Infectious Research Articles

Sex as a predictor of clinical phenotype and determinant of immune response in IgG4-related disease: a retrospective study of patients fulfilling the American College of Rheumatology-European League Against Rheumatism classification criteria.

IgG4-related disease is a multiorgan fibroinflammatory disease considered to have an autoimmune origin. Case series describing individual organ involvement have suggested differences in phenotypic expression between males and females. We aimed to characterise differences in IgG4-related disease manifestations between male and female patients in a large single-centre cohort. In this retrospective, single-centre cohort study, patients were recruited from the Massachusetts General Hospital Rheumatology Clinic (Boston, MA, USA) and classified according to the American College of Rheumatology-European Alliance of Associations for Rheumatology (ACR-EULAR) classification criteria. Only patients satisfying the ACR-EULAR classification criteria were included in the study. Data on age at diagnosis, organ involvement at baseline, treatment status, and pre-treatment laboratory values were collected. Circulating plasmablasts and B-cell subsets were quantitated by flow cytometry. Active disease was defined by an IgG4-related disease Responder Index score of more than 0. Laboratory values were analysed for patients who were untreated at baseline and had active IgG4-related disease. The main outcomes were assessed in all participants with available data. Of the 564 participants enrolled in the Massachusetts General Hospital Rheumatology Clinic IgG4-related disease Registry, 328 fulfilled ACR-EULAR classification criteria and were included between January, 2008, and May, 2023. There was a strong male predominance (male:female ratio 2·2:1) with 226 (69%) males and 102 (31%) females, which contrasted markedly with our general rheumatology clinic population (0·4:1; p<0·001). The male predominance increased with each decade of life starting at age 40 years. On average, male patients were 5·5 years older at diagnosis than female patients (63·7 years vs 58·2 years; p=0·0031). We observed male patients to have higher ACR-EULAR classification criteria scores at baseline with a median score of 35·0 (IQR 28·0-46·0), compared with 29·5 (25·0-39·0) for females (p=0·0010). The proportion of male patients with pancreatic and renal involvement was almost double the proportion observed in female patients (50% of the male patients had pancreatic involvement, compared with about 26% of the female patients; p<0·0001). Male patients were more likely to have serological abnormalities at baseline. The distribution of IgG4 values differed significantly between male an female sexes, favouring higher values in males. We found that male patients with IgG4-related disease were more likely to have active B-cell responses in the blood as defined by plasmablast expansions. IgG4-related disease is unusual among autoimmune diseases in that it is more likely to affect males than females and to present with a striking sex-dependent organ distribution and degree of B-cell response. These findings highlight important variation between IgG4-related disease and other conditions generally believed to have an autoimmune basis. Most autoimmune diseases, by contrast to IgG4-related disease, demonstrate pronounced predilections for affecting females more frequently than males. Hypotheses surrounding the cause and pathophysiology of this condition need to consider this unusual sex distribution among patients with IgG4-related disease. National Institutes of Health, National Institute of Allergy and Infectious Diseases, Rheumatology Research Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

An overview of the study designs and statistical methods used in the determination of predictors of melioidosis mortality in Malaysia: 2010-2021

&lt;b&gt;Background:&lt;/b&gt; In Malaysia, the mortality from melioidosis infection was reported to be higher than in other infectious diseases. The research on melioidosis is still limited in Malaysia but slightly increasing.&lt;br /&gt; &lt;b&gt;Objectives: &lt;/b&gt;The objective of the study was to give an overview of the study designs, statistical methods, and comparison of research in identifying the predictors of melioidosis mortality in Malaysia between January 2010 to December 2021.&lt;br /&gt; &lt;b&gt;Data sources:&lt;/b&gt; Pubmed/Medline.&lt;br /&gt; &lt;b&gt;Study eligibility criteria:&lt;/b&gt; Original English-language articles were abstracted. The articles that identified the predictors of melioidosis from mortality in Malaysia only included. Letters to the editor, editorials, reviews, systematic reviews, meta-analysis, case reports, and any other ineligible articles were excluded.&lt;br /&gt; &lt;b&gt;Results:&lt;/b&gt; A total of eight studies were identified related to predictors of melioidosis mortality in Malaysia. From the selected articles, 87.5% were retrospectively collected. Five out of eight articles (62.5%) used the logistic regression in identifying the predictors of melioidosis mortality. Only one (12.5%) used advanced survival analysis methods of Cox regression analysis. Another 25.0% used Chi-square test.&lt;br /&gt; &lt;b&gt;Conclusions:&lt;/b&gt; Logistic regression methods remain the most common methods of analysis in publications on predictors of melioidosis mortality in Malaysia while retrospective research designs are preferred. There is a limitation of research in predictors of melioidosis mortality and the use of advanced statistical techniques reported using the melioidosis data in Malaysia. More published research on melioidosis will provide input to the clinicians on a more detailed understanding of how to improve the diagnosis of melioidosis and the prognosis factors of this disease.

