WHO global research priorities for antimicrobial resistance in human health.

The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education.

The potential impact of novel tuberculosis vaccines on health equity and financial protection in low-income and middle-income countries.

Introduction: One in two patients developing tuberculosis (TB) in low-income and middle-income countries (LMICs) faces catastrophic household costs. We assessed the potential financial risk protection from introducing novel TB vaccines, and how health and economic benefits would be distributed across income quintiles.

Methods: We modelled the impact of introducing TB vaccines meeting the World Health Organization preferred product characteristics in 105 LMICs.

The potential impact of novel tuberculosis vaccine introduction on economic growth in low- and middle-income countries: A modeling study.

Background: Most individuals developing tuberculosis (TB) are working age adults living in low- and middle-income countries (LMICs). The resulting disability and death impact economic productivity and burden health systems. New TB vaccine products may reduce this burden.

The impact of alternative delivery strategies for novel tuberculosis vaccines in low-income and middle-income countries: a modelling study.

Background: Tuberculosis is a leading infectious cause of death worldwide. Novel vaccines will be required to reach global targets and reverse setbacks resulting from the COVID-19 pandemic. We estimated the impact of novel tuberculosis vaccines in low-income and middle-income countries (LMICs) in several delivery scenarios.

The cost and cost-effectiveness of novel tuberculosis vaccines in low- and middle-income countries: A modeling study.

Background: Tuberculosis (TB) is preventable and curable but eliminating it has proven challenging. Safe and effective TB vaccines that can rapidly reduce disease burden are essential for achieving TB elimination. We assessed future costs, cost-savings, and cost-effectiveness of introducing novel TB vaccines in low- and middle-income countries (LMICs) for a range of product characteristics and delivery strategies.

Recommendation mapping of the World Health Organization's guidelines on tuberculosis: A new approach to digitizing and presenting recommendations.

Objective: Having up-to-date health policy recommendations accessible in one location is in high demand by guideline users. We developed an easy to navigate interactive approach to organize recommendations and applied it to tuberculosis (TB) guidelines of the World Health Organization (WHO).

Study Design: We used a mixed-methods study design to develop a framework for recommendation mapping with seven key methodological considerations.

Identifying research questions for HIV, tuberculosis, tuberculosis-HIV, malaria, and neglected tropical diseases through the World Health Organization guideline development process: a retrospective analysis, 2008-2018.

Objectives: World Health Organization (WHO) guidelines for health programmes and healthcare delivery are the foundation of its technical leadership in public health and essential to decision-making globally. A key function of guideline development is to identify areas in which further evidence is needed because filling these gaps will lead to future improvements in population health. The objective of this study was to examine the knowledge gaps and research questions for addressing those gaps generated through the WHO guideline development process, with the goal of informing future strategies for improving and strengthening the guideline development process.

Vitamin D and Phenylbutyrate Supplementation Does Not Modulate Gut Derived Immune Activation in HIV-1.

Dysbiosis and a dysregulated gut immune barrier function contributes to chronic immune activation in HIV-1 infection. We investigated if nutritional supplementation with vitamin D and phenylbutyrate could improve gut-derived inflammation, selected microbial metabolites, and composition of the gut microbiota. Treatment-naïve HIV-1-infected individuals ( = 167) were included from a double-blind, randomized, and placebo-controlled trial of daily 5000 IU vitamin D and 500 mg phenylbutyrate for 16 weeks (Clinicaltrials.

Daily Nutritional Supplementation with Vitamin D₃ and Phenylbutyrate to Treatment-Naïve HIV Patients Tested in a Randomized Placebo-Controlled Trial.

Poor nutritional status is common among human immunodeficiency virus (HIV)-infected patients including vitamin D (vitD₃) deficiency. We conducted a double-blinded, randomized, and placebo-controlled trial in Addis Ababa, Ethiopia, to investigate if daily nutritional supplementation with vitD₃ (5000 IU) and phenylbutyrate (PBA, 2 × 500 mg) could mediate beneficial effects in treatment-naïve HIV patients. Primary endpoint: the change in plasma HIV-1 comparing week 0 to 16 using modified intention-to-treat (mITT, = 197) and per-protocol ( = 173) analyses.

Defining a migrant-inclusive tuberculosis research agenda to end TB.

Background: Pillar 3 of the End TB Strategy calls for the promotion of research and innovation at the country level to facilitate improved implementation of existing and novel interventions to end tuberculosis (TB). In an era of increasing cross-border migration, there is a specific need to integrate migration-related issues into national TB research agendas. The objective of the present review is to provide a conceptual framework to guide countries in the development and operationalization of a migrant-inclusive TB research agenda.

