João Vítor Perez de Souza

Duke University

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João Ricardo Nickenig Vissoci

Duke Institute for Health Innovation

Letícia Sayuri Murase

Universidade Estadual de Maringá

Rosilene Fressatti Cardoso

Universidade Estadual de Maringá

Catherine A. Staton

Duke University

Blandina T. Mmbaga

Kilimanjaro Christian Medical Centre

Regiane Bertin de Lima Scodro

Universidade Estadual de Maringá

Vera Lúcia Dias Siqueira

Universidade Estadual de Maringá

Jorge Juarez Vieira Teixeira

Universidade Estadual de Maringá

Judith Boshe

Kilimanjaro Christian Medical Centre

Katiany Rizzieri Caleffi-Ferracioli

Universidade Estadual de Maringá

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Universidade Estadual de Maringá

Duke University

Duke Institute for Health Innovation

Duke Medical Center

Kilimanjaro Christian Medical Centre

Duke University Hospital

Universidade de São Paulo

National University of the Littoral

European Union of Medical Specialists

Clinical Research Institute

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DIMINUIÇÃO DA CONCENTRAÇÃO INIBITÓRIA MÍNIMA DE CIPROFLOXACINO INDUZIDA PELA COMBINAÇÃO COM PIPERINA EM MICOBACTÉRIAS NÃO TUBERCULOSAS

The Brazilian Journal of Infectious Diseases (2022)

Andressa Araújo Machado do Nascimento Letícia Sayuri Murase Carolina Trevisolli Palomo João Vítor Perez de Souza Katiany Rizzieri Caleffi Ferracioli

As doenças causadas por micobactérias não tuberculosas (MNTs) são emergentes no cenário epidemiológico mundial. O tratamento das infecções por MNTs é desfavorecido pela multirresistência e pelas limitações de antibioticoterapia disponíveis. Diferente da tuberculose, não há um protocolo terapêutico bem estabelecido, neste sentido, a combinação de fármacos e o uso de novos compostos adjuvantes no tratamento antimicrobiano disponível são bem-vindos. Ciprofloxacino (CIP) é usado no tratamento de infecções em diferentes sítios anatômicos, como trato respiratório, um local comum de infecção por MNTs. Desta forma, combinar CIP com piperina (PIP), uma substância alcalóide que ganha destaque pelo relato de sinergismo associada a antimicrobianos, pode vir contribuir para melhorar a ação do antimicrobiano. Portanto, este trabalho tem como objetivo avaliar a atividade de CIP isolada e combinada com PIP, em MNTs com potencial patogênico. Foram estudadas as cepas M. smegmatis (mc² 155) e M. abscessus (ATCC 19977), e isolados clínicos M. smegmatis, M. abscessus subsp. abscessus, M. abscessus subsp massiliense, M. abscessus subsp. bolletii, M. fortuitum, M. kansasii e M. avium subsp. avium. A concentração inibitória mínima (MIC) foi determinada por microdiluição de acordo com Clinical and Standards Laboratory Institute. Subsequentemente, foi realizado ensaio de checkerboard para cada cepa/isolado selecionados, usando a combinação de CIP e PIP. Foi considerado relação sinérgica, o fator modulador igual ou superior a quatro, e não sinérgico quando inferior a quatro. As MICs [µg/mL] para CIP e PIP foram respectivamente: M. smegmatis mc² 155 [0,25; 32], M. abscessus ATCC 19977 [4; 32], M. smegmatis [0,25; 32], M. abscessus subsp. abscessus [0,25; 128], M. abscessus subsp massiliense [0,25; 64], M. abscessus subsp. bolletii [4; 64], M. fortuitum [0,25; 64], M. kansasii [0,25; >256] e M. avium subsp. avium [0,125; >256]. A PIP modulou a MIC de CIP com fator modulador de oito para M. smegmatis (mc² 155), quatro para M. abscessus (ATCC 19977), M. smegmatis, M. abscessus subsp massiliense, M. abscessus subsp. bolletii, M. kansasii e M. avium subsp. avium, e dois para M. abscessus subsp. abscessus e M. fortuitum. A diminuição da MIC da associação de PIP com CIP e o fator modulador superior a quatro na maioria das MNTs testadas apresentam grande potencial do uso sinérgico de PIP, de acordo com a experimentação in vitro.

