Mice infected with Mycobacterium tuberculosis are resistant to acute disease caused by secondary infection with SARS-CoV-2.

Mycobacterium tuberculosis (Mtb) and SARS-CoV-2 (CoV2) are the leading causes of death due to infectious disease. Although Mtb and CoV2 both cause serious and sometimes fatal respiratory infections, the effect of Mtb infection and its associated immune response on secondary infection with CoV2 is unknown. To address this question we applied two mouse models of COVID19, using mice which were chronically infected with Mtb. In both model systems, Mtb-infected mice were resistant to the pathological consequences of secondary CoV2 infection, and CoV2 infection did not affect Mtb burdens. Single cell RNA sequencing of coinfected and monoinfected lungs demonstrated the resistance of Mtb-infected mice is associated with expansion of T and B cell subsets upon viral challenge. Collectively, these data demonstrate that Mtb infection conditions the lung environment in a manner that is not conducive to CoV2 survival.

Zonular instability-associated morphologic features in eyes with primary angle closure disease using the swept-source anterior segment - optical coherence tomography system.

BACKGROUND: This study aims to investigate the morphologic features of the crystalline lens in Primary Angle Closure Disease (PACD) patients with zonular instability during cataract surgery using the swept-source CASIA 2 Anterior Segment-Optical Coherence Tomography (AS-OCT) system. METHODS: A total of 398 eyes (125 PACD eyes with zonular instability, 133 PACD eyes with zonular stability, and 140 cataract patient controls) of 398 patients who underwent cataract surgery combined or not glaucoma surgery between January 2021 and January 2023 were enrolled. The crystalline lens parameters were measured by CASIA2 AS-OCT. Then, logistic regression was performed to evaluate the risk factors associated with zonular instability. RESULTS: The results revealed that PACD eyes had a more anterior lens equator position, a steeper anterior curvature of lens, shorter Axial Length (AL), shallower Anterior Chamber Distance (ACD), higher Lens Vault (LV) and thicker Lens Thickness (LT), when compared to eyes in the cataract control group. Furthermore, PACD eyes in the zonular instability group had steeper front R, front Rs and Front Rf, flatter back Rf, thicker lens anterior part thickness, higher lens anterior-to-posterior part thickness ratios, shallower ACD, and greater LV, when compared to PACD eyes with zonular stability. The logistic regression analysis, which was adjusted for age and gender, revealed that zonular instability was positively correlated with anterior part thickness, lens anterior-to-posterior part thickness ratio, and LV, but was negatively correlated with lens anterior radius and ACD. CONCLUSION: Steeper anterior curvature, increased lens anterior part thickness, higher anterior-to-posterior part thickness ratio, shallower ACD, and greater LV are the anatomic features of PACD eyes associated with zonular instability.

Molecular epidemiology and transmission dynamics of multi-drug resistant tuberculosis strains using whole genome sequencing in the Amhara region, Ethiopia.

BACKGROUND: Drug resistant Mycobacterium tuberculosis prevention and care is a major challenge in Ethiopia. The World health organization has designated Ethiopia as one of the 30 high burden multi-drug resistant tuberculosis (MDR-TB) countries. There is limited information regarding genetic diversity and transmission dynamics of MDR-TB in Ethiopia. OBJECTIVE: To investigate the molecular epidemiology and transmission dynamics of MDR-TB strains using whole genome sequence (WGS) in the Amhara region. METHODS: Forty-five MDR-TB clinical isolates from Amhara region were collected between 2016 and 2018, and characterized using WGS and 24-loci Mycobacterium Interspersed Repetitive Units Variable Number of Tandem Repeats (MIRU-VNTR) typing. Clusters were defined based on the maximum distance of 12 single nucleotide polymorphisms (SNPs) or alleles as the upper threshold of genomic relatedness. Five or less SNPs or alleles distance or identical 24-loci VNTR typing is denoted as surrogate marker for recent transmission. RESULTS: Forty-one of the 45 isolates were analyzed by WGS and 44% (18/41) of the isolates were distributed into 4 clusters. Of the 41 MDR-TB isolates, 58.5% were classified as lineage 4, 36.5% lineage 3 and 5% lineage 1. Overall, TUR genotype (54%) was the predominant in MDR-TB strains. 41% (17/41) of the isolates were clustered into four WGS groups and the remaining isolates were unique strains. The predominant cluster (Cluster 1) was composed of nine isolates belonging to lineage 4 and of these, four isolates were in the recent transmission links. CONCLUSIONS: Majority of MDR-TB strain cluster and predominance of TUR lineage in the Amhara region give rise to concerns for possible ongoing transmission. Efforts to strengthen TB laboratory to advance diagnosis, intensified active case finding, and expanded contact tracing activities are needed in order to improve rapid diagnosis and initiate early treatment. This would lead to the interruption of the transmission chain and stop the spread of MDR-TB in the Amhara region.

