The Epidemiology of Rickettsial Infections in South India: Cohort Study

NCT04506944 | Completed

• 1 other identifier: MRC typhus cohort 1
• Study Type: observational
• Target: 32,566
• Locations: 1 country
• Sites: 1

Brief Summary

There is enough evidence to suggest that scrub typhus and spotted fever group rickettsioses are common causes of febrile illness in India. Serological evidence also exists for murine typhus, but is rarely tested for. Incidence, risk factors, clinical features and molecular epidemiology of these three infections are poorly understood. Delays in disease recognition and treatment may cause thousands of preventable deaths across India. The objectives of the research are to determine the incidence and risk factors of scrub typhus, spotted fever and murine typhus by severity, to determine clinical features of these neglected and often unrecognized infections. Further to study the effect of previous infection on incidence and severity of subsequent infections. Finally to study the association between vector parameters and scrub typhus risk. Enrolled will be 30,000 individuals who will be followed up for the development of fever using active and passive surveillance. Active surveillance will include household screening every 3-6 weeks. Fever cases occuring in the past two months will be tested for Scrub typhus, murine typhus and spotted fever IgG/IgM. 4000 individuals will be followed up by annual serological testing to identify asymptomatic infections. Participants notifying the study team with ongoing fever will undergo blood testing for acute diagnosis of rickettsial infection (IgM, PCR). In addition, we will enroll fever cases at study clinics who are not part of the main cohort. The research includes spatial and socio-economic risk factor analysis. Rodents carrying mite larvae will be trapped to compare the intensity of mite infestation between areas of high and low risk for human scrub typhus. The data on incidence, burden of disease and environmental determinants of scrub typhus, spotted fever and murine typhus will be used for health care planning and information campaigns for the public and medical professionals.

Conditions

Scrub Typhus; Spotted Fever; India; Murine Typhus

Outcome Measures

Primary Outcomes (3)

• Incidence of scrub typhus

  clinically apparent infection

  2 years

• Incidence of spotted fever

  clinically apparent infection

  2 years

• Incidence of murine typhus

  clinically apparent infection

  2 years

Secondary Outcomes (6)

• Incidence of serological infection (scrub typhus)

  2 years

• Incidence of serological infection (spotted fever)

  2 years

• Incidence of serological infection (murine typhus)

  2 years

• Incidence of complicated infection (scrub typhus)

  2 years

• Incidence of complicated infection (spotted fever)

  2 years

Study Arms (3)

General population

Whole population of scrub typhus endemic villages

Other: No intervention

hospital case population

cases recruited at study clinics who are not enrolled in general population cohort

Other: No intervention

Serological cohort

random subset of 4000 participants above the age of 10 drawn from general population cohort

Other: No intervention

Interventions

No intervention OTHER

No specific exposure is explored.

General population; Serological cohort; hospital case population

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

General population cohort: all residents in scrub typhus endemic villages Serological cohort: random sample of 4000 individuals older than 10 years present at the time of the initial baseline survey visit hospital case cohort: cases of all ages attending study clinics for undifferentiated fever of at least 5 days duration

You may qualify if:

• General population cohort: residing in study villages
• serological cohort: aged 10 years or older
• Hospital cohort: all ages

You may not qualify if:

• None

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• Medical Research Council: collaborator
• Christian Medical College, Vellore, India: collaborator
• Mahidol Oxford Tropical Medicine Research Unit: collaborator
• Australian Rickettsial Reference Laboratory: collaborator

Study Sites (1)

Christian Medical College

Vellore, Tamil Nadu, 632004, India

Location

Related Publications (1)

• Devamani C, Alexander N, Chandramohan D, Stenos J, Cameron M, Abhilash KPP, Mangtani P, Blacksell S, Vu HTT, Rose W, Schmidt WP. Incidence of Scrub Typhus in Rural South India. N Engl J Med. 2025 Mar 13;392(11):1089-1099. doi: 10.1056/NEJMoa2408645.

  PMID: 40073309 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples from human participants: serum for serological testing, buffy coat for rickettsia PCR Eschar and skin biopsies for rickettsia PCR Arthropod vector samples: PCR for rickettsia Rodent tissue samples: PCR for rickettsia

MeSH Terms

Conditions

Scrub Typhus; Spotted Fever Group Rickettsiosis; Typhus, Endemic Flea-Borne

Condition Hierarchy (Ancestors)

Rickettsiaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Vector Borne Diseases; Rickettsia Infections; Tick-Borne Diseases

Study Officials

• Wolf-Peter Schmidt, PhD

  London School of Hygiene and Tropical Medicine

  PRINCIPAL INVESTIGATOR

• Daniel Chandramohan, PhD

  London School of Hygiene and Tropical Medicine

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2020
• First Posted: August 10, 2020
• Study Start: August 1, 2020
• Primary Completion: August 5, 2022
• Study Completion: July 31, 2023
• Last Updated: October 5, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, ANALYTIC CODE
• Time Frame: from 12/2022 indefinitely
• Access Criteria: on request

Locations

IN (1)