A5084786927- Tuberculosis Research and Epidemiology
- Pneumonia and Respiratory Infections
- Pneumocystis jirovecii pneumonia detection and treatment
- Mycobacterium research and diagnosis
- HIV/AIDS drug development and treatment
- Clostridium difficile and Clostridium perfringens research
- Gut microbiota and health
- Disaster Response and Management
- Drug Transport and Resistance Mechanisms
- Antibiotics Pharmacokinetics and Efficacy
- Diagnosis and treatment of tuberculosis
- Infectious Diseases and Tuberculosis
- Antibiotic Resistance in Bacteria
- HIV/AIDS Research and Interventions
- Inflammatory Bowel Disease
- Image Processing Techniques and Applications
- COVID-19 Clinical Research Studies
- HIV, Drug Use, Sexual Risk
- Pharmacological Effects and Toxicity Studies
- Biochemical and Molecular Research
- Bacteriophages and microbial interactions
- Statistical Methods in Clinical Trials
- Biosimilars and Bioanalytical Methods
- Cancer therapeutics and mechanisms
- SARS-CoV-2 and COVID-19 Research
Gheskio Centers
2014-2024
Johns Hopkins University
2014
The World Health Organization has recommended use of molecular-based tests MTBDRplus and GeneXpert MTB/RIF to diagnose multidrug-resistant tuberculosis in developing high-burden countries. Both are based on detection mutations the Rifampin (RIF) Resistance-Determining Region DNA-dependent RNA Polymerase gene (rpoB). Such found 95–98% Mycobacterium strains determined be RIF-resistant by "gold standard" culture-based drug susceptibility testing (DST). We report phenotypic genotypic...
Despite their therapeutic benefits, antibiotics exert collateral damage on the microbiome and promote antimicrobial resistance. However, mechanisms governing recovery from are poorly understood. Treatment of Mycobacterium tuberculosis , world’s most common infection, represents longest exposure in humans. Here, we investigate gut dynamics over 20 months multidrug-resistant (TB) 6 drug-sensitive TB treatment We find that clearance shared predictive cofactors resolution TB-driven inflammation....
The composition of the gastrointestinal microbiota influences systemic immune responses, but how this affects infectious disease pathogenesis and antibiotic therapy outcome is poorly understood. This question rarely examined in humans due to difficulty dissociating immunologic effects antibiotic-induced pathogen clearance microbiome alteration. Here, we analyze data from two longitudinal studies tuberculosis (TB) (35 20 individuals) a cross sectional study 55 healthy controls, which...
Evidence of the effectiveness WHO-recommended design longer individualized regimens for multidrug- or rifampicin-resistant TB (MDR/RR-TB) is limited.
The COVID-19 pandemic poses a unique threat to patients with multidrug-resistant tuberculosis (MDR-TB). We describe case of patient pulmonary MDR-TB and in Port-au-Prince, Haiti, highlight the challenges approach managing both diseases.
Abstract Sputum culture reversion after conversion is an indicator of tuberculosis (TB) treatment failure. We analyze data from the endTB multi-country prospective observational cohort (NCT03259269) to estimate frequency (primary endpoint) among individuals receiving a longer (18-to-20 month) regimen for multidrug- or rifampicin-resistant (MDR/RR) TB who experienced conversion. also conduct Cox proportional hazard regression analyses identify factors associated with reversion, including...
Abstract We report outcomes for a cohort of patients with multidrug-resistant tuberculosis who received high-dose isoniazid in Haiti. Patients had faster time to culture conversion and higher odds successful outcome, despite high-level resistance. This suggests may have effectiveness even phenotypic
This study was conducted in treatment-naive adults with drug-susceptible pulmonary tuberculosis Port-au-Prince, Haiti, to assess the safety, bactericidal activity, and pharmacokinetics of nitazoxanide (NTZ). a prospective phase II clinical trial 30 tuberculosis. Twenty participants received 1 g NTZ orally twice daily for 14 days. A control group 10 standard therapy over The primary outcome change time culture positivity (TTP) an automated liquid system. most common adverse events seen were...
Standard methods for enumerating Mycobacterium tuberculosis in patient sputum can miss large populations of viable M. cells that are unable to grow either on solid medium or liquid unless the has been extensively diluted. Because these bacteria be detected after limiting dilution, they have termed differentially culturable detectable (DD-Mtb). Treatment with isoniazid (H), rifampin (R), pyrazinamide (Z), and ethambutol (E) (HRZE) 1 2 weeks shown increase representation DD-Mtb drug-sensitive...
We report outcomes and 12-month survival for the first cohort of patients to undergo multidrug-resistant tuberculosis (MDR-TB) treatment after earthquake in Haiti. From March 3, 2010 28, 2013, 110 initiated laboratory-confirmed MDR-TB at Groupe Haïtien d'Etude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO) Center Port-au-Prince, Twenty-seven (25%) were human immunodeficiency virus (HIV)-positive. As October 31, 95 (86%) either cured or alive on treatment, 4 (4%) defaulted, 11...
