Evaluation of the Latent Tuberculosis Care Cascade Among Public Health Clinics in the United States.

BACKGROUND: Tuberculosis (TB) elimination within the United States will require scaling up TB preventive services. Many public health departments offer care for latent tuberculosis infection (LTBI), although gaps in the LTBI care cascade are not well quantified. An understanding of these gaps will be required to design targeted public health interventions. METHODS: We conducted a cohort study through the Tuberculosis Epidemiologic Studies Consortium (TBESC) within 15 local health department (LHD) TB clinics across the United States. Data were abstracted on individuals receiving LTBI care during 2016-2017 through chart review. Our primary objective was to quantify the LTBI care cascade, beginning with LTBI testing and extending through treatment completion. RESULTS: Among 23 885 participants tested by LHDs, 46% (11 009) were male with a median age of 31 (interquartile range [IQR] 20-46). A median of 35% of participants were US-born at each site (IQR 11-78). Overall, 16 689 (70%) received a tuberculin skin test (TST), 6993 (29%) received a Quantiferon (QFT), and 1934 (8%) received a T-SPOT.TB; 5% (1190) had more than one test. Among those tested, 2877 (12%) had at least one positive test result (3% among US-born, and 23% among non-US-born, P < .01). Of 2515 (11%) of the total participants diagnosed with LTBI, 1073 (42%) initiated therapy, of whom 817 (76%) completed treatment (32% of those with LTBI diagnosis). CONCLUSIONS: Significant gaps were identified along the LTBI care cascade, with less than half of individuals diagnosed with LTBI initiating therapy. Further research is needed to better characterize the factors impeding LTBI diagnosis, treatment initiation, and treatment completion.

Testing modality associated with fast-track ART initiation in Botswana.

OBJECTIVES: The aim of this study was to identify community testing modalities associated with fast-track ART initiation in Botswana. METHODS: We conducted a retrospective cohort study that included all Botswana citizens 15 years or older who were newly identified as HIV-positive from 1 May 2017 to 31 January 2019, in Mahalapye and Southern districts. We used Poisson regression with robust error variance and generalised linear mixed models to control for cluster effects to model risk of ART initiation within 7 and 30 days of HIV diagnosis, testing modality factors. RESULTS: A total of 1436 individuals were newly identified HIV-positive, with men accounting for 60% across all testing modalities. 22% of all HIV-positive individuals were initiated on ART within 7 days. Clients diagnosed through index testing were more likely to be started on ART within 7 days (adjusted risk ratio [aRR] = 1.38, 95% CI 1.37-1.38) and 30 days (aRR = 1.17, 95% CI 1.09-1.26) than those diagnosed through mobile/outreach testing. CONCLUSIONS: Community HIV testing can complement facility-based testing by reaching individuals who may be less likely to seek HIV services at a facility, such as men. Monitoring ART initiation by testing modalities is critical to identify the optimal ones and to guide continuous programme improvement.

Correction to: Strengthening medical training programmes by focusing on professional transitions: a national bridging programme to prepare medical school graduates for their role as medical interns in Botswana.

CORRECTION: Forllowing publication of the original article [1], the first author reported that there was a typographical error in the name of one of his co-authors. The correct spelling is Alemayehu Bedada, not Alemayhu Bedada.

Strengthening medical training programmes by focusing on professional transitions: a national bridging programme to prepare medical school graduates for their role as medical interns in Botswana.

