Regular Plasmodium falciparum importation onto Bioko Island, Equatorial Guinea, hampers malaria elimination from the island

Stabler, T. C.; Dwivedi, A.; Guo, B.; Shrestha, B.; Joshi, S.; Rivas, M. R.; Donfack, O. T.; Guerra, C. A.; Garcia, G.; Daubenberger, C.; Silva, J. C.

doi:10.1101/2024.12.19.629489

bioRxiv · 10.1101/2024.12.19.629489

Regular Plasmodium falciparum importation onto Bioko Island, Equatorial Guinea, hampers malaria elimination from the island

Stabler, T. C.·Dwivedi, A.·Guo, B.·Shrestha, B.·Joshi, S.·Rivas, M. R.·Donfack, O. T.·Guerra, C. A.·Garcia, G.·Daubenberger, C.·Silva, J. C.

View original source ↗Export metadata ↓

Abstract

The Bioko Island Malaria Elimination Project (BIMEP) has made significant progress in reducing the prevalence of Plasmodium falciparum on Bioko Island, Equatorial Guinea. However, like other malaria endemic islands like Sao Tome and Principe and Zanzibar, Tanzania, elimination efforts are hampered by imported infections. In an effort to understand the local transmission dynamics and the influence of importation on Bioko Islands P. falciparum population, whole-genome sequences were generated from field samples collected during the BIMEPs 2019 Malaria Indicator Survey (MIS). Within the sub-Saharan African context, we observed Bioko Island parasites did not significantly differentiate from nearby continental neighbors. Among Bioko infections, within-host diversity and the quantity of polyclonal infections appear similar to an area of moderate malaria transmission. However, we observed higher than expected genetic diversity among Bioko parasites, similar to high transmission areas, suggesting imported strains are contributing to transmission on the island. Among Biokos closest geographical neighbors, the flow of parasites with Bioko appeared more pronounced with the Gabonese parasite population, implying more importation may be coming from this region than others. Overall, despite significant investment in malaria control, results illustrate the challenges of eliminating malaria without both interrupting local transmission and accounting for importation from higher transmission areas, likely due to human migration. For there to be sustained progress towards elimination, the BIMEP needs, if feasible, to conduct targeted interventions of outgoing/incoming travelers, and ideally expand malaria control interventions to the continental region of Equatorial Guinea. ImportancePlasmodium falciparum accounts for the majority of malaria deaths globally, with over 500,000 estimated deaths in 2023, predominantly in sub-Saharan Africa, despite strong investment in control and elimination interventions. Incorporating sequencing technologies into malaria surveillance is viewed as a powerful tool to improve control strategies, including identifying parasite transmission pathways. Here, we provide the first genomic characterization of P. falciparum on Bioko Island and Equatorial Guinea since malaria control began in 2004, and use these data to better understand the contribution of neighboring regions to Biokos P. falciparum population. Results highlight the need to account for offisland contributors to transmission and to understand how unmitigated transmission in neighboring regions can hamper progress. This study furthers our understanding of how the flow of parasites between regions impacts infectious disease control and provides foundational genomic data in a previously undescribed region that can be used to inform malaria elimination efforts.

Explore related subjects

genomics Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Stabler, T. C., Dwivedi, A., Guo, B., Shrestha, B., Joshi, S., Rivas, M. R., Donfack, O. T., Guerra, C. A., Garcia, G., Daubenberger, C., Silva, J. C.. 2024-12-23. Regular Plasmodium falciparum importation onto Bioko Island, Equatorial Guinea, hampers malaria elimination from the island. https://doi.org/10.1101/2024.12.19.629489

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Genomic correlates of metastatic competence and progression in human melanoma

