Dataset Information

Sera from patients with active pulmonary tuberculosis and their household contacts induce nuclear changes in neutrophils.

ABSTRACT:

Background

Resident alveolar macrophages, dendritic cells, and immigrating neutrophils (NEU) are the first cells to contact Mycobacterium tuberculosis in the lung. These cells, and additional lymphoid cells in the developing granuloma, release a series of components that may concentrate in the serum and affect disease progression.

Purpose

The aim of this study was to investigate the effect of the serum from tuberculosis (TB) patients and their household contacts (HHC) on the nuclear morphology of NEU.

Materials and methods

NEU from healthy (HLT) people were incubated with sera from patients with active pulmonary TB, their HHC, and unrelated people. Changes in the nuclear morphology of NEU were analyzed by light and electron microscopy.

Results

Sera from patients with TB induced changes in the nuclear morphology of NEU that included pyknosis, swelling, apoptosis, and netosis in some cases. Sera from some HHC induced similar changes, while sera from HLT people had no significant effects. Bacteria did not appear to participate in this phenomenon because bacteremia is not a recognized feature of nonmiliary TB, and because sera from patients that induced nuclear changes maintained their effect after filtration through 0.22 µm membranes. Neither anti-mycobacterial antibodies, TNF?, IL-6, IFN?, or IL-8 participated in the phenomenon. In contrast, soluble mycobacterial antigens were likely candidates, as small quantities of soluble M. tuberculosis antigens added to the sera of HLT people led to the induction of nuclear changes in NEU in a dose-dependent manner.

Conclusion

These results might help to detect subclinical TB within HHC, thus leading to a recommendation of prophylactic treatment.

SUBMITTER: Juarez-Ortega M

PROVIDER: S-EPMC6188193 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Sera from patients with active pulmonary tuberculosis and their household contacts induce nuclear changes in neutrophils.

Juárez-Ortega Mario M Rojas-Espinosa Oscar O Muñiz-Salazar Raquel R Becerril-Villanueva Enrique E Hernández-Solís Alejandro A Arce-Paredes Patricia P Islas-Trujillo Sergio S Cicero-Sabido Raúl R

Infection and drug resistance 20181010

<h4>Background</h4>Resident alveolar macrophages, dendritic cells, and immigrating neutrophils (NEU) are the first cells to contact <i>Mycobacterium tuberculosis</i> in the lung. These cells, and additional lymphoid cells in the developing granuloma, release a series of components that may concentrate in the serum and affect disease progression.<h4>Purpose</h4>The aim of this study was to investigate the effect of the serum from tuberculosis (TB) patients and their household contacts (HHC) on th ...[more]

PMID: 30349326

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Project description:Several studies showed that assessing levels of specific circulating microRNAs (miRNAs) is a non-invasive, rapid, and accurate method for diagnosing diseases or detecting alterations in physiological conditions. We aimed to identify a serum miRNA signature to be used for the diagnosis of tuberculosis (TB). To account for variations due to the genetic makeup, we enrolled adults from two study settings in Europe and Africa. The following categories of subjects were considered: healthy (H), active pulmonary TB (PTB), active pulmonary TB, HIV co-infected (PTB/HIV), latent TB infection (LTBI), other pulmonary infections (OPI), and active extra-pulmonary TB (EPTB). Sera from 10 subjects of the same category were pooled and, after total RNA extraction, screened for miRNA levels by TaqMan low-density arrays. After identification of "relevant miRNAs", we refined the serum miRNA signature discriminating between H and PTB on individual subjects. Signatures were analyzed for their diagnostic performances using a multivariate logistic model and a Relevance Vector Machine (RVM) model. A leave-one-out-cross-validation (LOOCV) approach was adopted for assessing how both models could perform in practice. The analysis on pooled specimens identified selected miRNAs as discriminatory for the categories analyzed. On individual serum samples, we showed that 15 miRNAs serve as signature for H and PTB categories with a diagnostic accuracy of 82% (CI 70.2-90.0), and 77% (CI 64.2-85.9) in a RVM and a logistic classification model, respectively. Considering the different ethnicity, by selecting the specific signature for the European group (10 miRNAs) the diagnostic accuracy increased up to 83% (CI 68.1-92.1), and 81% (65.0-90.3), respectively. The African-specific signature (12 miRNAs) increased the diagnostic accuracy up to 95% (CI 76.4-99.1), and 100% (83.9-100.0), respectively. Serum miRNA signatures represent an interesting source of biomarkers for TB disease with the potential to discriminate between PTB and LTBI, but also among the other categories.

