Variability of Infectious Aerosols Produced during Coughing by Patients with Pulmonary Tuberculosis

Fennelly, Kevin P.; Jones-López, Edward C.; Ayakaka, Irene; Kim, Soyeon; Menyha, Harriet; Kirenga, Bruce; Muchwa, Christopher; Joloba, Moses; Dryden‐Peterson, Scott; Reilly, Nancy; Okwera, Alphonse; Elliott, Alison M.; Smith, P. G.; Mugerwa, Roy D.; Eisenach, Kathleen D.; Ellner, Jerrold J.

doi:10.1164/rccm.201203-0444oc

Cited by 142 publications

(152 citation statements)

References 28 publications

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“…33 The interactions between Mtb and macrophages are more complex. While macrophages function as the first line of defense against Mtb infection, they also serve as the primary niche for Mtb replication.…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of miR-20a-5p triggers cell apoptosis to facilitate mycobacterial clearance through targeting JNK2 in human macrophages

et al. 2016

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Induction of cell apoptosis is one of the major host defense mechanisms through which macrophages control Mycobacterium tuberculosis (Mtb) infection. However, the mechanisms underlying macrophage apoptosis triggered by Mtb infection are still largely unknown. In this study, a microarray profiling survey revealed 14 miRNAs were down-regulated in CD14C monocytes from active pulmonary tuberculosis patients, and only the reduction of miR-20a-5p could be reversed after successful anti-tuberculosis treatment. Validation of miR-20a-5p expression was confirmed using real time qPCR. Moreover, miR-20a-5p expression also decreased in differentiated THP-1 macrophages after mycobacterial infection in vitro. Functional assays through forced or inhibited expression of miR-20a-5p in THP-1 macrophages demonstrated that miR-20a-5p functioned as a negative regulator of mycobacterial-triggered apoptosis. Importantly, inhibition of miR-20a-5p expression resulted in more efficient mycobacterial clearance from infected THP-1 macrophages while miR-20a-5p overexpression promoted mycobacterial survival. Mechanistically, miR-20a-5p was demonstrated to regulate Bim expression in a JNK2-dependent manner, unlike Bcl2, and luciferase assay showed JNK2 was a novel direct target of miR-20a-5p. Together, our findings indicate that downregulation of miR-20a-5p triggers macrophage apoptosis as a novel mechanism for host defense against mycobacterial infection.

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Section: Discussionmentioning

confidence: 99%

Down-regulation of miR-20a-5p triggers cell apoptosis to facilitate mycobacterial clearance through targeting JNK2 in human macrophages

et al. 2016

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“…While a smear-negative culture-positive status indicates paucibacillary TB disease, HIV-infected index cases may have had more pronounced immunosuppression, thus were more unwell and had less frequent or weaker cough to produce infectious aerosols (11). Indeed, a limitation of the current study is the absence of data on severity of immunosuppression, antiretroviral use, and indication of general health status or frailty of the index case, including duration of hospitalization.…”

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confidence: 90%

Contact Investigation: A Priority for Tuberculosis Control Programs

Saunders¹,

Datta²

2016

Am J Respir Crit Care Med

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“…Recent cough aerosol experiments have shown that the characteristics of the bioaerosol produced in patients with pulmonary TB (particle quantity and size) may be just as important as measures of mycobacterial load as smear grade or culture time-topositivity. [24] The collection of cough aerosol was beyond the scope of the study. We also did not perform chest X-rays as part of our ICF strategy.…”

Section: Fig 1 Consort Study Diagram *Patients Temporarily Visitinmentioning

confidence: 99%

The diagnostic gap: Characterising the profile of undiagnosed infectious tuberculosis patients in the community

Calligaro

Esmail²,

Mnguni

et al. 2016

S Afr Res J

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Background. In tuberculosis (TB)-endemic countries, about half the total TB caseload remains undiagnosed within the community. The proportion of such patients that can potentially transmit the disease has been poorly characterised, and there is insufficient data to inform on strategies to target potentially infectious TB cases in the community. Objective. To characterise the nature and profile of smear-positive patients diagnosed with TB in the community. Methods. We analysed data from culture-positive TB cases in the community during the course of an intensified case finding (ICF) study. The parent study was a randomised controlled trial comparing conventional and novel diagnostics for ICF in communities in Cape Town, South Africa and Harare, Zimbabwe, where trained healthcare workers screened patients at transmission hotspots. The results of the parent study are reported elsewhere. Results. A total of 2 261 persons were screened and 875 (39%) met the criteria for diagnostic testing. A total of 53/630 (8.4%) had confirmed tuberculosis. Smear microscopy detected 22/53 (42%) of the culture-positive patients. The specificity, positive predictive value (PPV) and negative predictive value (NPV) for smear microscopy were 98.4%, 70.0% and 95.3%, respectively. No clinical or demographic variable predicted smear positivity. Only decreased culture time-to-positivity was associated with smear grade (odds ratio 0.93, 95% confidence interval 0.91 -0.96; p<0.001). Conclusion. A considerable proportion of patients with undiagnosed TB in the community (almost half) were smear positive and hence potentially infectious. Interestingly, neither HIV status nor symptoms identified those patients who were potentially infectious, despite them having a higher mycobacterial burden. Respir J 2016;22(4):93-98. S Afr

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Variability of Infectious Aerosols Produced during Coughing by Patients with Pulmonary Tuberculosis

Cited by 142 publications

References 28 publications

Down-regulation of miR-20a-5p triggers cell apoptosis to facilitate mycobacterial clearance through targeting JNK2 in human macrophages

Down-regulation of miR-20a-5p triggers cell apoptosis to facilitate mycobacterial clearance through targeting JNK2 in human macrophages

Contact Investigation: A Priority for Tuberculosis Control Programs

The diagnostic gap: Characterising the profile of undiagnosed infectious tuberculosis patients in the community

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