Exploring the Biochemical Mechanisms of Fluoroquinolone Compounds against Tuberculosis by Utilizing Molecular Docking and Quantitative Structure-amino Acid Relationship

Background: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb). It is one of the leading causes of death of 1.5 million people each year. TB can be treated by directly observed treatment short course (DOTS), but due to multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis, consequences can be devastating if the single DOTS dose is missed by the patient. MDR and XDR-TB require much more attention and time to control the infection. The longer period of tuberculosis treatment has side effects and it is expensive. Objectives: This alarming condition demands the development of novel processes to diagnose the disease in its early stage as well as to produce more promising antimicrobial chemotherapeutics. The current study aimed to explore molecular mechanisms involving docking simulation-based quantitative structureamino acid relationship (QSAAR) in order to have a better understanding of the interactions between the fluoroquinolones and Mtb DNA gyrase. Methods: In this study, 24 fluoroquinolone (FQ) compounds present in the literature were selected and docked against the Mtb DNA gyrase. Further, the relationship between the minimum inhibitory concentration of the compounds and interacting amino acids was assessed using QSAAR. Results: The study has established a novel method of formulating a quantitative structure-amino acid relationship. A significant correlation (R-value=0.829) between biological activity and the docked amino acid residues responsible for producing anti-tubercular activities has been obtained. Conclusion: The predicted residues captured in the developed model have been explored to report the Mtb virulence.

Enfermedad crónica transmisible y no transmisible, y enfermedad cutánea del paciente migrante

The care of migrant patients includes initial screening and lifelong monitoring, highlighting the importance of preventing and tracking chronic, communicable and non-communicable diseases.The prevalence of hypertension, diabetes mellitus, dyslipidemia, and obesity varies by ethnicity, influenced by genetic factors, lifestyle, and socio-economic status. Preventive measures, health promotion, and risk factor identification are crucial.Chronic communicable diseases may manifest years after transmission, underscoring the necessity of primary care screening, especially for populations from endemic or high-risk areas.Imported skin lesions are a common reason for consultation among migrant and traveller patients. Their ethiology is varied, ranging from common conditions such as scabies, mycoses, and urticaria to tropical dermatoses like filariasis and leprosy.

The Potential Diversity of Intestinal Enterobacteriaceae in Broiler Chickens is Associated with Infectious Bursal Disease Virus Infection

The Potential Diversity of Intestinal Enterobacteriaceae in Broiler Chickens is Associated with Infectious Bursal Disease Virus Infection

Overview of the Current Advancements and Trends in the Transungual Drug Delivery System

Background: Drug delivery across human nails is termed a transungual drug delivery system. It is recommended for the amelioration of nail disorders and infectious nail diseases like onychomycosis. Thereby, vivid anti-fungal regimens have been prescribed in the form of different types of formulations, including nail lacquers, nail film, nail paint, and other types for treating onychomycosis. Method: All the formulations currently marketed or being marketed for the transungal drug delivery system were thoroughly studied, compared, and evaluated for their advantages and disadvantages so that a new vision can be sustained along the path of creating newer anti-fungal transunguals, keeping in mind the anatomy of the nail and various parameters that govern bioavailability of active pharmaceutical ingredients across the nail bed. Accordingly, different techniques are devised to enhance permeation across the nail. The various parameters used to evaluate these formulations depend upon their physical, chemical, and mechanical properties. Conclusion: The recent approaches in transungual novel drug delivery systems have been reported while exemplifying a few patented and marketed formulations, along with the clinical trial status of these formulations. There is a need for the development of new techniques to overcome all the loopholes present in the ongoing treatment techniques and the formulations used nowadays for the treatments of diseases that occur in nails. After thoroughly detailing transungal novel drug delivery systems, we envisage great opportunities for the researchers to carry out novel work in chemotherapy through nails.

Quinoline Derivatives as Promising Scaffolds for Antitubercular Activity: A Comprehensive Review.

