Risk-stratified treatment for drug-susceptible pulmonary tuberculosis.

The Phase 3 randomized controlled trial, TBTC Study 31/ACTG A5349 (NCT02410772) demonstrated that a 4-month rifapentine-moxifloxacin regimen for drug-susceptible pulmonary tuberculosis was safe and effective. The primary efficacy outcome was 12-month tuberculosis disease free survival, while the primary safety outcome was the proportion of grade 3 or higher adverse events during the treatment period. We conducted an analysis of demographic, clinical, microbiologic, radiographic, and pharmacokinetic data and identified risk factors for unfavorable outcomes and adverse events.

Percent of lung involved in disease on chest X-ray predicts unfavorable treatment outcome in pulmonary tuberculosis.

Unlabelled: Radiology may better define tuberculosis (TB) severity and guide duration of treatment. We aimed to systematically study baseline chest X-rays (CXR) and their association with TB treatment outcome using real-world data. We used logistic regression to associate TB treatment outcomes with CXR findings, including percent of lung involved in disease (PLI), cavitation, and Timika score, alone or in combination with other clinical characteristics, stratifying by drug resistance status and HIV (n = 2,809).

Pyrazinamide Safety, Efficacy, and Dosing for Treating Drug-Susceptible Pulmonary Tuberculosis: A Phase 3, Randomized Controlled Clinical Trial.

Optimizing pyrazinamide dosing is critical to improve treatment efficacy while minimizing toxicity during tuberculosis treatment. Study 31/AIDS Clinical Trials Group A5349 represents the largest phase 3 randomized controlled therapeutic trial to date for such an investigation. We sought to report pyrazinamide pharmacokinetic parameters, risk factors for lower pyrazinamide exposure, and relationships between pyrazinamide exposure and efficacy and safety outcomes.

Experience With Four-Month Rifapentine and Moxifloxacin-Based Tuberculosis Treatment in San Francisco.

Background: A multicountry randomized controlled trial has demonstrated that pan-susceptible pulmonary tuberculosis (TB) can be successfully treated with a 4-month regimen of daily isoniazid, rifapentine, moxifloxacin, and pyrazinamide (HPMZ). We piloted HPMZ in San Francisco (SF) using a modified version of the US Centers for Disease Control and Prevention HPMZ treatment guidelines.

Methods: In this retrospective cohort, patients consecutively referred to SF TB clinic were evaluated for HPMZ eligibility based on preestablished inclusion/exclusion criteria.

Pharmacokinetic-Pharmacodynamic Evidence From a Phase 3 Trial to Support Flat-Dosing of Rifampicin for Tuberculosis.

Background: The optimal dosing strategy for rifampicin in treating drug-susceptible tuberculosis (TB) is still highly debated. In the phase 3 clinical trial Study 31/ACTG 5349 (NCT02410772), all participants in the control regimen arm received 600 mg rifampicin daily as a flat dose. Here, we evaluated relationships between rifampicin exposure and efficacy and safety outcomes.

Respiratory, Cardiac, and Neuropsychiatric Manifestations of Postacute Sequelae of Coronavirus Disease 2019 in Lima, Peru.

Background: Few studies have examined the burden of postacute sequelae of coronavirus disease 2019 (COVID-19) (PASC) in low- and middle-income countries. We sought to characterize PASC with self-reported questionnaires and clinical examinations of end-organ function in Lima, Peru.

Methods: From January to July 2021, we recruited participants at least 8 weeks after COVID-19 diagnosis from a case registry in Lima, Peru.

Recent advances in the treatment of tuberculosis.

Background: Tuberculosis (TB) is a global health challenge and one of the leading causes of death worldwide. In the last decade, the TB treatment landscape has dramatically changed. After long years of stagnation, new compounds entered the market (bedaquiline, delamanid, and pretomanid) and phase III clinical trials have shown promising results towards shortening duration of treatment for both drug-susceptible (Study 31/A5349, TRUNCATE-TB, and SHINE) and drug-resistant TB (STREAM, NiX-TB, ZeNix, and TB-PRACTECAL).

Assessment of Need for Improved Identification of a Culprit Drug in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis.

Importance: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe hypersensitivity reaction. Identifying a culprit drug is critical for patient care, yet identification is based on clinical judgment. Data are limited on the accuracy in or approach to identifying a culprit drug.

Low detection rate of RT-PCR-confirmed COVID-19 using IgM/IgG rapid antibody tests in a large community sample in Lima, Peru.

Background: Rapid IgM/IgG antibody tests were largely used in lieu of RT-PCR tests as part of COVID-19 public health response activities in Lima, Peru. To assess their utility, we explored the relationship between the time since onset of several COVID-19-related symptoms and the sensitivity of a rapid combined IgM/IgG antibody test.

Methods: We collected data from a community sample of individuals (n = 492) who received concurrent RT-PCR and rapid IgM/IgG antibody testing between May 2020 and March 2021.