Genomic events and their timing that grant a primary tumour the competence to disseminate remain poorly defined. We performed sequencing of 247 stage I/II primary cutaneous melanomas (CMs) and 60 matched metastases without intervening therapy from a prospectively followed registry cohort with a median followup of 92 months, integrating copy-number, mutational, protein and spatial-transcriptomic analyses. Relapse was not distinguished by oncogenic point mutations, which were largely shared between primaries and metastases, but by somatic copy-number alterations (SCNAs) and global chromosomal instability. We defined OncoCycle, a six-gene copy-number signature (amplification of CDK4, MCL1 and CD276; biallelic loss of CDKN2A, CDKN2B and TP53BP1) that predicted relapse independently of established clinicopathological features in melanoma, and a pan-cancer analysis. In matched pairs, metastatic progression was driven by continued copy-number evolution and reduction in intra-tumoural heterogeneity, rather than by acquired point mutations, and OncoCycle alterations from primary tumours were preserved in metastasis seeding clones. Clonal reconstruction revealed both monoclonal and polyclonal metastasis seeding, and spatial transcriptomics resolved copy-number-defined metastatic subclones occupying and programming distinct immune and stromal niches. Thus, metastatic competence was primed early by focal SCNAs on a background of chromosomal instability, elaborated by continued copy-number evolution during dissemination and spatio-temporal interactions with the tumour-microenvironment.

genomics↗

bioRxiv2026

PfPHAST: Plasmodium falciparum Public Health Amplicon Sequencing Tool, a Streamlined Panel for Malaria Genomic Surveillance

Genomic tools can support malaria control policy through surveillance of Plasmodium falciparum populations, tracking antimalarial drug resistance, pfhrp2/3 deletions that compromise rapid diagnostic tests, and selection at the circumsporozoite protein (PfCSP) vaccine target, as well as through molecular correction of therapeutic efficacy studies (TES). Multiplex Amplicons for Drug, Diagnostic, Diversity, and Differentiation Haplotypes using Targeted Resequencing (MAD4HatTeR), a comprehensive amplicon sequencing panel covering up to 276 targets, supports these applications but is tailored to research rather than routine programmatic use. We developed P. falciparum Public Health Amplicon Sequencing Tool (PfPHAST), a 56-target derivative of MAD4HatTeR spanning drug resistance loci, pfhrp2/3 deletion, PfCSP genotyping, non-falciparum species identification, and 20 high-heterozygosity microhaplotype loci for TES classification. We compared PfPHAST and MAD4HatTeR using laboratory strain controls, including two-strain dilution series and a five-strain mixture, across parasite densities of 100 to 10,000 parasites/L. At matched per-target depth, PfPHAST achieved a higher quality-control pass rate than MAD4HatTeR (94.4% versus 90.0%) and distributed reads more evenly across targets. The panels showed comparable recall and precision for drug resistance codons and microhaplotypes, reaching near-complete recall above 40% within-sample allele frequency (WSAF) at all densities, with reduced sensitivity for minor alleles below 10% WSAF at low parasite density in both panels. Observed and expected WSAF correlated strongly for both panels, and both resolved a five-strain polyclonal mixture, including a 5% minor strain. By concentrating sequencing capacity on targets of greatest programmatic relevance, PfPHAST offers a scalable, lower-cost alternative to comprehensive research panels without sacrificing performance on shared targets, complementing MAD4HatTeR for routine molecular malaria surveillance.

genomics↗

bioRxiv2026

Structural variation in repeat elements is widespread in normal human tissues and in tumorigenesis

Somatic mosaicism contributes to genomic variation, yet postzygotic structural variants remain under-characterized. We performed long- and short-read WGS from multiple individuals (n=47 normal tissues; n=168 samples) and identified mosaic structural variants in all individuals and germ layers, impacting a median 285.2 kb/genome. Nearly half of breakpoints were independently validated, with tissue distributions reflecting both early and late developmental origins. Most mosaic variants were repeat-mediated and 8.3% overlapped functional elements, an enrichment compared to germline variants. To extend these analyses in samples where long-read sequencing is infeasible, we measured repeat alterations from short-read sequencing, recapitulating mosaic tissue-specific differences. We characterized tumor- and tissue- specific variation in repeats across 15 cancer types and found tumor-related repeat variation to be similar in scale to that of normal mosaic variation. Tracking repeat changes in cell-free DNA provided a noninvasive approach for tumor monitoring. Our analyses revealed widespread repeat-driven structural variation in health and disease.

genomics↗