Promoting consistency in microscopy for malaria research
A new microscopy manual is supporting researchers to deliver consistent and reliable data, as well as promoting standardisation in reports.
Assessments of the efficacy of antimalarial drugs and vaccines and of the performance of diagnostic devices all require sensitive, accurate and precise measurement of the numbers and species of malaria parasites. Microscopic examination of stained blood films continues to be a major reference standard for the detection, identification and quantitation of malaria parasites in the context of clinical and operational research.
The consistency and reliability of microscopy results depend on numerous factors, beginning with the quality of the materials and equipment used, and the protocols applied for slide reading and quality assurance. However, the most important influence is probably the proficiency of the microscopists who read the slides.
WWARN researchers have worked together with a group of experts convened by the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) to develop a manual for microscopy for the detection, identification and quantification of malaria parasites on stained thick and thin blood films in research settings.
The group of collaborating institutions comprised: TDR; WWARN; the Foundation for Innovative New Diagnostics (FIND); the Centers for Disease Control and Prevention (CDC), USA; and the Kenya Medical Research Institute (KEMRI), and later expanded to include: Amref Health Africa (Kenya); the Eijkman-Oxford Clinical Research Unit (EOCRU), Indonesia; Institut Pasteur du Cambodge (IPC); Institut de recherche pour le Développement (IRD), Senegal; the Global Good and Intellectual Ventures Laboratory (GG-IVL), USA; the Mahidol-Oxford Tropical Medicine Research Unit (MORU), Thailand; Queensland University of Technology (QUT), Australia, and the Shoklo Malaria Research Unit (SMRU), Thailand.
The manual developed by this group is intended to help researchers working in drug or vaccine efficacy trials or in diagnostics to deliver consistent and reliable data and to promote standardisation in reports.
“The interactions between the malaria parasite and the human host are affected by many aspects of their biology and are very complex. It is therefore crucial to standardise our approach to studying the disease so that we can have more confidence in the results and their interpretations,” says Dr Mehul Dhorda, Head of WWARN’s External Quality Assurance Programme. “Such standardisation of methods would facilitate pooled analyses which can better inform drug dosing and treatment strategies. They will be very useful in efforts to track the emergence and spread of antimalarial resistance.”
These procedures, and the standards on which they are based, were adapted from the WHO guidelines to cater to the particular requirements of research malaria microscopy. Routine clinical microscopy is typically performed to confirm the diagnosis of malaria before appropriate treatment can be given. In research contexts however, additional information is needed on the species, parasite stages and the density of the infecting parasites.
High diagnostic specificity is of particular importance in research microscopy as false positive results can significantly skew efficiency estimates. Accordingly, the recommended procedures incorporate best practices from various published procedures to cover all aspects of malaria microscopy to detect, identify and quantitate malaria parasites from stained blood films. They also include clear guidelines for quality assurance of microscopy and rigorous standards for proficiency testing of microscopists.
Dr John Reeder: Director of TDR, says: "The real power of research trials comes when we can step above individual studies and as a community compare across multiple sites. This consensus on methodology for research microscopy is a great step forward in bringing this power to malaria studies."
“Malaria research has been considerably hampered by a lack of standardisation in this primary method for detection of parasites,” says Dr. David Bell, Director, Infectious Diseases at Global Good, Intellectual Ventures Laboratory. “This multi-institution initiative will contribute to improving the quality and efficiency of efforts to understand, and eradicate malaria.”
The manual is available on the TDR website and on the WWARN procedure space with many other tools to facilitate standardisation. For further information, please email Dr Mehul Dhorda, Head of WWARN’s External Quality Assurance Programme: info@wwarn.org