Number Needed to Screen for Tuberculosis Disease Among Children: A Systematic Review.

CONTEXT: Improving detection of pediatric tuberculosis (TB) is critical to reducing morbidity and mortality among children. OBJECTIVE: We conducted a systematic review to estimate the number of children needed to screen (NNS) to detect a single case of active TB using different active case finding (ACF) screening approaches and across different settings. DATA SOURCES: We searched 4 databases (PubMed, Embase, Scopus, and the Cochrane Library) for articles published from November 2010 to February 2020. STUDY SELECTION: We included studies of TB ACF in children using symptom-based screening, clinical indicators, chest x-ray, and Xpert. DATA EXTRACTION: We indirectly estimated the weighted mean NNS for a given modality, location, and population using the inverse of the weighted prevalence. We assessed risk of bias using a modified AXIS tool. RESULTS: We screened 27 221 titles and abstracts, of which we included 31 studies of ACF in children < 15 years old. Symptom-based screening was the most common screening modality (weighted mean NNS: 257 [range, 5-undefined], 19 studies). The weighted mean NNS was lower in both inpatient (216 [18-241]) and outpatient (67 [5-undefined]) settings (107 [5-undefined]) compared with community (1117 [28-5146]) and school settings (464 [118-665]). Risk of bias was low. LIMITATIONS: Heterogeneity in the screening modalities and populations make it difficult to draw conclusions. CONCLUSIONS: We identified a potential opportunity to increase TB detection by screening children presenting in health care settings. Pediatric TB case finding interventions should incorporate evidence-based interventions and local contextual information in an effort to detect as many children with TB as possible.

Yersinia pseudotuberculosis doxycycline tolerance strategies include modulating expression of genes involved in cell permeability and tRNA modifications.

Antibiotic tolerance is typically associated with a phenotypic change within a bacterial population, resulting in a transient decrease in antibiotic susceptibility that can contribute to treatment failure and recurrent infections. Although tolerant cells may emerge prior to treatment, the stress of prolonged antibiotic exposure can also promote tolerance. Here, we sought to determine how Yersinia pseudotuberculosis responds to doxycycline exposure, to then verify if these gene expression changes could promote doxycycline tolerance in culture and in our mouse model of infection. Only four genes were differentially regulated in response to a physiologically-relevant dose of doxycycline: osmB and ompF were upregulated, tusB and cnfy were downregulated; differential expression also occurred during doxycycline treatment in the mouse. ompF, tusB and cnfy were also differentially regulated in response to chloramphenicol, indicating these could be general responses to ribosomal inhibition. cnfy has previously been associated with persistence and was not a major focus here. We found deletion of the OmpF porin resulted in increased antibiotic accumulation, suggesting expression may promote diffusion of doxycycline out of the cell, while OsmB lipoprotein had a minor impact on antibiotic permeability. Overexpression of tusB significantly impaired bacterial survival in culture and in the mouse, suggesting that tRNA modification by tusB, and the resulting impacts on translational machinery, promotes survival during treatment with an antibiotic classically viewed as bacteriostatic. We believe this may be the first observation of bactericidal activity of doxycycline under physiological conditions, which was revealed by reversing tusB downregulation.

COVID-19 Vaccine Intention among Rural Residents in Mexico: Validation of a Questionnaire.

The COVID-19 pandemic forced the scientific community and the pharmaceutical industry to develop new vaccines, in an attempt to reach herd immunity and stop the SARS-CoV-2 from spreading. However, to ensure vaccination among the general population, COVID-19 vaccine intention must be measured. So far, no studies have focused on rural residents in Latin America, which represent approximately 20% of the population of this geographical region. In this study, we present the validation of a self-developed questionnaire, which was validated in a pilot study with 40 Spanish-speaking Mexican rural residents in the state of Guerrero, Mexico. In this study, we describe the chronological validation of the questionnaire, including the assessment of its internal consistency and temporal reliability, which we measured with the Cronbach's alpha and Spearman's rank correlation coefficient, respectively. After the psychometrical analysis, we were able to validate a 20-item questionnaire, which intends to assess vaccine intention among the rural population. Aiming to develop a comprehensive policy and vaccination strategies, we hope this instrument provides valuable insight regarding COVID-19 vaccination willingness across rural communities in Mexico and Latin America. Finally, if we want to reach worldwide herd immunity, it is important to understand rural residents' position towards COVID-19 vaccination.

Evaluation of Disulfiram Drug Combinations and Identification of Other More Effective Combinations against Stationary Phase Borrelia burgdorferi.

Lyme disease, caused by Borrelia burgdorferi, is the most common vector-borne disease in USA, and 10-20% of patients will develop persistent symptoms despite treatment ("post-treatment Lyme disease syndrome"). B. burgdorferi persisters, which are not killed by the current antibiotics for Lyme disease, are considered one possible cause. Disulfiram has shown to be active against B. burgdorferi, but its activity against persistent forms is not well characterized. We assessed disulfiram as single drug and in combinations against stationary-phase B. burgdorferi culture enriched with persisters. Disulfiram was not very effective in the drug exposure experiment (survival rate (SR) 46.3%) or in combinations. Clarithromycin (SR 41.1%) and nitroxoline (SR 37.5%) were equally effective when compared to the current Lyme antibiotic cefuroxime (SR 36.8%) and more active than disulfiram. Cefuroxime + clarithromycin (SR 25.9%) and cefuroxime + nitroxoline (SR 27.5%) were significantly more active than cefuroxime + disulfiram (SR 41.7%). When replacing disulfiram with clarithromycin or nitroxoline in three-drug combinations, bacterial viability decreased significantly and subculture studies showed that combinations with these two drugs (cefuroxime + clarithromycin/nitroxoline + furazolidone/nitazoxanide) inhibited the regrowth, while disulfiram combinations did not (cefuroxime + disulfiram + furazolidone/nitazoxanide). Thus, clarithromycin and nitroxoline should be further assessed to determine their role as potential treatment alternatives in the future.