Rising Burden of Plasmodium vivax in Mizoram: An Emerging Threat to Malaria Elimination in Northeast India

Rising Burden of Plasmodium vivax in Mizoram: An Emerging Threat to Malaria Elimination in Northeast India | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Rising Burden of Plasmodium vivax in Mizoram: An Emerging Threat to Malaria Elimination in Northeast India Vanlalhriataa C, Karuppusamy Balasubramani, Pooja Telugu Prakash, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9056118/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background India has made tremendous progress in malaria elimination efforts; however, several malaria pockets with high, sustained endemicity remain that require continuous focus. The Northeast (NE) state of Mizoram, bordering Bangladesh and Myanmar, tops the list for disproportionately contributing to India’s malaria burden. Considered a P. falciparum -endemic region, this study details the shift in malaria epidemiology from P. falciparum to P. vivax in Mizoram, complicating malaria elimination efforts in an already highly vulnerable setting. Methods Malaria data for the NE states were obtained from the National Center for Vector-Borne Disease Control, while health centre-wise data for Mizoram’s Mamit district (2021–2025) were obtained from the Office of the Chief Medical Officer, Directorate of Health Services, Mizoram. Spatiotemporal analyses of malaria cases and environmental variables were performed using ArcGIS 10.4 to identify disease trends, clustering, and high-risk areas. Results In 2020, Siaha—Mizoram’s southern district bordering Myanmar—reported the first increase in P. vivax infections. At the state level, the steep shift in malaria incidence from P. falciparum to P. vivax is noticeable from 2022 onward; from 23% in 2021, P. vivax increased to 47% in 2024 and 42% in 2025. In Mizoram’s western district of Mamit, P. vivax contributed to 68% of the cases in 2025, and among children < 5 years, 86% of the infections were attributed to P. vivax . While P. falciparum transmission coincided with the monsoon season, P. vivax transmission was perennial. Conclusion The recent surge in Mizoram’s P. vivax cases appears to mirror the epidemiological shift from P. falciparum to P. vivax in bordering Myanmar. It is possible P. vivax parasites from Myanmar could have entered Mizoram through the southern districts of Siaha and Lawngtlai. As several studies in the last decade have reported chloroquine-resistant P. vivax infections in Myanmar, it is imperative that therapeutic efficacy studies are urgently carried out in Mizoram to ascertain the status of CQ-resistant parasites. Malaria Plasmodium vivax Mizoram North East India Spatiotemporal analysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction The malaria situation in India is complex, with varying incidence rates across different states affected by vector diversity, geo-climatic conditions, socio-economic development, and distribution of Plasmodium species. India’s malaria epidemiology in the 1960s was dominated by P. vivax , which contributed ~ 70% of the cases [ 1 ]. By the start of the 21st century, P. falciparum cases became roughly equal to P. vivax , and from 2014, P. falciparum infections became predominant [ 2 ]. Over the decades, the increase in P. falciparum could be attributed to increased genetic plasticity, especially in South East Asian parasites, which enabled them to acquire antimalarial resistance at a faster frequency and expand much faster [ 3 ]. On the other hand, P. vivax is still susceptible to most antimalarials [ 4 , 5 ], and chloroquine (CQ) continues to be the first-line antimalarial across India [ 6 ]. The distribution of P . falciparum and P . vivax varies across the different regions of India—the Central, East, and North-Eastern (NE) states have high prevalence of P. falciparum , while P. vivax , in addition to co-existing with P. falciparum in these malaria-endemic states, is also highly prevalent in the urban centres of India [ 7 ]. Over the past decade, India’s sustained efforts to eliminate malaria by 2030 have resulted in a steep decrease in malaria cases and deaths across most parts of the country, and India has formally exited the World Health Organization’s High Burden to High Impact group category in 2023 [ 8 ]. As of 2023, 122 out of 650 districts in India reported zero indigenous cases [ 9 ]. Despite the substantial progress in malaria case reduction, a few high-burden districts continue to report high caseloads and are a bottleneck to India’s malaria elimination efforts. The important ones are Mamit, Lunglei, and Lawngtlai, the western districts of the NE state of Mizoram, located along the Indo-Bangladesh border [ 10 ]. With an Annual Parasite Index (API) of 12.9 in 2024, Mizoram falls under Category 3 (intensified control phase) of the National Framework for Malaria Elimination 2016–2030 [ 10 ]. This classification reflects Mizoram’s high transmission intensity and the need for focused research and tailored interventions. Mizoram, situated in the Indo-Burma Biodiversity Hotspot, shares international borders with Myanmar and Bangladesh. Despite accounting for only ~ 0.09% of India’s population, Mizoram contributed to 6.6% of the country’s malaria cases in 2024, highlighting a disproportionate malaria burden [ 10 , 11 ]. The increased and persistent malaria burden could be attributed to multiple factors, including porous international borders, hilly terrain, dense forest cover, monsoon climate, occupational exposure during traditional jhum (shifting) cultivation, and limited understanding of local parasite and vector biology [ 12 ]. The health centres in Mizoram’s western districts bordering Bangladesh have consistently reported an annual parasite index (API) of > 10 [ 12 ]. It is pertinent to note that these districts share geographical boundaries and environmental conditions with Bangladesh’s Chittagong Hill Tracts (CHT), which contributes to ~ 90% of Bangladesh’s cases [ 12 , 13 ]. Historically, malaria in Mizoram has been predominated by Plasmodium falciparum , accounting for over 80% of cases [ 12 ]. However, since 2021, Mizoram has been witnessing a steep increase in P. vivax cases, rising from 1,872 in 2021 to 7,949 in 2024, accounting for 47% of total infections [ 10 ]. In addition to Bangladesh, Mizoram shares its borders with Myanmar, where P. vivax has replaced P. falciparum as the dominant parasite [ 8 ]. Furthermore, several reports of CQ-resistant P. vivax infections have also been reported in Myanmar [ 14 , 15 ]. Given the porous border and shared vectors, the risk of importing CQ-resistant parasites from Myanmar into Mizoram cannot be ignored [ 16 , 17 ]. The rise of P. vivax in Mizoram poses a complex and urgent challenge to malaria elimination efforts in this region. P. vivax ’s hypnozoite stages and their ability to relapse, make it harder to detect, treat, and eliminate compared to P. falciparum . For targeted malaria control measures to be implemented, it is imperative to understand the transmission dynamics of P. vivax . To understand the spatiotemporal spread, we have analysed the shifting epidemiology of P. vivax infections at district-level across Mizoram. Furthermore, to capture the heterogeneity of P. vivax risk, we have mapped the clustering of P. vivax cases at the primary health-centre level in Mamit district, and examined the relationship between environmental factors and P. vivax incidence. Methods Study design and data source: The present study utilized an ecological design to investigate the spatiotemporal distribution of malaria in Mizoram. State-wise malaria data for NE Indian states (2024) and year-wise malaria data for Mizoram from 2010 to 2025 were sourced from the official website of the National Center for Vector Borne Disease Control (NCVBDC). Primary health centres (PHCs), urban health centres (UHCs), and community health centres (CHCs) wise malaria data for Mamit district from 2021 to 2025 were obtained from the Office of the Chief Medical Officer CMO, Mamit district. As is done across India, Malaria cases in Mizoram are diagnosed by RDT and/or Microscopy. The environmental parameters such as temperature, rainfall, humidity, and elevation were obtained from the NASA Power [ 18 ] and Earth Data [ 19 ] portals. Spatial analysis: The state and district-level malaria cases were added to the spatial database and prepared as thematic layers with located bar diagrams. Health facility–wise malaria cases of Mamit district were geocoded and linked as attributes to their respective facility locations to prepare proportional dot maps. Choropleth mapping techniques were used to depict the geographic distribution of environmental parameters and intensity of malaria burden across the study area over time. All spatial visualization and analysis were performed using ArcGIS version 10.4, and MS Excel sheet. Results