A bibliometric analysis of tuberculosis research, 2007-2016.

Background: Tuberculosis (TB) research is a key component of the End TB Strategy. To track research output, we conducted a bibliometric analysis of TB research from the past decade.

Methods: The Web of Science database was searched for publications from January 2007 to December 2016 with "tuberculosis" in the title.

Daily adjunctive therapy with vitamin D and phenylbutyrate supports clinical recovery from pulmonary tuberculosis: a randomized controlled trial in Ethiopia.

Objective: Immunotherapy using vitamin D (vitD ) and phenylbutyrate (PBA) may support standard drug regimens used to treat infectious diseases. We investigated if vitD + PBA enhanced clinical recovery from pulmonary tuberculosis (TB).

Methods: A randomized controlled trial was conducted in Addis Ababa, Ethiopia.

Enzyme I facilitates reverse flux from pyruvate to phosphoenolpyruvate in Escherichia coli.

The bacterial phosphoenolpyruvate-carbohydrate phosphotransferase system (PTS) consists of cascading phosphotransferases that couple the simultaneous import and phosphorylation of a variety of sugars to the glycolytic conversion of phosphoenolpyruvate (PEP) to pyruvate. As the primary route of glucose uptake in E. coli, the PTS plays a key role in regulating central carbon metabolism and carbon catabolite repression, and is a frequent target of metabolic engineering interventions.

Biochemical and molecular identification and characterization of lactic acid bacteria and yeasts isolated from Ethiopian naturally fermented buttermilk.

Lactic acid bacteria (LAB) and yeasts were enumerated and identified from naturally fermented buttermilk. Isolates were first subjected to chemical tests and then to molecular characterization. Molecular identification involved pure sequencing of 16s rRNA (LAB) and 18s rRNA (yeast) genes.

Eosinophils and IL-4 Support Nematode Growth Coincident with an Innate Response to Tissue Injury.

It has become increasingly clear that the functions of eosinophils extend beyond host defense and allergy to metabolism and tissue regeneration. These influences have strong potential to be relevant in worm infections in which eosinophils are prominent and parasites rely on the host for nutrients to support growth or reproduction. The aim of this study was to investigate the mechanism underlying the observation that eosinophils promote growth of Trichinella spiralis larvae in skeletal muscle.

(13)C-metabolic flux analysis of co-cultures: A novel approach.

In this work, we present a novel approach for performing (13)C metabolic flux analysis ((13)C-MFA) of co-culture systems. We demonstrate for the first time that it is possible to determine metabolic flux distributions in multiple species simultaneously without the need for physical separation of cells or proteins, or overexpression of species-specific products. Instead, metabolic fluxes for each species in a co-culture are estimated directly from isotopic labeling of total biomass obtained using conventional mass spectrometry approaches such as GC-MS.

Eosinophils mediate protective immunity against secondary nematode infection.

Eosinophils are versatile cells that regulate innate and adaptive immunity, influence metabolism and tissue repair, and contribute to allergic lung disease. Within the context of immunity to parasitic worm infections, eosinophils are prominent yet highly varied in function. We have shown previously that when mice undergo primary infection with the parasitic nematode Trichinella spiralis, eosinophils play an important immune regulatory role that promotes larval growth and survival in skeletal muscle.

Eosinophil-derived IL-10 supports chronic nematode infection.

Eosinophilia is a feature of the host immune response that distinguishes parasitic worms from other pathogens, yet a discrete function for eosinophils in worm infection has been elusive. The aim of this study was to clarify the mechanism(s) underlying the striking and unexpected observation that eosinophils protect intracellular, muscle-stage Trichinella spiralis larvae against NO-mediated killing. Our findings indicate that eosinophils are specifically recruited to sites of infection at the earliest stage of muscle infection, consistent with a local response to injury.

Central metabolic responses to the overproduction of fatty acids in Escherichia coli based on 13C-metabolic flux analysis.

We engineered a fatty acid overproducing Escherichia coli strain through overexpressing tesA (“pull”) and fadR (“push”) and knocking out fadE (“block”). This “pull-push-block” strategy yielded 0.17 g of fatty acids (C12–C18) per gram of glucose (equivalent to 48% of the maximum theoretical yield) in batch cultures during the exponential growth phase under aerobic conditions.