Microneedle patch-based enzyme-linked immunosorbent assay to quantify protein biomarkers of tuberculosis.

There is a clinical need for differential diagnosis of the latent versus active stages of tuberculosis (TB) disease by a simple-to-administer test. Alpha-crystallin (Acr) and early secretory antigenic target-6 (ESAT-6) are protein biomarkers associated with the latent and active stages of TB, respectively, and could be used for differential diagnosis. We therefore developed a microneedle patch (MNP) designed for application to the skin to quantify Acr and ESAT-6 in dermal interstitial fluid by enzyme-linked immunosorbent assay (ELISA). We fabricated mechanically strong microneedles made of polystyrene and coated them with capture antibodies against Acr and ESAT-6. We then optimized assay sensitivity to achieve a limit of detection of 750 pg/ml and 3,020 pg/ml for Acr and ESAT-6, respectively. This study demonstrates the feasibility of an MNP-based ELISA for differential diagnosis of latent TB disease.

The Many Hosts of Mycobacteria 9 (MHM9): A conference report.

The Many Hosts of Mycobacteria (MHM) meeting series brings together basic scientists, clinicians and veterinarians to promote robust discussion and dissemination of recent advances in our knowledge of numerous mycobacterial diseases, including human and bovine tuberculosis (TB), nontuberculous mycobacteria (NTM) infection, Hansen's disease (leprosy), Buruli ulcer and Johne's disease. The 9th MHM conference (MHM9) was held in July 2022 at The Ohio State University (OSU) and centered around the theme of "Confounders of Mycobacterial Disease." Confounders can and often do drive the transmission of mycobacterial diseases, as well as impact surveillance and treatment outcomes. Various confounders were presented and discussed at MHM9 including those that originate from the host (comorbidities and coinfections) as well as those arising from the environment (e.g., zoonotic exposures), economic inequality (e.g. healthcare disparities), stigma (a confounder of leprosy and TB for millennia), and historical neglect (a confounder in Native American Nations). This conference report summarizes select talks given at MHM9 highlighting recent research advances, as well as talks regarding the historic and ongoing impact of TB and other infectious diseases on Native American Nations, including those in Southwestern Alaska where the regional TB incidence rate is among the highest in the Western hemisphere.

Host-Pathogen Interaction as a Novel Target for Host-Directed Therapies in Tuberculosis.

Tuberculosis (TB) has been a transmittable human disease for many thousands of years, and M. tuberculosis is again the number one cause of death worldwide due to a single infectious agent. The intense 6- to 10-month process of multi-drug treatment, combined with the adverse side effects that can run the spectrum from gastrointestinal disturbances to liver toxicity or peripheral neuropathy are major obstacles to patient compliance and therapy completion. The consequent increase in multidrug resistant TB (MDR-TB) and extensively drug resistant TB (XDR-TB) cases requires that we increase our arsenal of effective drugs, particularly novel therapeutic approaches. Over the millennia, host and pathogen have evolved mechanisms and relationships that greatly influence the outcome of infection. Understanding these evolutionary interactions and their impact on bacterial clearance or host pathology will lead the way toward rational development of new therapeutics that favor enhancing a host protective response. These host-directed therapies have recently demonstrated promising results against M. tuberculosis, adding to the effectiveness of currently available anti-mycobacterial drugs that directly kill the organism or slow mycobacterial replication. Here we review the host-pathogen interactions during M. tuberculosis infection, describe how M. tuberculosis bacilli modulate and evade the host immune system, and discuss the currently available host-directed therapies that target these bacterial factors. Rather than provide an exhaustive description of M. tuberculosis virulence factors, which falls outside the scope of this review, we will instead focus on the host-pathogen interactions that lead to increased bacterial growth or host immune evasion, and that can be modulated by existing host-directed therapies.

Global initiative for congenital toxoplasmosis: an observational and international comparative clinical analysis.

Globally, congenital toxoplasmosis remains a significant cause of morbidity and mortality, and outbreaks of infection with T. gondii represent a significant, emerging public health burden, especially in the developing world. This parasite is a threat to public health. Disease often is not recognized and is inadequately managed. Herein, we analyze the status of congenital toxoplasmosis in Morocco, Colombia, the United States, and France. We identify the unique challenges faced by each nation in the implementation of optimal approaches to congenital toxoplasmosis as a public health problem. We suggest that developed and developing countries use a multipronged approach, modeling their public health management protocols after those in France. We conclude that education, screening, appropriate treatment, and the development of novel modalities will be required to intervene successfully in caring for individuals with this infection. Gestational screening has been demonstrated to be cost-effective, morbidity-sparing, and life-saving. Recognition of the value and promise of public health interventions to prevent human suffering from this emerging infection will facilitate better patient and societal outcomes.