Characteristics of and Deaths among 333 Persons with Tuberculosis and COVID-19 in Cross-Sectional Sample from 25 Jurisdictions, United States.

Little is known about co-occurring tuberculosis (TB) and COVID-19 in low TB incidence settings. We obtained a cross-section of 333 persons in the United States co-diagnosed with TB and COVID-19 within 180 days and compared them to 4,433 persons with TB only in 2020 and 18,898 persons with TB during 2017‒2019. Across both comparison groups, a higher proportion of persons with TB-COVID-19 were Hispanic, were long-term care facility residents, and had diabetes. When adjusted for age, underlying conditions, and TB severity, COVID-19 co-infection was not statistically associated with death compared with TB infection only in 2020 (adjusted prevalence ratio 1.0 [95% CI 0.8‒1.4]). Among TB-COVID-19 patients, death was associated with a shorter interval between TB and COVID-19 diagnoses, older age, and being immunocompromised (non-HIV). TB-COVID-19 deaths in the United States appear to be concentrated in subgroups sharing characteristics known to increase risk for death from either disease alone.

Clonal diversity of Staphylococcus aureus isolates in clinical specimens from selected health facilities in Ethiopia.

Staphylococcus aureus is among the top three causative agents of nosocomial infection in Ethiopia. The majority of studies in Ethiopia have focused on the epidemiology of S. aureus in hospital settings, with limited molecular genotyping results. Molecular characterization of S. aureus is essential for identification of strains, and contributes to the control and prevention of S. aureus infection. The aim of the current study was to determine the molecular epidemiology of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) isolates recovered from clinical specimens in Ethiopia. A total of 161 MSSA and 9 MRSA isolates were characterized using pulsed-field gel electrophoresis (PFGE) and staphylococcal protein A (spa) typing. Based on the PFGE analysis, MSSA isolates were grouped into eight pulso-types groups (from A to I), while MRSA isolates clustered into three (A, B and C) pulso-types with more than 80% similarity. The spa typing analysis showed diversity of S. aureus with 56 distinct spa types. Spa type t355 was most prevalent (56/170, 32.9%), while eleven new spa types were detected including t20038, t20039, and t20042. The identified spa types were clustered into 15 spa-clonal complexes (spa-CCs) using BURP analysis; novel/unknown spa types were further subjected to MLST analysis. The majority of isolates belonged to spa-CC 152 (62/170, 36.4%), followed by spa-CC 121 (19/170, 11.2%), and spa-CC 005 (18 /170, 10.6%). Of the nine MRSA isolates, 2 (22.2%) were spa-CC 239 with staphylococcal cassette chromosome (SCC)mec III. These findings highlight the diversity of S. aureus strains in Ethiopia, as well as the presence of potentially epidemic strains circulating in the country necessitating further characterization of S. aureus for antimicrobial resistance detection and infection prevention purposes.

