Artigos e Materiais de Revistas Científicas - FM/MIP

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A coleção de Artigos e Materiais de Revistas Científicas engloba artigos originais, artigos de revisão, artigos de atualização, artigos técnicos, relatos de experiências, resenhas, ensaios, editoriais, cartas ao editor, debates, notas científicas e técnicas, depoimentos, entrevistas e pontos de vista. Consideram-se como artigos científicos originais os trabalhos redigidos para divulgação de informações e resultados sobre determinada pesquisa científica, publicados em periódico científico após avaliação por outros pesquisadores.

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Itraconazole Serum Trough Concentrations Using Oral Capsules for the Treatment of Chronic Pulmonary Aspergillosis: What is the Target?
(2023) OLIVEIRA, Vitor Falcao de; TABORDA, Mariane; ARCIERI, Vitor Ciampone; KRUSCHEWSKY, Wdson Luis Lima; COSTA, Andre Nathan; DUARTE, Nilo Jose Coelho; ROMANO, Paschoalina; EBNER, Persio de Almeida Rezende; MAGRI, Adriana Satie Goncalves Kono; ABDALA, Edson; LEVIN, Anna S. S.; MAGRI, Marcello Mihailenko Chaves
BackgroundIn regions where there is only itraconazole capsule as a therapeutic option for treatment of chronic pulmonary aspergillosis (CPA), measuring the serum concentrations becomes even more important for therapeutic success.ObjectiveEvaluate the initial itraconazole serum trough concentrations after the administration of oral capsule of itraconazole for the treatment of CPA.MethodsThe measurement was performed at least 7-days after initiation of therapy. The standard treatment at our institution was a 200 mg capsule every 12 h. We defined that an adequate serum trough concentration of itraconazole during treatment was 1-4 mg/L.ResultsThis study recruited 28 patients. The median value was 0.30 mg/L (IQR 0.01-0.70). Only 11% (n = 3) had adequate serum concentrations based on guideline recommendation. All patients with clinical deterioration had itraconazole serum levels <= 0.8 mg/L.ConclusionThe initial serum concentrations of itraconazole after capsule formulation administration were low. Increasing the dose should be considered when the itraconazole concentration is low, especially if it is <= 0.8 mg/L, and the patient presents with clinical deterioration. Larger studies are needed to evaluate the adequate concentrations recommended for CPA.
Evaluation of enterovirus concentration, species identification, and cerebrospinal fluid parameters in patients of different ages with aseptic meningitis in Sao Paulo, Brazil
(2024) HONORATO, Layla; FERREIRA, Noely Evangelista; DOMINGUES, Renan Barros; SENNE, Carlos; LEITE, Fernando Brunale Vilela de Moura; SANTOS, Marcio Vega dos; FERNANDES, Gustavo Bruniera Peres; PAIAO, Heuder Gustavo Oliveira; BOAS, Lucy Santos Vilas; COSTA, Antonio Charlys da; TOZETTO-MENDOZA, Tania Regina; WITKIN, Steven S.; MENDES-CORREA, Maria Cassia
Human enteroviruses (EV) are the most common cause of aseptic meningitis worldwide. Data on EV viral load in cerebrospinal fluid (CSF) and related epidemiological studies are scarce in Brazil. This study investigated the influence of EV viral load on CSF parameters, as well as identifying the involved species. CSF samples were collected in 2018-2019 from 140 individuals at The Hospital das Clinicas, Sao Paulo. The EV viral load was determined using real-time quantitative polymerase chain reaction, while EV species were identified by 5 ' UTR region sequencing. Median viral load was 5.72 log10 copies/mL and did not differ by subjects' age and EV species. Pleocytosis was observed in 94.3% of cases, with the highest white blood cell (WBC) counts in younger individuals. Viral load and WBC count were correlated in children (p = 0.0172). Elevated lactate levels were observed in 60% of cases and correlated with the viral load in preteen-teenagers (p = 0.0120) and adults (p = 0.0184). Most individuals had normal total protein levels (70.7%), with higher in preteen-teenagers and adults (p < 0.0001). By sequencing, 8.2% were identified as EV species A and 91.8% as species B. Age-specific variations in CSF characteristics suggest distinct inflammatory responses in each group.
