Malaria genomic surveillance

Interpretation and action guide for National Malaria Control Programmes

How to use: Select a theme and find the public health question. Read across the genomic interpretation, supporting evidence, follow-up triggers and programme action. Scroll horizontally within each open theme. Developed through contributions from an international community of malaria experts, this resource provides practical recommendations for interpreting genomic surveillance findings and informing public health action. It is intended to complement, rather than replace, applicable WHO guidance and national policies.
AAntimalarial drug resistance and treatment efficacy 3 guidance entries
Guidance entryPublic health questionGenomic interpretationSupporting evidenceTrigger for follow-upRecommended NMCP actionReviewer feedback / caveat
Molecular correction in therapeutic efficacy studiesIs recurrent parasitaemia consistent with recrudescence or reinfection?Paired pre- and post-treatment parasite genotypes are used in TES molecular correction; this is not itself a resistance-marker surveillance result.TES follow-up and paired samples; quality-assured genotyping; clinical/parasitological outcomes.Recurrent parasitaemia during TES follow-up requiring molecular correction.Use molecular-correction results in TES efficacy estimates; consider treatment-policy review using the appropriate WHO TES criteria.Separated from resistance monitoring as requested; do not treat molecular correction alone as a policy trigger.
Monitoring treatment-drug resistance markersAre validated treatment-resistance markers emerging, increasing or spreading?Track relevant validated markers, their frequencies and distribution; interpret molecular signals separately from demonstrated clinical failure.Representative molecular surveillance; marker validation status; drug-use context; TES where available.New validated markers, increasing frequencies or evidence of geographic spread warrant investigation.Confirm and characterise findings; intensify surveillance and prioritise TES or other investigations as appropriate.Do not equate any detected variant with confirmed resistance; the source's proposed 'two triggers = containment' rule requires independent validation.
Monitoring preventive-drug resistance markersAre resistance markers relevant to preventive antimalarial regimens changing?Monitor markers relevant to drugs used for chemoprevention, including antifolate-associated markers where applicable.Prevention regimen and coverage; representative sampling; clinical/programme effectiveness evidence.New or increasing relevant markers, interpreted in the context of the preventive regimen.Investigate trends and assess whether additional monitoring or programme review is warranted.Retain dhfr/dhps for preventive-drug surveillance rather than deleting solely because SP is not first-line treatment for uncomplicated malaria.
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BDiagnostic resistance and parasite identification 2 guidance entries
Guidance entryPublic health questionGenomic interpretationSupporting evidenceTrigger for follow-upRecommended NMCP actionReviewer feedback / caveat
Monitoring malaria diagnostic performanceCould pfhrp2/3 deletions explain false-negative HRP2-based RDT results?Molecular confirmation of deletions is relevant to diagnostic escape, but absence of amplification alone does not confirm a deletion.Confirmatory parasite detection; quality controls; representative symptomatic-case sampling; RDT results.Confirmed deletions associated with false-negative HRP2-based RDTs.Assess the need for diagnostic policy review under the applicable WHO protocol.The source cites a 5% threshold; confirm its precise WHO definition and denominator before presenting it as an automatic trigger.
Parasite species identificationWhich malaria parasite species are circulating?Species-specific molecular testing can identify non-falciparum or mixed infections where assay performance permits.Diagnostic findings, species-specific assays and epidemiological context.Unexpected species or discrepant species identification.Confirm findings and use species information to inform appropriate case management and surveillance.Placed with parasite use cases before vector topics, as requested.
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CTransmission, outbreaks and intervention targeting 3 guidance entries
Guidance entryPublic health questionGenomic interpretationSupporting evidenceTrigger for follow-upRecommended NMCP actionReviewer feedback / caveat
Molecular characterisation of malaria outbreaks and epidemicsWhat do parasite genetic patterns suggest about a suspected outbreak?Relatedness, diversity and resistance-marker patterns can help characterise an outbreak but do not by themselves establish transmission links.Case surveillance, time/place data, representative samples and epidemiological investigation.An epidemiologically identified case surge or unusual cluster warranting molecular characterisation.Integrate genomic evidence into outbreak investigation and proportionate response.Approved wording: molecular characterisation, not molecular confirmation; outbreak identification is epidemiological.