Screening for Latent Tuberculosis Infection in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Latent tuberculosis infection (LTBI) can progress to active tuberculosis disease, causing morbidity and mortality. Objective: To review the evidence on benefits and harms of screening for and treatment of LTBI in adults to inform the US Preventive Services Task Force (USPSTF). Data Sources: PubMed/MEDLINE, Cochrane Library, and trial registries through December 3, 2021; references; experts; literature surveillance through January 20, 2023. Study Selection: English-language studies of LTBI screening, LTBI treatment, or accuracy of the tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). Studies of LTBI screening and treatment for public health surveillance or disease management were excluded. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings; meta-analyses conducted when a sufficient number of similar studies were available. Main Outcomes and Measures: Screening test accuracy; development of active tuberculosis disease, transmission, quality of life, mortality, and harms. Results: A total of 113 publications were included (112 studies; N = 69 009). No studies directly evaluated the benefits and harms of screening. Pooled estimates for sensitivity of the TST were 0.80 (95% CI, 0.74-0.87) at the 5-mm induration threshold, 0.81 (95% CI, 0.76-0.87) at the 10-mm threshold, and 0.60 (95% CI, 0.46-0.74) at the 15-mm threshold. Pooled estimates for sensitivity of IGRA tests ranged from 0.81 (95% CI, 0.79-0.84) to 0.90 (95% CI, 0.87-0.92). Pooled estimates for specificity of screening tests ranged from 0.95 to 0.99. For treatment of LTBI, a large (n = 27 830), good-quality randomized clinical trial found a relative risk (RR) for progression to active tuberculosis at 5 years of 0.35 (95% CI, 0.24-0.52) for 24 weeks of isoniazid compared with placebo (number needed to treat, 112) and an increase in hepatotoxicity (RR, 4.59 [95% CI, 2.03-10.39]; number needed to harm, 279). A previously published meta-analysis reported that multiple regimens were efficacious compared with placebo or no treatment. Meta-analysis found greater risk for hepatotoxicity with isoniazid than with rifampin (pooled RR, 4.22 [95% CI, 2.21-8.06]; n = 7339). Conclusions and Relevance: No studies directly evaluated the benefits and harms of screening for LTBI compared with no screening. TST and IGRAs were moderately sensitive and highly specific. Treatment of LTBI with recommended regimens reduced the risk of progression to active tuberculosis. Isoniazid was associated with higher rates of hepatotoxicity than placebo or rifampin.

Association Between Vancomycin AUC and Clinical Failure in Patients with Streptococcal Bacteremia.

Background: Monitoring of vancomycin using the area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio is now preferred for serious methicillin-resistant Staphylococcus aureus infections. Vancomycin AUC/MIC monitoring is being investigated but is not yet well elucidated with other bacterial pathogens. Methods: A retrospective cross-sectional study was conducted assessing patients with streptococcal bacteremia treated with vancomycin definitive therapy. AUC was calculated using a Bayesian approach, and classification and regression tree analysis was used to identify a vancomycin AUC threshold predictive of clinical failure. Results: Eleven patients had a vancomycin AUC < 329 of which 8 (73%) experienced clinical failure, while 35 patients had a vancomycin AUC ≥ 329 of which 12 (34%) experienced clinical failure (P = .04). Hospital length of stay was longer in the AUC ≥ 329 group (15 vs 8 days, P = .05), whereas time to bacteremia clearance (29 [22-45] vs 25 [20-29] hours, P = .15) and toxicity incidence (13% vs 4%, P = 1) were similar between groups. Conclusions: This study identified a VAN AUC threshold of <329 to be predictive of clinical failure in patients with streptococcal bacteremia which should be interpreted as hypothesis-generating. Studies evaluating VAN AUC-based monitoring for streptococcal bloodstream infections along with other infection types are needed before implementation into clinical practice can be recommended.

Novel Automation of an Enzyme-Linked Immunosorbent Spot Assay Testing Method: Comparable Diagnostic Performance of the T-SPOT.TB Test Using Manual Density Gradient Cell Isolation versus Automated Positive Selection with the T-Cell Select Kit.

The diagnosis of latent tuberculosis (TB) infection (LTBI) is critical to improve TB treatment and control, and the T-SPOT.TB test is a commercial enzyme-linked immunosorbent spot assay used for this purpose. The objective of the study was to increase automation and extend the time between blood collection and processing for the T-SPOT.TB test from 0 to 8 h to 0 to 54 h. The previous maximum time between blood collection and processing for the T-SPOT.TB test is 32 h using T-Cell Xtend. For this, we compared the T-SPOT.TB test using manual peripheral blood mononuclear cell (PBMC) isolation by density gradient separation at 0 to 8 h (reference method, control arm) to an automated PBMC isolation method using magnetic beads (T-Cell Select kit) at 0 to 55 h postcollection. A total of 620 subjects were enrolled from 4 study sites, and blood samples were collected from each volunteer, comprising 1,850 paired samples in total. Overall agreement between both methods was 96.8% (confidence interval [CI], 95.9 to 97.6%), with 95.8% (CI, 93.5 to 97.5%) positive and 97.1% negative agreement (CI, 96.1 to 97.9%). In summary, there was a strong overall agreement between the automated and manual T-SPOT.TB test processing methods. The results suggest that the T-SPOT.TB test can be processed using automated positive selection with magnetic beads using T-Cell Select to decrease hands-on time. Also, this cell isolation method allowed for the time between blood collection and processing to range from 0 to 55 h. Additional studies in larger and diverse patient populations including immunocompromised and pediatric patients are needed.