Malaria distribution across North-East India in 2024 shows noticeable spatial heterogeneity, with Mizoram reporting the highest burden among all the northeastern states (Fig. 1 ). Temporal analysis (2010–2025) shows a steady increase in cases from 2011 to 2015, followed by a sharp decline for the next three years, followed by a moderate increase until 2021 (Fig. 1 C). Since 2022, malaria cases have risen again, along with an increasing proportion of P. vivax infections. From 23% (1,872 cases) in 2021, the P. vivax cases have increased steeply to 47% (7,949 cases) in 2024 and 42% (3,735 cases) in 2025. From 2019–2024, a highly heterogeneous distribution of malaria cases across Mizoram’s districts was seen (Fig. 2 ). Malaria endemicity is high in the western (Mamit and Lunglei), south-western (Lawngtlai), and southern (Siaha) districts. Mamit and Lunglei share international borders with Bangladesh, Siaha with Myanmar, while Lawngtlai shares its western and southern borders with Bangladesh and Myanmar, respectively. Malaria caseload steeply decreases in the central (Aizawl and Serchhip), northern (Kolasib), and eastern (Champhai) districts of Mizoram. Even though P. vivax cases have increased across all districts of Mizoram, the early rise, from 2020 onwards, was notable in Siaha, Lawngtlai, and Lunglei. Compared to 2019, cases increased 3.7-fold in Siaha (from 61 to 223), 2.9-fold in Lawngtlai (from 198 to 583), and 2.5-fold in Lunglei (from 127 to 326), respectively in 2020. In 2024, P. vivax accounted for 80% (1286 cases) of the malaria infections in Siaha. As of 2024, the proportion of P. vivax cases in the central and eastern districts of Mizoram has exceeded P. falciparum . Siaha District, located in the southernmost tip of Mizoram bordering Myanmar's Chin State display strong environment continuity across all six parameters (Fig. 3 ). The district experiences maximum temperatures in the range of 34–36°C, minimum temperatures around 12–14°C, and an overall temperature range of approximately 16–18°C reflecting moderate seasonal fluctuation, characteristic of a subtropical highland environment situated at 500–1,000 metres elevation. Annual rainfall in Siaha is around 1,500–1,800 mm, and humidity remains consistently at 65–70%, indicating a warm-humid environment. The adjacent Chin State shares these climatic characteristics in the bordering areas; however, its elevation rises higher to 1,200 and above, producing slightly cooler weather with a minimum temperature reaching below 12°C and a wider seasonal temperature range. The climatic similarities are profound in the immediate border zone but diminish eastward into Myanmar. The spatiotemporal distribution of malaria cases in Mamit district from 2021 to 2025 shows a clear increase in transmission intensity and a shift in parasite epidemiology (Fig. 4 ). In 2021, malaria cases were comparatively fewer and spatially scattered, with several health centres reporting no cases; among the reported, P. falciparum was the predominant species. In 2022, malaria transmission expanded in magnitude, as indicated by larger case clusters across multiple health centres, particularly in the western and southern parts of the district. Even though P. falciparum remained the dominant species, the proportion of P. vivax increased at several centres. A marked escalation was observed in 2023— P. vivax contributed substantially to the total caseload, with several centres showing comparable or higher P. vivax proportions than P. falciparum . This pattern persisted into 2024 and 2025, characterized by large, spatially clustered outbreaks and a clear shift towards P. vivax dominance across all health centres. Even though the number of malaria cases reduced across many PHCs, the proportion of P. vivax cases increased. The southern and western foci, including Marpara, Phuldungsei, W Phaileng, and Kawrtethawveng PHCs, reported high P. vivax caseloads in 2025. The month-wise demographic distribution of malaria cases in 2025 at Mamit district is shown in Fig. 5 . In 2025, P. vivax accounted for 68% of the total malaria cases at Mamit. Age-wise distribution (Fig. 5 A) shows that malaria predominantly affected adolescents, with the highest case load observed among those aged 15 + years. Even though the absolute number of cases was lower in children aged 0–4 years, a substantial proportion of P. vivax infections (86.2%) occurred in this age group. Sex-wise analysis (Fig. 5 B) revealed a higher burden of P. vivax infections in males (58.6%) than in females (41.4%). The month-wise distribution (Fig. 5 C) demonstrates clear seasonality in malaria transmission, especially for P. falciparum , with peaks during the monsoon months from May to August. In contrast, P. vivax cases persisted year-round, indicating a perennial transmission pattern. P. vivax consistently contributed the largest share of cases in every age group throughout the year. Even though fewer malaria cases were reported in absolute numbers during the dry months, P. vivax predominated . Discussion The malaria situation in Mizoram was dominated by P. falciparum (> 80%), and for the first time in over a quarter century, P. vivax has exceeded 50% of the total malaria infections [ 10 ]. Mizoram’s epidemiological shift toward P. vivax complicates malaria prevention and control in an already challenging geographical setting—poor roads and logistics, lack of infrastructure facilities, thick forest cover, and hard-to-access underserved communities. Asymptomatic and low-density P. vivax infections, along with their ability to stay dormant as persistent hypnozoite liver stages, complicate prompt diagnosis and treatment, and their control [ 20 ]. Even though P. vivax is considered benign, accumulating evidence indicates young children and pregnant women are highly vulnerable and experience adverse clinical impacts—severe anaemia affecting health and school performance, and maternal anaemia resulting in poor pregnancy outcomes, respectively [ 21 ]. The reasons for the steep increase in Mizoram’s P. vivax infections are not clear. Spatio-temporal analyses show a steep increase in P. vivax cases in the districts of Siaha and Lawngtlai from 2020 onwards. Our previous sub-centre wise analysis of malaria cases across Mizoram also showed the steep increase in P. vivax cases in 2020 at Siaha district [ 22 ]. The malaria-endemic Chin state of Myanmar shares its border with Siaha and Lawngtlai districts of Mizoram, and Bandarban district, part of malaria-endemic Bangladesh’s CHT [ 23 ]. In Myanmar, from 2014 to 2022, P. vivax cases have doubled; in 2023, P. vivax accounted for 81% of malaria cases [ 8 , 24 ]. Following Myanmar's 2021 military coup, malaria incidence has doubled in Chin state, with 40% P. vivax and 24% mixed ( P. vivax + P. falciparum ) infections [ 25 ]. Malaria emergence was observed in the non-malaria-endemic Falam Township, bordering the Siaha district of Mizoram, along with an increase in malaria incidence in already endemic Paletwa, Kanpetlet, Mindat, and Thantlang townships [ 25 ]. In addition to the increased malaria case counts, there are reports of drug resistance—a multicentric therapeutic efficacy study documented persistent day 28 P. vivax parasitemia after CQ treatment in Kyauktaw township of western Myanmar [ 14 ]. There are reports of high frequencies of mutations in pvmdr1 (Y976F, F1076L), pvdhfr , and pvdhps— key resistance-associated genes indicating sustained drug selection pressure and evolving chloroquine and antifolate tolerance in P. vivax across Myanmar [ 26 ]. Clinical and molecular evidence from Buthidaung in western Myanmar further supports the presence of chloroquine-resistant P. vivax , with pvcrt-o, pvmdr1, pvdhpr , and pvdhfr mutations [ 15 ]. Therapeutic failure for Chloroquine and Primaquine in P. vivax cases has been reported for decades, yet the treatment regimen remains unchanged in Myanmar [ 27 ]. Historically, drug-resistant parasites in Northeast India have been thought to originate in Southeast Asia, entering the region via porous borders with Myanmar [ 23 ]. Influx of refugees from Myanmar (Chin communities) to different villages of Mizoram's Champhai, Saitual, Siaha, and Lunglei districts, due to their shared ethnic and cultural ties with Mizos, might have facilitated P. vivax infections into Mizoram [ 28 ]. There is a need for a strategic shift from routine case management to border-focused malaria control in Mizoram, utilizing molecular surveillance in high-risk districts such as Siaha, Lawngtlai, Champhai, and Lunglei. Compared to other districts, the reason for the steep increase in P. vivax cases in Mamit and Lunglei (bordering Bangladesh), and Lawngtlai (bordering Bangladesh and Myanmar) is the ecological niche that strongly favours vector breeding and intense malaria transmission [ 12 ]. As seen in Mizoram, P. vivax cases have also increased steeply in