10.1016/j.bjid.2021.102305

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Validation of the Pediatric Resuscitation and Trauma Outcome (PRESTO) model in injury patients in Tanzania

BMJ Open (2023)

Elizabeth M. Keating Modesta Mitao Arthi Kozhumam João Vítor Perez de Souza Cecilia S Anthony

Sub-Saharan Africa has the highest rate of unintentional paediatric injury deaths. The Pediatric Resuscitation and Trauma Outcome (PRESTO) model predicts mortality using patient variables available in low-resource settings: age, systolic blood pressure (SBP), heart rate (HR), oxygen saturation, need for supplemental oxygen (SO) and neurologic status (Alert Verbal Painful Unresponsive (AVPU)). We sought to validate and assess the prognostic performance of PRESTO for paediatric injury patients at a tertiary referral hospital in Northern Tanzania.

10.1136/bmjopen-2022-070747

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Isoniazid and verapamil modulatory activity and efflux pump gene expression in Mycobacterium tuberculosis

The International Journal of Tuberculosis and Lung Disease (2020)

João Vítor Perez de Souza Letícia Sayuri Murase Katiany Rizzieri Caleffi-Ferracioli Carolina Trevisolli Palomo Regiane Bertin de Lima Scodro

INTRODUCTION: Resistance to first-line anti-tuberculosis drugs is a major concern in the treatment of the disease. New strategies, such as the use of efflux pump inhibitors (EPIs), are being investigated to improve the outcome of the treatment. Verapamil (VP), one such inhibitor, was shown to inhibit several efflux pump (EP) Mycobacterium tuberculosis proteins and demonstrate synergic activity with anti-TB drugs. OBJECTIVE: To evaluate the combinatory effect of isoniazid (INH) and VP in M. tuberculosis . METHODS: Minimal inhibitory concentrations and combinatory effects of INH+VP were determined using respectively resazurin microtitre assay plate (REMA) and resazurin drugs combination microtitre assay (REDCA). From the results, we selected three bacilli with different susceptibility profiles and assessed their expression of 10 EP genes through quantitative reverse transcription polymerase chain reaction after exposure to INH, VP and INH + VP for 48 h. RESULTS: A significant reduction of INH MIC was observed in INH-susceptible isolates upon combination with VP. In brief, gene expression assays revealed expression patterns that could be correlated with each resistance profile, presence or absence of gene mutations and combinatory effect with VP. CONCLUSION: Combining VP with INH showed important results in drug-susceptible strains, and clinical trials on combined VP + anti-TB drugs should be discussed.

Efflux

Resazurin

10.5588/ijtld.19.0458

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Using the ADAPT guidance to culturally adapt a brief intervention to reduce alcohol use among injury patients in Tanzania

PLOS Global Public Health (2025)

Catherine A. Staton Armand Zimmerman Msafiri Pesambili Ashley J. Phillips Anna Tupetz