Heterocyclic compounds and their derivatives play a significant role in the design and development of novel quinoline drugs. Among the various pharmacologically active heterocyclic compounds, quinolines stand out as the most significant rings due to their broad pharmacological roles, specifically antitubercular activity, and their presence in plant-based compounds. Quinoline is characterized by a benzene ring fused to a pyridine ring, with both rings sharing two adjacent carbon atoms. Other names, such as benzpyridine, benzopyridine, and 1-azanaphthalene also know it. The importance of quinoline lies in its incorporation as a key component in various natural compounds found in medicinal plant families like Fumariaceae, Berberidaceae, Rutaceae, Papavaraceae, and others. This article is expected to have a significant impact on the advancement of effective antitubercular medications. Through harnessing the potent activity of quinoline derivatives, the research aims to make valuable contributions to combating tuberculosis more efficiently and ultimately reducing the global burden of this infectious disease. Numerous nitrogen-containing heterocyclic compounds exhibit significant potential as antitubercular agents. These chemicals have fused aromatic nitrogen-heterocyclic nuclei that can change the number of electrons they have, which can change their chemical, physical, and biological properties. This versatility arises from their ability to bind to receptors in multiple modes, a critical aspect of drug pharmacological screening. Among these compounds, quinoline stands out as it incorporates a stable fusion of a benzene ring with a pyridine nucleus. Quinolines have demonstrated a diverse range of pharmacological activities, including but not limited to anti-tubercular, antitumor, anticoagulant, anti-inflammatory, antioxidant, antiviral, antimalarial, anti-HIV, and antimicrobial effects. Some molecules, such as lone-paired nitrogen species, include pyrrole, pyrazole, and quinoline. These molecules contain oxygen and take part in metabolic reactions with other molecules inside the cell. However, an excessive accumulation of reactive nitrogen species can lead to cytotoxicity, resulting in damage to essential biological macromolecules. Among these compounds, quinoline stands out as the oldest and most effective one, exhibiting a wide range of beneficial properties such as antitubercular, antimicrobial, anti-inflammatory, antioxidant, analgesic, and anticonvulsant activities. Notably, naturally occurring quinoline compounds, such as quinine, have proven to be potent antimalarial drugs. This review highlights quinoline derivatives' antitubercular potential, emphasizing recent research advancements. Utilizing IC50 values, the study underscores the efficacy of various quinoline substitutions, hybrids, and electron-withdrawing groups against MTB H37Rv. Continued research is essential for developing potent, low-toxicity quinoline derivatives to combat tuberculosis.

A Review of the Leishmanicidal Properties of Lectins.

Lectins are proteins widely distributed among plants, animals and microorganisms that have the ability to recognize and interact with specific carbohydrates. They have varied biological activities, such as the inhibition of the progression of infections caused by fungi, bacteria, viruses and protozoa, which is related to the interaction of these proteins with the carbohydrates present in the cell walls of these microorganisms. Leishmaniasis are a group of endemic infectious diseases caused by protozoa of the genus Leishmania. In vitro and in vivo tests with promastigotes and amastigotes of Leishmania demonstrated that lectins have the ability to interact with glycoconjugates present on the cell surface of the parasite, it prevents their development through various mechanisms of action, such as the production of ROS and alteration of membrane integrity, and can also interact with defense cells present in the human body, thus showing that these molecules can be considered alternative pharmacological targets for the treatment of leishmaniasis. The objective of the present work is to carry out a bibliographic review on lectins with leishmanicidal activity, emphasizing the advances and perspectives of research in this theme. Through the analysis of the selected studies, we were able to conclude that lectins have great potential for inhibiting the development of leishmaniasis. However, there are still few studies on this subject.

Natural Products Inspired Drug Discovery for Infectious Diseases

Natural Products Inspired Drug Discovery for Infectious Diseases

Implantación y uso de la telemedicina en la asistencia sanitaria del brote de viruela símica en el Área de Salud de Ibiza y Formentera

ObjectiveThe objective of this work is to describe how the use of the information and communication technologies has been used in the clinical control, follow-up and treatment of all the patients affected by monkeypox in our health area. Design and siteA descriptive, observational and retrospective work has been carried out to show the clinical management of the monkeypox cases assisted in the Health Area of Ibiza and Formentera (ASEF), in the field of the primary care. Participants and methodsAll patients affected by monkeypox who met the inclusion criteria were included in the study (a total of 79 patients), covering the period from 01/06/22 to 30/11/22. A protocol was designed in order to recruit the patients, extract the samples, monitor the close contacts, notify the cases to the health authorities, clinical assistance and administrative processing of the sick leaves. Results and conclusionsThe adherence of the patients with the control system was majoritarian. Telemedicine has been a useful tool for the exchange of information during the provision of continuous medical care to patients affected by the outbreak of monkeypox infection, guaranteeing their safety and privacy and allowing the management of an infectious disease that requires isolation, control, and medical monitoring.