Tripura, especially in the districts bordering Bangladesh’s CHT [ 10 ], underscoring the threat P. vivax poses to malaria elimination efforts in North-East India. Political unrest and instability in Myanmar and Bangladesh have made research and surveillance in these neighbouring areas difficult. Mizoram, bordering Myanmar and Bangladesh, provides a unique setting to study malaria epidemiology, including the evolution of drug-resistant parasites. In ongoing work, we have observed a significant proportion of asymptomatic P. vivax infections in community settings in Lunglei district, Mizoram (unpublished data), and Dhalai district, Tripura [ 29 ]. The increase in the clinical cases of P. vivax could be preceded or sustained by the asymptomatic P. vivax infections observed in the community. Worryingly, our ongoing molecular studies at Tripura have identified mutations in Pvmdr1 gene linked to chloroquine (CQ) resistance. Even though isolated reports of CQ resistance have been reported in India [ 4 ], CQ continues to be the first-line antimalarial against P. vivax . So far, no reports of CQ resistance have been reported from NE India. Therapeutic efficacy studies, especially with CQ alone arm, should be immediately carried out to assess if the increase in P. vivax cases in Mizoram is linked to CQ resistance. A key finding of our study is that P. vivax infections are disproportionately high (83%) among children under 5 years, and the 5–14-year group carried the highest caseload. These age-specific patterns are consistent with broader evidence that P. vivax primarily affects younger age groups in endemic settings [ 30 – 32 ], possibly due to children not having developed clinical immunity, and the parasite’s relapse dynamics increase cumulative exposure over time [ 31 , 33 ]. However, acquisition of clinical immunity is faster in P. vivax when compared to P. falciparum [ 30 , 34 , 35 ]. An increased P. vivax burden among males could be attributed to increased exposure to mosquitoes through outdoor activities, as observed in other parts of India [ 36 ]. Another interesting observation in this study is the perennial transmission pattern of P.vivax , unlike the seasonal pattern of P. falciparum . P. vivax can form dormant hypnozoites that relapse weeks to months after the primary infection, causing new infections outside of peak vector seasons that sustain transmission year-round [ 37 ]. With P. vivax establishing itself as the predominant parasite in Mizoram, its successful control and even eradication requires elimination of the hypnozoite reservoirs. As the hypnozoites cannot be diagnosed by RDT or microscopy, presumptive treatment with PQ, the hypnozoitocidal drug, is the preferred approach. Studies in temperate zones have shown the mass drug administration (MDA) of PQ to be very efficient in reducing and even eradicating P. vivax [ 38 – 40 ]. Even in the subtropical setting of Myanmar, PQ-MDA was shown to be very effective in reducing clinical and subclinical P. vivax infections in a low-endemic setting. 26 However, prior to initiating MDA programs, it is necessary to estimate the prevalence of Glucose-6-phosphate dehydrogenase (G6PD) deficiency in this region; PQ can trigger haemolysis in G6PD deficiency individuals [ 41 ]. In Myanmar, the prevalence of G6PD deficiency varies from 10 to 19.8% [ 42 – 44 ]. Entomological evidence from the North East states highlights the emergence of secondary anopheline species that sustain malaria transmission, particularly during dry seasons when primary vector populations are low.[ 45 – 47 ] In addition to An. minimus —the dominant malaria vector, An . philipinensis , An . nivipes , An . jamesii and An . jeyporiensis have been recently reported in Mizoram [ 48 ]. Understanding the role of secondary vectors and incorporating them into local surveillance and control strategies is crucial for achieving sustained malaria control in Mizoram and North East India. Even though P. vivax has been steadily increasing in Mizoram for the past five years, the month-wise age and sex stratified data of P. vivax were available only from August 2024; a longer window would have helped interpret P. vivax distribution with confidence, and is a major limitation of the study. Furthermore, spatial mapping of P. vivax infections at the sub-centre level across Mizoram’s districts would have given deeper insights into the spatio-temporal distribution of P. vivax transmission. Conclusion Situated at the intersection of the high-risk malaria zones of Myanmar and Bangladesh, Mizoram offers a strategic vantage point for studying malaria epidemiology and the evolution of drug resistance. Molecular surveillance, continuous therapeutic efficacy studies, improved diagnostics, strengthened entomological monitoring, and carefully implemented radical cure strategies are necessary to disrupt P. vivax transmission in Mizoram. Without rapid, adaptive, and region-specific interventions, malaria elimination in North-East India will be challenging, with far-reaching implications affecting malaria control in South-East Asia. Abbreviations NE Northeast CQ chloroquine CHT Chittagong Hill Tracts API annual parasite index NCVBDC National Center for Vector Borne Disease Control PHC primary health centres UHC urban health centres CHC community health centres PQ primaquine MDA mass drug administration G6PD glucose-6-phosphate dehydrogenase Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors have no competing interests to declare that are relevant to the content of this article. Funding No funding was received for this research. Author Contribution Conceptualization: PBN. Data curation: CV, PTP. Methodology: KB, SS. Formal analysis: KB, SS. Investigation: LP, LZ, LH. Writing first draft: CV, PTP. Review and finalization of draft: All authors. Supervision: PBN. Funding acquisition: None. Acknowledgement We acknowledge the National Center for Vector-Borne Disease Control, India, and the Ministry of Health and Family Welfare, Government of Mizoram, for the data. We also thank the health workers in the Mamit district for their assistance with data collection. Data Availability The state and district-wise datasets analysed during the current study are available in the NCVBDC website (https://ncvbdc.mohfw.gov.in/index1.php?lang=1&level=1&sublinkid=5784&lid=3689). Health centre-wise data are not publicly available and the request for datasets should be made to Dr. Lal Hlunpuii, Chief Medical Officer, Mamit, Mizoram (Email ID : [email protected] ). References Anvikar AR, Shah N, Dhariwal AC, Sonal GS, Pradhan MM, Ghosh SK, et al. Epidemiology of Plasmodium vivax Malaria in India. Am J Trop Med Hyg. 2016;95(6 Suppl):108–20. https://doi.org/10.4269/ajtmh.16-0163 . Singh MP, Rajvanshi H, Bharti PK, Anvikar AR, Lal AA. 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Shamuradova L, Alieva S, Kurdova-Mintcheva R, Rietveld A, Cibulskis R, Ejov M, et al. Achieving malaria elimination and certification in Turkmenistan. Malar J. 2012;11:O11. https://doi.org/10.1186/1475-2875-11-S1-O11 . Hsiang MS, Hwang J, Tao AR, Liu Y, Bennett A, Shanks GD, et al. Mass drug administration for the control and elimination of Plasmodium vivax malaria: an ecological study from Jiangsu province, China. Malar J. 2013;12:383. https://doi.org/10.1186/1475-2875-12-383 . Recht J, Ashley EA, White NJ. Use of primaquine and glucose-6-phosphate dehydrogenase deficiency testing: Divergent policies and practices in malaria endemic countries. PLoS Negl Trop Dis. 2018;12:e0006230. https://doi.org/10.1371/journal.pntd.0006230 . Han KT, Han ZY, Aye KH, Wai KT, Thi A, Cui L, et al. G6PD deficiency among malaria-infected national groups at the western part of Myanmar with implications for primaquine use in malaria elimination. Trop Med Health. 2021;49:47. https://doi.org/10.1186/s41182-021-00339-7 . Bwayo D, Kaddumukasa M, Ddungu H, Kironde F. Prevalence of glucose-6-phosphate dehydrogenase deficiency and its association with Plasmodium falciparum infection among children in Iganga distric in Uganda. BMC Res Notes. 2014;7:372. https://doi.org/10.1186/1756-0500-7-372 . Aung PL, Soe MT, Soe TN, Oo TL, Win KM, Cui L, et al. Factors hindering coverage of targeted mass treatment with primaquine in a malarious township of northern Myanmar in 2019–2020. Sci Rep. 2023;13:5963. https://doi.org/10.1038/s41598-023-32371-4 . Prakash A, Bhattacharyya DR, Mohapatra PK, Mahanta J. Role of the prevalent Anopheles species in the transmission of Plasmodium falciparum and P. vivax in Assam state, north–eastern India. Annals Trop Med Parasitol. 2004;98:559–68. https://doi.org/10.1179/000349804225021361 . Akhtar N, Nagpal BN, Kapoor N, Srivastava A, Valecha N. Role of An. culicifacies as a vector of malaria in changing ecological scenario of Northeastern states of India. J Vector Borne Dis. 2016;53:264–71. Singh K, Mohanty A, Malla WA, Ranjha R, Gam J, Ali R, et al. Evidence of secondary anopheline vectors in sustaining malaria transmission in Kokrajhar District, Assam, Northeastern India. Parasit Vectors. 