of Medicine, University of Mali, Mali
Professor Gao Qi, Senior Professor, Jiangsu Institute of Parasitic Diseases, Wuxi, China
Professor Azra Ghani, Chair in Infectious Disease Epidemiology, Faculty of Medicine, School of Public Health, Imperial College, London, United Kingdom of Great Britain and Northern Ireland
Dr Caroline Jones, Senior Social Scientist, KEMRI-Wellcome Trust Research Programme, Kenya
Dr S. Patrick Kachur, Columbia University Irving Medical Center, United States of America
Professor Evelyn Ansah, Director, Center for Malaria Research, University of Health and Allied Sciences, Ghana
Dr Nilima Kshirsagar, Emeritus Scientist, Indian Council of Medical Research, India
Dr Fedros Okumu, Public Health Researcher and Director of Science at Ifakara Health Institute, United Republic of Tanzania
Dr Arantxa Roca Feltrer, Head of Surveillance, Monitoring and Evaluation, Malaria Consortium, Madagascar
Professor Dyann Wirth, Director, Harvard Life Sciences, Harvard T.H. Chan School of Public Health, United States of America (MPAG Chair)
Members of SAGE
Professor Rakesh Aggarwal, Director, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), India
Professor Alejandro Cravioto, Professor Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico (SAGE Chair)
Dr Ilesh Jani, Director General, National Institute of Health, Ministry of Health, Mozambique
Dr Jaleela Jawad, Head of the Immunization Group, Public Health Directorate, Ministry of Health, Bahrain
Dr Sonali Kochhar, Clinical Associate Professor, Department of Global Health, University of Washington, United States of America
Professor Noni MacDonald, Professor of Paediatrics, Division of Paediatric Infectious Diseases, Dalhousie University, Canada
Professor Shabir Madhi, Professor of Vaccinology, University of the Witwatersrand, South Africa
Professor Peter McIntyre, Professor, Department of Women’s and Children’s Health, Dunedin School of Medicine, University of Otago, New Zealand
Dr Ezzeddine Mohsni, Senior Technical Adviser, Global Health Development (GHD), The Eastern Mediterranean Public Health Network (EMPHNET), Jordan
Professor Kim Mulholland, Murdoch Children’s Research Institute, University of Melbourne, Australia
Professor Kathleen Neuzil, Director, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, United States of America
Dr Hanna Nohynek, Chief Physician, Finnish Institute for Health and Welfare (Thl), Finland
Dr Folake Olayinka, USAID Immunization Team Lead, United States of America
Professor Punnee Pitisuttithum, Head, Department of Clinical Tropical Medicine, Mahidol University, Thailand
Professor Andrew J. Pollard, Professor, Department of Paediatrics, University of Oxford, United Kingdom of Great Britain and Northern Ireland
Members of the RTS,S/AS01 MPAG/SAGE Working Group
Professor Ifedayo Adetifa, KEMRI-Wellcome Trust Research Programme, Kenya
Professor Nick Andrews, Public Health England, United Kingdom of Great Britain and Northern Ireland
Dr Dafrossa Cyrily Lyimo, Independent consultant (and former National Immunization and Vaccine Development Programme Manager), United Republic of Tanzania
Dr Corine Karema, Independent consultant (and former Director of the Rwanda National Malaria Control Programme), Rwanda
Dr Eusebio Macete, Centro de Investigação em Saúde de Manhiça, Mozambique (Co-Chair)
Professor Kim Mulholland, Murdoch Children’s Research Institute, Australia
Professor Kathleen Neuzil, Center for Vaccine Development and Global Health (CVD), University of Maryland School of Medicine, United States of America
The late Ms Adelaide Shearley, John Snow Inc., Zimbabwe
Professor Peter Smith, London School of Hygiene & Tropical Medicine, United Kingdom of Great Britain and Northern Ireland (Chair)
Professor S. Patrick Kachur, Mailman School of Public Health, Columbia University, United States of America
Members of the RTS,S/AS01 MPAG/SAGE Working Group Secretariat
Dr Pedro Alonso, Global Malaria Programme
Dr Tracey Goodman, Expanded Programme on Immunization
Mr John Grove, Quality Assurance / Norms & Standards
Dr Joachim Hombach, Agenda, Policy & Strategy
Dr Melanie Marti, Agenda, Policy & Strategy
Dr Kate O’Brien, Immunization, Vaccines and Biologicals
Dr Vaseeharan Sathiyamoorthy, Research for Health
Rapporteur: Ms Cynthia Bergstrom, Consultant for WHO
Members of the WHO Editorial Board
Dr Madhava Ram Balakrishnan
Dr Shalini Desai, Expanded Programme on Immunization
Ms Eliane Furrer, Immunization, Vaccines and Biologicals
Ms Tracey Goodman, Expanded Programme on Immunization
Dr Mary Hamel, Immunization, Vaccines and Biologicals
Dr Joachim Hombach, Immunization, Vaccines and Biologicals
Dr Dianliang Lei, Norms, Standards and Biologicals
Dr Melanie Marti, Immunization, Vaccines and Biologicals
Dr Marie-Perre Preziosi, Immunization, Vaccines and Biologicals
Dr David Schellenberg, Global Malaria Programme
Ms Erin Shutes, Global Malaria Programme
Members of the Peer review group (External review group)
Members of the Peer review group include SAGE, MPAG, WHO Regional Offices, external subject matter experts, selected national immunization and malaria programme managers, other interested parties (who have not been involved in the process to that point) and industry. Request for peer-review from industry is coordinated through the International Federation of Pharmaceutical Manufacturers Association and the Developing Country Vaccine Manufacturer Network. The list of external reviewers is available upon request from the SAGE secretariat.