Mpox now a global emergency: a reality versus myths

The global landscape of infectious diseases significantly transformed after the COVID-19 pandemic. Among the growing concerns, mpox had emerged as a serious infectious illness that needed immediate and urgent action. Recognizing the seriousness of the situation, the World Health Organization (WHO) declared mpox a health emergency. The rise in mpox cases has sparked a flurry of arguments and debates among healthcare experts and the general public. This spike of attention, however, has resulted in a proliferation of myths and misconceptions about the condition. In response to this critical moment in global public health, the authors seek to clarify falsehoods while shedding light on the significant difficulties that mpox poses to the healthcare community and society.

Understanding public health nurses' experience, knowledge, and perception of bioterrorism training in Japan

Objectives Bioterrorism is a disease in which the attacks can be covert and latent, take time to manifest, and, when discovered, can result in large outbreaks. When detected, they can become large-scale outbreaks. Therefore, preparedness is essential for early detection and response for damage mitigation. Although public health nurses (PHNs) of public health centers are responsible for detecting and dealing with bioterrorism, their preparation status is not clear. Therefore, this study aimed to elucidate the status of training experience, knowledge, and awareness of bioterrorism among PHNs working in public health centers' infectious disease control departments in Japan's metropolitan areas.Methods This was a cross-sectional, descriptive study. The participants were PHNs in the infectious disease control departments of 88 public health centers in Tokyo and its three neighboring prefectures. This are densely populated metropolitan areas with many mass gathering events and a high probability of bioterrorism. An anonymous, self-administered questionnaire survey was conducted by mail in 2019. Two PHNs per location were surveyed regarding their attributes, training experience, knowledge, and perceptions.Results We received 71 responses (40.3%). A total of 10 (14.1%) PHNs reported having experience with bioterrorism training in the workplace. Regarding the knowledge of the four infectious diseases with a high probability of bioterrorism, more than 95% of the respondents answered they had heard of them. However, few were aware of related treatments or terrorist responses. Although survey respondents were aware of the seriousness of bioterrorism and the effectiveness of preparedness, they did not have sufficient opportunity or time to have training. They tended to be less confident in their response and were willing to have training.Conclusion PHNs who responded to this survey do not have sufficient training experience, knowledge, opportunities, and time for bioterrorism training, and establishing a training system to improve bioterrorism preparedness is a challenge. It will be necessary for PHN students to learn about the existence of bioterrorism. Further, PHNs in public health centers need to be trained at least once using online services, including brushing up on information as needed. Based on the lessons learned from the coronavirus disease 2019 pandemic, health centers will formulate a Health Crisis Management Plan. This will be effective in fiscal 2024, and we believe that it is essential that preparedness against bioterrorism be a part of this plan.

Rapid bacterial evaluation beyond the colony forming unit in osteomyelitis.

Examination of bacteria/host cell interactions is important for understanding the aetiology of many infectious diseases. The colony forming unit (CFU) has been the standard for quantifying bacterial burden for the past century, however, this suffers from low sensitivity and is dependent on bacterial culturability in vitro. Our data demonstrate the discrepancy between the CFU and bacterial genome copy number in an osteomyelitis-relevant co-culture system and we confirm diagnosis and quantify bacterial load in clinical bone specimens. This study provides an improved workflow for the quantification of bacterial burden in such cases.

Synthesis of novel silver-loaded clay AgF@Hec for the prevention of dental caries in vitro

Dental caries, a chronic infectious disease characterized by tooth mineral loss caused by plaque, is one of the major global public health problems. Silver diamine fluoride (SDF) has been proven to be a highly effective anti-caries drug due to its high bacterial inhibition and remineralization ability. However, the SDF solution is unstable, which immensely limits its clinical application. Therefore, new silver-load clay named AgF@Hec was designed by replacing the NH3 with hectorite in this study. Fourier transform infrared spectroscopy and x-ray diffraction spectroscopy were employed to confirm the structure of AgF@Hec. Dynamic light scattering analysis was used to reveal the effect of different hectorite concentrations on the stability of AgF@Hec. Moreover, AgF@Hec exhibits significant remineralization and hardness recovery of the initial carious lesions. Bacteriostatic experiments also proved that it has a significant inhibitory effect on A. Viscosus, S. mutans, S. sanguinis, S. salivarius, Lactobacillus sp. and both gram-positive and gram-negative bacteria. We therefore believed that AgF@Hec should be a promising biomaterial that can be applied in the prevention of dental caries.