BACKGROUND: The improvement of existing medical training programmes in resource-constrained settings is seen as key to addressing the challenge of retaining medical graduates trained at considerable cost both in-country and abroad. In Botswana, the establishment of the national Medical Internship Training Programme (MIT) in 2014 was a first step in efforts to promote retention through the expansion and standardization of internship training, but MIT faces a major challenge related to variability between incoming trainees due to factors such as their completion of undergraduate medical training in different settings. To address this challenge, in August 2016 we piloted a bridging programme for foreign and locally trained medical graduates that aimed to facilitate their transition into internship training. This study aimed to describe the programme and evaluate its impact on the participants' self-rated perceptions of their knowledge, experience, clinical skills, and familiarity with Botswana's healthcare system. METHODS: We conducted a national, intensive, two-week programme designed to facilitate the transition from medical student to intern and to prepare all incoming interns for their work in Botswana's health system. Participants included all interns entering in August 2016. Formats included lectures, workshops, simulations, discussions, and reflection-oriented activities. The Kellogg Foundation Outcomes Logic Model was used to evaluate the programme, and participants self-rated their knowledge, skills, and attitudes across each of the programme objectives on paired questionnaires before and after participation. RESULTS: 48/54 participants (89%) provided paired data. Participants reported a high degree of satisfaction with the programme (mean 4.2/5). Self-rated preparedness improved after participation (mean 3.2 versus 3.7, p < 0.001), as did confidence across 18/19 knowledge/skill domains, suggesting that participants felt that the programme prepared them for their internship training. Exploratory analysis revealed that 20/25 participants (80%) reporting either no effect or a negative effect following participation had rated themselves "extremely" or "quite" prepared beforehand, suggesting the programme grounded expectations for interns who initially were overconfident. In contrast, no interns who had initially rated themselves "moderately" or "somewhat" prepared reported a decline in their self-rated sense of preparedness. Interns commented on the benefits of learning about roles/responsibilities, interacting with clinicians from Botswana's healthcare sectors, and the sense of community the programme engendered. CONCLUSIONS: This programme was feasible to implement and was well-received by participants. Overall, participants perceived an enhancement of their knowledge, skills, and expectations about their role in Botswana's health system after completion of the programme. Our results are likely to be of interest to educators dedicated to training, professional transitions, and career pathways in similar settings in the region and beyond.

Ceftolozane-Tazobactam Pharmacokinetics in a Critically Ill Patient on Continuous Venovenous Hemofiltration.

Extended-infusion ceftolozane-tazobactam treatment at 1.5 g every 8 h was used to treat multidrug-resistant Pseudomonas aeruginosa in a critically ill patient on continuous venovenous hemofiltration. Serum drug concentrations were measured at 1, 4, 5, 6, and 8 h after the start of infusion. Prefilter levels of ceftolozane produced a maximum concentration of drug (Cmax) of 38.57 µg/ml, concentration at the end of the dosing interval (Cmin) of 31.63 µg/ml, time to Cmax (Tmax) of 4 h, area under the concentration-time curve from 0 to 8 h (AUC0-8) of 284.38 µg · h/ml, and a half-life (t1/2) of 30.7 h. The concentrations were eight times the susceptibility breakpoint for the entire dosing interval.

Adult-onset immunodeficiency in Thailand and Taiwan.

BACKGROUND: Autoantibodies against interferon-γ are associated with severe disseminated opportunistic infection, but their importance and prevalence are unknown. METHODS: We enrolled 203 persons from sites in Thailand and Taiwan in five groups: 52 patients with disseminated, rapidly or slowly growing, nontuberculous mycobacterial infection (group 1); 45 patients with another opportunistic infection, with or without nontuberculous mycobacterial infection (group 2); 9 patients with disseminated tuberculosis (group 3); 49 patients with pulmonary tuberculosis (group 4); and 48 healthy controls (group 5). Clinical histories were recorded, and blood specimens were obtained. RESULTS: Patients in groups 1 and 2 had CD4+ T-lymphocyte counts that were similar to those in patients in groups 4 and 5, and they were not infected with the human immunodeficiency virus (HIV). Washed cells obtained from patients in groups 1 and 2 had intact cytokine production and a response to cytokine stimulation. In contrast, plasma obtained from these patients inhibited the activity of interferon-γ in normal cells. High-titer anti-interferon-γ autoantibodies were detected in 81% of patients in group 1, 96% of patients in group 2, 11% of patients in group 3, 2% of patients in group 4, and 2% of controls (group 5). Forty other anticytokine autoantibodies were assayed. One patient with cryptococcal meningitis had autoantibodies only against granulocyte-macrophage colony-stimulating factor. No other anticytokine autoantibodies or genetic defects correlated with infections. There was no familial clustering. CONCLUSIONS: Neutralizing anti-interferon-γ autoantibodies were detected in 88% of Asian adults with multiple opportunistic infections and were associated with an adult-onset immunodeficiency akin to that of advanced HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research; ClinicalTrials.gov number, NCT00814827.).

Mycobacterium xenopi native vertebral osteomyelitis and discitis: Case & review of published cases.