Annual Tuberculosis Preventive Therapy for Persons With HIV Infection : A Randomized Trial.

BACKGROUND: Tuberculosis preventive therapy for persons with HIV infection is effective, but its durability is uncertain. OBJECTIVE: To compare treatment completion rates of weekly isoniazid-rifapentine for 3 months versus daily isoniazid for 6 months as well as the effectiveness of the 3-month rifapentine-isoniazid regimen given annually for 2 years versus once. DESIGN: Randomized trial. (ClinicalTrials.gov: NCT02980016). SETTING: South Africa, Ethiopia, and Mozambique. PARTICIPANTS: Persons with HIV infection who were receiving antiretroviral therapy, were aged 2 years or older, and did not have active tuberculosis. INTERVENTION: Participants were randomly assigned to receive weekly rifapentine-isoniazid for 3 months, given either annually for 2 years or once, or daily isoniazid for 6 months. Participants were screened for tuberculosis symptoms at months 0 to 3 and 12 of each study year and at months 12 and 24 using chest radiography and sputum culture. MEASUREMENTS: Treatment completion was assessed using pill counts. Tuberculosis incidence was measured over 24 months. RESULTS: Between November 2016 and November 2017, 4027 participants were enrolled; 4014 were included in the analyses (median age, 41 years; 69.5% women; all using antiretroviral therapy). Treatment completion in the first year for the combined rifapentine-isoniazid groups (n = 3610) was 90.4% versus 50.5% for the isoniazid group (n = 404) (risk ratio, 1.78 [95% CI, 1.61 to 1.95]). Tuberculosis incidence among participants receiving the rifapentine-isoniazid regimen twice (n = 1808) or once (n = 1802) was similar (hazard ratio, 0.96 [CI, 0.61 to 1.50]). LIMITATION: If rifapentine-isoniazid is effective in curing subclinical tuberculosis, then the intensive tuberculosis screening at month 12 may have reduced its effectiveness. CONCLUSION: Treatment completion was higher with rifapentine-isoniazid for 3 months compared with isoniazid for 6 months. In settings with high tuberculosis transmission, a second round of preventive therapy did not provide additional benefit to persons receiving antiretroviral therapy. PRIMARY FUNDING SOURCE: The U.S. Agency for International Development through the CHALLENGE TB grant to the KNCV Tuberculosis Foundation.

Standardizing clinical culture specimen collection in Ethiopia: a training-of-trainers.

BACKGROUND: Proper specimen collection is central to improving patient care by ensuring optimal yield of diagnostic tests, guiding appropriate management, and targeting treatment. The purpose of this article is to describe the development and implementation of a training-of-trainers educational program designed to improve clinical culture specimen collection among healthcare personnel (HCP) in Ethiopia. METHODS: A Clinical Specimen Collection training package was created consisting of a Trainer's Manual, Reference Manual, Assessment Tools, Step-by-Step Instruction Guides (i.e., job aides), and Core Module PowerPoint Slides. RESULTS: A two-day course was used in training 16 master trainers and 47 facility-based trainers responsible for cascading trainings on clinical specimen collection to HCP at the pre-service, in-service, or national-levels. The Clinical Specimen Collection Package is offered online via The Ohio State University's CANVAS online platform. CONCLUSIONS: The training-of-trainers approach may be an effective model for development of enhanced specimen collection practices in low-resource countries.

Burden and antimicrobial resistance of S. aureus in dairy farms in Mekelle, Northern Ethiopia.

