Association of Mycobacterium tuberculosis aerosolization and HIV coinfection in the index case with T cell responses in household contacts.

Exposure to pulmonary tuberculosis (PTB) culminates in heterogeneous outcomes, including variation in Mtb antigen-specific interferon-gamma (IFN-γ) T-cell responses. IFN-γ-independent cytokines, including tumor necrosis factor (TNF) and interleukin (IL-2), offer potential diagnostic improvements and insights into pathogenesis. We hypothesized that ESAT6/CFP10 TNF and IL-2 responses improve Mtb infection detection among exposed household contacts (HHCs) and are associated with index case Mtb aerosolization (i.

Household contact antigen-specic TNF and IL-2 T-cell responses and impact of index case Mycobacterium tuberculosis aerosolization and HIV Co-infection.

Exposure to pulmonary tuberculosis (PTB) culminates in heterogeneous outcomes, including variation in antigen-specific interferon-gamma (IFN-γ) T-cell responses. IFN-γ-independent cytokines, including tumor necrosis factor (TNF) and interleukin (IL-2), offer potential diagnostic improvements and insights into pathogenesis. We hypothesized that ESAT6/CFP10 TNF and IL-2 responses improve infection detection among exposed household contacts (HHCs) and are associated with index case aerosolization (i.

Mycobacterium tuberculosis cough aerosol culture status associates with host characteristics and inflammatory profiles.

Interrupting transmission events is critical to tuberculosis control. Cough-generated aerosol cultures predict tuberculosis transmission better than microbiological or clinical markers. We hypothesize that highly infectious individuals with pulmonary tuberculosis (positive for cough aerosol cultures) have elevated inflammatory markers and unique transcriptional profiles compared to less infectious individuals.

Tuberculosis Infectiousness is Associated with Distinct Clinical and Inflammatory Profiles.

Interrupting transmission events to prevent new acquisition of infection and disease is a critical part of tuberculosis (TB) control efforts. However, knowledge gaps in understanding the biology and determinants of TB transmission, including poor estimates of individual infectiousness and the lack of accurate and convenient biomarkers, undermine efforts to develop interventions. Cough-generated aerosol cultures have been found to predict TB transmission better than any microbiological or clinical markers in cohorts from Uganda and Brazil.

Towards pharmacogenomics-guided tuberculosis (TB) therapy: N-acetyltransferase-2 genotypes among TB-infected Kenyans of mixed ethnicity.

Background: Though persons of African descent have one of the widest genetic variability, genetic polymorphisms of drug-metabolising enzymes such as N-Acetyltransferase-2 (NAT2) are understudied. This study aimed to identify prevalent NAT2 single nucleotide polymorphisms (SNPs) and infer their potential effects on enzyme function among Kenyan volunteers with tuberculosis (TB) infection. Genotypic distribution at each SNP and non-random association of alleles were evaluated by testing for Hardy-Weinberg Equilibrium (HWE) and Linkage Disequilibrium (LD).

TBscreen: A passive cough classifier for tuberculosis screening with a controlled dataset.

Recent respiratory disease screening studies suggest promising performance of cough classifiers, but potential biases in model training and dataset quality preclude robust conclusions. To examine tuberculosis (TB) cough diagnostic features, we enrolled subjects with pulmonary TB ( = 149) and controls with other respiratory illnesses ( = 46) in Nairobi. We collected a dataset with 33,000 passive coughs and 1600 forced coughs in a controlled setting with similar demographics.

Sensitive Blood-Based Detection of HIV-1 and Mycobacterium tuberculosis Peptides for Disease Diagnosis by Immuno-Affinity Liquid Chromatography-Tandem Mass Spectrometry: A Method Development and Proof-of-Concept Study.

Background: Novel approaches that allow early diagnosis and treatment monitoring of both human immunodeficiency virus-1 (HIV-1) and tuberculosis disease (TB) are essential to improve patient outcomes.

Methods: We developed and validated an immuno-affinity liquid chromatography-tandem mass spectrometry (ILM) assay that simultaneously quantifies single peptides derived from HIV-1 p24 and Mycobacterium tuberculosis (Mtb) 10-kDa culture filtrate protein (CFP10) in trypsin-digested serum derived from cryopreserved serum archives of cohorts of adults and children with/without HIV and TB.

Results: ILM p24 and CFP10 results demonstrated good intra-laboratory precision and accuracy, with recovery values of 96.

Prevalence and predictors of tuberculosis infection among people living with HIV in a high tuberculosis burden context.

Background: Tuberculosis (TB) disease is the leading cause of mortality among people living with HIV (PLHIV). Interferon-gamma release assays (IGRAs) are approved for TB infection ascertainment. However, current IGRA data on the prevalence of TB infection in the context of near-universal access to antiretroviral therapy (ART) and TB preventive therapy (TPT) are lacking.

Trends, treatment outcomes, and determinants for attrition among adult patients in care at a large tertiary HIV clinic in Nairobi, Kenya: a 2004-2015 retrospective cohort study.

Background: Understanding trends in patient profiles and identifying predictors for adverse outcomes are key to improving the effectiveness of HIV care and treatment programs. Previous work in Kenya has documented findings from a rural setting. This paper describes trends in demographic and clinical characteristics of antiretroviral therapy (ART) treatment cohorts at a large urban, referral HIV clinic and explores treatment outcomes and factors associated with attrition during 12 years of follow-up.

Trends in clinical characteristics and outcomes of Pre-ART care at a large HIV clinic in Nairobi, Kenya: a retrospective cohort study.

Background: The success of antiretroviral therapy in resource-scarce settings is an illustration that complex healthcare interventions can be successfully delivered even in fragile health systems. Documenting the success factors in the scale-up of HIV care and treatment in resource constrained settings will enable health systems to prepare for changing population health needs. This study describes changing demographic and clinical characteristics of adult pre-ART cohorts, and identifies predictors of pre-ART attrition at a large urban HIV clinic in Nairobi, Kenya.