Clinical and epidemiological features of mpox in a Brazilian reference center for HIV and sexually transmitted infections: A cross-sectional study
(2024) COSTA, Alvaro Furtado; ROCHA, Simone Queiroz; FONSI, Mylva; NOGUEIRA, Roberta Schiavon; KALICHMAN, Artur Olhovetchi; MADRUGA, Jose Valdez Ramalho; GIANNA, Maria Clara; SOUZA, Rosa de Alencar; RODRIGUES, Rosangela; TAYRA, Angela; RAMOS, Lucas Rocker; SILVA, Roberto Jose Carvalho da; SARTORI, Ana Marli Christovam; PRADO, Walkiria Delnero Almeida; ABBUD, Adriano; TANCREDI, Mariza Vono
Background: The 2022 mpox outbreak has affected disproportionately people living with HIV (PLWH) and pre-exposure prophylaxis (PrEP) users. Methods: We conducted a cross-sectional study to evaluate factors associated with laboratory diagnosis of mpox among suspected cases, and access differences between PrEP users and PLWH with confirmed diagnostic. Results: 394 mpox suspected cases were analyzed, 309 (78.4%) confirmed. Most patients with mpox were PLWH (54.4%) and 99 (32%) PrEP users. Mpox cases were likely to be between 25 and 39 years old (aOR = 2.8; p = 0.042), men who have sex with men/bisexual or transgender women (aOR = 17.2; p < 0.001) and to have fever (aOR = 4.7; p < 0.001), adenomegaly (aOR = 7.2; p < 0.001) and multiple vesicular lesions (aOR = 4.2; p < 0.001). Comparing PrEP users to PLWH with confirmed mpox, PrEP users had lesions predominantly with exclusive genital involvement (p = 0.016); while PLWH had higher extragenital involvement (p = 0.018). Conclusions: PrEP users and PLWHA were the main epidemiological groups in our cohort. Recognizing the differences between vulnerable populations can contribute to the development public policies to control mpox in settings with reduced access to vaccines
Serosurvey of Toxoplasma gondii and Toxocara spp. co-infection in pregnant women in low-income areas of Brazil
(2024) PEREIRA, Edlayne Larissa Gretter Machado; FERREIRA, Isabella Braghin; VICTORINO, Roberta Brinholi; LESCANO, Susana Angelica Zevallos; GIUFFRIDA, Rogerio; KMETIUK, Louise Bach; BIONDO, Alexander Welker; SANTAREM, Vamilton Alvares
Introduction: Despite human toxoplasmosis and toxocariasis having been listed among the top six most neglected parasitic zoonoses worldwide, presenting similar associated risk factors and transmission routes, few studies have been conducted in pregnant women and the consequences of concurrent infection remain to be fully established. Accordingly, the present study has serologically assessed the co-infection and associated risk factors for Toxoplasma gondii and Toxocara spp. in pregnant women, assisted by the public Unified National Health System (SUS) in southeastern Brazil. Materials and Methods: Blood samples were collected and tested for IgG antibodies against Toxoplasma gondii by chemiluminescence immunoassay and against Toxocara spp. by enzyme-linked immunosorbent assay (ELISA). An epidemiological questionnaire was applied to gather socioeconomic information to assess the risk factors associated with seropositivity to toxocariasis/toxoplasmosis by univariate analysis followed by logistic regression. Results: Overall, seropositivity was 69/280 (24.6, 95% CI: 19.96-30.01) for T. gondii and 56/280 (20.0, 95% CI: 15.73-25.08) for Toxocara spp. Co-infection was observed in 25/280 (8.9, 95% CI: 6.12-12.85) pregnant women, with increased odds (OR: 3.3, CI 95%: 1.77-6.14, p = 0.0002). Logistic regression revealed that a higher educational level (high school or college) significantly reduced the likelihood of co-infection seropositivity, owning cats increased the odds of toxocariasis, and older pregnant women presented significantly higher T. gondii seropositivity. Conclusion: Co-infection herein highlights the importance of educational programs in the prevention of toxocariasis and toxoplasmosis in pregnant women and other high-risk populations.
The decline of measles antibody titers in previously vaccinated adults: a cross-sectional analysis
(2024) CASTINEIRAS, Anna Carla Pinto; SALES, Amanda Caroline; PICONE, Camila de Melo; DIOGO, Constancia Lima; ROSSI, atila Duque; GALLIEZ, Rafael Mello; JR, Orlando da Costa Ferreira; CASTINEIRAS, Terezinha Marta Pereira Pinto; LOPES, Marta Heloisa; SARTORI, Ana Marli Christovam
The global reemergence of measles in 2018-2019 reinforces the relevance of high coverage immunization to maintain the disease elimination. During an outbreak in the Sao Paulo State in 2019, several measles cases were reported in individuals who were adequately vaccinated according to the current immunization schedule recommends. This study aimed to assess measles IgG antibody seropositivity and titers in previously vaccinated adults. A cross-sectional study was conducted at CRIE-HC-FMUSP (Sao Paulo, Brazil) in 2019. It included healthy adults who had received two or more Measles-Mumps-Rubella vaccines (MMR) and excluded individuals with immunocompromising conditions. Measles IgG antibodies were measured and compared by ELISA (Euroimmun (R)) and chemiluminescence (LIASON (R)). The association of seropositivity and titers with variables of interest (age, sex, profession, previous measles, number of measles-containing vaccine doses, interval between MMR doses, and time elapsed since the last MMR dose) was analyzed. A total of 162 participants were evaluated, predominantly young (median age 30 years), women (69.8%) and healthcare professionals (61.7%). The median interval between MMR doses was 13.2 years, and the median time since the last dose was 10.4 years. The seropositivity rate was 32.7% by ELISA and 75.3% by CLIA, and a strong positive correlation was found between the tests. Multivariate analyses revealed that age and time since the last dose were independently associated with positivity. Despite being a single-center evaluation, our results suggest that measles seropositivity may be lower than expected in adequately immunized adults. Seropositivity was higher among older individuals and those with a shorter time since the last MMR vaccine dose.
Hydroxymethylnitrofurazone lymphatic uptake with nanostructured lipid carrier after oral administration in rats
(2024) SOUZA, Aline de; SCARIM, Caue Benito; COTRIM, Paulo Cesar; BARBOSA JUNIOR, Fernando; ROCHA, Bruno Alves; CALIXTO, Leandro Augusto; CORREIA, Cristiano Jesus; ARAUJO, Gabriel Lima de Barros; LOBENBERG, Raimar; BOU-CHACRA, Nadia Araci; BREITHAUPT-FALOPPA, Ana Cristina
Background: Leishmaniasis, caused by the protozoan Leishmania sp., infects phagocyte cells present in lymphatic organs. This study demonstrates the influence of nanostructured lipid carrier-loaded hydroxymethylnitrofurazone (NLC-NFOH) on lymphatic uptake using a chylomicron-blocking flow model in rats. Method: Lymphatic uptake of NFOH was assessed 1 h after oral administration of dimethyl sulfoxide with NFOH or NLC-NFOH with and without cycloheximide pretreatment. Result: Dimethyl sulfoxide with NFOH and NLC-NFOH showed NFOH serum concentrations of 0.0316 and 0.0291 mu g/ml, respectively. After chylomicron blocking, NFOH was not detected. Conclusion: Despite log P below 5, NFOH was successfully taken up by the lymphatic system. Long-chain fatty acids and particle size might be main factors in these findings. NLC-NFOH is a promising and convenient platform for treating leishmaniasis via oral administration.
