Community-Based Cohort Study of Hidden Malaria Infections, Diagnostic Gaps, & Mosquito Vector Dynamics in Odisha, India (CSCMi3)

August 10, 2026 updated by: Sam Wassmer, London School of Hygiene and Tropical Medicine

The Center for the Study of Complex Malaria in India (CSCMi 3.0): Hidden Plasmodium Infections: Reservoirs, Impact, and Biomarker Discovery

The goal of this prospective cohort study is to understand the factors responsible for the persistence of malaria transmission in some areas despite intensive control efforts. The study will measure the prevalence and incidence of asymptomatic and sub-patent Plasmodium infections and examine the factors that contribute to persistent transmission among residents of malaria-endemic areas of Odisha, India.

The main questions the study aims to answer are: Do asymptomatic and sub-patent Plasmodium infections contribute to persistent malaria transmission in endemic areas of Odisha? What is the frequency of false-negative results and incorrect species identification when microscopy and rapid diagnostic tests (RDTs) are compared with PCR? How is malaria epidemiology changing over time across areas with different transmission patterns, including shifts in Plasmodium species? What is the prevalence of asymptomatic gametocyte carriers, and how might they contribute to ongoing transmission? What are the characteristics and distribution of mosquito vectors in and around households, and how do they relate to transmission patterns? Can novel host- and parasite-derived biomarkers improve the detection of malaria infections, including asymptomatic cases?

Participants will provide blood samples for malaria testing by microscopy, RDT and PCR. A subset will provide additional samples for biomarker analysis as part of a nested sub-study. Participants will be followed over time to measure malaria infection prevalence, incidence and changes in transmission patterns. They will also take part in household-level assessments, including surveys and mosquito vector monitoring around their homes.

Study Overview

Status

Recruiting

Conditions

Detailed Description

Malaria transmission has declined in many parts of India as a result of expanded control efforts. However, persistent transmission continues in several regions despite high intervention coverage. Increasing evidence suggests that asymptomatic and subpatent Plasmodium infections may form an important hidden reservoir that sustains transmission and complicates malaria elimination. These infections are often missed by routine diagnostic methods such as microscopy and rapid diagnostic tests (RDTs), particularly in low-transmission or pre-elimination settings.

Local mosquito vector dynamics, including species composition, density and behaviour, are also likely to play a critical role in sustaining residual transmission, but remain insufficiently characterised in these settings.

This study is part of the Center for the Study of Complex Malaria in India 3 (CSCMi-3) and aims to characterise the epidemiology and biological determinants of hidden malaria infections in Odisha, India. It will also examine how vector, human and parasite factors interact to sustain transmission. The study is a prospective, community-based cohort conducted in selected rural villages across three endemic districts, representing different malaria transmission settings. Participants will be enrolled through household-based community surveys and followed longitudinally to monitor malaria infection dynamics over time.

The parent cohort study will enrol approximately 3,000 individuals, who will be followed through repeated visits to estimate the prevalence and incidence of asymptomatic malaria infections. The study will also assess the frequency of false-negative results and species misclassification by comparing routine diagnostic methods with molecular detection. In addition, it will evaluate Pfhrp2/Pfhrp3 gene deletions and explore potential shifts in Plasmodium species composition over time. Blood samples collected during study visits will be used for parasitological testing and laboratory analyses to better understand the persistence of malaria transmission.

Concurrent entomological surveys will be conducted in and around participant households to characterise mosquito vector species, density and seasonal patterns, and to examine their relationship with household-level infection patterns and ongoing transmission.

A nested biomarker sub-cohort will include a subset of participants who will undergo more frequent sampling to investigate circulating host- and parasite-derived biomarkers associated with malaria infection and transmission. These data will support the identification of biological indicators that may improve the detection of hidden infections and inform malaria surveillance strategies in elimination settings.

In parallel with the active community-based cohort, routinely collected malaria surveillance data from the Government of Odisha will be obtained for the study villages throughout the study period. These data will be used to characterise temporal trends in routine malaria surveillance, compare passive and active malaria case detection, and generate evidence to inform malaria surveillance and elimination strategies.

Together, the study will generate longitudinal epidemiological, diagnostic, biomarker and entomological data to improve understanding of residual malaria transmission and support evidence-based malaria surveillance, control and elimination strategies in India.

Study Type

Observational

Enrollment (Estimated)

3000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • India
    • Odisha
      • Bhubaneswar, Odisha, India, 751023
        • Recruiting
        • ICMR-National Institute of Health Research
        • Contact:
        • Principal Investigator:
          • Sanghamitra Pati, MD MPH PhD
        • Principal Investigator:
          • Madhusmita Bal, PhD
      • Raurkela, Odisha, India, 769042
        • Recruiting
        • Community Welfare Society Hospital (CWSH)
        • Contact:
        • Principal Investigator:
          • Sanjib Mohanty, MBBS MD
        • Principal Investigator:
          • Praveen Kishore Sahu, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

Study Population

Community residents living in selected rural villages in three districts of Odisha, India (Keonjhar, Boudh, and Malkangiri), representing different malaria transmission settings. Participants include males and females aged 12 months to 69 years who are enrolled through household-based community surveys and followed longitudinally to assess malaria infection, transmission dynamics, and biomarkers of infection. There are no restrictions based on residency duration, pregnancy status, social class, or underlying health conditions. For participants with severe anemia, study procedures are limited to finger-prick blood sampling in accordance with the study protocol.