2025;18:476. https://doi.org/10.1186/s13071-025-07110-5 . Characterization. and correlation studies of species composition of mosquitoes and its habitats in Mizoram, North East India. International Journal of Entomology Research. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 16 Apr, 2026 Reviews received at journal 15 Apr, 2026 Reviewers agreed at journal 18 Mar, 2026 Reviews received at journal 17 Mar, 2026 Reviewers agreed at journal 17 Mar, 2026 Reviewers invited by journal 16 Mar, 2026 Editor assigned by journal 11 Mar, 2026 Submission checks completed at journal 11 Mar, 2026 First submitted to journal 07 Mar, 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-9056118","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":608365859,"identity":"a63d86b1-4193-441a-9a93-5764baf37c59","order_by":0,"name":"Vanlalhriataa C","email":"","orcid":"","institution":"Central University of Kerala","correspondingAuthor":false,"prefix":"","firstName":"Vanlalhriataa","middleName":"","lastName":"C","suffix":""},{"id":608365860,"identity":"99625aeb-ba45-4ea5-ab6a-ffed157853e2","order_by":1,"name":"Karuppusamy Balasubramani","email":"","orcid":"","institution":"Central University of Tamil Nadu","correspondingAuthor":false,"prefix":"","firstName":"Karuppusamy","middleName":"","lastName":"Balasubramani","suffix":""},{"id":608365861,"identity":"fd5ece25-ff51-43c0-a251-2cd9449b29ab","order_by":2,"name":"Pooja Telugu Prakash","email":"","orcid":"","institution":"Central University of Kerala","correspondingAuthor":false,"prefix":"","firstName":"Pooja","middleName":"Telugu","lastName":"Prakash","suffix":""},{"id":608365862,"identity":"81a5783b-cf3f-48d6-879e-c104ad257ed1","order_by":3,"name":"Lalfakzuala Pautu","email":"","orcid":"","institution":"Department of Health \u0026 Family Welfare","correspondingAuthor":false,"prefix":"","firstName":"Lalfakzuala","middleName":"","lastName":"Pautu","suffix":""},{"id":608365863,"identity":"49575c9d-9686-4b32-9e90-d5b6d9399838","order_by":4,"name":"Lal Zawmi","email":"","orcid":"","institution":"Department of Health \u0026 Family Welfare","correspondingAuthor":false,"prefix":"","firstName":"Lal","middleName":"","lastName":"Zawmi","suffix":""},{"id":608365864,"identity":"ef5c7484-98b1-42f4-af94-1902a78a3027","order_by":5,"name":"Lal Hlunpuii","email":"","orcid":"","institution":"Department of Health \u0026 Family Welfare","correspondingAuthor":false,"prefix":"","firstName":"Lal","middleName":"","lastName":"Hlunpuii","suffix":""},{"id":608365865,"identity":"8293e4cb-61e6-4300-955b-e9e1ae2dc87f","order_by":6,"name":"Rajendra Pilankatta","email":"","orcid":"","institution":"Central University of Kerala","correspondingAuthor":false,"prefix":"","firstName":"Rajendra","middleName":"","lastName":"Pilankatta","suffix":""},{"id":608365866,"identity":"b40c176e-c813-46c8-864e-7ef82a459992","order_by":7,"name":"Nachimuthu Senthil Kumar","email":"","orcid":"","institution":"Mizoram University","correspondingAuthor":false,"prefix":"","firstName":"Nachimuthu","middleName":"Senthil","lastName":"Kumar","suffix":""},{"id":608365867,"identity":"838a4862-9a5f-4e4c-be98-ddc507292444","order_by":8,"name":"Ipsita Pal Bhowmick","email":"","orcid":"","institution":"Regional Medical Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Ipsita","middleName":"Pal","lastName":"Bhowmick","suffix":""},{"id":608365869,"identity":"c2560e71-c7e1-4e95-9ea2-f7b8376f324f","order_by":9,"name":"Praveen Balabaskaran Nina","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABD0lEQVRIiWNgGAWjYFADZiD+wMBgAKQYD8BFCGlhnAHRwkCkFpAaHhQtOIC59OFnEh8q7jCYs/Me/GxTc9iYX/rwgwM/GOzkGdh5sWq17Eszk5xx5hmDZTNfsnTOscNmkn1pBgd7GJING5j5ErBpMTjDYGzM23aYweAwj4F0bsNhG6CIwQEeBuYEoDsNsGth/2z89x9Yi/FvS6AW+zPsHw7+YajHo4XH8DFjA1iLmTSQYWbAwwNkMxzGqcWyh6fwYc+xwyBlZpY9x9KNJc7wFByWMThu2IZDizkP+4YDP2oOyxmcP2N840eNtWF/D/vGh28qquX5+c9gdxiU5sEUZ8OmHknLKBgFo2AUjALcAACEslZ5Hj07xQAAAABJRU5ErkJggg==","orcid":"","institution":"Central University of Kerala","correspondingAuthor":true,"prefix":"","firstName":"Praveen","middleName":"Balabaskaran","lastName":"Nina","suffix":""}],"badges":[],"createdAt":"2026-03-07 06:53:43","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9056118/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9056118/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105017987,"identity":"268459b7-2c8e-4c9e-a9bf-eaf7b8073679","added_by":"auto","created_at":"2026-03-20 01:22:45","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1990631,"visible":true,"origin":"","legend":"\u003cp\u003eSpatial distribution of malaria in North East India and temporal trend of malaria cases in Mizoram. (A) Location map of North East Indian states; (B) State-wise malaria cases in North East India in 2024; (C) Malaria trend with the proportions of \u003cem\u003eP. falciparum\u003c/em\u003e (pale blue) and \u003cem\u003eP. vivax\u003c/em\u003e (red) in Mizoram from 2010 to 2025.\u003c/p\u003e","description":"","filename":"Fig.1LocationTrendPfPv.png","url":"https://assets-eu.researchsquare.com/files/rs-9056118/v1/d5981ce36728832ac23472eb.png"},{"id":105017990,"identity":"5c540f8d-e5a7-4ec7-8f20-39c1312ae958","added_by":"auto","created_at":"2026-03-20 01:22:46","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":184920,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of malaria cases in Mizoram from 2019 to 2024. The colour gradient represents the cumulative malaria cases in the districts. The bar chart of each district illustrates the year-wise distribution of \u003cem\u003eP. falciparum\u003c/em\u003e (pale blue), \u003cem\u003eP. vivax\u003c/em\u003e (red), and mixed infections (blue) in Mizoram.\u003c/p\u003e","description":"","filename":"Fig.2MalariaMizoram20192024.png","url":"https://assets-eu.researchsquare.com/files/rs-9056118/v1/45d3c88fa2694895f1ac9b25.png"},{"id":105017989,"identity":"b2b31ce9-9d2a-441b-aa3b-4425ab697294","added_by":"auto","created_at":"2026-03-20 01:22:46","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":5623601,"visible":true,"origin":"","legend":"\u003cp\u003eSpatial distribution of average (a) Maximum Temperature, (b) Minimum Temperature, (c) Temperature Range, (d) Rainfall, (e) Relative Humidity, and (f) elevation. The legend of each figure is given separately. The darker shades of color ramp in figures represent relatively higher values. The international borders and district boundaries are presented in light grey and Mamit district is highlighted with dark line.\u003c/p\u003e","description":"","filename":"Fig.3EnvMizoramSaiha.png","url":"https://assets-eu.researchsquare.com/files/rs-9056118/v1/d7ccc4f28b9916cf11305478.png"},{"id":105017988,"identity":"d0c6c976-cae2-4e50-bef1-419805396233","added_by":"auto","created_at":"2026-03-20 01:22:45","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":3898057,"visible":true,"origin":"","legend":"\u003cp\u003eSpatiotemporal dynamics and shift in malaria transmission in PHC’s of Mamit district from 2021 to 2025. The size of the dot represents a relative case load with the proportions of \u003cem\u003eP. falciparum\u003c/em\u003e (sky blue) and \u003cem\u003eP. vivax \u003c/em\u003e(red)\u003cem\u003e.\u003c/em\u003eThe high case load centres are labeled which are located close to the Indo-Bangladesh border.\u003c/p\u003e","description":"","filename":"Fig.4MizoMamitPfPv.png","url":"https://assets-eu.researchsquare.com/files/rs-9056118/v1/e2a7b551bcf25f17ea7948ea.png"},{"id":105017986,"identity":"0779906d-4c96-488c-94e8-27f6c519479c","added_by":"auto","created_at":"2026-03-20 01:22:45","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":256097,"visible":true,"origin":"","legend":"\u003cp\u003eDemographic and seasonal distribution of malaria cases in Mamit district in the year 2025, with Age-wise (A) and Sex-wise (B) distribution of malaria cases by \u003cem\u003ePlasmodium\u003c/em\u003especies; and Month-wise distribution (C) of malaria cases across age groups and \u003cem\u003ePlasmodium\u003c/em\u003e species.\u003c/p\u003e","description":"","filename":"Fig.5AgeSexPfPvMamit.png","url":"https://assets-eu.researchsquare.com/files/rs-9056118/v1/f2ec33ef2875247e145fad94.png"},{"id":105018124,"identity":"75644f9f-0739-4dbf-8fe5-7ecb6ebc1ae6","added_by":"auto","created_at":"2026-03-20 01:22:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":14772231,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9056118/v1/c33516d4-176b-458d-bcfc-95b20fa99fec.