BACKGROUND: Staphylococcus aureus is a frequent colonizer of human and several animal species, including dairy cows. It is the most common cause of intramammary infections in dairy cows. Its public health importance increases inline to the continuous emergence of drug-resistant strains; such as Methicillin-resistant S. aureus (MRSA). Indeed, the recent emergence of human and veterinary adapted MRSA demands serious attention. The aim of this study was to determine the burden and drug resistance pattern of S. aureus in dairy farms in Mekelle and determine the molecular characteristics of MRSA. RESULTS: This study was done on 385 lactating dairy cows and 71 dairy farmers. The ages of the cows and farmworkers were between 3 and 14 and 17-63 years respectively. S. aureus was isolated from 12.5% of cows and 31% of farmworkers. Highest resistance was observed for penicillin (> 90%) followed by tetracycline (32-35%) and trimethoprim-sulphamethoxazole (10-27%). But no resistance was observed for vancomycin, daptomycin, and rifampin. Only one isolate was MRSA both phenotypically and harboring mecA. This isolate was from nasal of a farmworker and was MRSA SCCmec Iva, spa type t064 of CC8. Multi-drug resistance was observed in 6.2% of cow isolates and 13.6% of nasal isolates. CONCLUSIONS: In this study, S. aureus infected 12.5% of dairy cows and colonized 31% of farmworkers. Except for penicillin, resistance to other drugs was rare. Although no MRSA was found from dairy cows the existence of the human and animal adapted and globally spread strain, MRSA SCCmec IVa spa t064, warrants for a coordinated action to tackle AMR in both human and veterinary in the country.

Accuracy of the tuberculosis point-of-care Alere determine lipoarabinomannan antigen diagnostic test using α-mannosidase treated and untreated urine in a cohort of people living with HIV in Guatemala.

BACKGROUND: Improved point-of-care diagnostic tests for tuberculosis (TB) in severe immune suppressed people living with HIV (PLWH) are needed to decrease morbidity and mortality outcomes. The aim of the study is to evaluate the performance of the lipoarabinomannan antigen test (LAM-test) with and without α-mannosidase pre-treated urine in a cohort of PLWH in primary care clinics in Guatemala. We further determined TB incidence, and mortality rates and its risk factors in PLWH with TB symptoms. METHODS: Prospective longitudinal study of PLWH with TB symptoms. Urine samples were collected at 2 HIV sites to test the sensitivity of the LAM-test in urine with and without α-mannosidase pre-treatment. A composite reference standard of either a positive Mycobacterium tuberculosis complex culture and/or GeneXpert® MTB/RIF (Xpert, Cepheid, Sunnyvale, CA, USA) results was used in the LAM-test diagnostic accuracy studies. Cox proportional hazards regression was used to study mortality predictors. RESULTS: The overall sensitivity of the LAM-test was of 56.1% with 95% CI of (43.3-68.3). There were no differences in the LAM-test sensitivity neither by hospital nor by CD4 T cell values. LAM-test sensitivity in PLWH with < 200 CD4 T cells/µl was of 62.2% (95% CI 46.5-76.2). There were no significant differences in sensitivity when comparing LAM-test results obtained from untreated vs. α-mannosidase treated urine [55.2% (95% CI 42.6-67.4) vs. 56.9% (95% CI 44-69.2), respectively]. TB incidence in our cohort was of 21.4/100 person years (PYs) (95% CI 16.6-27.6), and mortality rate was of 11.1/100 PYs (95% CI 8.2-15.0). Importantly, PLWH with a positive LAM-test result had an adjusted hazard ratio (aHR) of death of 1.98 (1.0-3.8) with a significant p value of 0.044 when compared to PLWH with a negative LAM-test result. CONCLUSIONS: In this study, α-mannosidase treatment of urine did not significantly increase the LAM-test performance, however; this needs to be further evaluated in a large-scale study due to our study limitations. Importantly, high rates of TB incidence and mortality were found, and a positive LAM-test result predicted mortality in PLWH with TB clinical symptoms.

Toxicity profile of Doxorubicin-Cyclophosphamide and Doxorubicin-Cyclophosphamide followed by Paclitaxel regimen and its associated factors among women with breast cancer in Ethiopia: A prospective cohort study.