Guidelines methodologist and systematic review team
Two methodologists from the Cochrane Response – Gemma Villanueva and Nicholas Henschke – were commissioned to support the development of the malaria vaccine recommendations. They provided a systematic review of evidence, applied the PICO framework to conduct evidence assessments using GRADE, and supported the SAGE/MPAG Working Group in the transparent formulation of evidence-informed recommendations.
Designated writer/editor
Dr Laurence Slutsker drafted and consolidated a full evidence review for the SAGE/MPAG Working Group. WHO contracted Dr Slutsker under an Agreement for Performance of Work (APW).
Declaration of interests
All nine SAGE/MPAG Working Group members updated their Declarations of Interest in advance of the meeting. These were assessed by the WHO Secretariat. Six members reported interests; it was assessed that all members could fully participate. The full summary of interests for the SAGE/MPAG Working Group is available on the WHO Malaria Vaccine Implementation Programme website.
All 15 SAGE members participating in the meeting updated their Declarations of Interest in advance of the meeting. These were assessed by the WHO Secretariat. Eleven SAGE members reported interests and zero SAGE members recused themselves from the discussion and decision-making during the malaria vaccine session. The full summary of interests for SAGE members is available on the meeting website.
All 17 MPAG members participating in the meeting updated their Declarations of Interest in advance of the meeting. These were assessed by the WHO Secretariat. Thirteen members reported interests and five MPAG members reported relevant interests. Three members (Evelyn Ansah, Abdoulaye Djimde and Azra Ghani) recused themselves from the discussion and decision-making during the malaria vaccine session. It was assessed that the remaining members could fully participate in all sessions. The full summary of interests for MPAG members is available on the meeting website.
Professor Evelyn Ansah, University of Health & Allied Sciences, Ghana: declared research support and her role as the Ghana Co-Investigator on funding from PATH for the Health Utilization Study on a qualitative assessment of the pilot implementation of RTS,S. This interest was assessed as non-personal, specific and financially significant.
Professor Abdoulaye Djimde, Head, Molecular Epidemiology Drug Resistance Unit, University of Mali, Mali: declared his role as a sub-investigator on the RTS,S – SMC trial which contributed minimal salary support through the London School of Tropical Medicine & Hygiene. Professor Djimde was a co-author on: Chandramohan
D, Zongo
I, Sagara
I, Cairns
M, Yerbanga
RS, Diarra
M, Nikièma
F, Tapily
A, Sompougdou
F, Issiaka
D, Zoungrana
C, Sanogo
K, Haro
A, Kaya
M, Sienou
AA, Traore
S, Mahamar
A, Thera
I, Diarra
K, Dolo
A, Kuepfer
I, Snell
P, Milligan
P, Ockenhouse
C, Ofori-Anyinam
O, Tinto
H, Djimde
A, Ouédraogo
JB, Dicko
A, Greenwood
B. Seasonal Malaria Vaccination with or without Seasonal Malaria Chemoprevention. N Engl J Med. 2021
Sep
9;385(11):1005–1017. doi: 10.1056/NEJMoa2026330. Epub 2021 Aug 25. PMID: 34432975 [
PubMed: 34432975] [
CrossRef]. This interest is assessed as non-personal, specific and financially significant.