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Rising Burden of Plasmodium vivax in Mizoram: An Emerging Threat to Malaria Elimination in Northeast India","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe malaria situation in India is complex, with varying incidence rates across different states affected by vector diversity, geo-climatic conditions, socio-economic development, and distribution of \u003cem\u003ePlasmodium\u003c/em\u003e species. India\u0026rsquo;s malaria epidemiology in the 1960s was dominated by \u003cem\u003eP. vivax\u003c/em\u003e, which contributed\u0026thinsp;~\u0026thinsp;70% of the cases [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. By the start of the 21st century, \u003cem\u003eP. falciparum\u003c/em\u003e cases became roughly equal to \u003cem\u003eP. vivax\u003c/em\u003e, and from 2014, \u003cem\u003eP. falciparum\u003c/em\u003e infections became predominant [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Over the decades, the increase in \u003cem\u003eP. falciparum\u003c/em\u003e could be attributed to increased genetic plasticity, especially in South East Asian parasites, which enabled them to acquire antimalarial resistance at a faster frequency and expand much faster [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. On the other hand, \u003cem\u003eP. vivax\u003c/em\u003e is still susceptible to most antimalarials [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], and chloroquine (CQ) continues to be the first-line antimalarial across India [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The distribution of \u003cem\u003eP\u003c/em\u003e. \u003cem\u003efalciparum\u003c/em\u003e and \u003cem\u003eP\u003c/em\u003e. \u003cem\u003evivax\u003c/em\u003e varies across the different regions of India\u0026mdash;the Central, East, and North-Eastern (NE) states have high prevalence of \u003cem\u003eP. falciparum\u003c/em\u003e, while \u003cem\u003eP. vivax\u003c/em\u003e, in addition to co-existing with \u003cem\u003eP. falciparum\u003c/em\u003e in these malaria-endemic states, is also highly prevalent in the urban centres of India [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOver the past decade, India\u0026rsquo;s sustained efforts to eliminate malaria by 2030 have resulted in a steep decrease in malaria cases and deaths across most parts of the country, and India has formally exited the World Health Organization\u0026rsquo;s High Burden to High Impact group category in 2023 [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. As of 2023, 122 out of 650 districts in India reported zero indigenous cases [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Despite the substantial progress in malaria case reduction, a few high-burden districts continue to report high caseloads and are a bottleneck to India\u0026rsquo;s malaria elimination efforts. The important ones are Mamit, Lunglei, and Lawngtlai, the western districts of the NE state of Mizoram, located along the Indo-Bangladesh border [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. With an Annual Parasite Index (API) of 12.9 in 2024, Mizoram falls under Category 3 (intensified control phase) of the National Framework for Malaria Elimination 2016\u0026ndash;2030 [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. This classification reflects Mizoram\u0026rsquo;s high transmission intensity and the need for focused research and tailored interventions.\u003c/p\u003e \u003cp\u003eMizoram, situated in the Indo-Burma Biodiversity Hotspot, shares international borders with Myanmar and Bangladesh. Despite accounting for only\u0026thinsp;~\u0026thinsp;0.09% of India\u0026rsquo;s population, Mizoram contributed to 6.6% of the country\u0026rsquo;s malaria cases in 2024, highlighting a disproportionate malaria burden [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The increased and persistent malaria burden could be attributed to multiple factors, including porous international borders, hilly terrain, dense forest cover, monsoon climate, occupational exposure during traditional jhum (shifting) cultivation, and limited understanding of local parasite and vector biology [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The health centres in Mizoram\u0026rsquo;s western districts bordering Bangladesh have consistently reported an annual parasite index (API) of \u0026gt;\u0026thinsp;10 [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. It is pertinent to note that these districts share geographical boundaries and environmental conditions with Bangladesh\u0026rsquo;s Chittagong Hill Tracts (CHT), which contributes to ~\u0026thinsp;90% of Bangladesh\u0026rsquo;s cases [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHistorically, malaria in Mizoram has been predominated by \u003cem\u003ePlasmodium falciparum\u003c/em\u003e, accounting for over 80% of cases [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, since 2021, Mizoram has been witnessing a steep increase in \u003cem\u003eP. vivax\u003c/em\u003e cases, rising from 1,872 in 2021 to 7,949 in 2024, accounting for 47% of total infections [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In addition to Bangladesh, Mizoram shares its borders with Myanmar, where \u003cem\u003eP. vivax\u003c/em\u003e has replaced \u003cem\u003eP. falciparum\u003c/em\u003e as the dominant parasite [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Furthermore, several reports of CQ-resistant \u003cem\u003eP. vivax\u003c/em\u003e infections have also been reported in Myanmar [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Given the porous border and shared vectors, the risk of importing CQ-resistant parasites from Myanmar into Mizoram cannot be ignored [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe rise of \u003cem\u003eP. vivax\u003c/em\u003e in Mizoram poses a complex and urgent challenge to malaria elimination efforts in this region. \u003cem\u003eP. vivax\u003c/em\u003e\u0026rsquo;s hypnozoite stages and their ability to relapse, make it harder to detect, treat, and eliminate compared to \u003cem\u003eP. falciparum\u003c/em\u003e. For targeted malaria control measures to be implemented, it is imperative to understand the transmission dynamics of \u003cem\u003eP. vivax\u003c/em\u003e. To understand the spatiotemporal spread, we have analysed the shifting epidemiology of \u003cem\u003eP. vivax\u003c/em\u003e infections at district-level across Mizoram. Furthermore, to capture the heterogeneity of \u003cem\u003eP. vivax\u003c/em\u003e risk, we have mapped the clustering of \u003cem\u003eP. vivax\u003c/em\u003e cases at the primary health-centre level in Mamit district, and examined the relationship between environmental factors and \u003cem\u003eP. vivax\u003c/em\u003e incidence.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and data source:\u003c/h2\u003e \u003cp\u003eThe present study utilized an ecological design to investigate the spatiotemporal distribution of malaria in Mizoram. State-wise malaria data for NE Indian states (2024) and year-wise malaria data for Mizoram from 2010 to 2025 were sourced from the official website of the National Center for Vector Borne Disease Control (NCVBDC). Primary health centres (PHCs), urban health centres (UHCs), and community health centres (CHCs) wise malaria data for Mamit district from 2021 to 2025 were obtained from the Office of the Chief Medical Officer CMO, Mamit district. As is done across India, Malaria cases in Mizoram are diagnosed by RDT and/or Microscopy. The environmental parameters such as temperature, rainfall, humidity, and elevation were obtained from the NASA Power [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] and Earth Data [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] portals.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSpatial analysis:\u003c/h3\u003e\n\u003cp\u003eThe state and district-level malaria cases were added to the spatial database and prepared as thematic layers with located bar diagrams. Health facility\u0026ndash;wise malaria cases of Mamit district were geocoded and linked as attributes to their respective facility locations to prepare proportional dot maps. Choropleth mapping techniques were used to depict the geographic distribution of environmental parameters and intensity of malaria burden across the study area over time. All spatial visualization and analysis were performed using ArcGIS version 10.4, and MS Excel sheet.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eMalaria distribution across North-East India in 2024 shows noticeable spatial heterogeneity, with Mizoram reporting the highest burden among all the northeastern states (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTemporal analysis (2010\u0026ndash;2025) shows a steady increase in cases from 2011 to 2015, followed by a sharp decline for the next three years, followed by a moderate increase until 2021 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). Since 2022, malaria cases have risen again, along with an increasing proportion of \u003cem\u003eP. vivax\u003c/em\u003e infections. From 23% (1,872 cases) in 2021, the \u003cem\u003eP. vivax\u003c/em\u003e cases have increased steeply to 47% (7,949 cases) in 2024 and 42% (3,735 cases) in 2025.