The interplay of suppressive soil bacteria and plant root exudates determines germination of microsclerotia of Verticillium longisporum.

Our research provides first-time insights into the crucial interaction between plant root exudates and soil bacteria in regulating the germination of Verticillium longisporum microsclerotia, a significant structure in the survival and proliferation of this soil-borne pathogen. We describe so far unknown mechanisms, which are key to understand how root infections on oilseed rape can occur. By pinpointing primary metabolites in root exudates as key factors in overcoming bacteria-induced dormancy and promote microsclerotia germination, our study highlights the potential for exploiting plant - as well as soil microbe-derived - compounds to control V. longisporum. This work underscores the importance of elucidating the nuanced interactions within the soil ecosystem to devise innovative strategies for managing root infective plant diseases, thereby contributing to the resilience and health of cropping systems.

Epidemic and infection control measures in charitable institutions for children in the 19th — early 20th century (based on the materials from Saint-Petersburg)

Based on the documents stored in archives, here we present the analysis of the evolution of forms of the epidemic and infection control measures in charitable institutions for children in Saint-Petersburg with the deve-lopment of medicine, the introduction of sanitary and hygienic standards, and guidelines based on the acquired experience. The causes of mass infection of the pupils have been identified, which were associated with the lack of well-established daily hygienic practices for pupils, their close contact within the institution, and the presence of visiting caregivers in orphanages who had extensive contacts outside. At the state level, until the end of the 19th century, there were no uniform sanitary norms and rules, as well as specialized schemes for their identification and con-trol. As the analysis shows, this resulted in the fact that the trustee boards of orphanages and doctors assigned to them were forced, sometimes with the help of police, to independently introduce restrictive measures at the ad-ministrative level, determine treatment methods and manage all emerging issues aimed at preserving health of the pupils, while often not having sufficient professional knowledge and experience for this. The documents sug-gest that due to the lack of established diagnostic system, the treatment methods practically did not differ for vari-ous infectious diseases, and the recommendations of doctors for a long time mainly consisted of changing the diet, purifying the air, isolating patients, and burning possessions of sick children. Considering religious education in all charitable institutions, lents and fast days were supposed to be observed, which required the approval of the clergy, who, although as a rule did not create serious obstacles, but granted individual and limited permits. In the beginning of the 19th century, smallpox vaccination began, and such practices gradually expanded thanks to the state and benefactors, but due to the lack of support from church, as well as conservatism and superstition of a significant proportion of parents, they did not become widespread and routine.

Rapid Detection of Bacterial Resistance to β-Lactam Antibiotics with a Relay-Response Chemiluminescence Assay.

Bacterial resistance caused by β-lactamases has been a major threat to public health around the world, seriously weakening the efficacy of β-lactam antibiotics, the most widely used therapeutic agents against infectious diseases. To detect the bacterial resistance to β-lactam antibiotics, particularly specific type of β-lactam antibiotics, in a rapid manner, we report herein a relay-response chemiluminescence assay. This assay mainly consists of two reagents: a β-lactam-caged thiophenol and a thiophenol-sensitive chemiluminescence reporter, both of which are synthetically feasible. The selective hydrolysis of β-lactam by β-lactamase leads to the releasing of free thiophenol, which then triggers the emission of a chemiluminescence signal in a relay manner. Three thiophenol-caged β-lactams, structural analogues of cephalothin, cefotaxime, and meropenem, respectively, have been synthesized. And the application of this assay with these analogues of β-lactam antibiotics allows fast detection of β-lactamase-expressing resistant bacteria and, more impressively, provides detailed information on the resistant scope of bacteria.

WGS of intrauterine E. coli from cows with early postpartum uterine infection reveals a non-uterine specific genotype and virulence factors.