Project description:The World Health Organization (WHO) recently changed its guidance for tuberculosis (TB) preventive treatment (TPT) recommending TPT for all pulmonary TB (PTB) exposed household contacts (HHC) to prevent incident TB disease (iTBD), regardless of TB infection (TBI) status. However, this recommendation was conditional as the strength of evidence was not strong. We assessed risk factors for iTBD in recently-exposed adult and pediatric Indian HHC, to determine which HHC subgroups might benefit most from TPT. We prospectively enrolled consenting HHC of adult PTB patients in Pune and Chennai, India. They underwent clinical, microbiologic and radiologic screening for TB disease (TBD) and TBI, at enrollment, 4-6, 12 and 24 months. TBI testing was performed by tuberculin skin test (TST) and Quantiferon®- Gold-in-Tube (QGIT) assay. HHC without baseline TBD were followed for development of iTBI and iTBD. Using mixed-effect Poisson regression, we assessed baseline characteristics including TBI status, and incident TBI (iTBI) using several TST and/or QGIT cut-offs, as potential risk factors for iTBD. Of 1051 HHC enrolled, 42 (4%) with baseline TBD and 12 (1%) with no baseline TBI test available, were excluded. Of the remaining 997 HHC, 707 (71%) had baseline TBI (TST #x2265; 5 mm or QGIT #x2265; 0.35 IU/ml). Overall, 20 HHC (2%) developed iTBD (12 cases/1000 person-years, 95%CI: 8-19). HIV infection (aIRR = 29.08, 95% CI: 2.38-355.77, p = 0.01) and undernutrition (aIRR = 6.16, 95% CI: 1.89-20.03, p = 0.003) were independently associated with iTBD. iTBD was not associated with age, diabetes mellitus, smoking, alcohol, and baseline TBI, or iTBI, regardless of TST (#x2265; 5 mm, #x2265; 10 mm, #x2265; 6 mm increase) or QGIT (#x2265; 0.35 IU/ml, #x2265; 0.7 IU/ml) cut-offs. Given the high overall risk of iTBD among recently exposed HHCs, and the lack of association between TBI status and iTBD, our findings support the new WHO recommendation to offer TPT to all HHC of PTB patients residing in a high TB burden country such as India, and do not suggest any benefit of TBI testing at baseline or during follow-up to risk stratify recently-exposed HHC for TPT.

Project description:BACKGROUND:Despite free TB services available in public health facilities, TB patients often face severe financial burden due to TB. WHO set a new global target that no TB-affected families experience catastrophic costs due to TB. To monitor the progress and strategize the optimal approach to achieve the target, there is a great need to assess baseline cost data, explore potential proxy indicators for catastrophic costs, and understand what intervention mitigates financial burden. In Cambodia, nationwide active case finding (ACF) targeting household and neighbourhood contacts was implemented alongside routine passive case finding (PCF). We analyzed household cost data from ACF and PCF to determine the financial benefit of ACF, update the baseline cost data, and explore whether any dissaving patterns can be a proxy for catastrophic costs in Cambodia. METHODS:In this cross-sectional comparative study, structured interviews were carried out with 108 ACF patients and 100 PCF patients. Direct and indirect costs, costs before and during treatment, costs as percentage of annual household income and dissaving patterns were compared between the two groups. RESULTS:The median total costs were lower by 17% in ACF than in PCF ($240.7 [IQR 65.5-594.6] vs $290.5 [IQR 113.6-813.4], p = 0.104). The median costs before treatment were significantly lower in ACF than in PCF ($5.1 [IQR 1.5-25.8] vs $22.4 [IQR 4.4-70.8], p<0.001). Indirect costs constituted the largest portion of total costs (72.3% in ACF and 61.5% in PCF). Total costs were equivalent to 11.3% and 18.6% of annual household income in ACF and PCF, respectively. ACF patients were less likely to dissave to afford TB-related expenses. Costs as percentage of annual household income were significantly associated with an occurrence of selling property (p = 0.02 for ACF, p = 0.005 for PCF). CONCLUSIONS:TB-affected households face severe financial hardship in Cambodia. ACF has the great potential to mitigate the costs incurred particularly before treatment. Social protection schemes that can replace lost income are critically needed to compensate for the most devastating costs in TB. An occurrence of selling household property can be a useful proxy for catastrophic cost in Cambodia.

Project description:BackgroundGlobally, there has been growing evidence that suggests the effectiveness of active case finding (ACF) for tuberculosis (TB) in high-risk populations. However, the evidence is still insufficient as to whether ACF increases case notification beyond what is reported in the routine passive case finding (PCF). In Cambodia, National TB Control Programme has conducted nationwide ACF with Xpert MTB/RIF that retrospectively targeted household and neighbourhood contacts alongside routine PCF. This study aims to investigate the impact of ACF on case notifications during and after the intervention period.MethodsUsing a quasi-experimental cluster randomized design with intervention and control arms, we compared TB case notification during the one-year intervention period with historical baseline cases and trend-adjusted expected cases, and estimated additional cases notified during the intervention period (separately for Year 1 and Year 2 implementation). The proportion of change in case notification was compared between intervention and control districts for Year 1. The quarterly case notification data from all intervention districts were consolidated, aligning different implementation quarters, and separately analysed to explore the additionality. The effect of the intervention on the subsequent case notification during the post-intervention period was also assessed.ResultsIn Year 1, as compared to expected cases, 1467 cases of all forms (18.5%) and 330 bacteriologically-confirmed cases (9.6%) were additionally notified in intervention districts, whereas case notification in control districts decreased by 2.4% and 2.3%, respectively. In Year 2, 2737 cases of all forms (44.3%) and 793 bacteriologically-confirmed cases (38%) were additionally notified as compared to expected cases. The proportions of increase in case notifications from baseline cases and expected cases to intervention period cases were consistently higher in intervention group than in control group. The consolidated quarterly data showed sharp rises in all forms and bacteriologically-confirmed cases notified during the intervention quarter, with 64.6% and 68.4% increases (compared to baseline cases), and 46% and 52.9% increases (compared to expected cases), respectively. A cumulative reduction of case notification for five quarters after ACF reached more than -200% of additional cases.ConclusionsThe Cambodia's ACF with Xpert MTB/RIF that retrospectively targeted household and neighbourhood contacts resulted in the substantial increase in case notification during the intervention period and reduced subsequent case notification during the post-intervention period. The applicability of retrospective contact investigation in other high-burden settings should be explored.

Dataset Information

Sera from patients with active pulmonary tuberculosis and their household contacts induce nuclear changes in neutrophils.

Background

Purpose

Materials and methods

Results

Conclusion

Publications

Sera from patients with active pulmonary tuberculosis and their household contacts induce nuclear changes in neutrophils.

Similar Datasets

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