Article
Immunology
Moujane Soumia, Halima Hajji, Mohamed El Mzibri, Filali Zegzouti Younesd, Bouachrine Mohammed, Benlyas Mohameda, Moualij Benaissa
Summary: This study identified small molecules with inhibitory activity on the E6-E6AP interaction through simulation, which is of great significance for the development of anti-HPV drugs.
Article
Biochemistry & Molecular Biology
Masuma Khawary, Saurabh Pandey, Omprakash Sharma, Raunak Raunak, Manish Sharma, Ruchi Malik, Deeksha Tripathi
Summary: This study developed a computational model for M.tb Trigger Factor and identified two potential inhibitors, which could be significant for the development of novel therapies against tuberculosis.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Pediatrics
Ilker Devrim, Fatma Devrim, Nuri Bayram, Huseyin Akturk, Ahu Aksay, Demet Can, Hursit Apa
Summary: In children receiving isoniazid for latent tuberculosis, the overall incidence of hepatotoxicity is low and generally reversible. The grade of hepatotoxicity affects the recovery duration and restarting of therapy.
MINERVA PEDIATRICS
(2021)
Article
Biochemistry & Molecular Biology
Mahvish Khan, Saif Khan, Freah L. Alshammary, Sama Zaidi, Vineeta Singh, Iqrar Ahmad, Harun Patel, Vijai Kumar Gupta, Shafiul Haque
Summary: A major obstacle in the treatment of tuberculosis is the resistance of the causative agent, Mycobacterium tuberculosis. Different parts of Morus alba were found to have activity against M. tuberculosis. Four plant compounds were identified to have promising activity against five target proteins of M. tuberculosis. Further molecular dynamics studies showed the stability of the complexes formed between one of the compounds and three target proteins. Wet lab validation of this study can lead to new treatment options for TB patients.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Muhammad Hanif, Sara Khan, Umar Farooq, Faisal Nouroz, Rizwana Sarwar
Summary: The goal of this study was to find new compounds to treat multidrug-resistant tuberculosis by targeting Chorismate synthase. The findings suggest that compounds ZF1 and ZF2 may be more effective and selective anti-TB agents than currently available drugs. The study also revealed the role of L19 in the retention of ligand inside the active pocket.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Mohd Shahbaaz, Sameer H. Qari, Magda H. Abdellattif, Mostafa A. Hussien
Summary: This study aims to analyze the structural basis of drug resistance in Mycobacterium tuberculosis and predict novel mutations that may cause similar deleterious effects. Experimental and computational techniques were used to study the stability of the protein and determine the impact of these mutations. Molecular dynamic simulations validated the structural effects of these mutations. The outcome of this study can contribute to the identification of new drug resistance-associated mutations and facilitate drug design and discovery processes.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Immunology
Chishala Chabala, Anna Turkova, Anneke C. Hesseling, Kevin M. Zimba, Marieke van der Zalm, Monica Kapasa, Megan Palmer, Maxwell Chirehwa, Lubbe Wiesner, Eric Wobudeya, Aarti Kinikar, Vidya Mave, Syed Hissar, Louise Choo, Kristen LeBeau, Veronica Mulenga, Robb Aarnoutse, Diana Gibb, Helen McIlleron
Summary: The fixed-dose combination tablets delivering higher doses of first-line antituberculosis drugs in children resulted in lower drug exposures, both in children with lower weights and those receiving adult doses. Further adjustments are needed to achieve target exposures in adults.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Medicine, General & Internal
Victor Abiola Adepoju, Ademola Adelekan, Aderonke Agbaje, Femi Quaitey, Tobi Ademola-Kay, Ann Uduak Udoekpo, Olusola Daniel Sokoya
Summary: Despite Nigeria's high burden of childhood tuberculosis, there is limited data on the implementation of Isoniazid Preventive Therapy among children. This study reveals suboptimal completion rates of Isoniazid therapy among children in Lagos, Nigeria, with only six out of ten children completing the six-month treatment.
WORLD JOURNAL OF CLINICAL CASES
(2023)
Article
Pediatrics
Amyn A. Malik, Saira Farooq, Maria Jaswal, Hiba Khan, Kumail Nasir, Usama Fareed, Shumail Shahbaz, Farhana Amanullah, Nauman Safdar, Aamir J. Khan, Salmaan Keshavjee, Mercedes C. Becerra, Hamidah Hussain
Summary: The study showed that in a low-resource setting in south Asia, the use of daily isoniazid and rifapentine for one month as tuberculosis prevention in children and adolescents is safe and feasible. 63% of household contacts successfully completed all stages of the prevention cascade, and 94% of those who initiated the 1HP regimen completed it.