Professor Azra Ghani, Infectious Diseases Epidemiology, Imperial College, UK: declared research support to Imperial College from the Global Fund on different projects related to modelling impact estimates for malaria including global scenarios that incorporate RTS,s from 2016 to 2019 and in 2021. This interest is assessed as non-personal, specific and financially significant; and research support funding from multiple organizations for work on malaria and COVID-19 research including Bill & Melinda Gates Foundation (BMGF), MVI, MMV, IVCC, MRC, Wellcome Trust, NIH over three years (current). Included data analysis and modelling of public health impact of routine implementation and assessment of seasonal implementation related to RTS,s. This interest is assessed as non-personal, specific and financially significant.
Professor Caroline Jones, Senior Social Scientist, KEMRIWellcome Trust Research, Kenya: declared her role as a mentor for a post-doctorate student on the study conducted in collaboration with PATH entitled “Dynamics of health care utilization strategies in the context of RTS,S/AS01 vaccine introduction: a qualitative longitudinal study in Kenya” (2018- 2020). The institution received support for the post-doc who has now left the institution. This interest is assessed as non-personal, specific and non-financially significant.* Although specific to the malaria vaccine, the interest was assessed as that of the post-doc, not Professor Jones as the mentor.
Professor Dyann Wirth, Richard Pearson Strong Professor and Chair, Harvard T.H. Chan School of Public Health, USA: declared a research grant to Harvard University received from PATH and her role as the Principal Investigator for Mal095 using RTS,S to look at the issue of allele specific immunity. This interest is assessed as non-personal, specific and financially significant.* Although related to the malaria vaccine, this work is to understand gaps in immunity provided by RTS,S and will inform the development of future malaria vaccines. This research is not being considered as evidence for the decision on the malaria vaccine and the work will continue regardless of the outcome.
10.3. Guidelines for the treatment of malaria
Since the first and second editions of the Guidelines were issued in 2006 and 2010, respectively, WHO’s methods for preparing guidelines have continued to evolve. The third edition of the Guidelines for the treatment of malaria was prepared in accordance with the updated WHO standard methods for guideline development (1). This involved planning, “scoping” and needs assessment, establishment of a GDG, formulation of key questions (PICO questions: population, participants or patients; intervention or indicator; comparator or control; outcome), commissioning of reviews, Grading of Recommendations, Assessment, Development and Evaluation (GRADE) and making recommendations. This method ensures a transparent link between the evidence and the recommendations. The GRADE system is a uniform, widely adopted approach based on explicit methods for formulating and evaluating the strength of recommendations for specific clinical questions on the basis of the robustness of the evidence.
The GDG, co-chaired by Professor Fred Binka and Professor Nick White (other participants are listed below), organized a technical consultation on preparation of the third edition of the Guidelines. Declarations of conflicts of interest were received from all participants. A WHO Guideline Steering Group facilitated the scoping meeting, which was convened in February 2013, to set priorities and identify which sections of the second edition of the Guidelines were to be reviewed and to define potential new recommendations. Draft PICO questions were formulated for collation and review of the evidence. A review of data on pharmacokinetics and pharmacodynamics was considered necessary to support dose recommendations, and a subgroup was formed for this purpose.
After the scoping meeting, the Cochrane Infectious Diseases Group at the Liverpool School of Tropical Medicine in Liverpool, United Kingdom, was commissioned to undertake systematic reviews and to assess the quality of the evidence for each priority question. The reviews involved extensive searches for published and unpublished reports of trials and highly sensitive searches of the Cochrane Infectious Diseases Group trials register, the Cochrane Central Register of Controlled Trials, MEDLINE®, Embase and LILACS. All the reviews have been published on line in the Cochrane Library. When insufficient evidence was available from randomized trials, published reviews of non-randomized studies were considered.
The subgroup on dose recommendations reviewed published studies from MEDLINE® and Embase on the pharmacokinetics and pharmacodynamics of antimalarial medicines. For analyses of pharmacokinetics and simulations of dosing, they used raw clinical and laboratory data from the Worldwide Antimalarial Resistance Network on the concentrations of antimalarial agents in plasma or whole blood measured with validated assays in individual patients. The data had either been included in peer-reviewed publications or been submitted to regulatory authorities for drug registration. Population pharmacokinetics models were constructed, and the plasma or whole blood concentration profiles of antimalarial medicines were simulated (typically 1000 times) for different weight categories.