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFrom 2019\u0026ndash;2024, a highly heterogeneous distribution of malaria cases across Mizoram\u0026rsquo;s districts was seen (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Malaria endemicity is high in the western (Mamit and Lunglei), south-western (Lawngtlai), and southern (Siaha) districts. Mamit and Lunglei share international borders with Bangladesh, Siaha with Myanmar, while Lawngtlai shares its western and southern borders with Bangladesh and Myanmar, respectively. Malaria caseload steeply decreases in the central (Aizawl and Serchhip), northern (Kolasib), and eastern (Champhai) districts of Mizoram. Even though \u003cem\u003eP. vivax\u003c/em\u003e cases have increased across all districts of Mizoram, the early rise, from 2020 onwards, was notable in Siaha, Lawngtlai, and Lunglei. Compared to 2019, cases increased 3.7-fold in Siaha (from 61 to 223), 2.9-fold in Lawngtlai (from 198 to 583), and 2.5-fold in Lunglei (from 127 to 326), respectively in 2020. In 2024, \u003cem\u003eP. vivax\u003c/em\u003e accounted for 80% (1286 cases) of the malaria infections in Siaha. As of 2024, the proportion of \u003cem\u003eP. vivax\u003c/em\u003e cases in the central and eastern districts of Mizoram has exceeded \u003cem\u003eP. falciparum\u003c/em\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSiaha District, located in the southernmost tip of Mizoram bordering Myanmar's Chin State display strong environment continuity across all six parameters (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The district experiences maximum temperatures in the range of 34\u0026ndash;36\u0026deg;C, minimum temperatures around 12\u0026ndash;14\u0026deg;C, and an overall temperature range of approximately 16\u0026ndash;18\u0026deg;C reflecting moderate seasonal fluctuation, characteristic of a subtropical highland environment situated at 500\u0026ndash;1,000 metres elevation. Annual rainfall in Siaha is around 1,500\u0026ndash;1,800 mm, and humidity remains consistently at 65\u0026ndash;70%, indicating a warm-humid environment. The adjacent Chin State shares these climatic characteristics in the bordering areas; however, its elevation rises higher to 1,200 and above, producing slightly cooler weather with a minimum temperature reaching below 12\u0026deg;C and a wider seasonal temperature range. The climatic similarities are profound in the immediate border zone but diminish eastward into Myanmar.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe spatiotemporal distribution of malaria cases in Mamit district from 2021 to 2025 shows a clear increase in transmission intensity and a shift in parasite epidemiology (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). In 2021, malaria cases were comparatively fewer and spatially scattered, with several health centres reporting no cases; among the reported, \u003cem\u003eP. falciparum\u003c/em\u003e was the predominant species. In 2022, malaria transmission expanded in magnitude, as indicated by larger case clusters across multiple health centres, particularly in the western and southern parts of the district. Even though \u003cem\u003eP. falciparum\u003c/em\u003e remained the dominant species, the proportion of \u003cem\u003eP. vivax\u003c/em\u003e increased at several centres. A marked escalation was observed in 2023\u0026mdash;\u003cem\u003eP. vivax\u003c/em\u003e contributed substantially to the total caseload, with several centres showing comparable or higher \u003cem\u003eP. vivax\u003c/em\u003e proportions than \u003cem\u003eP. falciparum\u003c/em\u003e. This pattern persisted into 2024 and 2025, characterized by large, spatially clustered outbreaks and a clear shift towards \u003cem\u003eP. vivax\u003c/em\u003e dominance across all health centres. Even though the number of malaria cases reduced across many PHCs, the proportion of \u003cem\u003eP. vivax\u003c/em\u003e cases increased. The southern and western foci, including Marpara, Phuldungsei, W Phaileng, and Kawrtethawveng PHCs, reported high \u003cem\u003eP. vivax\u003c/em\u003e caseloads in 2025.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe month-wise demographic distribution of malaria cases in 2025 at Mamit district is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. In 2025, \u003cem\u003eP. vivax\u003c/em\u003e accounted for 68% of the total malaria cases at Mamit. Age-wise distribution (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA) shows that malaria predominantly affected adolescents, with the highest case load observed among those aged 15\u0026thinsp;+\u0026thinsp;years. Even though the absolute number of cases was lower in children aged 0\u0026ndash;4 years, a substantial proportion of \u003cem\u003eP. vivax\u003c/em\u003e infections (86.2%) occurred in this age group. Sex-wise analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eB) revealed a higher burden of \u003cem\u003eP. vivax\u003c/em\u003e infections in males (58.6%) than in females (41.4%).\u003c/p\u003e \u003cp\u003eThe month-wise distribution (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eC) demonstrates clear seasonality in malaria transmission, especially for \u003cem\u003eP. falciparum\u003c/em\u003e, with peaks during the monsoon months from May to August. In contrast, \u003cem\u003eP. vivax\u003c/em\u003e cases persisted year-round, indicating a perennial transmission pattern. \u003cem\u003eP. vivax\u003c/em\u003e consistently contributed the largest share of cases in every age group throughout the year. Even though fewer malaria cases were reported in absolute numbers during the dry months, \u003cem\u003eP. vivax\u003c/em\u003e predominated .\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe malaria situation in Mizoram was dominated by \u003cem\u003eP. falciparum\u003c/em\u003e (\u0026gt;\u0026thinsp;80%), and for the first time in over a quarter century, \u003cem\u003eP. vivax\u003c/em\u003e has exceeded 50% of the total malaria infections [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Mizoram\u0026rsquo;s epidemiological shift toward \u003cem\u003eP. vivax\u003c/em\u003e complicates malaria prevention and control in an already challenging geographical setting\u0026mdash;poor roads and logistics, lack of infrastructure facilities, thick forest cover, and hard-to-access underserved communities. Asymptomatic and low-density \u003cem\u003eP. vivax\u003c/em\u003e infections, along with their ability to stay dormant as persistent hypnozoite liver stages, complicate prompt diagnosis and treatment, and their control [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Even though \u003cem\u003eP. vivax\u003c/em\u003e is considered benign, accumulating evidence indicates young children and pregnant women are highly vulnerable and experience adverse clinical impacts\u0026mdash;severe anaemia affecting health and school performance, and maternal anaemia resulting in poor pregnancy outcomes, respectively [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe reasons for the steep increase in Mizoram\u0026rsquo;s \u003cem\u003eP. vivax\u003c/em\u003e infections are not clear. Spatio-temporal analyses show a steep increase in \u003cem\u003eP. vivax\u003c/em\u003e cases in the districts of Siaha and Lawngtlai from 2020 onwards. Our previous sub-centre wise analysis of malaria cases across Mizoram also showed the steep increase in \u003cem\u003eP. vivax\u003c/em\u003e cases in 2020 at Siaha district [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The malaria-endemic Chin state of Myanmar shares its border with Siaha and Lawngtlai districts of Mizoram, and Bandarban district, part of malaria-endemic Bangladesh\u0026rsquo;s CHT [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In Myanmar, from 2014 to 2022, \u003cem\u003eP. vivax\u003c/em\u003e cases have doubled; in 2023, \u003cem\u003eP. vivax\u003c/em\u003e accounted for 81% of malaria cases [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Following Myanmar's 2021 military coup, malaria incidence has doubled in Chin state, with 40% \u003cem\u003eP. vivax\u003c/em\u003e and 24% mixed (\u003cem\u003eP. vivax\u0026thinsp;+\u0026thinsp;P. falciparum\u003c/em\u003e) infections [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Malaria emergence was observed in the non-malaria-endemic Falam Township, bordering the Siaha district of Mizoram, along with an increase in malaria incidence in already endemic Paletwa, Kanpetlet, Mindat, and Thantlang townships [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In addition to the increased malaria case counts, there are reports of drug resistance\u0026mdash;a multicentric therapeutic efficacy study documented persistent day 28 \u003cem\u003eP. vivax\u003c/em\u003e parasitemia after CQ treatment in Kyauktaw township of western Myanmar [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. There