Tuberculosis case finding in first-degree relative contacts not living with index tuberculosis cases in Kampala, Uganda

Chheng, Phalkun; Nsereko, Mary; Malone, LaShaunda L.; Okware, Brenda; Zalwango, Sarah; Joloba, Moses; Boom, W. Henry; Mupere, Ezekiel; Stein, Catherine M.

doi:10.2147/clep.s82389

Cited by 9 publications

(6 citation statements)

References 29 publications

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“…A total of 79 Ugandans (Supplementary Tables 1 and 2) who were recruited from the Kawempe Community Health Study were included in this analysis 9,52 . Index individuals with pulmonary TB were identified by culture for confirmed pulmonary TB at the Uganda National Referral Tuberculosis Treatment Center at Upper Mulago Hospital in Kampala, Uganda, between 2002 and 2012.…”

Section: Methodsmentioning

confidence: 99%

IFN-γ-independent immune markers of Mycobacterium tuberculosis exposure

Smith

et al. 2019

Nat Med

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SUMMARY Exposure to Mycobacterium tuberculosis (Mtb) results in heterogeneous clinical outcomes including primary progressive tuberculosis (TB) and latent Mtb infection (LTBI). Mtb infection is identified using the tuberculin skin test (TST) and IFN-γ release assay (IGRA), and a positive result may prompt chemoprophylaxis to prevent progression to TB. Here, we report a cohort of Ugandan household contacts, highly exposed to Mtb yet IGRA and TST negative, “resisting” development of classical LTBI. We show that “resisters” possess IgM, class-switched IgG antibody responses and non IFN-γ T-cell responses to Mtb-specific proteins ESAT6 and CFP10, immunologic evidence of exposure to Mtb. Compared to subjects with classical LTBI, “resisters” display enhanced antibody avidity and distinct Mtb-specific IgG Fc profiles. These data reveal a distinct adaptive immune profile among Mtb exposed subjects, supporting an expanded definition of the host response to Mtb exposure with implications for public health and the design of clinical trials.

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Section: Methodsmentioning

confidence: 99%

IFN-γ-independent immune markers of Mycobacterium tuberculosis exposure

Smith

et al. 2019

Nat Med

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205

214

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“…The yield was higher at 1.4% among the neighbor contacts. Cheng et al (2015) from Uganda showed that first degree relatives’ contacts were more likely to be symptomatic for TB [ 18 ]. It was also shown by Lienherdt et al (2003) in Gambia that development of TB cases increased with first degree relatives compared with more distant and non-genetically related households [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…Besides, earlier contact investigation studies in Ethiopia used only household contacts of SS+ index cases [ 11 , 14 ]. While there is some evidence that TB among close contacts of SS-[ 15 – 17 ] and in contacts other than households [ 18 , 19 ] is high, this has not been demonstrated in routine program settings.…”

Section: Introductionmentioning

confidence: 99%

The Yield of Community-Based “Retrospective” Tuberculosis Contact Investigation in a High Burden Setting in Ethiopia

et al. 2016

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ObjectiveTo determine the yield and determinants of retrospective TB contact investigation in selected zones in Ethiopia.Materials and MethodsThis was a community-based cross-sectional study conducted during June-October 2014.Trained lay providers performed symptom screening for close contacts of index cases with all types of TB registered for anti-TB treatment within the last three years. We used logistic regression to determine factors associated with TB diagnosis among the contacts.ResultsOf 272,441 close contacts of 47, 021 index cases screened, 13,886 and 2, 091 had presumptive and active TB respectively. The yield of active TB was thus 768/100, 000, contributing 25.4% of the 7,954 TB cases reported from the study zones over the study period. The yield was highest among workplace contacts (12,650/100, 000). Active TB was twice more likely among contacts whose index cases had been registered for TB treatment within the last 12 months compared with those who had been registered 24 or more months earlier (adjusted odds ratio, AOR: 1.77 95% CI 1.42–2.21). Sex or clinical type of TB in index cases was not associated with the yield. Smear negative (SS-) index cases (AOR: 1.74 955 CI 1.13–2.68), having index cases who registered for treatment within <12 months (AOR: 2.41 95% CI 1.51–3.84) and being household contact (AOR: 0.072 95% CI 0.01–0.52) were associated with the occurrence of active TB in children.ConclusionsThe yield of retrospective contact investigation was about six times the case notification in the study zones, contributing a fourth of all TB cases notified over the same period. The yield was highest among workplace contacts and in those with recent past history of contact. Retrospective contact screening can serve as additional strategy to identify high risk groups not addressed through currently recommended screening approaches.

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“…Briefly, newly diagnosed tuberculosis patients were identified at the Uganda National Referral Tuberculosis Treatment Center at Upper Mulago Hospital in Kampala, Uganda. The index cases were enrolled if they had culture confirmed pulmonary tuberculosis and had at least one household contact living with them[ 19 ]. Between 2002 and 2012, 2585 household contacts were enrolled and followed prospectively for up to two years for development of tuberculosis disease or diagnosis of latent tuberculosis infection by serial TSTs at 0, 3, 6, 12, 18,and 24 months.…”

Section: Methodsmentioning

confidence: 99%

Transcriptional networks are associated with resistance to Mycobacterium tuberculosis infection

et al. 2017

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RationaleUnderstanding mechanisms of resistance to M. tuberculosis (M.tb) infection in humans could identify novel therapeutic strategies as it has for other infectious diseases, such as HIV.ObjectivesTo compare the early transcriptional response of M.tb-infected monocytes between Ugandan household contacts of tuberculosis patients who demonstrate clinical resistance to M.tb infection (cases) and matched controls with latent tuberculosis infection.MethodsCases (n = 10) and controls (n = 18) were selected from a long-term household contact study in which cases did not convert their tuberculin skin test (TST) or develop tuberculosis over two years of follow up. We obtained genome-wide transcriptional profiles of M.tb-infected peripheral blood monocytes and used Gene Set Enrichment Analysis and interaction networks to identify cellular processes associated with resistance to clinical M.tb infection.Measurements and main resultsWe discovered gene sets associated with histone deacetylases that were differentially expressed when comparing resistant and susceptible subjects. We used small molecule inhibitors to demonstrate that histone deacetylase function is important for the pro-inflammatory response to in-vitro M.tb infection in human monocytes.ConclusionsMonocytes from individuals who appear to resist clinical M.tb infection differentially activate pathways controlled by histone deacetylase in response to in-vitro M.tb infection when compared to those who are susceptible and develop latent tuberculosis. These data identify a potential cellular mechanism underlying the clinical phenomenon of resistance to M.tb infection despite known exposure to an infectious contact.

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Tuberculosis case finding in first-degree relative contacts not living with index tuberculosis cases in Kampala, Uganda

Cited by 9 publications

References 29 publications

IFN-γ-independent immune markers of Mycobacterium tuberculosis exposure

IFN-γ-independent immune markers of Mycobacterium tuberculosis exposure

The Yield of Community-Based “Retrospective” Tuberculosis Contact Investigation in a High Burden Setting in Ethiopia

Transcriptional networks are associated with resistance to Mycobacterium tuberculosis infection

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