Clinical Outcomes of Individuals with COVID-19 and Tuberculosis during the Pre-Vaccination Period of the Pandemic: A Systematic Review.

Background: Tuberculosis, like COVID-19, is most often a pulmonary disease. The COVID-19 pandemic has severely disrupted tuberculosis services in myriad ways: health facility closures, lockdowns, travel bans, overwhelmed healthcare systems, restricted export of antituberculous drugs, etc. The effects of the shared risk on outcomes of the two diseases is not known, particularly for the first year of the pandemic, during the period before COVID-19 vaccines became widely available.

Disparities in SARS-CoV-2 Vaccination-to-Infection Risk During the COVID-19 Pandemic in Massachusetts.

This cohort study examines the alignment of vaccination and SARS-CoV-2 risk in Massachusetts by creating and applying a vaccination-to-infection risk ratio.

Diagnostic Performance Assessment of Saliva RT-PCR and Nasopharyngeal Antigen for the Detection of SARS-CoV-2 in Peru.

Widely available and reliable testing for SARS-CoV-2 is essential for the public health response to the COVID-19 pandemic. We estimated the diagnostic performance of reverse transcription PCR (RT-PCR) performed on saliva and the SD Biosensor STANDARD Q antigen test performed on nasopharyngeal swab compared to the reference standard, nasopharyngeal swab (NP) RT-PCR. We enrolled participants living and/or seeking care in health facilities in North Lima, Peru from November 2020 to January 2021.

Disparities in SARS-CoV-2 Testing in Massachusetts During the COVID-19 Pandemic.

This cohort study examines disparities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing during the coronavirus disease 2019 (COVID-19) pandemic in Massachusetts.

Helminth Egg Automatic Detector (HEAD): Improvements in development for digital identification and quantification of Helminth eggs and its application online.

Conventional analytical techniques for evaluating Helminth eggs are based on different steps to concentrate them in a pellet for direct observation and quantification under a light microscope, which can generate under-counts or over-counts and be time consuming. To enhance this process, a new approach via automatic identification was implemented in which various image processing detectors were developed and incorporated into a Helminth Egg Automatic Detector (HEAD) system. This allowed the identification and quantification of pathogenic eggs of global medical importance.

SARS-CoV-2 Testing Disparities in Massachusetts.

Objective: Early deficiencies in testing capacity contributed to poor control of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the context of marked improvement in SARS-CoV-2 testing infrastructure, we sought to examine the alignment of testing with epidemic intensity to mitigate subsequent waves of COVID-19 in Massachusetts.

Methods: We compiled publicly available weekly SARS-CoV-2 molecular testing data for period (May 27 to October 14, 2020) following the initial COVID-19 wave.

Omadacycline for the Treatment of Disease: A Case Series.

Background: Omadacycline is an aminomethylcycline antimicrobial approved by the US Food and Drug Administration in 2018 for community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. It has in vitro activity against nontuberculous mycobacteria, including complex, but clinical data for this indication are lacking.

Methods: Omadacycline use was reviewed at an 804-bed academic medical center.

Delayed Relapse of Paracoccidioidomycosis in the Central Nervous System: A Case Report.

Paracoccidioidomycosis is a dimorphic fungal infection endemic in Latin America. We report a patient with a history of pulmonary paracoccidioidomycosis who presented with relapsed disease in the central nervous system 4 years after initial treatment. We review current treatment strategies for paracoccidioidomycosis and neuroparacoccidioidomycosis.

Quantitative assessment of the activity of antituberculosis drugs and regimens.

: Identification of optimal drug doses and drug combinations is crucial for optimized treatment of tuberculosis. : An unprecedented level of research activity involving multiple approaches is seeking to improve tuberculosis treatment. This report is a review of the quantitative methods currently used on clinical data sets to identify drug exposure targets and optimal drug combinations for tuberculosis treatment.

Outcomes of a Career Development Program for Underrepresented Minority Investigators in the AIDS Clinical Trials Group.

We surveyed awardees of the Minority HIV Investigator Mentoring Program (MHIMP) of the AIDS Clinical Trials Group. Most reported clinical specialization in infectious diseases or HIV medicine (86%), and all but 1 (95%) are engaged in medical/health sciences research. The MHIMP helped retain early-career minority investigators in HIV/AIDS-related research.

Efficacy and Safety of High-Dose Rifampin in Pulmonary Tuberculosis. A Randomized Controlled Trial.

Rationale: We examined whether increased rifampin doses could shorten standard therapy for tuberculosis without increased toxicity.

Objectives: To assess the differences across three daily oral doses of rifampin in change in elimination rate of Mycobacterium tuberculosis in sputum and frequency of rifampin-related adverse events.

Methods: We conducted a blinded, randomized, controlled phase 2 clinical trial of 180 adults with new smear-positive pulmonary tuberculosis, susceptible to isoniazid and rifampin.