BACKGROUND: Management of patients with breast cancer undergoing chemotherapy is complicated by a very high rate of adverse drug reactions which is even more challenging in developing countries like Ethiopia where the toxicity profile of chemotherapy is lacking. The present study aimed at evaluating the toxicity profile of Doxorubicin-Cyclophosphamide (AC) and Doxorubicin-Cyclophosphamide→Paclitaxel (AC→T) regimens among 146 patients with breast cancer in Ethiopia. METHODS: This prospective cohort study, with the median of six months' follow-up, was conducted from January 1 to September 30, 2017 GC at the only nationwide oncology center, Tikur Anbessa Specialized Hospital (TASH), Addis Ababa, Ethiopia. Seventy-one patients received AC, while 75 received AC-T regimen. The toxicity with the highest grade during any cycle was considered as the toxicity grade for that patient. SPSS version 22 was used for analysis. RESULTS: The overall frequent non-hematological adverse drug reactions reported for both regimens were fatigue 144 (98.7%), dysgeusia 142 (97.3%), skin hyperpigmentation 141 (96.6%), nausea 136 (93.2%), vomiting 129 (88.4%), gastritis 122 (83.6%), peripheral neuropathy 108 (74%), and myalgia/arthralgia 110 (75.3%). Neutropenia 107 (73.3%), leukopenia 102 (69.9%), and anemia 51 (34.9%) were the most frequent overall grade hematological toxicities reported. However, those received AC regimen suffered more from grade 2 and above leukopenia (35.2% vs. 17.3%, P = 0.014), anemia (16.9% vs. 2.7%, P = 0.004), and alkaline phosphatase increment (11.3% vs. 2.7%, P = 0.039) than AC-T regimen. On the contrary, those received AC-T regimen suffered more from severe arthralgia/myalgia (2.8% vs. 2%, P = 0.001), peripheral neuropathy (1.4% vs. 36%, P = 0.000), and gastritis (14.1% vs. 29.3%, P = 0.026) than AC regimen. Pretreatment blood cell counts, having stage IV breast tumor, older age, and lower body surface area were significant predictors of grade 2 to above hematological toxicities. Older age, arthralgia/myalgia, and skin hyperpigmentation occurred during the cohort were significant predictors of grade 2 to above oral mucositis, peripheral neuropathy, and fatigue, respectively. CONCLUSION: Patients who received the AC regimen suffered more from hematological abnormalities, while those on the AC-T regimen experienced more of non-hematological toxicities. Overall, we report high incidences of AC and AC-T regimens-induced toxicities in Ethiopian women with breast cancer, and they may require prior support based on pretreatment blood counts, age and body surface area, and close follow-up during chemotherapy.

The Lung Mucosa Environment in the Elderly Increases Host Susceptibility to Mycobacterium tuberculosis Infection.

As we age, there is an increased risk for the development of tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection. Few studies consider that age-associated changes in the alveolar lining fluid (ALF) may increase susceptibility by altering soluble mediators of innate immunity. We assessed the impact of adult or elderly human ALF during Mtb infection in vitro and in vivo. We identified amplification of pro-oxidative and proinflammatory pathways in elderly ALF and decreased binding capability of surfactant-associated surfactant protein A (SP-A) and surfactant protein D (SP-D) to Mtb. Human macrophages infected with elderly ALF-exposed Mtb had reduced control and fewer phagosome-lysosome fusion events, which was reversed when elderly ALF was replenished with functional SP-A/SP-D. In vivo, exposure to elderly ALF exacerbated Mtb infection in young mice. Our studies demonstrate how the pulmonary environment changes as we age and suggest that Mtb may benefit from declining host defenses in the lung mucosa of the elderly.

Predictors of unfavorable outcome in neurosyphilis: Multicenter ID-IRI Study.