Harmful alcohol use is a leading risk factor for injury-related death and disability in low- and middle-income countries (LMICs). Brief negotiational interventions (BNIs) in emergency departments (EDs) effectively reduce alcohol intake and re-injury rates. However, most BNIs are developed in high-income countries, with limited evidence of their effectiveness in LMICs. To address this gap, we culturally adapted a BNI for alcohol-related injury patients at Kilimanjaro Christian Medical Centre (KCMC), a tertiary hospital in Tanzania. Our study followed the ADAPT guidance to culturally adapt an existing high-income country BNI for use in the KCMC, a tertiary hospital in Tanzania. The adaptation included: 1) a systematic review of effective alcohol harm reduction interventions in similar settings; 2) consultations with local and international healthcare professionals experienced in counseling and substance abuse treatment; 3) group discussions to refine goals and finalize adaptations. The adapted BNI protocol and assessment scales ensured intervention fidelity. At KCMC, 30% of injury patients screened positive for alcohol use disorder (AUD), with a five-fold increased risk of injury, primarily from road traffic accidents and violence. A systematic review highlighted limited data on patient-level interventions in low-resource settings. Our adapted BNI, ‘ Punguza Pombe Kwa Afya Yako (PPKAY)’, based on the FRAMES model, showed high feasibility and acceptability, with 84% of interventions achieving ≥80% adherence and 98% patient satisfaction. PPKAY is the first culturally adapted alcohol BNI for injury patients in an African ED. Our study demonstrates our approach to adapting substance use interventions for use in low resource settings and shows that cultural adaptation of alcohol use interventions is feasible, beneficial and empowering for our team. Our study lays a framework and method for other low resourced settings to integrate cultural adaptation into the implementation of a BNI in low resource EDs.

Alcohol use disorder

10.1371/journal.pgph.0004200

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347 Efficacy of the Weapon Screening Protocol in Mitigating Workplace Violence at Duke Emergency Department

Annals of Emergency Medicine (2024)

Lauren Siewny Laure Denis R. Isley João Vítor Perez de Souza João Ricardo Nickenig Vissoci

10.1016/j.annemergmed.2024.08.347

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The role of metalloproteases inLeishmaniaspecies infection in the New World: a systematic review

Parasitology (2018)

Letícia Sayuri Murase João Vítor Perez de Souza Quirino Alves de Lima Neto Tatiane França Perles de Mello Bruna Muller Cardoso

Abstract This is a systematic review on the role of metalloproteases in the pathogenicity of the American tegumentary leishmaniasis (ATL) caused by New World Leishmania species. The review followed the PRISMA method, searching for articles in PubMed, EMBASE, LILACS and ISI Web of Science, by employing the following terms: ‘leishmaniasis’, ‘cutaneous leishmaniasis’, ‘mucocutaneous leishmaniasis’, ‘diffuse cutaneous leishmaniasis’, ‘Leishmania’ and ‘metalloproteases’. GP63 of New World Leishmania species is a parasite metalloproteases involved in the degradation and cleavage of many biological molecules as kappa-B nuclear factor, fibronectin, tyrosine phosphatases. GP63 is capable of inhibiting the activity of the complement system and reduces the host's immune functions, allowing the survival of the parasite and its dissemination. High serological/tissue levels of host matrix metalloproteases (MMP)-9 have been associated with tissue damage during the infection, while high transcriptional levels of MMP-2 related with a satisfactory response to treatment. Host MMPs serological and tissue levels have been investigated using Western Blot, zymography, and Real Time polymerase chain reaction. GP63 detection characterizes species and virulence in promastigotes isolated from lesions samples using techniques mentioned previously. The monitoring of host MMPs levels and GP63 in Leishmania isolated from host samples could be used on the laboratory routine to predict the prognostic and treatment efficacy of ATL.

Kinetoplastida

Zymography

10.1017/s0031182018000367

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DETECÇÃO FENOTÍPICA DE RESISTÊNCIA INDUZIDA A CLARITROMICINA EM MICOBACTÉRIAS NÃO TUBERCULOSAS DE CRESCIMENTO RÁPIDO IN VITRO

The Brazilian Journal of Infectious Diseases (2022)

João Vítor Perez de Souza Letícia Sayuri Murase Carolina Trevisolli Palomo Renata Alexandre de Oliveira Giulienne Karla Pereira da Silva

