Tuberculosis immunoreactivity surveillance in Malawi (Timasamala) version 1.0
Loading...
Date
2022-06-09
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Kamuzu University of Health Sciences
Abstract
Summary
This cross-sectional epidemiological study will evaluate a novel methodology of tuberculosis (TB)
surveillance, determine the prevalence of TB immunoreactivity in young children, adolescents and
young adults in Blantyre, Malawi, and determine the risk factors and spatial distribution of TB
infection. We intend to recruit children aged 1-5 years old, adolescents 10-17 years, and adults 18-40
years and test them for immunoreactivity to M. tuberculosis using the QIAreach-QFT interferongamma
release assay (IGRA). We will recruit from two places: community cross-sectional household
testing, and convenience sampling within primary health clinics (PHCs). Results will be used to identify
areas of high TB risk in Blantyre, inform targeted interventions, and provide recommendations for
future TB surveillance methodologies.
Type of study
Cross-sectional epidemiological survey, with nested case-control and qualitative acceptability and
feasibility studies.
Problem to be studied
Current methods of TB surveillance are resource-intensive, requiring many people to be tested to
detect neighbourhood variation in TB epidemiology, and are unable to capture transmission dynamics
as TB disease is often far removed from the causative transmission event. Using new, more accessible
diagnostics for TB exposure (such as QIAreach-QFT), and pragmatic methodologies such as
convenience sampling in health centres, may make it more feasible for cities in high-burden settings
to “Know Their Epidemic”. However, these methodologies have not been previously evaluated.
Objectives
Aim: To evaluate the feasibility, acceptability, utility and potential impact of a TB surveillance
methodology using immunoreactivity testing to understand spatial and population variation in TB
infection risk
Specific objectives
To determine the annual risk of TB infection (ARTI) in Blantyre, and explore the individual- and
area-level risk factors for infection
2. To compare the outputs of convenience sampling in PHCs with that obtained from
conventional cross-sectional community sampling, with respect to the estimated ARTI and the
characteristics of participants recruited
3. To test the hypothesis that urban areas with high TB case notifications have higher rates of TB
infection amongst children aged 1-5 years
4. To evaluate the feasibility and acceptability of performing surveillance using blood tests for
TB infection and other infectious diseases
To identify high-risk spatial areas and groups
within Blantyre, and model the potential population-level impact of targeted TB case-finding
and prevention interventions
Methodology
Children aged 12-60 months (1-5 years) of age will be recruited from 1) consecutive children attending
three primary health clinics: Bangwe, Limbe and Ndirande, and 2) cross-sectional population-weighted
random household sampling across their catchment areas. 3181 children or 100 children with a
positive IGRA will be recruited from each setting. Additionally, from the community household
sampling, adolescents 10-17 years and adults 18-40 years present in recruited households (estimated
approximately 3,000 in total) will be recruited through convenience sampling.
Guardians and participants will be approached for informed consent, and will complete a baseline
questionnaire which includes demographic and clinical information, as well as their home geolocation
using the validated ePal app. Participants will then be tested for TB infection using the QIAreach-QFT
IGRA blood test. Serum samples will also be taken and stored for future analysis.
Children (1-5 years) testing positive will be assessed for any evidence of active TB disease, and
depending on the outcome referred for either further investigations or TB preventive therapy. Their
household contacts are also recommended to receive screening for TB disease. Those testing positive
will be followed up at 3 and 9 months to ensure they have been entered into care. Participants testing
positive and age- and sex-matched controls will also be included in a nested case-control study which
investigates the role of novel diagnostics in this cohort. A subset will also be invited into a qualitative
study on the acceptability and feasibility of this approach.
Adolescents and adults testing positive will be notified of their results via phone. They will be
reminded of information given during recruitment about implications of a positive test result. WHO
does not recommend routine TB preventive therapy in adults and adolescents without HIV or other
risk factors. In this group, the risk of developing active TB disease in the following 2 years after a
positive test result is very low. In this study, all participants will be advised to seek care at a clinic if
they develop TB symptoms, and to seek HIV testing if their HIV status is unknown. Expected findings
1. We expect to be able to measure the annual risk of TB infection (ARTI) in Blantyre, and identify
and treat children at high risk of developing TB disease. We hypothesise that the ARTI will vary
by age, sex and other risk factors. We expect to identify and characterise neighbourhoods in
Blantyre where there is a high risk of TB infection
2. We expect that the more cost-effective methodology of recruiting from PHCs will give similar
results to that from more intensive cross-sectional sampling, and may therefore be a useful
sampling methodology for programmatic use in Blantyre and in other settings.
3. We anticipate that the areas with the highest risk of infection may differ from areas which
have a high rate of case notifications, for example including areas with more men and people
who are HIV-negative, which may reflect groups who are currently underdiagnosed.
4. We expect that this will be an acceptable, feasible methodology which may be used by TB
programmes in other settings to perform cost-effective surveillance for TB.
We plan to use these findings in the planning of future spatially-targeted interventions, and to inform
further work to estimate the population-level impact of reducing the pool of TB infection on future TB
transmission and burden. Findings from this study will be disseminated to Blantyre DHO, the Malawi
Description
Type of study
Cross-sectional epidemiological survey, with nested case-control and qualitative acceptability and
feasibility studies