Modeling Malaria Rebound After Mass Drug Administration: The Role of Importation and Waning Immunity in Lake Victoria, Kenya

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Mbugua, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8799575/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background: Mass Drug Administration (MDA) is a WHO-recommended strategy for accelerating malaria elimination. However, its effectiveness in highly mobile populations remains uncertain. Studies show rapid parasitological rebound after cessation of MDA, this suggests that drug-based clearance alone is insufficient in interconnected settings. Although the resurgence is attributed to a combination of waning chemoprophylaxis and parasite importation, the relative contribution of these mechanisms and the quantitative conditions required for sustained elimination remain poorly defined. Methods: We developed a stochastic model of Susceptible-Infected-Recovered-Susceptible (SIRS) compartmentalized to a longitudinal PCR prevalence trial Ngodhe Island (artemisinin-piperaquine + primaquine) in 2016. Based on Bayesian estimation of transmission potential and daily importation rates, we simulated scenarios for a period of 4 years (2016–2019). We compared the epidemiological effects of increasing the MDA schedules (annual versus bimodal, which is two rounds during the two low transmission seasons) and measured the combined effect of integrating enhanced vector control coverage (90% LLIN coverage), port-of-entry screening (80% reduction in importation) and reactive focal MDA. Results: Model simulations have indicated that an intensifying MDA schedule (annual versus bimodal) is not associated with a proportional decrease in mean prevalence, the mean prevalence plateaus at 4.1% as a result of an importation induced equilibrium. This finding implies that, without reducing external seeding, the system will have an equilibrium at the pace of importation faster than the drug pulses can suppress transmission rates. Single-intervention strategies did not meet elimination thresholds but a combination strategy with bimodal MDA combined with improved vector control and importation screening exhibited a non-linear type of intervention combination, as it was able to drive and maintain mean prevalence below the pre-elimination threshold (< 1%). Conclusions: With high mobility like in Ngodhe Island, increasing the frequency of mass treatment is not a viable solution to suppress the reintroduction of parasites. Our results provide mechanistic evidence that elimination requires a shift from the current mono-therapeutic scaling to interventions that are multi-modal. The rollout of importation control and vector control should be made a priority alongside MDA, as chemoprevention alone is not sufficient in interrupting transmission. Mass Drug Administration Malaria elimination Importation Bayesian modelling Force of infection Posterior predictive checks Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 17 Apr, 2026 Reviews received at journal 13 Apr, 2026 Reviews received at journal 01 Apr, 2026 Reviewers agreed at journal 01 Apr, 2026 Reviewers agreed at journal 27 Mar, 2026 Reviewers agreed at journal 27 Mar, 2026 Reviewers invited by journal 27 Mar, 2026 Editor assigned by journal 10 Feb, 2026 Submission checks completed at journal 07 Feb, 2026 First submitted to journal 05 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8799575","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":613419651,"identity":"2c0ee49f-ebbd-4460-b0ba-80face8a8ad4","order_by":0,"name":"Rachael Wachuka","email":"","orcid":"","institution":"Mount Kenya University","correspondingAuthor":false,"prefix":"","firstName":"Rachael","middleName":"","lastName":"Wachuka","suffix":""},{"id":613419652,"identity":"07681873-7b96-4500-adf4-d5be76923ef9","order_by":1,"name":"Samuel Mwalili","email":"","orcid":"","institution":"Jomo Kenyatta University of Agriculture and Technology (JKUAT)","correspondingAuthor":false,"prefix":"","firstName":"Samuel","middleName":"","lastName":"Mwalili","suffix":""},{"id":613419653,"identity":"e5fdec71-aa73-4c0e-877b-18b03be3536d","order_by":2,"name":"Winnie Kulei","email":"","orcid":"","institution":"Mount Kenya University","correspondingAuthor":false,"prefix":"","firstName":"Winnie","middleName":"","lastName":"Kulei","suffix":""},{"id":613419654,"identity":"19ed6aec-6abf-44c1-8bee-afbed98cb080","order_by":3,"name":"Peter M. 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However, its effectiveness in highly mobile populations remains uncertain. Studies show rapid parasitological rebound after cessation of MDA, this suggests that drug-based clearance alone is insufficient in interconnected settings. Although the resurgence is attributed to a combination of waning chemoprophylaxis and parasite importation, the relative contribution of these mechanisms and the quantitative conditions required for sustained elimination remain poorly defined.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eWe developed a stochastic model of Susceptible-Infected-Recovered-Susceptible (SIRS) compartmentalized to a longitudinal PCR prevalence trial Ngodhe Island (artemisinin-piperaquine\u0026thinsp;+\u0026thinsp;primaquine) in 2016. Based on Bayesian estimation of transmission potential and daily importation rates, we simulated scenarios for a period of 4 years (2016\u0026ndash;2019). We compared the epidemiological effects of increasing the MDA schedules (annual versus bimodal, which is two rounds during the two low transmission seasons) and measured the combined effect of integrating enhanced vector control coverage (90% LLIN coverage), port-of-entry screening (80% reduction in importation) and reactive focal MDA.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eModel simulations have indicated that an intensifying MDA schedule (annual versus bimodal) is not associated with a proportional decrease in mean prevalence, the mean prevalence plateaus at 4.1% as a result of an importation induced equilibrium. This finding implies that, without reducing external seeding, the system will have an equilibrium at the pace of importation faster than the drug pulses can suppress transmission rates. Single-intervention strategies did not meet elimination thresholds but a combination strategy with bimodal MDA combined with improved vector control and importation screening exhibited a non-linear type of intervention combination, as it was able to drive and maintain mean prevalence below the pre-elimination threshold (\u0026lt;\u0026thinsp;1%).\u003c/p\u003e\u003ch2\u003eConclusions:\u003c/h2\u003e \u003cp\u003eWith high mobility like in Ngodhe Island, increasing the frequency of mass treatment is not a viable solution to suppress the reintroduction of parasites. Our results provide mechanistic evidence that elimination requires a shift from the current mono-therapeutic scaling to interventions that are multi-modal. The rollout of importation control and vector control should be made a priority alongside MDA, as chemoprevention alone is not sufficient in interrupting transmission.\u003c/p\u003e","manuscriptTitle":"Modeling Malaria Rebound After Mass Drug Administration: The Role of Importation and Waning Immunity in Lake Victoria, Kenya","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-30 10:06:26","doi":"10.21203/rs.3.rs-8799575/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-04-17T13:33:12+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-14T00:57:30+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-01T22:04:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"289406494047238175135128072494287564543","date":"2026-04-01T17:11:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"310778301561338964162208079914591360630","date":"2026-03-27T15:32:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"315036435493367988685522682216544234353","date":"2026-03-27T12:25:53+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-27T11:55:53+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-10T14:58:46+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-07T15:40:05+00:00","index":"","fulltext":""},{"type":"submitted","content":"Malaria Journal","date":"2026-02-05T16:40:52+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"malaria-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"malj","sideBox":"Learn more about [Malaria Journal](http://malariajournal.biomedcentral.com/)","snPcode":"12936","submissionUrl":"https://submission.nature.com/new-submission/12936/3","title":"Malaria Journal","twitterHandle":"@malariajournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6cff8844-d10c-40df-a003-0e61173f8ff5","owner":[],"postedDate":"March 30th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-30T10:06:26+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-30 10:06:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8799575","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8799575","identity":"rs-8799575","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}