The GDG met in two technical meetings, in November 2013 and June 2014, to develop and finalize recommendations based on the GRADE tables constructed on the basis of answers to the PICO questions. The Guidelines were written by a subcommittee of the group. At various times during preparation of the Guidelines, sections of the document or recommendations were reviewed by external experts and users who were not members of the group; these external peer reviewers are listed below. Treatment recommendations were agreed by consensus, supported by systematic reviews and review of information on pharmacokinetics and pharmacodynamics. Areas of disagreement were discussed extensively to reach consensus; voting was not required.
Members of the GDG
Professor K.I. Barnes, Division of Clinical Pharmacology, University of Cape Town, South Africa
Professor F. Binka, (co-Chair), University of Health and Allied Sciences, Ho, Volta Region, Ghana
Professor A. Bjorkman, Division of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
Professor M.A. Faiz, Dev Care Foundation, Dhaka, Bangladesh
Professor O. Gaye, Service de Parasitologie, Faculté de Médicine, Université Cheikh Anta Diop, Dakar-Fann, Senegal
Dr S. Lutalo, King Faisal Hospital, Kigali, Rwanda
Dr E. Juma, Kenya Medical Research Institute, Centre for Clinical Research, Nairobi, Kenya
Dr A. McCarthy, Tropical Medicine and International Health Clinic, Division of Infectious Diseases, Ottawa Hospital General Campus, Ottawa, Canada
Professor O. Mokuolu, Department of Paediatrics, University of Ilorin Teaching Hospital, Ilorin, Nigeria
Dr D. Sinclair, International Health Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
Dr L. Slutsker, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
Dr E. Tjitra, National Institute of Health and Development, Ministry of Health, Jakarta, Indonesia
Dr N. Valecha, National Institute of Malaria Research, New Delhi, India
Professor N. White (co-Chair), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Members of the sub-group on dose recommendations
Professor K. Barnes, (co-Chair)
Professor F. Binka
Dr S. Lutalo
Dr E. Juma
Professor O. Mokuolu
Dr S. Parikh, Department of Medicine, Yale University School of Public Health, Connecticut, USA
Dr D. Sinclair
Dr J. Tarning, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Dr D.J. Terlouw, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi
Professor N. White (co-Chair)
Guideline Steering Group
Dr A. Bosman, Global Malaria Programme, WHO, Geneva, Switzerland
Dr K. Carter, Malaria Regional Adviser, WHO Regional Office for the Americas, Washington D.C., United States of America
Dr N. Dhingra-Kumar, Health Systems Policies and Workforce, WHO, Geneva, Switzerland
Dr M. Gomes, Special Programme for Research and Training in Tropical Diseases, WHO, Geneva, Switzerland
Dr P.E. Olumese (Secretary), Global Malaria Programme WHO, Geneva, Switzerland
Dr F. Pagnoni, Special Programme for Research and Training in Tropical Diseases, WHO, Geneva, Switzerland
Dr A.E.C. Rietveld, Global Malaria Programme WHO, Geneva, Switzerland
Dr P. Ringwald, Global Malaria Programme WHO, Geneva, Switzerland
Dr M. Warsame, Global Malaria Programme WHO, Geneva, Switzerland
Dr W. Were, Child and Adolescent Health, WHO, Geneva, Switzerland
External reviewers
Dr F. ter-Kuile, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
Dr R. McGready, Shoklo Malaria Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Professor F. Nosten, Shoklo Malaria Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Guidelines methodologist
Professor P. Garner, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
Declaration of interests
Participants in the technical consultation for the review of the Guidelines for the treatment of malaria and the external expert reviewers of the Guidelines reported relevant interests, in accordance with WHO procedures. These were discussed extensively by the committee. Although it was considered that none of the declared interests had direct relevance to the deliberations or recommendations of the meeting, the panel members with declared interests were excluded from the subcommittees on GRADE and recommendations and the drafting group. The declared interests, as per WHO regulations, were reviewed through the Legal Department of WHO.
Dr K. Barnes reported being a grants co-recipient from the Medicines for Malaria Venture to undertake clinical trials to evaluate antimalarial medicines.
Dr F. Binka reported being a member of the INDEPTH network that was a recipient of a research grant from the Bill & Melinda Gates Foundation to conduct Phase IV post licensure studies on “Euratesim”.
Dr P. Garner reported receiving a grant from the Department for International Development (UK) to help ensure global guidelines and decisions are based on reliable evidence.
Dr N. Valecha reported serving as an investigator for a clinical trial supported by the Department of Science and Technology India, and Ranbaxy Laboratories Limited. There were no monetary benefits and no conflicts with the subject of this review.
Professor N. White reported being an advisor to all pharmaceutical companies developing new antimalarial medicines. This is done on a pro bono basis; it did not include consultancy fees or any form of remuneration.