Epidemiology, treatment patterns, and disease burden of cytomegalovirus in hematopoietic cell transplant recipients in selected countries outside of Europe and North America: A systematic review
(2023) CHO, Sung-Yeon; AR, Muhlis Cem; MACHADO, Clarisse M.; WU, Depei; SINGH, Inderjeet; SANDHU, Anudeep; DEMUTH, Dirk; SLAVIN, Monica
Background: Cytomegalovirus (CMV) disease impacts morbidity and mortality in hematopoietic cell transplant (HCT) recipients. This systematic review summarized data on the epidemiology, management, and burden of CMV post-HCT outside of Europe and North America.Methods: The MEDLINE, Embase, and Cochrane databases were searched for observational studies and treatment guidelines in HCT recipients across 15 selected countries from Asia-Pacific, Latin America, and Middle East (search period: 1 January 2011-17 September 2021). Outcomes included incidence of CMV infection/disease, recurrence, risk factors, CMV-related mortality, treatments, refractory, resistant CMV, and burden.Results: Of 2708 references identified, 68 were eligible (67 studies and one guideline; 45/67 studies specific to adult allogeneic HCT recipients). The rates of CMV infection and disease within 1 year of allogeneic HCT were 24.9%-61.2% (23 studies) and 2.9%-15.7% (10 studies), respectively. Recurrence occurred in 19.8%-37.9% of cases (11 studies). Up to 10% of HCT recipients died of CMV-related causes. In all countries, first-line treatment for CMV infection/disease involved intravenous ganciclovir or valganciclovir. Conventional treatments were associated with serious adverse events such as myelosuppression (10.0%) or neutropenia only (30.0%, 39.8%) and nephrotoxicity (11.0%) (three studies), frequently leading to treatment discontinuation (up to 13.6%). Refractory CMV was reported in 2.9%, 13.0%, and 28.9% of treated patients (three studies) with resistant CMV diagnosed in 0%-10% of recipients (five studies). Patient-reported outcomes and economic data were scarce.Conclusion: The incidence of CMV infection and disease post-HCT is high outside of North America and Europe. CMV resistance and toxicity highlight a major unmet need with current conventional treatments.
Quantitative PCR as a marker for preemptive therapy and its role in therapeutic control in Trypanosoma cruzi/HIV coinfection
(2024) FREITAS, Vera Lucia Teixeira de; NOVAES, Christina Terra Gallafrio; SARTORI, Ana Marli Christovam; CARVALHO, Noemia Barbosa; SILVA, Sheila Cristina Vicente da; NAKANISHI, erika Shimoda; SALVADOR, Fernando; CASTRO, Cleudson Nery de; BEZERRA, Rita Cristina; WESTPHALEN, Elizabeth Visone Nunes; OLIVEIRA, Caroline Medeji Ramos de; BUSSER, Felipe Delatorre; HO, Yeh-Li; BUCCHERI, Renata; BONILLA, Carolina; SHIKANAI-YASUDA, Maria Aparecida
Background Trypanosoma cruzi and HIV coinfection can evolve with depression of cellular immunity and increased parasitemia. We applied quantitative PCR (qPCR) as a marker for preemptive antiparasitic treatment to avoid fatal Chagas disease reactivation and analyzed the outcome of treated cases. Methodology This mixed cross-sectional and longitudinal study included 171 Chagas disease patients, 60 coinfected with HIV. Of these 60 patients, ten showed Chagas disease reactivation, confirmed by parasites identified in the blood, cerebrospinal fluid, or tissues, 12 exhibited high parasitemia without reactivation, and 38 had low parasitemia and no reactivation. Results We showed, for the first time, the success of the timely introduction of benznidazole in the non-reactivated group with high levels of parasitemia detected by qPCR and the absence of parasites in reactivated cases with at least 58 days of benznidazole. All HIV+ patients with or without reactivation had a 4.0-5.1 higher chance of having parasitemia than HIV seronegative cases. A positive correlation was found between parasites and viral loads. Remarkably, treated T. cruzi/HIV-coinfected patients had 77.3% conversion from positive to negative parasitemia compared to 19.1% of untreated patients. Additionally, untreated patients showed similar to 13.6 times higher Odds Ratio of having positive parasitemia in the follow-up period compared with treated patients. Treated and untreated patients showed no differences regarding the evolution of Chagas disease. The main factors associated with all-cause mortality were higher parasitemia, lower CD4 counts/mu L, higher viral load, and absence of antiretroviral therapy. Conclusion We recommend qPCR prospective monitoring of T. cruzi parasitemia in HIV+ coinfected patients and point out the value of pre-emptive therapy for those with high parasitemia. In parallel, early antiretroviral therapy introduction is advisable, aiming at viral load control, immune response restoration, and increasing survival. We also suggest an early antiparasitic treatment for all coinfected patients, followed by effectiveness analysis alongside antiretroviral therapy.
Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study
(2023) RAZAVI-SHEARER, Devin M.; GAMKRELIDZE, Ivane; PAN, Calvin Q.; JIA, Jidong; BERG, Thomas; GRAY, Richard T.; LIM, Young-Suk; CHEN, Chien-Jen; OCAMA, Ponsiano; DESALEGN, Hailemichael; ABBAS, Zaigham; ABDALLAH, Ayat R.; AGHEMO, Alessio; AHMADBEKOVA, Sabohat; AHN, Sang Hoon; AHO, Inka; AKARCA, Ulus S.; MASRI, Nasser M. Al; ALALWAN, Abduljaleel M.; ALAVIAN, Seyed M.; AL-BUSAFI, Said A.; ALEMAN, Soo; ALFALEH, Faleh Z.; ALGHAMDI, Abdullah S.; AL-HAMOUDI, Waleed K.; ALJUMAH, Abdulrahman A.; AL-NAAMANI, Khalid; AL-RIFAI, Ahmad; ALSERKAL, Yousif M.; ALTRAIF, Ibrahim H.; AMARSANAA, Jazag; ANDERSON, Motswedi; I, Monique Andersson; ARMSTRONG, Paige; ASSELAH, Tarik; ATHANASAKIS, Kostas; BAATARKHUU, Oidov; BEN-ARI, Ziv; BENSALEM, Aicha; BESSONE, Fernando; BIONDI, Mia J.; BIZRI, Abdul Rahman N.; BLACH, Sarah; BRAGA, Wornei S. M.; BRANDAO-MELLO, Carlos E.; BROSGART, Carol L.; BROWN, Kimberly A.; JR, Robert S. Brown; BRUGGMANN, Philip; BRUNETTO, Maurizia R.; BUTI, Maria; CABEZAS, Joaquin; CASANOVAS, Teresa; CHAE, Chungman; CHAN, Henry Lik Yuen; CHEINQUER, Hugo; CHEN, Pei-Jer; CHENG, Kent Jason G.; CHEON, Myeong-Eun; CHIEN, Cheng-Hung; CHOUDHURI, Gourdas; CHRISTENSEN, Peer Brehm; CHUANG, Wan-Long; CHULANOV, Vladimir; GARZA, Laura E. Cisneros; COFFIN, Carla S.; CONTRERAS, Fernando A.; COPPOLA, Nicola; CORNBERG, Markus; COWIE, Benjamin; CRAMP, Matthew E.; CRAXI, Antonio; CRESPO, Javier; CUI, Fuqiang; CUNNINGHAM, Chris W.; DALGARD, Olav; KNEGT, Robert J. De; LEDINGHEN, Victor De; DORE, Gregory J.; DRAZILOVA, Sylvia; DUBERG, Ann-Sofi; EGEONU, Steve; ELBADRI, Mohammed; EL-KASSAS, Mohamed; EL-SAYED, Manal H.; ESTES, Chris; ETZION, Ohad; FARAG, Elmobashar; FERRADINI, Laurent; FERREIRA, Paulo R. A.; FLISIAK, Robert; FORNS, Xavier; FRANKOVA, Sona; FUNG, James; GANE, Edward J.; GARCIA, Virginia; GARCIA-SAMANIEGO, Javier; GEMILYAN, Manik; GENOV, Jordan; GHEORGHE, Liliana S.; GHOLAM, Pierre M.; GISH, Robert G.; GOLEIJ, Pouya; GOTTFREDSSON, Magnus; GREBELY, Jason; GSCHWANTLER, Michael; GUINGANE, Nanelin Alice; HAJARIZADEH, Behzad; HAMID, Saeed S.; HAMOUDI, Waseem; HARRIS, Aaron M.; HASAN, Irsan; HATZAKIS, Angelos; HELLARD, Margaret E.; HERCUN, Julian; HERNANDEZ, Javier; HOCKICKOVA, Ivana; HSU, Yao-Chun; HU, Ching-Chih; HUSA, Petr; JANICKO, Martin; JANJUA, Naveed; JARCUSKA, Peter; JAROSZEWICZ, Jerzy; JELEV, Deian; JERUMA, Agita; JOHANNESSEN, Asgeir; KABERG, Martin; KAITA, Kelly D. E.; KALIASKAROVA, Kulpash S.; KAO, Jia-Horng; KELLY-HANKU, Angela; KHAMIS, Faryal; KHAN, Aamir G.; KHEIR, Omer O.; KHOUDRI, Ibtissam; KONDILI, Loreta A.; KONYSBEKOVA, Aliya; KRISTIAN, Pavol; KWON, Jisoo A.; LAGGING, Martin; LALEMAN, Wim; LAMPERTICO, Pietro; LAVANCHY, Daniel; LAZARO, Pablo; V, Jeffrey Lazarus; LEE, Alice U.; LEE, Mei-Hsuan; LIAKINA, Valentina; LUKSIC, Boris; MALEKZADEH, Reza; MALU, Abraham O.; MARINHO, Rui T.; MENDES-CORREA, Maria Cassia; MERAT, Shahin; MESHESHA, Berhane Redae; MIDGARD, Havard; MOHAMED, Rosmawati; MOKHBAT, Jacques E.; MOONEYHAN, Ellen; MORENO, Christophe; MORTGAT, Laure; MULLHAUPT, Beat; MUSABAEV, Erkin; MUYLDERMANS, Gaetan; NAVEIRA, Marcelo C. M.; NEGRO, Francesco; V, Alexander Nersesov; Van Thi Thuy Nguyen; NING, Qing; NJOUOM, Richard; NTAGIRABIRI, Renovat; NURMATOV, Zuridin S.; OGUCHE, Stephen; OMUEMU, Casimir E.; ONG, Janus P.; OPARE-SEM, Ohene K.; ORMECI, Necati; ORREGO, Mauricio; OSIOWY, Carla; V, George Papatheodoridis; PECK-RADOSAVLJEVIC, Markus; PESSOA, Mario G.; PHAM, Trang N. D.; PHILLIPS, Richard O.; PIMENOV, Nikolay; PINCAY-RODRIGUEZ, Loreley D. R.; PLASESKA-KARANFILSKA, Dijana; POP, Cora; POUSTCHI, Hossein; PRABDIAL-SING, Nishi