Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04506944 |
| Other study ID # |
MRC typhus cohort 1 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
August 1, 2020 |
| Est. completion date |
July 31, 2023 |
Study information
| Verified date |
October 2023 |
| Source |
London School of Hygiene and Tropical Medicine |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial 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.
Description:
The aim of the cohort study is to better understand the epidemiology, sero-epidemiology and
transmission of scrub typhus, murine typhus and tick-borne spotted fever. The overall focus
of the work will be on scrub typhus, being the most important of the three from the public
health perspective. We aim to determine the "severity pyramid" of serological, symptomatic
and severe infection. The results from this study will help clinicians to understand the
natural course of scrub typhus infection, health policy makers to estimate the global burden
and the scope for community-based interventions, and immunologists to better understand the
immunogenicity of single and repeat infections.
The specific objectives are to:
1. Estimate the incidence of symptomatic and severe scrub typhus infection in the
community.
2. Estimate the incidence of serological (asymptomatic) scrub typhus infection.
3. Estimate the effect of previous scrub typhus infection (sero-positive at baseline) on
the risk of subsequent infection and disease severity (subclinical vs clinically
apparent). This includes the effect of antibodies in mothers on the risk of severe
infection in young children via residual maternal antibodies.
4. Estimate the effect of potential risk factors such as age, gender, occupation,
water/sanitation access and comorbidity on the risk of scrub typhus infection.
5. Estimate the effect of spatial-temporal risk factors for scrub typhus by identifying
high risk areas, accounting for human population density and land use.
6. Compare the rate of rodent trappings and vector parameters of chiggers between high risk
and low risk areas identified under 5).
7. Estimate the disease burden associated with scrub typhus and the economic impact of
scrub typhus in terms of loss of earnings and health expenditure.
8. Estimate the incidence of asymptomatic and symptomatic murine typhus and spotted fever
infection and explore associated socio-demographic, spatial and vector-related risk
factors.
STUDY OVERVIEW
The study will be a population-based cohort study over two years (i.e. two scrub typhus
seasons) in about 30,000 people living in approximately 40 villages with a sero-prevalence of
at least 15% (see flow diagram above). These individuals will be followed-up through active
surveillance for recent febrile illnesses (clinical cohort). For passive surveillance,
participants will be encouraged to notify the study team in case of fever or come to one of 4
local study clinics. At study clinics we will also enrol fever cases who are not part of the
clinical cohort, i.e. have not been enrolled prior to their fever. The study will include a
smaller cohort (sero-cohort) for serological surveillance of 4000 people drawn from the
30,000 people of the clinical cohort. Longitudinal serological surveys linked to active
surveillance are essential to estimate true attack rates unbiased by disease severity. The
sero-cohort will consist of three annual blood testing in the same group of participants over
two scrub typhus seasons (baseline, inter-season, endline).
Target population- A pilot study showed that scrub typhus infection is highly focal This
makes it difficult to define a target population for the purpose of making inferences. We
will define the target population in terms of the village level sero-prevalence. The aim is
to correlate the incidence of scrub typhus with the sero-prevalence at village level. This
will allow using the results of the study to predict the expected incidence and burden of
scrub typhus in other settings with a known sero-prevalence, and eventually estimate the
global burden of scrub typhus (not part of the study but a potential extension of the work).
The target population for the study is therefore "villages in which the IgG sero-prevalence
is at least 15%".
