Xpert MTB/RIF Ultra assay for tuberculosis disease and rifampicin resistance in children.

Background: Every year, an estimated one million children and young adolescents become ill with tuberculosis, and around 226,000 of those children die. Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)-recommended rapid diagnostic test that simultaneously detects Mycobacterium tuberculosis complex and rifampicin resistance. We previously published a Cochrane Review 'Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for tuberculosis disease and rifampicin resistance in children'.

CRISPR detection of circulating cell-free Mycobacterium tuberculosis DNA in adults and children, including children with HIV: a molecular diagnostics study.

Background: Tuberculosis remains a leading cause of global mortality, especially for adults and children living with HIV (CLHIV) underdiagnosed by sputum-based assays. Non-sputum-based assays are needed to improve tuberculosis diagnosis and tuberculosis treatment monitoring. Our aim in this study was to determine whether ultrasensitive detection of Mycobacterium tuberculosis cell-free DNA (Mtb-cfDNA) in blood can diagnose tuberculosis and evaluate tuberculosis treatment responses.

HIV-Associated Tuberculosis in Children and Adolescents: Evolving Epidemiology, Screening, Prevention and Management Strategies.

Children and adolescents living with HIV continue to be impacted disproportionately by tuberculosis as compared to peers without HIV. HIV can impact TB screening and diagnosis by altering screening and diagnostic test performance and can complicate prevention and treatment strategies due to drug-drug interactions. Post-tuberculosis lung disease is an underappreciated phenomenon in children and adolescents, but is more commonly observed in children and adolescents with HIV-associated tuberculosis.

Vikela Ekhaya: A Novel, Community-based, Tuberculosis Contact Management Program in a High Burden Setting.

Background: The prevention of tuberculosis (TB) in child contacts of TB cases and people living with human immunodeficiency virus (HIV) is a public health priority, but global access to TB preventive therapy (TPT) remains low. In 2019, we implemented Vikela Ekhaya, a novel community-based TB contact management program in Eswatini designed to reduce barriers to accessing TPT.

Methods: Vikela Ekhaya offered differentiated TB and HIV testing for household contacts of TB cases by using mobile contact management teams to screen contacts, assess their TPT eligibility, and initiate and monitor TPT adherence in participants' homes.

Screening tests for active pulmonary tuberculosis in children.

Background: Globally, children under 15 years represent approximately 12% of new tuberculosis cases, but 16% of the estimated 1.4 million deaths. This higher share of mortality highlights the urgent need to develop strategies to improve case detection in this age group and identify children without tuberculosis disease who should be considered for tuberculosis preventive treatment.

The Magnitude of Interferon Gamma Release Assay Responses in Children With Household Tuberculosis Contact Is Associated With Tuberculosis Exposure and Disease Status.

Background: The clinical utility of the magnitude of interferon gamma (IFNγ) in response to mycobacterial antigens is unknown. We assessed the association between quantitative IFNγ response and degree of Mycobacterium tuberculosis exposure, infection and tuberculosis (TB) disease status in children.

Methods: We completed cross-sectional analysis of children (≤15 years) exposed to an adult with bacteriologically confirmed TB, 2007-2012 in Cape Town, South Africa.

Evaluating antibiotic use and developing a tool to optimize prescribing in a family-centered HIV clinic in Eswatini.

In a human immunodeficiency virus (HIV) clinic for children and their families in Eswatini, we sought to understand the use of antibiotics and identify specific areas for improvement. We performed a retrospective patient chart review as part of a quality improvement (QI) initiative to assess antimicrobial use before and after implementation of a standardized antimicrobial guide. For each prescribing period, 100 random patient encounters were selected for review if the indication for antibiotics, duration, and dose were consistent with World Health Organization (WHO) guidelines.

Predictors of suboptimal adherence to isoniazid preventive therapy among adolescents and children living with HIV.

This study identified factors associated with adherence to a 6-month isoniazid preventive therapy (IPT) course among adolescents and children living with HIV. Forty adolescents living with HIV and 48 primary caregivers of children living with HIV completed a Likert-based survey to measure respondent opinions regarding access to care, quality of care, preferred regimens, perceived stigma, and confidence in self-efficacy. Sociodemographic data were collected and adherence measured as the average of pill counts obtained while on IPT.