Neurosyphilis (NS) has different clinical manifestations and can appear during any stage of syphilis. We aimed to identify the factors affecting poor outcome in NS patients. Patients with positive cerebrospinal fluid Venereal Disease Research Laboratory test, and positive serological serum treponemal or nontreponemal tests were classified as definite NS. The data of 141 patients with definite NS were submitted from 22 referral centers. Asymptomatic NS, syphilitic meningitis, meningovascular syphilis, tabes dorsalis, general paresis, and taboparesis were detected in 22 (15.6%), 67 (47.5%), 13 (9.2%), 10 (7%), 13 (9.2%), and 16 patients (11.3%), respectively. The number of HIV-positive patients was 43 (30.4%). The most common symptoms were headache (n = 55, 39%), fatigue (n = 52, 36.8%), and altered consciousness (50, 35.4%). Tabetic symptoms were detected in 28 (19.8%), paretic symptoms in 32 (22.6%), and vascular symptoms in 39 patients (27.6%). Eye involvement was detected in 19 of 80 patients (23.7%) who underwent eye examination and ear involvement was detected in eight of 25 patients (32%) who underwent ear examination. Crystallized penicillin was used in 109 (77.3%), procaine penicillin in seven (4.9%), ceftriaxone in 31 (21.9%), and doxycycline in five patients (3.5%). According to multivariate regression analysis, while headache was a protective factor in NS patients, double vision was significantly associated to poor outcome. We concluded that double vision indicated unfavorable outcome among NS patients. A high clinical suspicion is needed for the diagnosis NS. As determined in our study, the presence of headache in syphilitic patients can help in early diagnosis of central nervous system disease.

Evaluation of Mycobacterium tuberculosis lipoarabinomannan antigen assay and rapid serology blood test for the diagnosis of bovine tuberculosis in Ethiopia.

BACKGROUND: Bovine tuberculosis (bTB) is prevalent in dairy cattle in Ethiopia. Currently used diagnostic tools such as the single intradermal comparative tuberculin test (SICTT) are time consuming and labor intensive. A rapid, easy-to-use and cost-effective diagnostic test would greatly contribute to the control of bTB in developing countries like Ethiopia. In the present study, two point-of-care diagnostic tests were evaluated for the detection of bTB: LIONEX® Animal TB Rapid test, a membrane-based test for the detection of antibodies to Mycobacterium bovis in blood and ALERE® Determine TB Lipoarabinomannan (LAM) Ag, an immunoassay for the detection of lipoarabinomannan (LAM) antigen (Ag) of mycobacteria in urine. A combination of the SICTT and gamma interferon (IFN-γ) test was used as the gold standard for the validation of these point-of-care tests, as it was not feasible to slaughter the study animals to carry out the historical gold standard of mycobacterial culture. A total of 175 heads of cattle having three different bTB infection categories (positive SICTT, negative SICTT, and unknown SICTT status) were used for this study. RESULT: The sensitivity and specificity of TB LAM Ag were 72.2% (95% CI = 62.2, 80.4) and 98.8% (95% CI = 93.6, 99.7), respectively, while the sensitivity and specificity of the LIONEX Animal TB rapid test assay were 54% (95% CI = 44.1 64.3) and 98.8% (95% CI = 93.6, 99.7) respectively. The agreement between TB LAM Ag and SICTT was higher (κ = 0.85; 95% CI = 0.65-0.94) than between TB LAM Ag and IFN-γ (κ = 0.67; 95% CI = 0.52-0.81). The agreement between LIONEX Animals TB Rapid blood test and SICTT was substantial, (κ = 0.63; 95% CI = 0.49-0.77) while the agreement between LIONEX Animal TB rapid blood test and IFN-γ test was moderate (κ = 0.53; 95% CI = 0.40-0.67). Analysis of receiver operating curve (ROC) indicated that the area under the ROC curve (AUC) for TB LAM Ag was 0.85 (95% CI = 0.79-0.91) while it was 0.76 (95% CI; =0.69-0.83) for LIONEX Animal TB rapid test assay. CONCLUSION: This study showed that TB LAM Ag had a better diagnostic performance and could potentially be used as ancillary either to SICTT or IFN-γ test for diagnosis of bTB.

Trapping Lithium into Hollow Silica Microspheres with a Carbon Nanotube Core for Dendrite-Free Lithium Metal Anodes.

Li metal anodes, which have attracted much attention for their high specific capacity and low redox potential, face a great challenge in realizing their practical application. The fatal issue of dendrite formation gives rise to internal short circuit and safety hazards and needs to be addressed. Here we propose a rational strategy of trapping Li within microcages to confine the deposition morphology and suppress dendrite growth. Microcages with a carbon nanotube core and porous silica sheath were prepared and proved to be effective for controlling the electrodeposition behavior. In addition, the insulative coating layer prevents concentrated electron flow and decreases the possibility of "hot spots" formation. Because of the Li trapper and uniform electron distribution, the electrode with delicate structure exhibits a dendrite-free morphology after plating 2 mA h cm-2 of Li. As the dendrite growth is suppressed, the as-obtained electrode maintains a high plating/stripping efficiency of 99% over 200 cycles. This work delivers new insights into the design of rational Li metal anodes and hastens the practical application of Li metal batteries.

