Garcia-Prats Research Group

Dr. Garcia-Prats is a general pediatrician with expertise in global child health developed over 13 years of working full time in Africa, before joining the Department of Pediatrics in 2019. He is an Associate Professor in the Divisions of General Pediatrics and Adolescent Medicine and Global Pediatrics.

He worked from 2006-2012 for the Baylor International Pediatric AIDS Initiative in Lesotho and Tanzania doing pediatric HIV clinical work, program development, capacity building and technical support.

From 2012-2019 he was based with the Desmond Tutu TB Centre (DTTC) at Stellenbosch University (Cape Town, South Africa) where he pursued clinical research in multidrug-resistant (MDR) tuberculosis (TB) and the pharmacokinetics and safety of anti-tuberculosis drugs in children. Thanks to the support of mentors at Stellenbosch University and elsewhere, he developed expertise in the clinical management of TB and MDR-TB in children, and in the design and implementation of clinical trials and other observational research in the therapeutics of childhood TB.

His interests and experience in TB and global health are broad, extending beyond TB therapeutics to include TB diagnosis, HIV care, and malnutrition. He is interested in pediatric drug development and improving access to better medicines for children globally.

Dr. Garcia-Prats is committed to doing high quality, high-impact clinical and translational research that improves the treatment and prevention of TB and MDR-TB in children, especially those in resource-limited settings, and to developing other scientists and clinicians with similar aspirations.

Mission

To perform high quality clinical and translational research that positively impacts the care of vulnerable children with TB, HIV and other illnesses in underserved areas globally, with a commitment to excellence, innovation, pragmatism, and partnership, and in a spirit of service and humility.

Research

Dr. Garcia-Prats primary research areas of interest are on MDR-TB, the pharmacokinetics and safety of anti-TB drugs, better TB treatment and prevention strategies and better pediatric drug development and access to child-friendly formulations.

With his team here at The University of Wisconsin-Madison and with outstanding colleagues at Stellenbosch University and in other centers globally, Dr. Garcia-Prats works to address the highest priority knowledge gaps in these areas, and to leverage that new knowledge to improve policy and practice.

He aims to be a thought leader in this area and an advocate for children affected by TB.

Focus Areas

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Pharmacokinetics, safety of TB drugs in children

Why is this important? The right doses of TB medicines in children will maximize their benefit and limit the risk of adverse effects. The right dose cannot be extrapolated directly from adults and each drug needs to be studied in children with TB to identify the optimal dose and safety at that dose. Not doing so puts children at risk unnecessarily. The pharmacokinetics of many drugs currently being used in children for drug-resistant TB have not been well studied.

Key examples:
The MDRPK1 and MDRPK2 studies were NIH-funded observational studies of the pharmacokinetics and safety of second-line TB drugs in South African children routinely treated for drug-resistant TB. Work from both of these studies has informed international dosing recommendations for second-line TB drugs, including for levofloxacin, moxifloxacin, and linezolid, and defined more optimal MDR-TB treatment and facilitated access to novel regimens.

Radtke KK, Hesseling AC, Winckler JL, Draper HR, Solans BP, Thee S, Wiesner L, van der Laan LE, Fourie B, Nielsen J, Schaaf HS, Savic RM, Garcia-Prats AJ. Moxifloxacin pharmacokinetics, cardiac safety, and dosing for the treatment of rifampicin-resistant tuberculosis in children. Clin Infect Dis. 2021 Jul 21;. doi: 10.1093/cid/ciab641. [Epub ahead of print] PubMed PMID: 34286843.

Garcia-Prats AJ, Schaaf HS, Draper HR, Garcia-Cremades M, Winckler J, Wiesner L, Hesseling AC, Savic RM. Pharmacokinetics, optimal dosing, and safety of linezolid in children with multidrug-resistant tuberculosis: Combined data from two prospective observational studies. PLoS Med. 2019 Apr;16(4):e1002789. doi: 10.1371/journal.pmed.1002789. eCollection 2019 Apr. PubMed PMID: 31039153; PubMed Central PMCID: PMC6490911.

Design and implementation of innovative clinical trials of TB drugs and treatment strategies in children

Why is this important? Carefully designed clinical trials of new and repurposed TB drugs are needed in children, but to date these studies have been very delayed, limiting much needed access to new drugs. Optimally designed pediatric trials of new and repurposed drugs for TB need to be started sooner and implemented efficiently. Dr. Garcia-Prats is a leader in implementation and design of trials of novel TB drugs in children and other pediatric TB trials, including as the PI of industry sponsored trials, investigator-initiated trials and as a protocol chair or vice-chair of trials through the NIH IMPAACT network (https://www.impaactnetwork.org). Many of these challenges are crosscutting across diseases, including for COVID.

