Malaria remains a major public health challenge in India, with transmission dynamics varying widely across ecological, epidemiological, sociobehavioural and health system contexts. Achieving the national malaria elimination target by 2030 requires integrated, context-specific evidence to design effective interventions. This study aims to generate a comprehensive understanding of malaria transmission and factors surrounding it across diverse eco-epidemiological settings in India by assessing malaria burden, identifying determinants of transmission, evaluating health system performance and equity, characterising vector bionomics and insecticide resistance, and examining the influence of environmental drivers.

This longitudinal, multicentric study will be conducted in collaboration with the national programme in 12 districts spanning 10 states in India, covering a population of around 25 000 individuals representing varied ecological contexts (urban, periurban, rural, forest-foothill and coastal) and malaria endemicity levels. In each district, two clusters (villages) with a population of 1000 individuals will be included. A baseline mass survey will estimate malaria prevalence using bivalent rapid diagnostic tests (RDTs) and blood smear microscopy, with low-density parasitaemia detected by PCR in a subset of RDT-negative samples. Participants will be followed for 1 year, with monthly screening of symptomatic individuals using RDT and microscopy, and testing a subset of asymptomatic individuals to detect subclinical infections. Sociobehavioural data will be collected through structured interviews and household observations, with purposive inclusion of vulnerable groups, pregnant women, migrants, elderly persons, individuals with disabilities and tribal populations to assess equity dimensions through mixed-methods approaches. Health system performance will be evaluated through key informant interviews with programme officials, health workers, patients, private practitioners and traditional healers. Entomological surveillance will document vector species composition, density, infection rates and assessment of susceptibility status and intensity of insecticide resistance to commonly used public health insecticides. Environmental variables, including temperature, rainfall and humidity, will be linked with entomological and epidemiological data to explore spatiotemporal relationships.

The protocol was approved by the Institute Human Ethics Committee of ICMR-Vector Control Research Centre (IHEC 03-0125/N/F). All standard ethical practices will be adhered to. The findings will be shared with stakeholders and published in reputed open-access journals.

Although multiple studies have offered self-collection for human papillomavirus (HPV)-based cervical screening in community settings, there are no randomised controlled trials (RCTs) that have compared implementation outcomes of programme approaches for self-collection. This trial will compare two such approaches in low-resource settings in the states of Tamil Nadu and Mizoram, India.

A cluster RCT will be conducted over a year, offering self-collection to 3000 women aged 30–49 from 28 clusters (average size 101) in selected districts. Clusters in tribal, rural and urban low-income settings will be randomised to two arms. The intervention arm, co-designed with multiple stakeholders, will involve campaigns to offer self-collection in the community. The comparison arm will be offered self-collection at the nearest health facilities.

HPV-based cervical screening will be performed at central laboratories using clinically validated screening assays that can identify the highest risk carcinogenic HPV types (Group 1a–c - HPV16/18/31/33/45/52/58, ±35). Ablative treatment will be based on positivity with this extended genotyping triage, while those with any of the lower carcinogenic HPV types (Group 1d - 39, 51, 56, 59, ±35, Groups 2a/b - 66, 68) will undergo further assessment with visual inspection with acetic acid. Outcomes will be evaluated quantitatively and qualitatively using RE-AIM and the Theoretical Framework of Acceptability.

The primary outcome will be percentage of women well-managed (screened and appropriately treated) in both arms, with secondary outcomes including proportion screened, proportion treated, acceptability (willingness to screen, rescreen, and/or recommend to others) to women, community and healthcare providers, adoption (by providers), implementation fidelity, costs, sustainability assessment and systematically identified implementation barriers and facilitators. The reach, effectiveness and acceptability of community-based self-collection and the use of extended genotyping for triage in resource-constrained, hard-to-reach populations will be assessed, with lessons that can inform future statewide and national programmes.

Ethics approval has been obtained from the Institutional Review Board (IRB) and Ethics Committee of the Christian Medical College Vellore, Tamil Nadu, India (IRB Min. No 14314; INTERVEN), the Alfred Hospital Ethics Committee (HREC Ref 80134, Local Reference: project 601/21), Melbourne, Australia, the IARC Ethics Committee (IEC 21-32), Lyon, France, the Salem Polyclinic Institutional Ethics Committee (SPCIEC/2022/June/01/02), Tamil Nadu, India and the Institutional Ethics Committee, Civil Hospital, Aizawl, Mizoram, India (No.B.12018/1/13-CHA(A)/IEC/115). The study is also approved by the State Scientific Advisory Committee, Directorate of Public Health and Preventive Medicine, Chennai, Tamil Nadu (R. No. 011575/HEB/A2/2023). The Alfred Hospital Approval, as an authorised Australian ethics committee for national mutual recognition, is recognised and registered with the University of Melbourne Human Research Ethics Committee (2024-25255-57650-1). Written informed consent will be obtained from participants. The results of the trial will be disseminated through a peer-reviewed medical journal, and also through workshops, reports and conferences.

The trial has been registered with the Clinical Trials Registry - India: CTRI/2022/04/042327.