BACKGROUND: The WHO provides standardized outcome definitions for rifampicin-resistant (RR) and multidrug-resistant (MDR) TB. However, operationalizing these can be challenging in some clinical settings, incorrect classification may generate bias reporting research. Outcomes calculated by algorithms increase standardization adapted to suit the research question. We evaluated concordance between clinician-assigned treatment outcomes based on one of two algorithms, which identified failure at...
We examined the correlation between three different methods of
ProblemIn 2010, Haiti sustained a devastating earthquake that crippled the health-care infrastructure in capital city, Port-au-Prince, and left 1.5 million people homeless.Subsequently, there was an increase reported tuberculosis affected population.Approach We conducted active case finding camp for internally displaced persons nearby slum.Community health workers screened at household level.People with persistent cough were referred to physician.The National Tuberculosis Program continued...
Abstract Diagnostics that more accurately detect and quantify viable Mycobacterium tuberculosis (Mtb) in the sputum of patients undergoing therapy are needed. Current culture- molecular-based tests have shown limited efficacy for monitoring treatment response TB patients, either due to presence sub-populations Mtb which fail grow under standard culture conditions (termed differentially detectable/culturable Mtb, DD Mtb) or prolonged half-life DNA sputum. Here, we report an optimized...
Recent World Health Organization guidance on drug-resistant tuberculosis treatment de-prioritised injectable agents, in use for decades, and endorsed all-oral longer regimens. However, questions remain about the role of agent, particularly context regimens using new repurposed drugs. We compared effectiveness an injectable-containing regimen to that among patients with who received bedaquiline and/or delamanid as part their multidrug regimen.Patients a positive baseline culture were...
Certain populations of Mycobacterium tuberculosis go undetected by standard diagnostics but can be enumerated using limiting dilution assays. These differentially detectable M. (DD tuberculosis) may have relevance for persistence due to their drug tolerance. It is unclear how well DD from patients modeled a recently developed
We developed a standardized method, possible poor treatment response (PPTR), to help ascertain efficacy endpoints in Study S31/A5349 (NCT02410772), an open-label trial comparing two 4-month rifapentine-based regimens with standard 6-month regimen for the of pulmonary tuberculosis (TB).
Clarity about the role of delamanid in longer regimens for multidrug-resistant TB is needed after discordant Phase IIb and III randomized controlled trial results. The found that addition to a background regimen hastened culture conversion; results were equivocal. We evaluated effect adding 24 weeks three-drug MDR/RR-TB on two- six-month conversion endTB observational study. used pooled logistic regression estimate analogue intention-to-treat (aITT) adjusting baseline confounders...
In 2015, the initiative Expand New Drug Markets for TB (endTB) began, with objective of reducing barriers to access new and repurposed drugs. Here we describe major implementation challenges encountered in 17 endTB countries. We provide insights on how national programmes other stakeholders can scale-up programmatic use drugs, while building scientific evidence about their safety efficacy. For any drug or diagnostic, multiple market slow pace scale-up. During 2015–2019, was successful...
Abstract Background Quantification of recurrence risk following successful treatment is crucial to evaluating regimens for multidrug- or rifampicin-resistant (MDR/RR) tuberculosis (TB). However, such analyses are complicated when some patients die become lost during post-treatment follow-up. Methods We analyzed data on 1991 who successfully completed a longer MDR/RR-TB regimen containing bedaquiline and/or delamanid between 2015 and 2018 in 16 countries. Using 5 approaches handling deaths,...
Multidrug-resistant tuberculosis (MDR-TB) outcomes are poor partly because of the long treatment duration; World Health Organization conditionally recommends a shorter course regimen to potentially improve outcomes. Here, we describe drug susceptibility patterns cohort MDR-TB patients in Haiti and determine number likely effective drugs if they were treated with recommended regimen. We retrospectively examined adults initiating between 2008 2015 at Haitian Group for Study Kaposi's Sarcoma...
Rationale: Treatment outcomes may be compromised among patients with multidrug- or rifampicin-resistant tuberculosis additional fluoroquinolone resistance. Evidence is needed to inform optimal treatment for these patients. Objectives: We compared the effectiveness of longer individualized regimens comprised bedaquiline 5 8 months, linezolid, and clofazimine those reinforced at least 1 third-tier drug and/or duration bedaquiline. Methods: emulated a target trial compare initiating remaining...
Background: There are limited data on the effectiveness of differentiated service delivery (DSD) for HIV care during sociopolitical turmoil. We assessed outcomes with a DSD model that includes patient choice between community-based antiretroviral therapy (ART) centers, home-based ART dispensing, or facility-based at GHESKIO clinic period severe civil unrest in Port-au-Prince, Haiti. Methods: This retrospective analysis included patients least one visit May 1, 2019, and December 31, 2021....