LANCET CHILD & ADOLESCENT HEALTH
(2021)
Article
Health Care Sciences & Services
Xin Chen, Jingyi Zhang, Liyun Jiang, Fangrong Yan
Summary: The article introduces a Bayesian phase I/II basket trial design called shotgun-2, which aims to determine indication-specific optimal biological doses. Simulation studies show that this design improves the accuracy of selecting optimal biological doses and provides a useful tool for drug development.
STATISTICAL METHODS IN MEDICAL RESEARCH
(2023)
Article
Infectious Diseases
Chiara Tersigni, Giulia Boiardi, Lorenzo Tofani, Elisabetta Venturini, Carlotta Montagnani, Barbara Bortone, Leila Bianchi, Elena Chiappini, Maria Iris Cassetta, Stefania Fallani, Andrea Novelli, Luisa Galli
Summary: This study evaluated serum concentrations of INH and RIF in children with TB, finding that younger children and adolescents tended to have lower plasma concentrations compared to older age groups. Monitoring drug plasma concentrations in children under 2 years of age and adolescents can help tailor treatment more effectively.
BMC INFECTIOUS DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Mohd Shahbaaz, Dmitry A. Maslov, Aleksey A. Vatlin, Valery N. Danilenko, Maria Grishina, Alan Christoffels
Summary: In the current era of a pandemic, infections of COVID-19 and Tuberculosis (TB) enhance the detrimental effects of both diseases in suffering individuals. The resistance mechanisms evolving in Mycobacterium tuberculosis are limiting the efficiency of current therapeutic measures and pressurizing the stressed medical infrastructures.
Article
Health Care Sciences & Services
Zhihui Xia, Youping Tan, Yumei Yang
Summary: This paper focuses on the outbreak of tuberculosis among university students in China and the impact of psychological problems on their academic lives. By applying the Bi-LSTM model and the CNN model neural network algorithm, a feasible solution for batch rapid analysis of psychological changes reflected in the daily text of university students is proposed.
JOURNAL OF HEALTHCARE ENGINEERING
(2022)
Article
Biochemistry & Molecular Biology
Tatiana F. Vieira, Fabio G. Martins, Joel P. Moreira, Tiago Barbosa, Sergio F. Sousa
Summary: This study utilized a computational approach to identify six potential compounds as inhibitors of PknB, providing structural information for further experimental testing and the design of more effective derivatives.
Article
Infectious Diseases
Grey Idalia Benoit Vasquez, Ana Lucia Morrobel, Dione Benjumea-Bedoya, Helena del Corral-Londono
Summary: This study aims to identify barriers and facilitators for Isoniazid Preventive Therapy (IPT) administration in children under 5 in the Area IV Directorate of Health of the Dominican Republic. Through a descriptive study and content analysis, it was found that socioeconomic and cultural conditions, lack of information and coordination, and inconsistent regulations are barriers for IPT administration, while a person-centred approach to care and modifiable health system factors are facilitators for IPT uptake.
BMC INFECTIOUS DISEASES
(2022)
Article
Microbiology
Moti Chapagain, Tawanda Gumbo, Scott K. Heysell, Shashikant Srivastava
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2020)
Article
Microbiology
Maxwell T. Chirehwa, Richard Court, Mariana de Kock, Lubbe Wiesner, Nihal de Vries, Joseph Harding, Tawanda Gumbo, Gary Maartens, Rob Warren, Paolo Denti, Helen McIlleron
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2020)
Editorial Material
Immunology
Jotam G. Pasipanodya, Tawanda Gumbo
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Pharmacology & Pharmacy
Shashikant Srivastava, Kayle N. Cirrincione, Devyani Deshpande, Tawanda Gumbo
Summary: The combination of tedizolid, moxifloxacin, and faropenem showed effective killing of nonreplicating persisters (NRP) of Mycobacterium tuberculosis. There was no significant difference in efficacy compared to the standard TB regimen, and no emergence of drug resistance was observed in the study. Further clinical studies are needed to validate these findings.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Microbiology
Shashikant Srivastava, Jann-Yuan Wang, Gesham Magombedze, Moti Chapagain, Hung-Ling Huang, Devyani Deshpande, Scott K. Heysell, Jotam G. Pasipanodya, Tawanda Gumbo
Summary: This study analyzed data from 32 Taiwanese patients to calculate kill slopes and time-to-extinction of bacterial burden under standard therapy and HFS-Mkn model, revealing differences in treatment outcomes and predicting the effectiveness of some short-course chemotherapy regimens.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Infectious Diseases
Tawanda Gumbo, Carleton M. Sherman, Devyani Deshpande, Jan-Willem Alffenaar, Shashikant Srivastava