As micobactérias não tuberculosas (MNTs) compõem um grupo de patógenos emergentes. Este grupo heterogêneo causa infecções em diversos sítios anatômicos e é especialmente incidente em pacientes imunossuprimidos. Dentre as limitadas opções terapêuticas disponíveis para o tratamento das micobacterioses, a claritromicina (CLA) destaca-se como fármaco de primeira escolha, principalmente contra MNTs de crescimento rápido (RGM). Apesar de sua grande utilidade na terapia, estudos demonstraram que algumas espécies de RGMs podem apresentar resistência induzida à CLA. Esta característica é extremamente relevante para o tratamento das micobacterioses e testes de susceptibilidade que controlem para este evento devem ser aplicados. Nesse sentido, o objetivo deste trabalho foi realizar a detecção de resistência induzida a CLA em três espécies de RGMs in vitro. A concentração inibitória mínima (CIM) de CLA frente a isolado clínico de Mycobacterium massiliense, M. smegmatis e M. fortuitum foi determinada pelo ensaio resazurin broth microdilution assay, em microplacas com 96 cavidades. Brevemente, foram realizadas diluições consecutivas de CLA (intervalo de 62 e 0,0625 µg/mL) em caldo Mueller Hinton Broth cátion ajustado e em seguida, uma suspensão de micobactérias padronizada foi adicionada e as placas foram incubadas por 3 e 14 dias a 35 °C, em atmosfera normal. Após a incubação, foi adicionado 30 µL de resazurina a 0,01% em cada cavidade da microplaca e o crescimento bacteriano foi avaliado visualmente após 24h da revelação. Com 3 dias de incubação, notou-se que os isolados clínicos testados eram sensíveis à CLA com CIMs variando entre 1 e 2 µg/mL. Por outro lado, análises realizadas após 14 dias de incubação revelaram aumentos expressivos na CIM de CLA. M. massiliense foi a espécie que demonstrou maior aumento, modificando sua CIM de 1 para 16 µg/mL, enquanto M. smegmatis e M. fortuitum também demonstraram resistência induzida, com aumento de 1 para 8 ug/mL e 2 para 16 µg/mL após 14 dias de incubação, respectivamente. Os resultados obtidos concordam com evidências da literatura e mostram como a resistência induzida à CLA é comum em espécies de RGM. Para garantir uma terapêutica eficaz, a aplicação dos testes de susceptibilidade que permitam a identificação da resistência induzida à CLA são necessários.

10.1016/j.bjid.2021.102304

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346 A Comparative Analysis of Machine Learning Models in Predicting Emergency Department Patient Volumes in a University Hospital

Annals of Emergency Medicine (2024)

Jason Theiling Lauren Siewny João Vítor Perez de Souza João Ricardo Nickenig Vissoci Charles J. Gerardo

10.1016/j.annemergmed.2024.08.346

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Systematic review of disulfiram as an antibacterial agent: what is the evidence?

International Journal of Antimicrobial Agents (2022)

Jean Eduardo Meneguello Letícia Sayuri Murase João Vítor Perez de Souza Cheila Guimarães de Oliveira Luciana Dias Ghiraldi‐Lopes

Disulfiram

Antimicrobial drug

Drug repositioning

10.1016/j.ijantimicag.2022.106578

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Three Decades of Clinical Trials on Immunotherapy for Human Leishmaniases: a Systematic Review and Meta-Analysis

Immunotherapy (2021)

Camila Alves Mota Jully Oyama Mariana de Souza Terron Monich Aline Ávila Brustolin João Vítor Perez de Souza

Aim: Current treatments for leishmaniases are not satisfactory, thus alternatives are needed. We searched for clinical trials with immunotherapeutic approaches for patients with leishmaniasis. Materials & methods: Out of 205 articles, 24 clinical trials were selected, and eight submitted to meta-analysis. Results: A reduction in healing time was observed in patients with tegumentary leishmaniasis treated with pentavalent antimony plus granulocyte-macrophage colony-stimulating factor, and therapeutic vaccines. Overall meta-analysis indicated that immunotherapy associated with the standard chemotherapy generated a significantly reduced risk of treatment failure than the pentavalent antimony alone (p = 0.03). Conclusion: Our review confirmed the efficacy of immunotherapies for the treatment of cutaneous and visceral leishmaniasis and highlighted the importance of clinical trials using immunotherapies for leishmaniases.

10.2217/imt-2020-0184

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