N.; QURESHI, Huma; RAMJI, Alnoor; RAUTIAINEN, Henna; RAZAVI-SHEARER, Kathryn; REMAK, William M.; RIBEIRO, Sofia; RIDRUEJO, Ezequiel; RIOS-HINCAPIE, Cielo Y.; ROBALINO, Marcia C.; ROBERTS, Lewis R.; ROBERTS, Stuart K.; RODRIGUEZ, Manuel; ROULOT, Dominique; RWEGASHA, John; RYDER, Stephen D.; SADIROVA, Shakhlo; SAEED, Umar; SAFADI, Rifaat; SAGALOVA, Olga; SAID, Sanaa S.; SALUPERE, Riina; SANAI, Faisal M.; SANCHEZ-AVILA, Juan F.; SARASWAT, Vivek A.; SARGSYANTS, Narina; SARRAZIN, Christoph; SARYBAYEVA, Gulya; SCHRETER, Ivan; SEGUIN-DEVAUX, Carole; SETO, Wai-Kay; SHAH, Samir R.; I, Ala Sharara; SHEIKH, Mahdi; SHOUVAL, Daniel; SIEVERT, William; SIMOJOKI, Kaarlo; SIMONOVA, Marieta Y.; SINN, Dong Hyun; SONDERUP, Mark W.; SONNEVELD, Milan J.; SPEARMAN, C. Wendy; SPERL, Jan; STAUBER, Rudolf E.; STEDMAN, Catherine A. M.; SYPSA, Vana; TACKE, Frank; TAN, Soek-Siam; TANAKA, Junko; TERGAST, Tammo L.; TERRAULT, Norah A.; THOMPSON, Alexander J.; THOMPSON, Peyton J.; TOLMANE, Ieva; TOMASIEWICZ, Krzysztof; TSANG, Tak-Yin; UZOCHUKWU, Benjamin S. C.; WELZEN, Berend Van; VANWOLLEGHEM, Thomas; VINCE, Adriana; VOELLER, Alexis S.; WAHEED, Yasir; WAKED, Imam; WALLACE, Jack; WANG, Cong; WEIS, Nina; WONG, Grace L-H; WONG, Vincent W-S; WU, Jaw-Ching; YAGHI, Cesar G.; YESMEMBETOV, Kakharman; YIP, Terry C-F; YOSRY, Ayman; YU, Ming-Lung; YUEN, Man-Fung; YURDAYDIN, Cihan; ZEUZEM, Stefan; ZUCKERMAN, Eli; RAZAVI, Homie A.
Background The 2016 World Health Assembly endorsed the elimination of hepatitis B virus (HBV) infection as a public health threat by 2030; existing therapies and prophylaxis measures make such elimination feasible, even in the absence of a virological cure. We aimed to estimate the national, regional, and global prevalence of HBV in the general population and among children aged 5 years and younger, as well as the rates of diagnosis, treatment, prophylaxis, and the future burden globally. Methods In this modelling study, we used a Delphi process with data from literature reviews and interviews with country experts to quantify the prevalence, diagnosis, treatment, and prevention measures for HBV infection. The PRoGReSs Model, a dyn amic Markov model, was used to estimate the country, regional, and global prevalence of HBV infection in 2022, and the effects of treatment and prevention on disease burden. The future incidence of morbidity and mortality in the absence of additional interventions was also estimated at the global level. Findings We developed models for 170 countries which resulted in an estimated global prevalence of HBV infection in 2022 of 3.2% (95% uncertainty interval 2.7-4.0), corresponding to 257.5 million (216.6-316.4) individuals positive for HBsAg. Of these individuals, 36.0 million were diagnosed, and only 6.8 million of the estimated 83.3 million eligible for treatment were on treatment. The prevalence among children aged 5 years or younger was estimated to be 0.7% (0.6-1.0), corresponding to 5.6 million (4.5-7.8) children with HBV infection. Based on the most recent data, 85% of infants received three-dose HBV vaccination before 1 year of age, 46% had received a timely birth dose of vaccine, and 14% received hepatitis B immunoglobulin along with the full vaccination regimen. 3% of mothers with a high HBV viral load received antiviral treatment to reduce mother-to-child transmission. Interpretation As 2030 approaches, the elimination targets remain out of reach for many countries under the current frameworks. Although prevention measures have had the most success, there is a need to increase these efforts and to increase diagnosis and treatment to work towards the elimination goals.
