Resource compilation: Responding to the threat of pfhrp2/3 deletions

NOTE: As of February 2024 the contents of this compilation has been migrated to this MESA collection (where all subsequent updates will applied)

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In May 2021, the WHO Malaria Policy Advisory Group (MPAG) released a statement for urgent action in all endemic countries to address the threat of pfhrp2/3 gene deletions and most expeditiously in the Horn of Africa.

WHO has issued guidance on investigating suspected pfhrp2/3 deletions and is encouraging a harmonized approach to mapping and reporting of pfhrp2/3 deletions. This MESA compilation brings together a list of resources available:

WHO guidance

• False-negative RDT results and P. falciparum histidine-rich protein 2/3 gene deletions: Information note
• Response plan to pfhrp2 gene deletions – NOTE that this document is being revised and will be updated by early 2024.

WHO protocols

WHO has published Template protocols to support surveillance and research for pfhrp2/3 gene deletions. Two types of protocols are available:

• Surveillance-only: Surveillance template protocol for pfhrp2/pfhrp3 gene deletions [English PDF] / [French PDF] – NOTE that this document was modified on 19 January 2023. The modifications are listed in the following file: corrigenda (surv. only)
• Surveillance combined with biobanking: Master protocol for surveillance of pfhrp2/3 deletions and biobanking to support future research [English PDF] / [French PDF] – NOTE that this document was modified on 19 January 2023. The modifications are listed in the following file: corrigenda (surv. & biobanking)

* WHO can provide assistance in the molecular analyses through its reference laboratory network
(contact: malaria_rdt@who.int)

WHO tracking

• Pfhrp2/3 Surveillance Tracker Dashboard  – WHO questionnaire to track planned and ongoing surveillance of pfhrp2/3 deletions
• Malaria Threats Map – WHO mapping tool to track published reports of pfhrp2/3 deletions
• WHO Systematic Review  – Prevalence of Plasmodium falciparum lacking histidine-rich proteins 2 and 3: a systematic review (Bull. WHO; 2020)

Online tools​​​​​​

• pfhrp2/3 Planner – Interactive web-based app that can be used to design a pfhrp2/3 deletion study and to analyse the results of such a study
• pfhrp2/3 Deletion Risk Explorer – Interactive web-based app that allow users to explore how changes in the underlying modelling assumptions impact the risk of pfhrp2/3 continuing to spread.

Malaria RDT products (including non-HRP2 based tests)​​​​​​

• Selecting and procuring malaria RDTs – WHO Global Malaria Programme procurement information
• Results of WHO product testing of malaria RDTs (Round 8) – Includes performance assessment against HRP2-negative parasites (see Table 9)
• List of Malaria RDTs according to the Global Fund Quality Assurance Policy – Products eligible for GF procurement after assessment by: (i) the WHO Prequalification (PQ) of Diagnostics Programme; or (ii) the Global Fund’s Expert Review Panel for Diagnostics (ERPD) [October 2023]
• WHO List of Prequalified In Vitro Diagnostic products – IVDs that meet WHO prequalification requirements [August 2023]
• In Vitro Diagnostics Under Assessment (WHO Prequalification) – Progress of the active applications in the prequalification of IVDs assessment pipeline [September 2023; List of Malaria RDTs]
• Malaria diagnostics market and technology landscape (Unitaid – 2022) – Includes analysis of the current malaria RDT market and R&D pipeline

Community of Practice​​​​​​

•  Community of Practice (CoP) on pfhrp2/3 gene deletions – Mobilizing and providing peer and technical support [registration form]

Additional references

REVIEWS

Sampling:

• Mayor A et al. (2023) Trends Parasitology – Sampling for malaria molecular surveillance

Laboratory & screening methodologies:

• Beshir KB et al. (2022) Malaria Journal – Screening strategies and laboratory assays to support Plasmodium falciparum histidine-rich protein deletion surveillance: where we are and what is needed

Systematic reviews & meta-analyses:

• Zeleke AJ et al. (2022) Malaria Journal
• Molina-de la Fuente I et al. (2021) Malaria Journal
• Nyataya J et al. (2020) MDPI
• Kojom LP et al. (2020) Malaria Journal
• Agaba BB et al. (2019) Malaria Journal

MEDIA

• WHO video: Malaria diagnosis – Addressing the issue of HRP2 gene deletions [with French or Spanish subtitles]
• MESA interview: Malaria parasites ‘invisible’ to rapid tests: A conversation with Selam Mihreteab (Eritrea)
• Malaria Minute podcast (JHSPH): Malaria parasites mutate again to evade RDTs, rapid diagnostic tests
• The Conversation (article): Some malaria parasites are evading detection tests, causing an urgent threat to public health

VIRTUAL EVENTS and CONFERENCES

• MESA Forum (2023): Community of Practice on pfhrp2/3 gene deletions [Forum materials]
• MESA Forum (2022): Responding to the threat of malaria parasites evading HRP2-RDTs [Forum materials]
• ASTMH-2020 Symposium (#167): Tracking the Threat of pfhrp2/3 Gene Deletions and Future Alternatives to HRP2-based Malaria Diagnosis [MESA Correspondents Report]
• ASTMH-2017 Symposium (#62): Malaria Rapid Diagnostic Testing: Understanding and Managing the Threat of PfHRP2/3-Negative Plasmodium falciparum [MESA Correspondents Report + Presentation Videos]

PROCEDURE for WHO COMPLAINTS

Any problems experienced by countries concerning RDT performance can be formally communicated to WHO:

• Reporting safety, quality, performance issues for medical devices including in vitro diagnostics (generic procedure for complaints related to in vitro diagnostics)
• Complaints Handling by WHO (concerning a prequalified in vitro diagnostic)