are reports of high frequencies of mutations in \u003cem\u003epvmdr1\u003c/em\u003e (Y976F, F1076L), \u003cem\u003epvdhfr\u003c/em\u003e, and \u003cem\u003epvdhps\u0026mdash;\u003c/em\u003ekey resistance-associated genes indicating sustained drug selection pressure and evolving chloroquine and antifolate tolerance in \u003cem\u003eP. vivax\u003c/em\u003e across Myanmar [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Clinical and molecular evidence from Buthidaung in western Myanmar further supports the presence of chloroquine-resistant \u003cem\u003eP. vivax\u003c/em\u003e, with \u003cem\u003epvcrt-o, pvmdr1, pvdhpr\u003c/em\u003e, and \u003cem\u003epvdhfr\u003c/em\u003e mutations [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Therapeutic failure for Chloroquine and Primaquine in \u003cem\u003eP. vivax\u003c/em\u003e cases has been reported for decades, yet the treatment regimen remains unchanged in Myanmar [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Historically, drug-resistant parasites in Northeast India have been thought to originate in Southeast Asia, entering the region via porous borders with Myanmar [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Influx of refugees from Myanmar (Chin communities) to different villages of Mizoram's Champhai, Saitual, Siaha, and Lunglei districts, due to their shared ethnic and cultural ties with Mizos, might have facilitated \u003cem\u003eP. vivax\u003c/em\u003e infections into Mizoram [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. There is a need for a strategic shift from routine case management to border-focused malaria control in Mizoram, utilizing molecular surveillance in high-risk districts such as Siaha, Lawngtlai, Champhai, and Lunglei.\u003c/p\u003e \u003cp\u003eCompared to other districts, the reason for the steep increase in \u003cem\u003eP. vivax\u003c/em\u003e cases in Mamit and Lunglei (bordering Bangladesh), and Lawngtlai (bordering Bangladesh and Myanmar) is the ecological niche that strongly favours vector breeding and intense malaria transmission [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. As seen in Mizoram, \u003cem\u003eP. vivax\u003c/em\u003e cases have also increased steeply in Tripura, especially in the districts bordering Bangladesh\u0026rsquo;s CHT [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], underscoring the threat \u003cem\u003eP. vivax\u003c/em\u003e poses to malaria elimination efforts in North-East India. Political unrest and instability in Myanmar and Bangladesh have made research and surveillance in these neighbouring areas difficult. Mizoram, bordering Myanmar and Bangladesh, provides a unique setting to study malaria epidemiology, including the evolution of drug-resistant parasites. In ongoing work, we have observed a significant proportion of asymptomatic \u003cem\u003eP. vivax\u003c/em\u003e infections in community settings in Lunglei district, Mizoram (unpublished data), and Dhalai district, Tripura [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. The increase in the clinical cases of \u003cem\u003eP. vivax\u003c/em\u003e could be preceded or sustained by the asymptomatic \u003cem\u003eP. vivax\u003c/em\u003e infections observed in the community. Worryingly, our ongoing molecular studies at Tripura have identified mutations in \u003cem\u003ePvmdr1\u003c/em\u003e gene linked to chloroquine (CQ) resistance. Even though isolated reports of CQ resistance have been reported in India [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], CQ continues to be the first-line antimalarial against \u003cem\u003eP. vivax\u003c/em\u003e. So far, no reports of CQ resistance have been reported from NE India. Therapeutic efficacy studies, especially with CQ alone arm, should be immediately carried out to assess if the increase in \u003cem\u003eP. vivax\u003c/em\u003e cases in Mizoram is linked to CQ resistance.\u003c/p\u003e \u003cp\u003eA key finding of our study is that \u003cem\u003eP. vivax\u003c/em\u003e infections are disproportionately high (83%) among children under 5 years, and the 5\u0026ndash;14-year group carried the highest caseload. These age-specific patterns are consistent with broader evidence that \u003cem\u003eP. vivax\u003c/em\u003e primarily affects younger age groups in endemic settings [\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], possibly due to children not having developed clinical immunity, and the parasite\u0026rsquo;s relapse dynamics increase cumulative exposure over time [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. However, acquisition of clinical immunity is faster in \u003cem\u003eP. vivax\u003c/em\u003e when compared to \u003cem\u003eP. falciparum\u003c/em\u003e [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. An increased \u003cem\u003eP. vivax\u003c/em\u003e burden among males could be attributed to increased exposure to mosquitoes through outdoor activities, as observed in other parts of India [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Another interesting observation in this study is the perennial transmission pattern of \u003cem\u003eP.vivax\u003c/em\u003e, unlike the seasonal pattern of \u003cem\u003eP. falciparum\u003c/em\u003e. \u003cem\u003eP. vivax\u003c/em\u003e can form dormant hypnozoites that relapse weeks to months after the primary infection, causing new infections outside of peak vector seasons that sustain transmission year-round [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWith \u003cem\u003eP. vivax\u003c/em\u003e establishing itself as the predominant parasite in Mizoram, its successful control and even eradication requires elimination of the hypnozoite reservoirs. As the hypnozoites cannot be diagnosed by RDT or microscopy, presumptive treatment with PQ, the hypnozoitocidal drug, is the preferred approach. Studies in temperate zones have shown the mass drug administration (MDA) of PQ to be very efficient in reducing and even eradicating \u003cem\u003eP. vivax\u003c/em\u003e [\u003cspan additionalcitationids=\"CR39\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Even in the subtropical setting of Myanmar, PQ-MDA was shown to be very effective in reducing clinical and subclinical \u003cem\u003eP. vivax\u003c/em\u003e infections in a low-endemic setting.\u003csup\u003e26\u003c/sup\u003e However, prior to initiating MDA programs, it is necessary to estimate the prevalence of Glucose-6-phosphate dehydrogenase (G6PD) deficiency in this region; PQ can trigger haemolysis in G6PD deficiency individuals [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. In Myanmar, the prevalence of G6PD deficiency varies from 10 to 19.8% [\u003cspan additionalcitationids=\"CR43\" citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEntomological evidence from the North East states highlights the emergence of secondary anopheline species that sustain malaria transmission, particularly during dry seasons when primary vector populations are low.[\u003cspan additionalcitationids=\"CR46\" citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e] In addition to \u003cem\u003eAn. minimus\u003c/em\u003e\u0026mdash;the dominant malaria vector, \u003cem\u003eAn\u003c/em\u003e. \u003cem\u003ephilipinensis\u003c/em\u003e, \u003cem\u003eAn\u003c/em\u003e. \u003cem\u003enivipes\u003c/em\u003e, \u003cem\u003eAn\u003c/em\u003e. \u003cem\u003ejamesii\u003c/em\u003e and \u003cem\u003eAn\u003c/em\u003e. \u003cem\u003ejeyporiensis\u003c/em\u003e have been recently reported in Mizoram [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]. Understanding the role of secondary vectors and incorporating them into local surveillance and control strategies is crucial for achieving sustained malaria control in Mizoram and North East India.\u003c/p\u003e \u003cp\u003eEven though \u003cem\u003eP. vivax\u003c/em\u003e has been steadily increasing in Mizoram for the past five years, the month-wise age and sex stratified data of \u003cem\u003eP. vivax\u003c/em\u003e were available only from August 2024; a longer window would have helped interpret \u003cem\u003eP. vivax\u003c/em\u003e distribution with confidence, and is a major limitation of the study. Furthermore, spatial mapping of \u003cem\u003eP. vivax\u003c/em\u003e infections at the sub-centre level across Mizoram\u0026rsquo;s districts would have given deeper insights into the spatio-temporal distribution of \u003cem\u003eP. vivax\u003c/em\u003e transmission.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eSituated at the intersection of the high-risk malaria zones of Myanmar and Bangladesh, Mizoram offers a strategic vantage point for studying malaria epidemiology and the evolution of drug resistance. Molecular surveillance, continuous therapeutic efficacy studies, improved diagnostics, strengthened entomological monitoring, and carefully implemented radical cure strategies are necessary to disrupt \u003cem\u003eP. vivax\u003c/em\u003e transmission in Mizoram. Without rapid, adaptive, and region-specific interventions, malaria elimination in North-East India will be challenging, with far-reaching implications affecting malaria control in South-East Asia.