Clinical characteristics, diagnosis, and treatment of central nervous system sporotrichosis: Systematic review and meta-analysis
(2024) OLIVEIRA, Vitor Falcao de; PETRUCCI, Julia Figueiredo; TABORDA, Mariane; BRENER, Pedro Zanetta; KREMER, Pedro Guilherme De Barros Brito; RANDI, Bruno Azevedo; MAGRI, Adriana Satie Goncalves Kono; MAGRI, Marcello Mihailenko Chaves; LEVIN, Anna S.; SILVA, Guilherme Diogo
BackgroundThe clinical features of central nervous system (CNS) sporotrichosis are derived from case reports and a limited series of cases. Our objective was to carry out a systematic review and meta-analysis of CNS sporotrichosis.MethodsWe searched PubMed/MEDLINE, Embase, Scopus, and LILACS on 9 September 2023. Our inclusion criteria were documentation of Sporothrix and demonstrated CNS involvement. A metaproportion or metamean analysis was performed to estimate a summary proportion with 95% confidence intervals.ResultsWe included 52 cases of CNS sporotrichosis published from 1966 to 2023. Forty-six patients were male (88%, 95% CI: 77-95), and the mean age was 39 years (95% CI: 36-43). Close contact with cats was reported in 55% of cases (95% CI: 37-72). Thirty-two (61.5%) patients were from Brazil, 18 patients from the United State of America (34.6%). Only two Sporothrix species were reported: S. schenckii (26/41, 63%), and S. brasiliensis (15/41, 37%). The most common neurological symptom was headache. Meningitis was chronic in approximately 80% of cases. A significant majority of the patients were immunocompromised. HIV infection was the primary cause of immunosuppression (85%, 95% CI: 61-95). Overall mortality was 56% (22/39). The comparison of Kaplan-Meier survival curve showed a higher mortality with a statistically significant difference in immunosuppressed patients (p = .019).ConclusionCNS sporotrichosis represents a notable cause of chronic meningitis, especially in individuals living in the Americas with HIV infection and concurrent skin lesions.
Compliance with yellow fever and measles vaccines in the revaccination program post-hematopoietic cell transplantation
(2023) TESTA, Lucia H. de Almeida H.; SIMIONE, Anderson J.; SANTOS, Ana Claudia F. dos; COLTURATO, Iago; BARBIERI, Fernanda; SOUZA, Mair Pedro de; COLTURATO, Vergilio R.; MACHADO, Clarisse M.
Introduction: Measles, mumps, rubella, and even poliomyelitis outbreaks have recently perplexed infectious disease clinicians and epidemiologists globally due to the decline in vaccination coverage rates in children and adults. Measles and yellow fever (YF) have represented an increasing burden on the Brazilian public health system in recent decades. Both diseases are preventable by live-attenuated viral vaccines (LAVV), which have restricted use in hematopoietic cell transplant (HCT) recipients.Methods: Autologous and allogeneic HCT recipients returning for regular appointments at the outpatient clinic were invited to participate in the study. Patients transplanted for at least 2 years and with a printed copy of the vaccination record were included.Results: We assessed the vaccination records of 273 HCT recipients after the second year of HCT (193 allogeneic and 80 autologous) and observed lower compliance with the YF vaccine (58 patients, 21.2%) than with the measles vaccine (138 patients, 50.5%, p = .0001). This is the largest published series of YF vaccination in HCT recipients so far. No severe adverse events occurred. Although expected, chronic graft-versus-host disease (GVHD) did not affect the compliance with measles (p = .08) or YF vaccination (p = .7). Indeed, more allogeneic recipients received measles vaccine in comparison with autologous patients (p < .0001), suggesting that chronic GVHD was not the main reason for not being vaccinated. Children and allogeneic HCT were more likely to receive measles vaccine. Time elapsed from HCT >5 years favored both measles and YF vaccination.Conclusion: A better understanding of the reasons for low compliance with LAVV is necessary to overcome this problem.
Data-driven, cross-disciplinary collaboration: lessons learned at the largest academic health center in Latin America during the COVID-19 pandemic
(2024) RITTO, Ana Paula; ARAUJO, Adriana Ladeira de; CARVALHO, Carlos Roberto Ribeiro de; SOUZA, Heraldo Possolo De; FAVARETTO, Patricia Manga e Silva; SABOYA, Vivian Renata Boldrim; GARCIA, Michelle Louvaes; KULIKOWSKI, Leslie Domenici; KALLAS, Esper Georges; PEREIRA, Antonio Jose Rodrigues; COBELLO JUNIOR, Vilson; SILVA, Katia Regina; ABDALLA, Eidi Raquel Franco; SEGURADO, Aluisio Augusto Cotrim; SABINO, Ester Cerdeira; RIBEIRO JUNIOR, Ulysses; FRANCISCO, Rossana Pulcineli Vieira; MIETHKE-MORAIS, Anna; LEVIN, Anna Sara Shafferman; SAWAMURA, Marcio Valente Yamada; FERREIRA, Juliana Carvalho; SILVA, Clovis Artur; MAUAD, Thais; GOUVEIA, Nelson da Cruz; LETAIF, Leila Suemi Harima; BEGO, Marco Antonio; BATTISTELLA, Linamara Rizzo; DUARTE, Alberto Jose da Silva; SEELAENDER, Marilia Cerqueira Leite; MARCHINI, Julio; FORLENZA, Orestes Vicente; ROCHA, Vanderson Geraldo; MENDES-CORREA, Maria Cassia; COSTA, Silvia Figueiredo; CERRI, Giovanni Guido; BONFA, Eloisa Silva Dutra de Oliveira; CHAMMAS, Roger; BARROS FILHO, Tarcisio Eloy Pessoa de; BUSATTO FILHO, Geraldo
Introduction The COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency.Methods At the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank. Additionally, a COVID-19 curated collection was created within the institutional digital library of academic papers to map the research output.Results Over the course of the experience, the possible benefits and challenges of this type of research support approach were identified and discussed, leading to a set of recommended strategies to enhance collaboration within the research institution. Demographic and clinical data from COVID-19 hospitalizations were compiled in a database including adults and a minority of children and adolescents with laboratory confirmed COVID-19, covering 2020-2022, with approximately 350 fields per patient. To date, this database has been used in 16 published studies. Additionally, we assessed 700 adults 6 to 11 months after hospitalization through comprehensive, multidisciplinary in-person evaluations; this database, comprising around 2000 fields per subject, was used in 15 publications. Furthermore, thousands of blood samples collected during the acute phase and follow-up assessments remain stored for future investigations. To date, more than 3,700 aliquots have been used in ongoing research investigating various aspects of COVID-19. Lastly, the mapping of the overall research output revealed that between 2020 and 2022 our academic system produced 1,394 scientific articles on COVID-19.Discussion Research is a crucial component of an effective epidemic response, and the preparation process should include a well-defined plan for organizing and sharing resources. The initiatives described in the present paper were successful in our aim to foster large-scale research in our institution. Although a single model may not be appropriate for all contexts, cross-disciplinary collaboration and open data sharing should make health research systems more efficient to generate the best evidence.