Escherichia coli has been attributed to playing a major role in a cascade of events that affect the prevalence and severity of uterine disease in cattle. The objectives of this project were to (i) define the association between the prevalence of specific antimicrobial resistance and virulence factor genes in E. coli with the clinical status related to uterine infection, (ii) identify the genetic relationship between E. coli isolates from cows with diarrhea, with mastitis, and with and without metritis, and (iii) determine the association between the phenotypic and genotypic antimicrobial resistance identified on the E. coli isolated from postpartum cattle. Bacterial isolates (n = 148) were obtained from a larger cross-sectional study. Cows were categorized into one of three clinical groups before enrollment: metritis, cows with purulent discharge, and control cows. For genomic comparison, public genomes (n = 130) from cows with diarrhea, mastitis, and metritis were included in a genome-wide association study, to evaluate differences between the drug classes or the virulence factor category among clinical groups. A distinct E. coli genotype associated with metritis could not be identified. Instead, a high genetic diversity among the isolates from uterine sources was present. A virulence factor previously associated with metritis (fimH) using PCR was not associated with metritis. There was moderate accuracy for whole-genome sequencing to predict phenotypic resistance, which varied depending on the antimicrobial tested. Findings from this study contradict the traditional pathotype classification and the unique intrauterine E. coli genotype associated with metritis in dairy cows.IMPORTANCEMetritis is a common infectious disease in dairy cattle and the second most common reason for treating a cow with antimicrobials. The pathophysiology of the disease is complex and is not completely understood. Specific endometrial pathogenic Escherichia coli have been reported to be adapted to the endometrium and sometimes lead to uterine disease. Unfortunately, the specific genomic details of the endometrial-adapted isolates have not been investigated using enough genomes to represent the genomic diversity of this organism to identify specific virulence genes that are consistently associated with disease development and severity. Results from this study provide key microbial ecological advances by elucidating and challenging accepted concepts for the role of Intrauterine E. coli in metritis in dairy cattle, especially contradicting the existence of a unique intrauterine E. coli genotype associated with metritis in dairy cows, which was not found in our study.

A Scoping Review of Health Equity Interventions in Governmental Public Health.

Despite major efforts in research, practice, and policy, racial and ethnic disparities in health and health care persist in the United States. Interventions in collaboration with governmental public health may provide ways to address these persistent racial and ethnic health and health care disparities and improve health outcomes. To conduct a comprehensive review of health equity interventions performed in collaboration with public health agencies. This scoping review includes intervention studies from Ovid MEDLINE, PsycINFO, and Academic Search Premier, published between 2017 and 2023. The search strategy used terminology focused on 4 concepts: race/ethnicity, equity, health departments, and epidemiologic studies. The following inclusion criteria were determined a priori: (1) intervention tailored to reduce racial/ethnic health disparities, (2) public health department involvement, (3) health outcome measures, (4) use of epidemiologic study methods, (5) written in English, (6) implemented in the United States, (7) original data (not a commentary), and (8) published between January 2017 and January 2023. This review focused primarily on 4 dimensions of racial health equity interventions including intervention components, intervention settings, intervention delivery agents, and intervention outcomes. This review indicated that health equity interventions involving public health agencies focused on the following categories: (1) access to care, (2) health behavior, (3) infectious disease testing, (4) preventing transmission, and (5) cancer screening. Critical strategies included in interventions for reaching racial/ethnic minoritized people included using community settings, mobile clinics, social media/social networks, phone-based interventions, community-based workers, health education, active public health department involvement, and structural/policy change. This scoping review aims to provide an evidence map to inform public health agencies, researchers, and funding agencies on gaps in knowledge and priority areas for future research and to identify existing health equity interventions that could be considered for implementation by public health leaders.

A Modified BPaL Regimen for Tuberculosis Treatment replaces Linezolid with Inhaled Spectinamides.

Tuberculosis (TB) is an airborne infectious disease that spreads via aerosols containing Mycobacterium tuberculosis (Mtb), the causative agent of TB. TB can be cured by administration of 3-4 drugs for 6-9 months but there are limited treatment options for patients infected with multidrug (MDR) and extensively resistant (XDR) strains of Mtb. BPaL is a new all-oral combination of drugs consisting of Bedaquiline (B), Pretomanid (Pa) and Linezolid (L). This regimen was able to cure ∼90% of MDR and XDR TB patients in clinical trials but many patients developed severe adverse events (AEs) associated to the long-term administration of linezolid. We evaluated a new regimen in which Linezolid in the BPaL regimen was replaced with inhaled spectinamide 1599. In the current study, we demonstrate that 4-weeks of treatment with inhaled spectinamide 1599 in combination with Bedaquiline and Pretomanid has equivalent efficacy to the BPaL drug combination and avoids the L-associated-AEs.