Hotspot districts of persistent Plasmodium vivax malaria pose a formidable challenge to malaria elimination in India

Malaria remains a vector-borne disease of significant public health importance globally, especially in low- and middle-income countries. According to the World Malaria Report 2024, global malaria cases increased from 252 million in 2022 to 263 million in 2023, with the incidence rate increasing from 58.6 to 60.4 per 1000 population at risk. Plasmodium falciparum (P. falciparum) continues to be the most lethal malaria parasite globally, while Plasmodium vivax (P. vivax) is the most widely distributed, especially across Asia and the Americas. Notably, P. vivax cases increased from 4.9 million (2% of total cases) in 2021 to 6.9 million (3%) in 2022, highlighting a resurgence in several endemic countries.¹

India remains a major contributor to the global malaria burden. In 2023, the country accounted for an estimated 2.04 million cases, nearly half of all cases reported in the WHO South-East Asia Region.¹ The National Centre for Vector Borne Disease Control (NCVBDC) reported 227,564 confirmed cases in 2023 and 255,500 in 2024, with P. vivax comprising approximately 39% and 40%, respectively. In 2024, 88% malaria cases were concentrated in eight high-burden states: Odisha, Chhattisgarh, Uttar Pradesh, Jharkhand, Maharashtra, Tripura, Mizoram, and West Bengal.²

Malaria transmission in India is geographically heterogeneous, influenced by variations in vector species, healthcare access, and socio-environmental factors. At the same time, P. falciparum and P. vivax predominate, and sporadic cases of Plasmodium malariae and Plasmodium ovale are also reported. India adopted the WHO Global Technical Strategy through the National Framework for Malaria Elimination (NFME) in 2016, supported by two National Strategic Plans 2017–2022 and 2023–2027.³ These malaria elimination efforts led to a 21% decline in malaria cases by 2019 and a further 45% reduction by 2020. However, a surge in cases is being observed since 2021. From 2000 to 2024, P. vivax accounted for 30–55% of the national malaria cases, with over 102,028 cases reported in 2024, underscoring the need for species-specific control strategies.²

P. vivax poses unique challenges to malaria elimination. Its dormant liver-stage hypnozoites can cause relapses weeks or months after the initial infection, sustaining transmission in the absence of new mosquito bites. Rapid diagnostic tests (RDTs) have suboptimal sensitivity for P. vivax, leading to underdiagnosis, while subclinical infections are more common, undermining routine surveillance.⁴ Adherence to the 14-day primaquine regimen (PQ-14) is presumably poor, and primaquine is contraindicated in infants, pregnant and lactating women, individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, limiting treatment coverage.5, 6, 7 Additionally, treatment efficacy is complicated by CYP2D6 related pharmacogenetic variability.⁷

Since G6PD testing is not widely available in India, general guidelines are issued to patients before primaquine administration.⁵ Given the complex epidemiology of P. vivax malaria and the demographic diversity across Indian states, granular sub-national analysis is essential. This study identifies persistent P. vivax hotspot districts in India from 2000 to 2023. It evaluates the impact of two key interventions, switching from 5 day course of primaquine to 14 day administration of primaquine regimen (PQ-14) in 2007⁸ and the deployment of long-lasting insecticidal nets (LLINs) beginning in 2016.9, 10, 11 Using district-level NCVBDC data, districts were defined as hotspots if they consistently ranked in the top 5% for P. vivax case counts and slide positivity rate (SPR) for at least half of the time between 2000 and 2023. Interrupted time series models assessed the impact of interventions on annual trends. Methodological details are provided in the Appendix.

From 2000 to 2023, India experienced a 9-fold decline in total malaria cases, from ∼2 million to 227,564 respectively. P. vivax cases dropped 11-fold, from ∼985,000 in 2000 to 89,619 in 2023, while P. falciparum cases dropped 8-fold, from over 1 million to 137,945. Based on our analysis (Fig. 1), 13 districts were identified as persistent P. vivax hotspots, contributing approximately 20% (18,242) of India's total P. vivax malaria cases in 2023. These included Kolkata Municipal Corporation (KMC, West Bengal); Bijapur (Chhattisgarh); Latehar, Hazaribagh, Palamu, Giridih, Garhwa, and Chatra (Jharkhand); Sonbhadra, Allahabad, and Mirzapur (Uttar Pradesh); Chennai (Tamil Nadu), and Nuapada (Odisha). KMC alone accounted for 18.5% of national P. vivax cases in 2023. Temporal trends revealed substantial heterogeneity. In Jharkhand districts such as Latehar and Palamu, cases rose between 2004 and 2011 before declining. In contrast, Sonbhadra and Chennai showed sporadic spikes, likely driven by urbanization and migration. Chennai alone contributed >94% of Tamil Nadu's P. vivax cases in 2023, highlighting urban transmission.

Fig. 1.