Rapid viral metagenomics using SMART-9N amplification and nanopore sequencing
(2023) CLARO, I. M.; RAMUNDO, M. S.; COLETTI, T. M.; SILVA, C. A. M. da; VALENCA, I. N.; CANDIDO, D. S.; SALES, F. C. S.; MANULI, E. R.; JESUS, J. G. de; PAULA, A. de; FELIX, A. C.; ANDRADE, P. D. S.; PINHO, M. C.; SOUZA, W. M.; AMORIM, M. R.; PROENCA-MODENA, J. L.; KALLAS, E. G.; LEVI, J. E.; FARIA, N. R.; SABINO, E. C.; LOMAN, N. J.; QUICK, J.
Emerging and re-emerging viruses are a global health concern. Genome sequencing as an approach for monitoring circulating viruses is currently hampered by complex and expensive methods. Untargeted, metagenomic nanopore sequencing can provide genomic information to identify pathogens, prepare for or even prevent outbreaks. SMART (Switching Mechanism at the 5′ end of RNA Template) is a popular approach for RNA-Seq but most current methods rely on oligo-dT priming to target polyadenylated mRNA molecules. We have developed two random primed SMART-Seq approaches, a sequencing agnostic approach ‘SMART-9N’ and a version compatible rapid adapters available from Oxford Nanopore Technologies ‘Rapid SMART-9N’. The methods were developed using viral isolates, clinical samples, and compared to a gold-standard amplicon-based method. From a Zika virus isolate the SMART-9N approach recovered 10kb of the 10.8kb RNA genome in a single nanopore read. We also obtained full genome coverage at a high depth coverage using the Rapid SMART-9N, which takes only 10 minutes and costs up to 45% less than other methods. We found the limits of detection of these methods to be 6 focus forming units (FFU)/mL with 99.02% and 87.58% genome coverage for SMART-9N and Rapid SMART-9N respectively. Yellow fever virus plasma samples and SARS-CoV-2 nasopharyngeal samples previously confirmed by RT-qPCR with a broad range of Ct-values were selected for validation. Both methods produced greater genome coverage when compared to the multiplex PCR approach and we obtained the longest single read of this study (18.5 kb) with a SARS-CoV-2 clinical sample, 60% of the virus genome using the Rapid SMART-9N method. This work demonstrates that SMART-9N and Rapid SMART-9N are sensitive, low input, and long-read compatible alternatives for RNA virus detection and genome sequencing and Rapid SMART-9N improves the cost, time, and complexity of laboratory work.
Clinical Aspects and Etiologic Investigation of Pediatric Patients With Acute Liver Failure
(2023) LUGLIO, Michele; MARQUES, Tatiana de Carvalho Silva; PEREIRA, Maria Fernanda Badue; DELGADO, Artur Figueiredo; CARVALHO, Werther Brunow de; TANNURI, Ana Cristina Aoun; SANDY, Natascha Silva; LITVINOV, Nadia; PAULA, Camila Sanson Yoshino de; SANTOS, Ariane Guissi dos; LAZARI, Carolina dos Santos; GOUVEA, Michele Soares Gomes; PAULA, Anderson Vicente de; MENDOZA, Tania Regina Tozetto; TANIGAWAH, Ryan Yukimatsu; LIMAH, Fabiana Roberto; HIRAYAMAH, Andre Bubna; SANTOS, Isabela Gusson Galdino dos; PINHOG, Joao Renato Rebello; SABINOG, Ester Cerdeira; MENDES-CORREAHG, Maria Cassia; ALVESH, Venancio Avancini Ferreira; MARQUESC, Heloisa Helena de Sousa
A new outbreak of hepatitis of unknown origin raised awareness in the international community. A few reports have attempted to associate new cases with adenovirus infection and the immunologic effects of previous SARS-CoV-2 infections through a superantigen mechanism. Moreover, according to a case series, viral isolates were identified in 7 of 10 cases of pediatric patients with hepatitis of unknown origin and acute liver failure. Adenovirus was detected by respiratory secretion polymerase chain reaction in 2 patients, with neither presenting with SARS-CoV-2 acute infection. Clinical and laboratory descriptions and cross-referencing epidemiologic and pathophysiological data can help identify possible disease etiologies.