Key examples and outputs:
Garcia-Prats AJ, Frias M, van der Laan L, De Leon A, Gler MT, Schaaf HS, Hesseling AC, Malikaarjun S, Hafkin J. Delamanid Added to an Optimized Background Regimen in Children with Multidrug-Resistant Tuberculosis: Results of a Phase I/II Clinical Trial. Antimicrob Agents Chemother. 2022 Apr 11;:e0214421. doi: 10.1128/aac.02144-21. [Epub ahead of print] PubMed PMID: 35404075.

Garcia-Prats AJ, Svensson EM, Winckler J, Draper HR, Fairlie L, van der Laan LE, Masenya M, Schaaf HS, Wiesner L, Norman J, Aarnoutse RE, Karlsson MO, Denti P, Hesseling AC. Pharmacokinetics and safety of high-dose rifampicin in children with TB: the Opti-Rif trial. J Antimicrob Chemother. 2021 Nov 12;76(12):3237-3246. doi: 10.1093/jac/dkab336. PubMed PMID: 34529779; PubMed Central PMCID: PMC8598292.

Garcia-Prats AJ, Salazar-Austin N, Conway JH, Radtke K, LaCourse SM, Maleche-Obimbo E, Hesseling AC, Savic RM, Nachman S. Coronavirus Disease 2019 (COVID-19) Pharmacologic Treatments for Children: Research Priorities and Approach to Pediatric Studies. Clin Infect Dis. 2021 Mar 15;72(6):1067-1073. doi: 10.1093/cid/ciaa885. PubMed PMID: 32594142; PubMed Central PMCID: PMC7337679.

Informing the clinical care of children with TB and drug-resistant TB through innovative evidence syntheses and rapid translation of clinical research findings into practical guidance

Why is this important? Results of observational pharmacokinetic and safety studies, and clinical trials, have immediate practical importance. These data are vital for informing international guidance on drug doses and treatment strategies for TB and DR-TB. Synthesizing available data to make the best use of what is often limited data from small studies helps translate research findings into the best possible practical guidance. Dr. Garcia-Prats provides technical support development of TB treatment guidelines for the WHO.

Key examples:
A 2013 comprehensive review of all the second-line TB medications in children for the World Health Organization Committee on the Selection and Use of Essential Medicines  identified important knowledge gaps, and informed guidelines at the time.

Harausz EP, Garcia-Prats AJ, Law S, Schaaf HS, Kredo T,et al. Treatment and outcomes in children with multidrug-resistant tuberculosis: A systematic review and individual patient data meta-analysis. PLoS Med. 2018 Jul;15(7):e1002591. doi: 10.1371/journal.pmed.1002591. eCollection 2018 Jul. PubMed PMID: 29995958; PubMed Central PMCID: PMC6040687.

Improving access for children to child-friendly, acceptable, palatable TB treatment and prevention

Why is this important? Having formulations that are child-friendly – acceptable, palatable, and allow accurate dosing across children of all ages – is critical for equitable treatment of children with TB and other diseases. Dr. Garcia-Prats leads work that evaluates the effect of manipulating (crushing, suspending) formulations intended for adults to inform their use in children, and mixed-methods studies to evaluate medications palatability and acceptability in children. Through direct work and in collaboration with key partner organizations, such as the WHO’s Global Accelerator for Pediatric formulations (GAP-f), he is working to improve timely access to child-friendly TB drug formulations for children in high-burden settings.

Key examples:
Winckler JL, Draper HR, Schaaf HS, van der Laan LE, Hesseling AC, Garcia-Prats AJ. Acceptability of levofloxacin, moxifloxacin and linezolid among children and adolescents treated for TB. Int J Tuberc Lung Dis. 2020 Dec 1;24(12):1316-1318. doi: 10.5588/ijtld.20.0544. PubMed PMID: 33317680; PubMed Central PMCID: PMC8320765.

Svensson EM, du Bois J, Kitshoff R, de Jager VR, Wiesner L, Norman J, Nachman S, Smith B, Diacon AH, Hesseling AC, Garcia-Prats AJ. Relative bioavailability of bedaquiline tablets suspended in water: Implications for dosing in children. Br J Clin Pharmacol. 2018 Jun 27;. doi: 10.1111/bcp.13696. [Epub ahead of print] PubMed PMID: 29952141; PubMed Central PMCID: PMC6138504.

Innovative Projects

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Better Evidence and Formulations for Improved MDR-TB Treatment for Children (BENEFIT Kids)

Description

Dr. Garcia-Prats is the overall Principal Investigator of the $18.9 million Unitaid-funded project (2019-2022) called BENEFIT Kids, led by Stellenbosch University (Co-Principal Investigator Anneke Hesseling, SU).