CD4+Foxp3+CD25+/- Tregs characterize liver tissue specimens of patients suffering from drug-induced autoimmune hepatitis: A clinical-pathological study.

BACKGROUND: The diagnosis of drug-induced autoimmune hepatitis (DIAIH) and its differentiation from idiopathic autoimmune hepatitis (AIH) is challenging. This study aimed to differentiate DIAIH from AIH by comparing the biochemical changes, histological features, and frequencies of CD4+Foxp3+CD25+/- regulatory T cells (Tregs) in liver tissues or peripheral blood lymphocytes. METHODS: A total of 15 DIAIH patients and 24 AIH patients who underwent liver biopsies at initial presentation were enrolled in this study. The liver histological changes were assessed by HE staining. The phenotypic recognition and distribution of CD4+Foxp3+CD25+/- Tregs in liver tissues were evaluated by single/double immunostains in serial sections. The CD4+Foxp3+CD25+/- Tregs in peripheral blood were analyzed by flow cytometry. RESULTS: The median values of ALT and AST were 404.50 U/L and 454.10 U/L in DIAIH patients and 309.50 U/L and 315.00 U/L in AIH patients, respectively. More importantly, for the first time we found that patients with DIAIH had higher levels of serum ALT and AST, more severe degree of lobular inflammation, higher frequencies of zone 3 necrosis and higher number of lobular CD4+Foxp3+CD25-Tregs compared with AIH (P < 0.05). Furthermore, there were positive correlations in DIAIH between the degree of lobular inflammation and either the AST/ALT level or the number of lobular CD4+Foxp3+CD25- Tregs (P < 0.05). However, the frequency of peripheral blood CD4+Foxp3+CD25+/- Tregs were not significantly different between DIAIH and AIH. CONCLUSIONS: The differences of ALT, AST and the number of lobular CD4+Foxp3+CD25- Tregs between patients with DIAIH and those with AIH are clinically helpful in differentiating these two diseases in their early stage.

High Rate of Treatment Completion in Program Settings With 12-Dose Weekly Isoniazid and Rifapentine for Latent Mycobacterium tuberculosis Infection.

Background: Randomized controlled trials have demonstrated that the newest latent tuberculosis (LTBI) regimen, 12 weekly doses of directly observed isoniazid and rifapentine (3HP), is as efficacious as 9 months of isoniazid, with a greater completion rate (82% vs 69%); however, 3HP has not been assessed in routine healthcare settings. Methods: Observational cohort of LTBI patients receiving 3HP through 16 US programs was used to assess treatment completion, adverse drug reactions, and factors associated with treatment discontinuation. Results: Of 3288 patients eligible to complete 3HP, 2867 (87.2%) completed treatment. Children aged 2-17 years had the highest completion rate (94.5% [155/164]). Patients reporting homelessness had a completion rate of 81.2% (147/181). In univariable analyses, discontinuation was lowest among children (relative risk [RR], 0.44 [95% confidence interval {CI}, .23-.85]; P = .014), and highest in persons aged ≥65 years (RR, 1.72 [95% CI, 1.25-2.35]; P < .001). In multivariable analyses, discontinuation was lowest among contacts of patients with tuberculosis (TB) disease (adjusted RR [ARR], 0.68 [95% CI, .52-.89]; P = .005) and students (ARR, 0.45 [95% CI, .21-.98]; P = .044), and highest with incarceration (ARR, 1.43 [95% CI, 1.08-1.89]; P = .013) and homelessness (ARR, 1.72 [95% CI, 1.25-2.39]; P = .001). Adverse drug reactions were reported by 1174 (35.7%) patients, of whom 891 (76.0%) completed treatment. Conclusions: Completion of 3HP in routine healthcare settings was greater overall than rates reported from clinical trials, and greater than historically observed using other regimens among reportedly nonadherent populations. Widespread use of 3HP for LTBI treatment could accelerate elimination of TB disease in the United States.