Geospatial distribution of Plasmodium vivax malaria hotspot districts in India and the impact ofPQ-14and LLIN interventions on malaria trends (2000–2023). This figure comprises three panels. Panel A displays the geographic distribution of the 13 hotspot districts that persistently reported high P. vivax malaria burden between 2000 and 2023, based on National Centre for Vector Borne Disease Control (NCVBDC) surveillance data. Hotspots were defined as districts in the top 5% for both case count and slide positivity rate (SPR) for at least 50% of the study period. Panel B and C shows the annual trend in total malaria cases and P. vivax cases in India from 2000 to 2023. Vertical dashed lines indicate the introduction of the 14-day primaquine regimen (PQ-14) in 2007 and the rollout of long-lasting insecticidal nets (LLINs) beginning in 2016.

The 2007 policy shift from a 5-day to 14-day primaquine regimen was associated with the modest but statistically significant national decline in P. vivax cases. Annual reduction rates increased from 9.6% under PQ-5 to 9.8% under PQ-14. At the district level, impacts varied. Palamu, Allahabad, and Nuapada saw annual reductions exceeding 20%, while KMC experienced only a 5.8% annual decline, with high case counts persisting in 2009 and 2010. LLIN introduction had a more pronounced impact on malaria reduction. National P. vivax cases declined at a rate of 22.4% annually after LLIN deployment. Hotspot districts showed notable annual reductions since the year of introduction respectively; 74.5% in Sonbhadra (2021), 45.6% in Chatra (2018), and 44.9% in Giridih (2016). Similar trends were observed for P. falciparum malaria cases, underscoring LLINs’ cross-species effectiveness.

Despite these efforts, P. vivax continues to dominate in several regions, accounting for 39% of India's malaria burden in 2023. More than half of these cases (48,612) originated in West Bengal, Uttar Pradesh, Jharkhand, and Odisha. Nine out of 13 hotspots form a contiguous belt in eastern India, suggesting shared ecological and operational challenges. Jharkhand alone harbours six persistent hotspots, requiring urgent programmatic attention. Among the 13 hotspot districts in 2023, all except KMC (15,477) reported fewer than 950 P. vivax cases. However, historical data underscore the susceptibility of these districts to P. vivax transmission. This historical susceptibility warrants continued vigilance and sustained surveillance to prevent potential resurgence. It is important to safeguard the progress achieved towards malaria elimination, particularly given the persistent receptivity of these areas and the presence of vulnerable populations. Kolkata's sustained burden is linked to urban sprawl, dense population, and large migrant communities from endemic rural areas, many of whom reside in temporary settlements with poor housing and limited access to malaria services.^12,13 The city also frequently reports outbreak of dengue and malaria, indicating the need for integrated malaria control strategies. Anopheles stephensi and An. culicifacies, the major vectors of P. vivax in India, usually rest outdoors and prefer to bite early in the evening, often before people go to bed.¹⁴ Due to this behaviour, their contact with LLINs is reduced, which in turn lowers the overall effectiveness of LLIN-based malaria control efforts. Hence, persistent operational challenges in hotspot districts include poor adherence to PQ-14, exclusion of vulnerable groups from the radical cure, insecticide resistance, low LLIN usage, and behavioural factors like outdoor sleeping.¹⁵ Delays in diagnosis, weak follow-up, and frequent relapses further complicate control efforts and reduces the effectiveness of malaria control strategies. The early appearance of P. vivax gametocytes, allows transmission well before the onset of symptoms or treatment initiation, further adds to the P. vivax burden.¹⁵

To meet the goal of malaria elimination by 2030, India must prioritize enhanced surveillance and targeted interventions in P.vivax hotspot districts. Similar efforts should also be extended to P. falciparum-dominated districts, as the intervention strategies and findings are likely to be applicable to both settings. Key strategies include LLIN coverage, improving vector monitoring, and promoting community engagement. Public-private partnerships, and cross-border coordination, both interstate and international will be critical.16, 17, 18 Hypnozoitocidal treatment options like a shortened 7-day primaquine regimen⁶ or tafenoquine (with G6PD testing), that support this malaria elimination effort.⁶ Directly observed therapy for PQ-14 could improve adherence and reduce relapses.⁶ Furthermore, to accurately assess the impact of current malaria control measures, enhanced surveillance systems are needed to differentiate relapse-driven cases from newly acquired infections. Also, there is a need for future studies to systematically track and evaluate adherence to radical cure regimens and its association with recurrent episodes in the hotspot districts.

Over the past two decades, India has reduced its P. vivax malaria burden by 91%. However, persistent hotspots in urban and eastern districts threaten the goal of malaria elimination. Focused, region-specific strategies that address the biological and social complexities of P. vivax are urgently needed. With sustained investment, innovation, and coordinated action, a malaria-free India by 2030 remains an achievable goal.

Contributors

MR: Conceptualization of the idea and manuscript, initial draft, literature review, editing, and finalization. AR: Methodology, data analysis, initial draft, literature review, writing, and editing. KT: Methodology, data analysis, graphics, writing the draft, and editing. AV: Data curation, writing, input on program policies, and editing. RS: Writing review and editing. SAN: Writing review and editing. CPY: Review and editing. AS: Review and editing. All authors finalized and approved the manuscript.

Data sharing statement

The data used in this study belongs to National Centre of Vector-Borne Disease Control and can be requested from the National Centre. There is no original data generated in this analysis.

Editor note

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Declaration of interests

None declared.