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNortheast\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCQ\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003echloroquine\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCHT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eChittagong Hill Tracts\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAPI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eannual parasite index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNCVBDC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNational Center for Vector Borne Disease Control\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePHC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eprimary health centres\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eUHC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eurban health centres\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCHC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecommunity health centres\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePQ\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eprimaquine\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMDA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emass drug administration\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eG6PD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eglucose-6-phosphate dehydrogenase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors have no competing interests to declare that are relevant to the content of this article.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNo funding was received for this research.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConceptualization: PBN. Data curation: CV, PTP. Methodology: KB, SS. Formal analysis: KB, SS. Investigation: LP, LZ, LH. Writing first draft: CV, PTP. Review and finalization of draft: All authors. Supervision: PBN. Funding acquisition: None.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe acknowledge the National Center for Vector-Borne Disease Control, India, and the Ministry of Health and Family Welfare, Government of Mizoram, for the data. We also thank the health workers in the Mamit district for their assistance with data collection.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe state and district-wise datasets analysed during the current study are available in the NCVBDC website (https://ncvbdc.mohfw.gov.in/index1.php?lang=1\u0026amp;level=1\u0026amp;sublinkid=5784\u0026amp;lid=3689). Health centre-wise data are not publicly available and the request for datasets should be made to Dr. Lal Hlunpuii, Chief Medical Officer, Mamit, Mizoram (Email ID :[email protected]).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAnvikar AR, Shah N, Dhariwal AC, Sonal GS, Pradhan MM, Ghosh SK, et al. Epidemiology of Plasmodium vivax Malaria in India. Am J Trop Med Hyg. 2016;95(6 Suppl):108\u0026ndash;20. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.4269/ajtmh.16-0163\u003c/span\u003e\u003cspan address=\"10.4269/ajtmh.16-0163\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSingh MP, Rajvanshi H, Bharti PK, Anvikar AR, Lal AA. 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Role of An. culicifacies as a vector of malaria in changing ecological scenario of Northeastern states of India. J Vector Borne Dis. 2016;53:264\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSingh K, Mohanty A, Malla WA, Ranjha R, Gam J, Ali R, et al. Evidence of secondary anopheline vectors in sustaining malaria transmission in Kokrajhar District, Assam, Northeastern India. Parasit Vectors. 2025;18:476. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s13071-025-07110-5\u003c/span\u003e\u003cspan address=\"10.1186/s13071-025-07110-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCharacterization. and correlation studies of species composition of mosquitoes and its habitats in Mizoram, North East India. International Journal of Entomology Research.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Malaria, Plasmodium vivax, Mizoram, North East India, Spatiotemporal analysis","lastPublishedDoi":"10.21203/rs.3.rs-9056118/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9056118/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e \u003cb\u003eBackground\u003c/b\u003e \u003c/p\u003e \u003cp\u003eIndia has made tremendous progress in malaria elimination efforts; however, several malaria pockets with high, sustained endemicity remain that require continuous focus. The Northeast (NE) state of Mizoram, bordering Bangladesh and Myanmar, tops the list for disproportionately contributing to India\u0026rsquo;s malaria burden. Considered a \u003cem\u003eP. falciparum\u003c/em\u003e-endemic region, this study details the shift in malaria epidemiology from \u003cem\u003eP. falciparum\u003c/em\u003e to \u003cem\u003eP. vivax\u003c/em\u003e in Mizoram, complicating malaria elimination efforts in an already highly vulnerable setting.\u003c/p\u003e \u003cp\u003e \u003cb\u003eMethods\u003c/b\u003e \u003c/p\u003e \u003cp\u003eMalaria data for the NE states were obtained from the National Center for Vector-Borne Disease Control, while health centre-wise data for Mizoram\u0026rsquo;s Mamit district (2021\u0026ndash;2025) were obtained from the Office of the Chief Medical Officer, Directorate of Health Services, Mizoram. Spatiotemporal analyses of malaria cases and environmental variables were performed using ArcGIS 10.4 to identify disease trends, clustering, and high-risk areas.\u003c/p\u003e \u003cp\u003e \u003cb\u003eResults\u003c/b\u003e \u003c/p\u003e \u003cp\u003eIn 2020, Siaha\u0026mdash;Mizoram\u0026rsquo;s southern district bordering Myanmar\u0026mdash;reported the first increase in \u003cem\u003eP. vivax\u003c/em\u003e infections. At the state level, the steep shift in malaria incidence from \u003cem\u003eP. falciparum\u003c/em\u003e to \u003cem\u003eP. vivax\u003c/em\u003e is noticeable from 2022 onward; from 23% in 2021, \u003cem\u003eP. vivax\u003c/em\u003e increased to 47% in 2024 and 42% in 2025. In Mizoram\u0026rsquo;s western district of Mamit, \u003cem\u003eP. vivax\u003c/em\u003e contributed to 68% of the cases in 2025, and among children\u0026thinsp;\u0026lt;\u0026thinsp;5 years, 86% of the infections were attributed to \u003cem\u003eP. vivax\u003c/em\u003e. While \u003cem\u003eP. falciparum\u003c/em\u003e transmission coincided with the monsoon season, \u003cem\u003eP. vivax\u003c/em\u003e transmission was perennial.\u003c/p\u003e \u003cp\u003e \u003cb\u003eConclusion\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe recent surge in Mizoram\u0026rsquo;s \u003cem\u003eP. vivax\u003c/em\u003e cases appears to mirror the epidemiological shift from \u003cem\u003eP. falciparum\u003c/em\u003e to \u003cem\u003eP. vivax\u003c/em\u003e in bordering Myanmar. It is possible \u003cem\u003eP. vivax\u003c/em\u003e parasites from Myanmar could have entered Mizoram through the southern districts of Siaha and Lawngtlai. As several studies in the last decade have reported chloroquine-resistant \u003cem\u003eP. vivax\u003c/em\u003e infections in Myanmar, it is imperative that therapeutic efficacy studies are urgently carried out in Mizoram to ascertain the status of CQ-resistant parasites.\u003c/p\u003e","manuscriptTitle":"Rising Burden of Plasmodium vivax in Mizoram: An Emerging Threat to Malaria Elimination in Northeast India","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-20 01:22:40","doi":"10.21203/rs.3.rs-9056118/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-16T06:41:48+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-15T11:29:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"282207725928001412149010022917837719091","date":"2026-03-18T15:14:28+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-17T10:12:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"213304039657958702483633469656310843361","date":"2026-03-17T08:22:36+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-16T11:52:54+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-11T09:56:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-11T09:55:20+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2026-03-07T06:47:48+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d8f756e9-facf-4447-a438-418397437b7e","owner":[],"postedDate":"March 20th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-16T20:38:13+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-20 01:22:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9056118","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9056118","identity":"rs-9056118","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}