Mycobacterium xenopi is a rare cause of spinal osteomyelitis and discitis. Here we report the case of a 68-year-old woman with history of splenectomy for Felty's syndrome who developed M. xenopi lumbar discitis and osteomyelitis following repeated corticosteroid spinal injections for chronic back pain. Review of the 18 cases of M. xenopi spinal osteomyelitis cases described in the literature revealed common threads of immunocompromised hosts and prior spinal manipulation.

Predictors of in-hospital mortality in a cohort of people living with HIV (PLHIV) admitted to an academic medical intensive care unit from 2009 to 2014: A retrospective cohort study.

Outcomes for critically ill people living with human immunodeficiency virus (PLHIV) have changed with the use of antiretroviral therapy (ART). To identify these outcomes and correlates of mortality in a contemporary critically ill cohort in an urban academic medical center in Baltimore, a city with a high burden of HIV, we conducted a retrospective cohort study of individuals admitted to a medical intensive care unit (MICU) at a tertiary care center between 2009 and 2014. PLHIV who were at least 18 years of age with an index MICU admission of ≥24 hours during the 5-year study period were included in this analysis. Data were obtained for participants from the time of MICU admission until hospital discharge and up to 180 days after MICU admission. Logistic regression was used to identify independent predictors of hospital mortality. Between June 2009 and June 2014, 318 PLHIV admitted to the MICU met inclusion criteria. Eighty-six percent of the patients were non-Hispanic Blacks. Poorly controlled HIV was very common with 70.2% of patients having a CD4 cell count <200 cells/mm3 within 3 months prior to admission and only 34% of patients having an undetectable HIV viral load. Hospital mortality for the cohort was 17%. In a univariate model, mortality did not differ by demographic variables, CD4 cell count, HIV viral load, or ART use. Regression analysis adjusted by relevant covariates revealed that MICU patients admitted from the hospital ward were 6.4 times more likely to die in hospital than those admitted from emergency department. Other positive predictors were a diagnosis of end-stage liver disease, cardiac arrest, ventilator-dependent respiratory failure, vasopressor requirement, non-Hodgkin lymphoma, and symptomatic cytomegalovirus disease. In conclusion, in this critically ill cohort with HIV infection, most predictors of mortality were not directly related to HIV and were similar to those for the general population.

Identification of mycobacteria in solid-culture media by matrix-assisted laser desorption ionization-time of flight mass spectrometry.

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has recently been introduced into the clinical microbiology laboratory as a rapid and accurate method to identify bacteria and yeasts. In this paper we describe our work on the use of MALDI-TOF MS for the identification of mycobacterial isolates. We developed a protocol for protein extraction from mycobacteria and utilized it to construct a database containing 42 clinically relevant type and reference strains of mycobacteria. The database was used to identify 104 clinical isolates of mycobacteria. All members of the Mycobacterium tuberculosis complex were identified accurately at the complex level but could not be separated at the species level. All other organisms were identified at the species level, with the exception of one strain of M. kansasii (accurately identified but with a low spectral score) and three pairs of closely related strains: M. abscessus and M. massiliense, M. mucogenicum and M. phocaicum, and M. chimaera and M. intracellulare. These pairs of organisms can currently be identified only by multilocus gene sequence analysis. We conclude that MALDI-TOF MS analysis can be incorporated into the work flow of the microbiology laboratory for rapid and accurate identification of most strains of mycobacteria isolated from solid growth media.

Pathophysiology and Treatment Options for Hepatic Fibrosis: Can It Be Completely Cured?

Hepatic fibrosis is a dynamic process that occurs as a wound healing response against liver injury. During fibrosis, crosstalk between parenchymal and non-parenchymal cells, activation of different immune cells and signaling pathways, as well as a release of several inflammatory mediators take place, resulting in inflammation. Excessive inflammation drives hepatic stellate cell (HSC) activation, which then encounters various morphological and functional changes before transforming into proliferative and extracellular matrix (ECM)-producing myofibroblasts. Finally, enormous ECM accumulation interferes with hepatic function and leads to liver failure. To overcome this condition, several therapeutic approaches have been developed to inhibit inflammatory responses, HSC proliferation and activation. Preclinical studies also suggest several targets for the development of anti-fibrotic therapies; however, very few advanced to clinical trials. The pathophysiology of hepatic fibrosis is extremely complex and requires comprehensive understanding to identify effective therapeutic targets; therefore, in this review, we focus on the various cellular and molecular mechanisms associated with the pathophysiology of hepatic fibrosis and discuss potential strategies to control or reverse the fibrosis.

