The household contact study design for genetic epidemiological studies of infectious diseases

Stein, Catherine M.; Hall, Noémi B.; Malone, LaShaunda L.; Mupere, Ezekiel

doi:10.3389/fgene.2013.00061

Cited by 24 publications

(33 citation statements)

References 37 publications

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“…The household contact study [16] started enrolling culture-confirmed TB patients and their households in Kampala, Uganda in April 2002, and this analysis includes patients enrolled through January 1, 2008 and followed through December 2010. An index case was defined as the first identified culture-confirmed TB case in the household.…”

Section: Methodsmentioning

confidence: 99%

Clinical and epidemiological characteristics of individuals resistant to M. tuberculosis infection in a longitudinal TB household contact study in Kampala, Uganda

Zalwango

Malone

et al. 2014

BMC Infect Dis

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BackgroundDespite sustained exposure to a person with pulmonary tuberculosis (TB), some M. tuberculosis (Mtb) exposed individuals maintain a negative tuberculin skin test (TST). Our objective was to characterize these persistently negative TST (PTST-) individuals and compare them to TST converters (TSTC) and individuals who are TST positive at study enrollment.MethodsDuring a TB household contact study in Kampala, Uganda, PTST-, TSTC, and TST + individuals were identified. PTST- individuals maintained a negative TST over a 2 year observation period despite prolonged exposure to an infectious tuberculosis (TB) case. Epidemiological and clinical characteristics were compared, a risk score developed by another group to capture risk for Mtb infection was computed, and an ordinal regression was performed.ResultsWhen analyzed independently, epidemiological risk factors increased in prevalence from PTST- to TSTC to TST+. An ordinal regression model suggested age (p < 0.01), number of windows (p < 0.01) and people (p = 0.07) in the home, and sleeping in the same room (p < 0.01) were associated with PTST- and TSTC. As these factors do not exist in isolation, we examined a risk score, which reflects an accumulation of risk factors. This compound exposure score did not differ significantly between PTST-, TSTC, and TST+, except for the 5–15 age group (p = 0.009).ConclusionsThough many individual factors differed across all three groups, an exposure risk score reflecting a collection of risk factors did not differ for PTST-, TSTC and TST + young children and adults. This is the first study to rigorously characterize the epidemiologic risk profile of individuals with persistently negative TSTs despite close exposure to a person with TB. Additional studies are needed to characterize possible epidemiologic and host factors associated with this phenotype.

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Section: Methodsmentioning

confidence: 99%

Clinical and epidemiological characteristics of individuals resistant to M. tuberculosis infection in a longitudinal TB household contact study in Kampala, Uganda

Zalwango

Malone

et al. 2014

BMC Infect Dis

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“…Some studies have been family-based, while others used a traditional case-control design. The advantage of family-based studies of TB is that exposure is more certain even if variable [34, 35]. …”

Section: Previous Genetic Studies Of Tbmentioning

confidence: 99%

Genomics of Human Pulmonary Tuberculosis: from Genes to Pathways

et al. 2017

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Purpose of review Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains a major public health threat globally. Several lines of evidence support a role for host genetic factors in resistance/susceptibility to TB disease and MTB infection. However, results across candidate gene and genome-wide association studies (GWAS) are largely inconsistent, so a cohesive genetic model underlying TB risk has not emerged. Recent Findings Despite the difficulties in identifying consistent genetic associations, genetic studies of TB and MTB infection have revealed a few well-documented loci. These well validated genes are presented in this review, but there remains a large gap in how these genes translate into better understanding of TB. To address this, we present a pathway based extension of standard association analyses, seeding the results with the best validated genes from candidate gene and GWAS studies. Summary Several pathways were significantly enriched using pathway analyses that may help to explain population patterns of TB risk. In conclusion, we advocate for novel approaches to the study of host genetic analysis of TB that extend traditional association approaches.

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“…Stein et al (2013) describe a household contact study design which involves collecting data on households that may include both related and unrelated individuals. They argue that this research study design may be a powerful approach for jointly studying genetic and environmental exposures.…”

Section: Family Based Study Designsmentioning

confidence: 99%

Novel Approaches to the Analysis of Family Data in Genetic Epidemiology

2016

Frontiers Research Topics

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The household contact study design for genetic epidemiological studies of infectious diseases

Cited by 24 publications

References 37 publications

Clinical and epidemiological characteristics of individuals resistant to M. tuberculosis infection in a longitudinal TB household contact study in Kampala, Uganda

Clinical and epidemiological characteristics of individuals resistant to M. tuberculosis infection in a longitudinal TB household contact study in Kampala, Uganda

Genomics of Human Pulmonary Tuberculosis: from Genes to Pathways

Novel Approaches to the Analysis of Family Data in Genetic Epidemiology

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