Community-Based Cohort Study of Hidden Malaria Infections, Diagnostic Gaps, & Mosquito Vector Dynamics in Odisha, India (CSCMi3)
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.
Descripción general del estudio
Estado
Condiciones
Descripción detallada
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.
Tipo de estudio
Inscripción (Estimado)
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Samuel Wassmer, PhD
- Número de teléfono: +44 7930357115
- Correo electrónico: sam.wassmer@lshtm.ac.uk
Ubicaciones de estudio
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Odisha
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Bhubaneswar, Odisha, India, 751023
- Reclutamiento
- ICMR-National Institute of Health Research
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Contacto:
- Madhusmita Bal, PhD
- Número de teléfono: +916742301322
- Correo electrónico: bal.madhusmita@icmr.gov.in
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Investigador principal:
- Sanghamitra Pati, MD MPH PhD
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Investigador principal:
- Madhusmita Bal, PhD
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Raurkela, Odisha, India, 769042
- Reclutamiento
- Community Welfare Society Hospital (CWSH)
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Contacto:
- Praveen Kishore Sahu, PhD
- Número de teléfono: +91 8895501174
- Correo electrónico: drpraveenksahu@cwshospital.org
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Investigador principal:
- Sanjib Mohanty, MBBS MD
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Investigador principal:
- Praveen Kishore Sahu, PhD
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Niño
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Método de muestreo
Población de estudio
Descripción
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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
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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.
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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. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Prevalence and incidence of Plasmodium infection - Project 1
Periodo de tiempo: Nine time points between Years 1 and 5, including one baseline visit and eight follow-up visits conducted every six months.
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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.
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Nine time points between Years 1 and 5, including one baseline visit and eight follow-up visits conducted every six months.
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Diagnostic performance of malaria microscopy and rapid diagnostic tests compared with PCR - Project 1
Periodo de tiempo: Baseline and follow-up visits conducted every six months over five years.
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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.
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Baseline and follow-up visits conducted every six months over five years.
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Novel circulating infection biomarkers of host and parasite origin - Biomarker Sub-study, Project 2
Periodo de tiempo: Sixteen time points between Years 1 and 5, with eight time points each for Groups A and B.
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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
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Sixteen time points between Years 1 and 5, with eight time points each for Groups A and B.
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Samuel Wassmer, PhD, London School of Hygiene & Tropical Medicine, London
- Investigador principal: Sanjib Mohanty, MBBS MD, Community Welfare Society Hospital, Odisha, India
Publicaciones y enlaces útiles
Publicaciones Generales
- Longley RJ, White MT, Takashima E, Brewster J, Morita M, Harbers M, Obadia T, Robinson LJ, Matsuura F, Liu ZSJ, Li-Wai-Suen CSN, Tham WH, Healer J, Huon C, Chitnis CE, Nguitragool W, Monteiro W, Proietti C, Doolan DL, Siqueira AM, Ding XC, Gonzalez IJ, Kazura J, Lacerda M, Sattabongkot J, Tsuboi T, Mueller I. Development and validation of serological markers for detecting recent Plasmodium vivax infection. Nat Med. 2020 May;26(5):741-749. doi: 10.1038/s41591-020-0841-4. Epub 2020 May 11.
- Khan N, Awasthi G, Das A. How can the complex epidemiology of malaria in India impact its elimination? Trends Parasitol. 2023 Jun;39(6):432-444. doi: 10.1016/j.pt.2023.03.006. Epub 2023 Apr 6.
- Kumari P, Sinha S, Gahtori R, Yadav CP, Pradhan MM, Rahi M, Pande V, Anvikar AR. Prevalence of Asymptomatic Malaria Parasitemia in Odisha, India: A Challenge to Malaria Elimination. Am J Trop Med Hyg. 2020 Oct;103(4):1510-1516. doi: 10.4269/ajtmh.20-0018.
- van Eijk AM, Sutton PL, Ramanathapuram L, Sullivan SA, Kanagaraj D, Priya GSL, Ravishankaran S, Asokan A, Sangeetha V, Rao PN, Wassmer SC, Tandel N, Patel A, Desai N, Choubey S, Ali SZ, Barla P, Oraon RR, Mohanty S, Mishra S, Kale S, Bandyopadhyay N, Mallick PK, Huck J, Valecha N, Singh OP, Pradhan K, Singh R, Sharma SK, Srivastava HC, Carlton JM, Eapen A. The burden of submicroscopic and asymptomatic malaria in India revealed from epidemiology studies at three varied transmission sites in India. Sci Rep. 2019 Nov 19;9(1):17095. doi: 10.1038/s41598-019-53386-w.
- Carlton JM, Eapen A, Kessler A, Anvikar AR, Hoffmann A, Singh OP, Sullivan SA, Albert S, Sahu PK, Mohanty S, Wassmer SC. Advances in Basic and Translational Research as Part of the Center for the Study of Complex Malaria in India. Am J Trop Med Hyg. 2022 Oct 11;107(4_Suppl):97-106. doi: 10.4269/ajtmh.21-1333. Print 2022 Oct 11.
Enlaces Útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 30518
- U19AI181587 (Subvención/contrato del NIH de EE. UU.)
Plan de datos de participantes individuales (IPD)
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Descripción del plan IPD
Marco de tiempo para compartir IPD
Criterios de acceso compartido de IPD
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- SAVIA
- CIF
Información sobre medicamentos y dispositivos, documentos del estudio
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