Oral Polio Vaccine to Protect Against COVID-19: Out of the Box Strategies?

The global coronavirus disease 2019 pandemic has raised significant concerns of developing rapid, broad strategies to protect the vulnerable population and prevent morbidity and mortality. However, even with an aggressive approach, controlling the pandemic has been challenging, with concerns of emerging variants that likely escape vaccines, nonadherence of social distancing/preventive measures by the public, and challenges in rapid implementation of a global vaccination program that involves mass production, distribution, and execution. In this review, we revisit the utilization of attenuated vaccinations, such as the oral polio vaccine, which are safe, easy to administer, and likely provide cross-protection against respiratory pathogens. We discuss the rationale and data supporting its use and detail description of available vaccines that could be repurposed for curtailing the pandemic.

Subacute Polymicrobial Bacterial Pericarditis Mimicking Tuberculous Pericarditis: A Case Report.

BACKGROUND Bacterial pericarditis can present a diagnostic challenge due to the difficulty of obtaining tissue for bacterial identification. This report is of a 34-year-old man who presented with fever and cough. Diagnosis was initially delayed without a tissue sample, but the patient was later found to have polymicrobial bacterial pericarditis. CASE REPORT A 34-year-old man from the Democratic Republic of Congo presented to the emergency room with cough, fever, and night sweats. He was admitted and found to have pericardial thickening and fluid collection with calcifications. A tissue sample was not obtained for diagnosis, and he was discharged on RIPE (rifampin, isoniazid, pyrazinamide, and ethambutol) and steroids for presumed tuberculosis pericarditis. He worsened clinically and was readmitted to the hospital with evolving pericardial effusion with air present, in addition to new pleural effusion and parenchymal consolidation. He subsequently underwent thoracotomy and pericardial biopsy. Tissue cultures and sequence-based bacterial analysis eventually revealed the presence of Prevotella oris and Fusobacterium nucleatum. He improved dramatically with appropriate antibiotic therapy. CONCLUSIONS This report demonstrates the importance of undergoing further diagnostic work-up for bacterial pericarditis, especially in resource-rich settings. Although tuberculosis pericarditis should remain high on the differential, it is imperative not to anchor on that diagnosis. Instead, when feasible and safe, tissue biopsy should be obtained and sent for organism identification. AFB smears and cultures, Xpert MTB/RIF, and sequence-based bacterial analysis have all been used for identification. Delay in diagnosis can lead to progression of disease and unnecessary incorrect therapies.

Pulmonary nontuberculous mycobacterial disease: new insights into risk factors for susceptibility, epidemiology, and approaches to management in immunocompetent and immunocompromised patients.

Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and cause a wide range of diseases in humans. Pulmonary involvement, the most common disease manifestation of NTM infection, is being increasingly encountered in clinical settings. In addition, specific phenotypic and genetic characteristics of persons predisposed to contract pulmonary NTM disease are now beginning to be recognized. Prior to treatment, patients should meet clinical and microbiologic criteria for NTM disease. Treatment involves prolonged courses of antibiotics in various combination regimens that are often discontinued because of serious side effects. In some cases, complete cure of pulmonary disease is difficult to achieve. Rather, clinical improvement may be a more feasible goal. Surgical treatment is warranted for select patients.

Histoplasmosis of the gallbladder.

Histoplasmosis of the gallbladder is an extremely rare condition. We present the case of cholecystitis due to progressive, disseminated histoplasmosis in an immunocompetent woman.

Challenges in the diagnosis of tuberculous meningitis.