Tuberculosis among Children and Adolescents at HIV Treatment Centers in Sub-Saharan Africa.

HIV-infected children and adolescents are at increased risk for tuberculosis (TB). Antiretroviral therapy (ART) reduces TB risk in HIV-infected adults, but its effectiveness in HIV-infected children and adolescents is unknown. We analyzed data from 7 integrated pediatric HIV/TB centers in 6 countries in sub-Saharan Africa.

Transition to Dolutegravir Is Associated With an Increase in the Rate of Body Mass Index Change in a Cohort of Virally Suppressed Adolescents.

Background: Antiretroviral therapy (ART) regimens that contain dolutegravir (DTG) have been associated with increases in body mass index (BMI) in adults. However, this relationship has not been well described in adolescents.

Methods: In a retrospective observational cohort of 460 virally suppressed (<200 copies/mL) adolescents living with human immunodeficiency virus at a clinical site in Eswatini, body mass index (BMI) measurements were analyzed between 1 year prior to the transition to DTG and up to 1 year after DTG transition.

Distinct Risk Factors for Clinical and Bacteriologically Confirmed Tuberculosis among Child Household Contacts in a High-Burden Setting.

The identification and screening of children at high risk of tuberculosis is essential to the control and prevention of child tuberculosis (TB). BUTIMBA, an active case finding and household contact-tracing project implemented between 2013 and 2015 in Eswatini, evaluated 5,413 contacts of 1,568 index cases, of whom 82 (1.5%) were diagnosed with TB disease.

Predicting Sexually Transmitted Infections Among HIV+ Adolescents and Young Adults: A Novel Risk Score to Augment Syndromic Management in Eswatini.

Background: Despite poor predictive power, syndromic screening is standard of care for diagnosing sexually transmitted infections (STIs) in low-resource, high HIV-burden settings. Predictive models may augment syndromic screening when diagnostic testing is not universally available for screening high-risk patient populations such as adolescents and young adults living with HIV.

Setting: Four hundred fifteen adolescents and young adults living with HIV, age 15-24 years, participated from 3 clinical sites in Eswatini, provided urine, sexual and medical history, and completed physical examination.

Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for active tuberculosis and rifampicin resistance in children.

Background: Every year, at least one million children become ill with tuberculosis and around 200,000 children die. Xpert MTB/RIF and Xpert Ultra are World Health Organization (WHO)-recommended rapid molecular tests that simultaneously detect tuberculosis and rifampicin resistance in adults and children with signs and symptoms of tuberculosis, at lower health system levels. To inform updated WHO guidelines on molecular assays, we performed a systematic review on the diagnostic accuracy of these tests in children presumed to have active tuberculosis.

Point-of-Care Testing to Guide Treatment and Estimate Risk Factors for Sexually Transmitted Infections in Adolescents and Young People With Human Immunodeficiency Virus in Eswatini.

Background: The World Health Organization (WHO) estimates 127 million new cases of (CT), 87 million new cases of (NG), and 156 million new cases of (TV) each year, which corresponds to 355 (219-606), 303 (216-468), and 243 (97.6-425) thousand disability-adjusted life-years. In low-resource settings, however, sexually transmitted infections (STIs) are treated syndromically and many individuals with asymptomatic infection may be missed, especially adolescents and young adults with human immunodeficiency virus (HIV).

Pregnancy-Induced Alterations in NK Cell Phenotype and Function.

Pregnant women are particularly susceptible to complications of influenza A virus infection, which may result from pregnancy-induced changes in the function of immune cells, including natural killer (NK) cells. To better understand NK cell function during pregnancy, we assessed the ability of the two main subsets of NK cells, CD56, and CD56 NK cells, to respond to influenza-virus infected cells and tumor cells. During pregnancy, CD56 and CD56 NK cells displayed enhanced functional responses to both infected and tumor cells, with increased expression of degranulation markers and elevated frequency of NK cells producing IFN-γ.