Aim

The aim of the project is to improve access to better MDR-TB prevention and treatment for children.
The project works in three countries (South Africa, India and the Philippines) with a consortium of international partners on three primary work streams:

  1. Optimizing existing evidence: Two large evidence syntheses in collaboration with the WHO to inform international treatment recommendations for children.
  2. Generating new evidence: Five complementary clinical trials of repurposed and new TB drugs, child-friendly TB drug formulations and MDR-TB prevention strategies in children.
  3. Targeted formulation development and optimization: Incentivizing generic drug manufacturers to optimize child-friendly formulations of key 2nd-line TB drugs.

The team collaborates closely with the World Health Organization and the project is already contributing to international policy and practice.

Timeline

October 2019 to September 2022

Funder

Unitaid

Countries

South Africa, the Philippines, India, Thailand

Partners

Stellenbosch University (South Africa), University of California San Francisco, Johns Hopkins University, De La Salle Medical and Health Sciences Institute (the Philippines), BJ Medical College (India), Uppsala University (Sweden), the TB Alliance, Chiang Mai University (Thailand)

For more information on BENEFIT Kids and for project updates:

Optimizing and operationalizing pediatric drug-resistant TB treatment (MDRPK2)

Description, Aim

Dr. Garcia-Prats was the PI (Co-PI Rada Savic, UCSF) of this observational study of the pharmacokinetics and safety of model-optimized doses of key second-line TB drugs in children routinely treated for drug-resistant TB. This study enrolled 89 children with MDR-TB and has generated key data on linezolid, moxifloxacin, bedaquiline and clofazimine that have informed WHO dosing guidelines for children.

Timeline

March 2016 to February 2021

Funder

NIH (NICHD, NIAID)

Countries

South Africa

Partners

Stellenbosch University, University of California San Francisco

Anthony
Anthony “Tony” Garcia-Prats, MD, MSc, PhD

Research Team

Bryan Vonasek, MD

Biography

Dr. Vonasek is a Pediatric Infectious Diseases Fellow aspiring to a career as an academic investigator focusing on high-impact clinical and implementation research to improve detection and treatment of pediatric infectious diseases for underserved populations globally. He grew up in central Minnesota, and after undergrad served as a US Peace Corps Volunteer in Malawi. After that, he attended medical school here at UW and then residency in pediatrics and global child health at Baylor College of Medicine in Houston, Texas. He rejoined UW as a fellow and started working with Dr. Garcia-Prats in 2020.

Research interests

Currently, Dr. Vonasek’s two major areas of research focus are 1) improving TB case finding in low-resource settings, and 2) understanding the burden of infections in children with severe acute malnutrition. With Dr. Garcia-Prats’ mentorship, he is currently implementing a research project assessing the accuracy of novel, non-invasive strategies for diagnosis of tuberculosis in young children with severe acute malnutrition in Malawi. He will be a Fogarty Global Health Fellow in Lilongwe Malawi (2022-2023) studying bacteremia in children with severe acute malnutrition.

Key Publications:
Vonasek BJ, Chiume M, Crouse HL, Mhango S, Kondwani A, Ciccone EJ, Kazembe PN, Gaven W, Fitzgerald E. Risk factors for mortality and management of children with complicated severe acute malnutrition at a tertiary referral hospital in Malawi. Paediatr Int Child Health. 2020 Aug;40(3):148-157. doi: 10.1080/20469047.2020.1747003. Epub 2020 Apr 3. PubMed PMID: 32242509.

Vonasek BJ, Kay A, Devezin T, Bacha JM, Kazembe P, Dhillon D, Dlamini S, Haq H, Thahane L, Simon K, Matshaba M, Sanders J, Minde M, Wanless S, Nyasulu P, Mandalakas A. Tuberculosis symptom screening for children and adolescents living with HIV in six high HIV/TB burden countries in Africa. AIDS. 2021 Jan 1;35(1):73-79. doi: 10.1097/QAD.0000000000002715. PubMed PMID: 33048868; PubMed Central PMCID: PMC7752241.

Vonasek BJ, Ness T, Takwoingi Y, Kay AW, van Wyk SS, Ouellette L, Marais BJ, Steingart KR, Mandalakas AM. Screening tests for active pulmonary tuberculosis in children. Cochrane Database Syst Rev. 2021 Jun 28;6:CD013693. doi: 10.1002/14651858.CD013693.pub2. PubMed PMID: 34180536; PubMed Central PMCID: PMC8237391.

Vonasek BJ, Radtke KK, Vaz P, Buck WC, Chabala C, McCollum ED, Marcy O, Fitzgerald E, Kondwani A, Garcia-Prats AJ. Tuberculosis in children with severe acute malnutrition. Expert Rev Respir Med. 2022 Mar;16(3):273-284. doi: 10.1080/17476348.2022.2043747. Epub 2022 Feb 28. Review. PubMed PMID: 35175880; NIHMSID:NIHMS1783479.

Bryan Vonasek, MD
Bryan Vonasek, MD