Tuberculosis (TB) continues to pose a significant public health problem. Tuberculous meningitis (TBM) is the most severe form of extra-pulmonary TB. TBM carries a high mortality rate, including for those receiving treatment for TB. Diagnosis of TBM is difficult for clinicians as it can clinically present similarly to other forms of meningitis. The difficulty in diagnosis often leads to a delay in treatment and subsequent mortality. Those who survive are left with long-term sequelae leading to lifelong disability. The microbiologic diagnosis of TBM requires the isolation of Mycobacterium tuberculosis from the cerebrospinal fluid (CSF) of an infected patient. The diagnosis of tuberculous meningitis continues to be challenging for clinicians. Unfortunately, many cases of TBM cannot be confirmed based on clinical and imaging findings as the clinical findings are nonspecific, while laboratory techniques are largely insensitive or slow. Until recently, the lack of accessible and timely tests has contributed to a delay in diagnosis and subsequent morbidity and mortality for many patients, particularly those in resourcelimited settings. The availability of Xpert Ultra and point-of-care lipoarabinomannan (LAM) testing could represent a new era of prompt diagnosis and early treatment of tuberculous meningitis. However, clinicians must be cautious when ruling out TBM with Xpert Ultra due to its low negative predictive value. Due to the limitations of current diagnostics, clinicians should utilize a combination of diagnostic modalities in order to prevent morbidity in patients with TBM.

A Case of Bartonella Quintana Culture-Negative Endocarditis.

BACKGROUND Culture-negative Bartonella quintana endocarditis is challenging to diagnose and is associated with high mortality rates. Diagnostic confirmation of Bartonella quintana infection requires specialized assays, as identifying Bartonella henselae endocarditis by serology can be difficult due to the high rate of serological cross-reactivity. This is a case report of culture-negative Bartonella quintana endocarditis that was diagnosed with epidemiologic data, histology, and nucleic acid amplification testing. CASE REPORT A 28-year-old man with a history of homelessness was admitted to hospital with worsening productive cough, weight loss, and abdominal pain. A transthoracic echocardiogram (TTE) showed pulmonary valve vegetation and several aortic valve vegetations. His hospital course was complicated by cardiogenic shock and septic shock requiring transfer to a tertiary care medical intensive care unit. Although blood cultures remained negative for bacterial infection, serology testing was positive for Bartonella henselae and Bartonella quintana IgM and IgG. Nucleic acid amplification testing for 16S ribosomal RNA (rRNA) using valve tissue was diagnostic for Bartonella quintana. CONCLUSIONS This case of culture-negative Bartonella quintana endocarditis demonstrates the use of diagnostic nucleic acid amplification methods to confirm the diagnosis.

Is Mycobacterium avium paratuberculosis the Trigger in the Crohn's Disease Spectrum?

We present and discuss a 30-month investigation of a patient that presented with abdominal pain, postprandial diarrhea, bloating, and night sweats and was treated for Crohn's disease without significant improvement. The patient underwent an ileocecetomy with removal of an atonic segment with resolution of functional gastrointestinal symptoms, but profound night sweats continued postoperatively. The patient was presumptively treated for a mixed mycobacterial infection, blood cultures later grew Mycobacterium avium paratuberculosis (MAP), and she improved over time. We discuss MAP and its possible relationship to Crohn's disease.

Clinical characteristics of critically ill patients with suspected influenza during the 2009-10 and 2013-14 outbreaks.

PURPOSE: Pandemic influenza A pdm09 (pH1N1) virus was the predominant isolate identified during the 2009-10 and 2013-14 influenza outbreaks, causing significant morbidity and mortality. We describe clinical characteristics of critically ill patients during 2 pH1N1 outbreaks. METHODS: Single-center, retrospective cohort study of patients admitted to the intensive care unit receiving oseltamivir for suspected influenza during 2 outbreak periods. Demographics and comorbidities were collected from the medical record. Outcomes included use of adjunct oxygenation therapies and oseltamivir dosing. RESULTS: One hundred twenty-four patients were included (2009, n=53; 2013, n=71). Demographics were as follows: mean (SD) age, 52.3 (14.2) years; mean (SD) Acute Physiology and Chronic Health Evaluation II score, 19.4 (9.2); 71% had greater than or equal to 2 comorbidities; and mortality was 27%. Inhaled nitric oxide was administered more commonly in 2009 (P=.01), whereas neuromuscular blockade (P=.02) and epoprostenol were administered more commonly in 2013 (P=.01). Patients in 2009 were more likely to receive high-dose oseltamivir (P=.02; odds ratio, 1.8; 95% confidence interval, 1.18-6.62). No differences in clinical outcomes were observed between 2009 and 2013. CONCLUSIONS: Use of adjunct oxygenation therapies and nontraditional antiviral dosing has changed significantly since the 2009 pandemic, although this has not resulted in a measurable impact on clinical outcomes.