Transmission intensity and intervention stratificationWhere do genomic patterns suggest differences in transmission relevant to intervention targeting?MOI/COI, diversity, relatedness and population structure provide context-dependent indicators; they are not universally calibrated transmission measures.Case incidence, spatial and temporal sampling, entomology, intervention coverage and sampling design.Consistent spatial or temporal patterns that merit investigation alongside routine surveillance.Use triangulated evidence to refine surveillance and intervention targeting.Merged 5 and 10 as suggested; remove deterministic 'high MOI = high transmission' interpretations and unvalidated universal thresholds.
Evaluating intervention effectsHave parasite population patterns changed following interventions?Changes in diversity, relatedness or lineage frequencies may support evaluation but are not proof that an intervention caused the change.Longitudinal pre/post data, comparison areas where feasible, coverage and epidemiological trends.Unexpected or persistent transmission patterns after intervention.Review programme performance and investigate alternative explanations before modifying interventions.Explicitly avoid causal attribution from genomic change alone.
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DElimination and importation 2 guidance entries
Guidance entryPublic health questionGenomic interpretationSupporting evidenceTrigger for follow-upRecommended NMCP actionReviewer feedback / caveat
Evidence supporting malaria elimination assessmentWhat genomic evidence can support assessment of interrupted indigenous transmission?Genomic evidence may help investigate transmission origin but cannot alone establish malaria-free certification eligibility.High-quality case-based surveillance, epidemiological investigations, travel history and WHO certification criteria.Suspected indigenous transmission or uncertain case origin during elimination assessment.Integrate supporting genomic evidence into the broader elimination assessment.PCR is not a mandatory WHO malaria-free certification requirement. Genomic evidence may support investigations but does not replace certification criteria.
Investigating imported versus locally acquired infectionsIs an infection more consistent with importation or local acquisition?Genetic assignment or relatedness can support probabilistic origin inference when reference populations are informative.Travel and exposure history, epidemiological case investigation and appropriate geographic reference data.Uncertain origin or suspected importation relevant to case classification and response.Investigate case origin and prevent onward transmission as indicated.Keep distinct from certification; avoid definitive origin labels where neighbouring populations are genetically similar.
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EVector resistance and infection 2 guidance entries
Guidance entryPublic health questionGenomic interpretationSupporting evidenceTrigger for follow-upRecommended NMCP actionReviewer feedback / caveat
Monitoring insecticide resistanceAre molecular indicators of vector insecticide resistance present or changing?Resistance-associated variants can contribute to surveillance but do not replace phenotypic resistance testing.WHO susceptibility bioassays, vector species identification, insecticide exposure and local entomology.New or increasing resistance signals requiring confirmation.Use integrated resistance evidence to inform vector-control review.Genetic marker detection alone is insufficient to prescribe vector-control changes.
Detecting sporozoite infection in vectorsAre sampled mosquitoes infected with malaria parasites?Detection of parasite material in mosquitoes supports infection surveillance but requires appropriate assay interpretation.Validated assays, vector identification, sampling context and entomological indicators.Detection of parasite infection in sampled vectors.Integrate results into assessment of transmission risk and targeting.Avoid claiming that any positive molecular result alone proves local transmission.
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FVector species and distribution 1 guidance entries
Guidance entryPublic health questionGenomic interpretationSupporting evidenceTrigger for follow-upRecommended NMCP actionReviewer feedback / caveat
Molecular identification and surveillance of malaria vector species and their distributionWhich vector species are present, newly detected or changing in distribution?Species identification and georeferenced occurrence data can identify unexpected species and apparent distribution changes.Species-specific molecular confirmation, entomological sampling, location/time metadata and historical baseline.Confirmed unexpected or invasive species detection or a substantiated change in distribution.Verify findings, update vector surveillance/risk maps and assess appropriate species-specific response.Merged 12, 13 and 15 as requested; response urgency must depend on species, setting and confirmation.
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Contributors

  • Agaba Bosco
  • Deus Ishengoma
  • Alfred Ngwa
  • David Oladejo
  • Vera Mitesser
  • Migbaru Keffale
  • Stephanie van Wyk
  • Bernardete Rafael
  • Francis Mubigalo
  • Alfredo Mayor
  • Eddie Lulamba
  • Chiyun Lee
  • Olateju Idowu
  • Hazel Beverly Gwarinda
  • Blaženka Danica Letinić
  • Emma Griffiths
  • Kathryn Murie
  • Paulo Arnaldo
  • Victoire Nsabatien
  • Richard Pearson
  • Mehul Dhorda
  • Igiraneza Clement
  • Tracey Calvert-Joshua

Source: reviewer-feedback revision of the grouped malaria use cases workbook. Original use-case numbers are recorded in the searchable row metadata; the source workbook remains unchanged. Numerical action thresholds and other technical recommendations require verification against current authoritative guidance before operational use.