Description

Inclusion Criteria:

  • Individuals 12 months to 69 years, all social classes, and all types of health status will be enrolled

Exclusion Criteria:

  • Individuals unable or unwilling to provide informed consent (or parental consent/assent for minors) Individuals unable to comply with study procedures or follow-up visits according to investigator judgement

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Project 1
This prospective, community-based cohort will enrol approximately 3,000 participants from 15 villages across three districts of Odisha, India: Keonjhar, Boudh and Malkangiri, with five villages selected from each district. Participants aged 12 months to 69 years will be followed for four years, with study visits every six months before and after the monsoon season. At each visit, participants will undergo clinical assessment and finger-prick blood collection for malaria testing by rapid diagnostic test (RDT), microscopy and PCR. Samples will also be used for haemoglobin measurement and for the collection of plasma and erythrocytes for molecular and serological analyses, to monitor malaria epidemiology and transmission dynamics.
Project 2

This nested prospective sub-cohort will enroll approximately 1,000 participants selected from the parent cohort across six villages, with two villages selected from each district. Participants will be recruited from three villages, one per district, beginning at the 12-month visit of the parent study in Year 2, and from the remaining three villages, one per district, in Year 3.

Participants will undergo more frequent longitudinal sampling to characterise malaria transmission and infection dynamics using sero-epidemiology and circulating host- and parasite-derived biomarkers. Finger-prick blood samples will be collected for rapid diagnostic testing (RDT), microscopy, PCR-based detection of Plasmodium infection, and bead-based assays measuring anti-Plasmodium antibodies and other infection biomarkers.

Concurrent entomological assessments conducted as part of the parent cohort will provide context on vector dynamics in relation to observed infection patterns and transmission.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prevalence and incidence of Plasmodium infection - Project 1
Time Frame: Nine time points between Years 1 and 5, including one baseline visit and eight follow-up visits conducted every six months.
Prevalence and incidence of Plasmodium infection among study participants, determined by polymerase chain reaction (PCR)-based detection of Plasmodium species in finger-prick blood samples collected during longitudinal community surveys. The study will estimate the prevalence, incidence and persistence of asymptomatic, subpatent and submicroscopic infections, together with species-specific infections.
Nine time points between Years 1 and 5, including one baseline visit and eight follow-up visits conducted every six months.
Diagnostic performance of malaria microscopy and rapid diagnostic tests compared with PCR - Project 1
Time Frame: Baseline and follow-up visits conducted every six months over five years.
Diagnostic performance of malaria microscopy and rapid diagnostic tests (RDTs) compared with PCR, assessed by false-negative and false-positive results, positive and negative predictive values, and species concordance for Plasmodium detection.
Baseline and follow-up visits conducted every six months over five years.
Novel circulating infection biomarkers of host and parasite origin - Biomarker Sub-study, Project 2
Time Frame: Sixteen time points between Years 1 and 5, with eight time points each for Groups A and B.
Identification and quantification of circulating host- and parasite-derived biomarkers associated with malaria infection, using multiplex and molecular assays in longitudinal blood samples collected from the biomarker sub-cohort
Sixteen time points between Years 1 and 5, with eight time points each for Groups A and B.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

London School of Hygiene and Tropical Medicine

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)
Community Welfare Society Hospital (CWSH), Rourkela, Odisha, India
ICMR-National Institute of Health Research, Bhubaneswar, Odisha, India

Investigators

  • Principal Investigator: Samuel Wassmer, PhD, London School of Hygiene & Tropical Medicine, London
  • Principal Investigator: Sanjib Mohanty, MBBS MD, Community Welfare Society Hospital, Odisha, India

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 2, 2025

Primary Completion (Estimated)

May 31, 2029

Study Completion (Estimated)

May 31, 2029

Study Registration Dates

First Submitted

August 10, 2026

First Submitted That Met QC Criteria

August 10, 2026

First Posted (Actual)

August 18, 2026

Study Record Updates

Last Update Posted (Actual)

August 18, 2026

Last Update Submitted That Met QC Criteria

August 10, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 30518
  • U19AI181587 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual participant data underlying the results reported in publications will be shared. This includes demographic data, clinical and laboratory measurements, malaria diagnostic results (RDT, microscopy, PCR), serological measurements, and selected entomological indicators collected during the study. Direct identifiers will be removed prior to data sharing.

IPD Sharing Time Frame

De-identified individual participant data and supporting documents will be available beginning after publication of the primary study results. Data will remain available for up to 5 years following publication, subject to institutional data governance and data sharing policies.

IPD Sharing Access Criteria

De-identified individual participant data and supporting documents, including the study protocol, statistical analysis plan, informed consent forms and analytic code, will be made available to qualified researchers who submit a methodologically sound research proposal. Requests will be reviewed and approved by the study investigators and participating institutions. Access will be provided through a controlled data-sharing mechanism and may require a data-use agreement to ensure appropriate use of the data and protection of participant confidentiality. Only the data necessary to address the approved research question will be shared.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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