Evaluation of the QuantiFERON-Tuberculosis Gold Plus Assay in Children with Tuberculosis Disease or Following Household Exposure to Tuberculosis.

Interferon-gamma release assays are increasingly used in children to establish evidence of tuberculosis (TB) infection and to assist in the diagnosis of TB disease. The QuantiFERON-TB Gold In-Tube assay is being phased out in favor of a next-generation test, the QuantiFERON-TB Gold Plus (QFT-Plus) assay. The QFT-Plus assay is designed with two antigen tubes to differentially stimulate CD4 and CD8 T cells.

Interferon-γ Release Assay Performance for Tuberculosis in Childhood.

Background: Interferon-γ release assays (IGRAs) are important adjunctive tests for diagnosing tuberculosis (TB) disease in children.

Methods: We analyzed California TB registry data for patients ≤18 years with laboratory-confirmed TB disease during 2010-2015 to identify case characteristics associated with test selection and performance and measure IGRA sensitivity.

Results: In total, 778 cases of TB were reported; 360 were laboratory confirmed.

Diagnostic and Treatment Monitoring Potential of A Stool-Based Quantitative Polymerase Chain Reaction Assay for Pulmonary Tuberculosis.

A quantifiable, stool-based, () test has potential complementary value to respiratory specimens. Limit of detection (LOD) was determined by spiking control stool. Clinical test performance was evaluated in a cohort with pulmonary tuberculosis (TB) ( = 166) and asymptomatic household TB child contacts ( = 105).

Leveraging tuberculosis case relative locations to enhance case detection and linkage to care in Swaziland.

Background: In Swaziland, as in many high HIV/TB burden settings, there is not information available regarding the household location of TB cases for identifying areas of increased TB incidence, limiting the development of targeted interventions. Data from "Butimba", a TB REACH active case finding project, was re-analyzed to provide insight into the location of TB cases surrounding Mbabane, Swaziland.

Objective: The project aimed to identify geographical areas with high TB burdens to inform active case finding efforts.

School and household tuberculosis contact investigations in Swaziland: Active TB case finding in a high HIV/TB burden setting.

Background: Investigation of household contacts exposed to infectious tuberculosis (TB) is widely recommended by international guidelines to identify secondary cases of TB and limit spread. There is little data to guide the use of contact investigations outside of the household, despite strong evidence that most TB infections occur outside of the home in TB high burden settings. In older adolescents, the majority of infections are estimated to occur in school.

Increased Proinflammatory Responses of Monocytes and Plasmacytoid Dendritic Cells to Influenza A Virus Infection During Pregnancy.

Pregnancy-induced alterations in immunity may contribute to the increased morbidity associated with influenza A virus infection during pregnancy. We characterized the immune response of monocytes and plasmacytoid dendritic cells (pDCs) to influenza A virus infection in 21 pregnant and 21 nonpregnant women. In pregnant women, monocytes and pDCs exhibit an exaggerated proinflammatory immune response to 2 strains of influenza A virus, compared with nonpregnant women, characterized by increased expression of major histocompatibility complex class II (approximately 2.

Getting to Zero: Tuberculosis Elimination in California.

This review of tuberculosis epidemiology is intended to provide a historical perspective on the public health approach to tuberculosis (TB) control in California. This historical context offers a lens through which to view current epidemiologic trends and insight into how new therapeutic tools can be applied. Since 1993, the year detailed case reporting was instituted, California has had a decrease in recent TB transmission as evidenced by a reduction in pediatric cases and an increased percentage of cases attributable to progression of latent infection to TB disease in the foreign-born population.

Application of Mass Cytometry (CyTOF) for Functional and Phenotypic Analysis of Natural Killer Cells.

Mass cytometry is a novel platform for high-dimensional phenotypic and functional analysis of single cells. This system uses elemental metal isotopes conjugated to monoclonal antibodies to evaluate up to 42 parameters simultaneously on individual cells with minimal overlap between channels. The platform can be customized for analysis of both phenotypic and functional markers.