Summary: The study found that adding faropenem to a linezolid plus pyrazinamide backbone regimen has a slow sterilizing effect on Mycobacterium tuberculosis and is unlikely to shorten therapy duration. Furthermore, the efficacy of these combination regimens against drug-resistant tuberculosis needs further investigation.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Infectious Diseases
Richard Court, Chad M. Centner, Maxwell Chirehwa, Lubbe Wiesner, Paolo Denti, Nihal de Vries, Joseph Harding, Tawanda Gumbo, Gary Maartens, Helen McIlleron
Summary: A high incidence of early neuropsychiatric toxicity was observed in patients treated with terizidone, with neuropathy being independently associated with cycloserine clearance and high-dose pyridoxine.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Microbiology
Maxwell T. Chirehwa, Richard Court, Mariana de Kock, Lubbe Wiesner, Nihal de Vries, Joseph Harding, Tawanda Gumbo, Gary Maartens, Rob Warren, Paolo Denti, Helen McIlleron
Summary: This study investigated the use of ethionamide in treating multidrug-resistant and rifampicin-resistant tuberculosis, focusing on the distribution of MICs, pharmacokinetics, and probability of achieving target concentrations. Results showed that the WHO-recommended doses of ethionamide were inadequate in achieving target concentrations even for the lowest MIC measured in the cohort.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Biology
Gesham Magombedze, Jotam G. Pasipanodya, Tawanda Gumbo
Summary: The study proposes a new method combining mathematical modeling and machine learning to derive effective predictive biomarkers for tuberculosis long-term treatment outcomes. The new method demonstrated higher sensitivity and specificity compared to current methods, with a potential to accelerate evaluation of novel TB regimens and personalize therapy duration. These biomarkers have the potential to aid in better clinical trial designs and improve treatment outcomes in routine programs.
COMMUNICATIONS BIOLOGY
(2021)
Article
Microbiology
Yongge Liu, Mischka Moodley, Jotam G. Pasipanodya, Tawanda Gumbo
Summary: Antimicrobial susceptibility testing based on clinical breakpoints incorporating PK/PD and clinical outcomes is becoming a new standard. However, for most antituberculosis drugs, breakpoints are determined by epidemiological cutoff values of MIC without considering PK/PD or dose. In this study, the PK/PD breakpoint for delamanid at 100 mg twice daily was determined by Monte Carlo experiments. The study showed that an MIC of 0.016 mg/L is the delamanid PK/PD breakpoint.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Infectious Diseases
Tawanda Gumbo, Shashikant Srivastava, Devyani Deshpande, Jotam G. Pasipanodya, Alexander Berg, Klaus Romero, David Hermann, Debra Hanna
Summary: This study evaluated the effect of different drug combinations on Mycobacterium tuberculosis using the hollow-fibre system model (HFS-TB). The results showed that HFS-TB is a highly tractable tool for choosing combination regimens with little variability between teams, and between replicates.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Microbiology
Ronald G. Hall, Shuhan Liu, William C. Putnam, Rajareddy Kallem, Tawanda Gumbo, Manjunath P. Pai
Summary: Echinocandins like anidulafungin are first-line therapies for candidemia and invasive candidiasis, but their dosing may be suboptimal in obese patients. This study aimed to evaluate the impact of body size on anidulafungin pharmacokinetics (PK) and found that a higher maintenance dose of anidulafungin is needed in larger adults to achieve the desired effect.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Letter
Immunology
Shashikant Srivastava, Tawanda Gumbo
OPEN FORUM INFECTIOUS DISEASES
(2023)
Article
Infectious Diseases
Sanjay Singh, Gunavanthi D. Boorgula, Santosh Aryal, Julie Philley, Tawanda Gumbo, Shashikant Srivastava
Summary: This study investigated the pharmacokinetics/pharmacodynamics of sarecycline in treating Mycobacterium avium complex pulmonary disease (MAC-PD) and found that sarecycline demonstrated good anti-MAC activity in the intracellular model, with an EC50 similar between intracellular and extracellular MAC.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Infectious Diseases
Shashikant Srivastava, Moti Chapagain, Johanna van Zyl, Devyani Deshpande, Tawanda Gumbo
Summary: This study confirmed that inhaled delivery of vancomycin can achieve optimal exposure target for tuberculosis treatment, and explored the interaction effects of vancomycin with other drugs in the process of Mycobacterium tuberculosis eradication.
JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE
(2021)