Launch of the Sao Paulo Wellcome Trust-funded multidisciplinary research program on optimising antimicrobial use in highly populated urban environments
(2023) LEVIN, Anna S.; COSTA, Silvia F.; RAZZOLINI, Maria Tereza P.; PADOVEZE, Maria Clara; NUNES, Fatima L. S.
Hemoperitoneum after a Bothrops snakebite: Case report
(2024) RIBEIRO, Adriana Baqueiro Abad; SANTORO, Marcelo Larami; DUARTE, Marcelo Ribeiro; VIRGULINO, Cristiana Cruz; OLIVEIRA, Gerson Sobrinho Salvador de; FRANCA, Francisco Oscar de Siqueira
Snakebites are frequent in tropical countries. Brazil has an average of 27,000 cases per year, with a fatality rate of 0.5%, and the Bothrops genus is the most common causative agent, accounting for about 70-90% of the accidents. This report describes a case of human envenomation by a juvenile Bothrops jararaca snake in Sa similar to o Paulo, Brazil, in a 71 years-old man, previously healthy. He presented a life-threatening envenomation, which developed to severe hypotension, acute kidney injury and extensive peritoneal hemorrhage. The hemoperitoneum was diagnosed due to persistent hypotension associated with anemia, pain and gastrointestinal complaints. Abdominal Computed Tomography scans showed a moderate to large amount of presumable hematic material inside the abdominal cavity, predominantly in the perihepatic and perisplenic spaces. The intra-abdominal hemorrhage was not surgically addressed, and the patient was discharged 5 days after hospitalization, with the progressive absorption of the hemoperitoneum. Systemic bleeding is one of the complications and main causes of death in Bothrops envenomations. Acute peritoneal hemorrhage is one of these serious complications that must be carefully addressed since its management must take into account the risk of bleeding caused by toxins that affect hemostasis. The case described highlights the importance of early diagnosis and adequate management of this potentially fatal complication in snakebites.
Intranasal Liposomal Formulation of Spike Protein Adjuvanted with CpG Protects and Boosts Heterologous Immunity of hACE2 Transgenic Mice to SARS-CoV-2 Infection
(2023) RUSSO, Momtchilo; MENDES-CORREA, Maria Cassia; LINS, Bruna B.; KERSTEN, Victor; PERNAMBUCO, Paulo C. A.; MARTINS, Toni Ricardo; TOZETTO-MENDOZA, Tania Regina; BOAS, Lucy Santos Vilas; GOMES, Brisa Moreira; DATI, Livia Mendonca Munhoz; DUARTE-NETO, Amaro Nunes; REIGADO, Gustavo Roncoli; FREDERICO, Ana Beatriz T.; CUNHA, Danielle R. de A.; PAULA, Anderson Vicente de; SILVA, Jose Igor G. da; VASCONCELOS, Carlos F. Moreira; CHAMBERGO, Felipe S.; NUNES, Viviane Abreu; BOM, Ana Paula Dinis Ano; CASTILHO, Leda R.; MARTINS, Rodrigo A. P.; HIRATA, Mario Hiroyuki; MIROTTI, Luciana; TRIPP, Ralph A.
Mucosal vaccination appears to be suitable to protect against SARS-CoV-2 infection. In this study, we tested an intranasal mucosal vaccine candidate for COVID-19 that consisted of a cationic liposome containing a trimeric SARS-CoV-2 spike protein and CpG-ODNs, a Toll-like receptor 9 agonist, as an adjuvant. In vitro and in vivo experiments indicated the absence of toxicity following the intranasal administration of this vaccine formulation. First, we found that subcutaneous or intranasal vaccination protected hACE-2 transgenic mice from infection with the wild-type (Wuhan) SARS-CoV-2 strain, as shown by weight loss and mortality indicators. However, when compared with subcutaneous administration, the intranasal route was more effective in the pulmonary clearance of the virus and induced higher neutralizing antibodies and anti-S IgA titers. In addition, the intranasal vaccination afforded protection against gamma, delta, and omicron virus variants of concern. Furthermore, the intranasal vaccine formulation was superior to intramuscular vaccination with a recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 spike glycoprotein (Oxford/AstraZeneca) in terms of virus lung clearance and production of neutralizing antibodies in serum and bronchial alveolar lavage (BAL). Finally, the intranasal liposomal formulation boosted heterologous immunity induced by previous intramuscular vaccination with the Oxford/AstraZeneca vaccine, which was more robust than homologous immunity.
Thermal and chronological stability of monocyte distribution width (MDW), the new biomarker for sepsis (vol 60, pg e232, 2022)
(2024) BORDIGNON, Jardel Cristiano; GARDONA, Rodrigo Galvao Bueno; VASCONCELLOS, Leonardo de Souza; IACHINSKI, Joslaine Schuartz; DAMBROS, Robbson Haugusto; ARRUDA, Gisele; REIS, Beatriz Castro; ABDALA, Edson
A Randomized, Controlled, Noninferiority, Multicenter Trial of Systemic vs Intralesional Treatment With Meglumine Antimoniate for Cutaneous Leishmaniasis in Brazil
(2023) LYRA, Marcelo R.; OLIVEIRA, Liliane F. A.; SCHUBACH, Armando O.; SAMPAIO, Raimunda N. R.; RODRIGUES, Bruna C.; HUEB, Marcia; COTA, Glaucia; SILVA, Rosiana E.; FRANCESCONI, Fabio; POMPILIO, Mauricio A.; FRANCA, Adriana O.; AMATO, Valdir S.; SOUZA, Regina M.; OLIVEIRA, Raquel V. C.; VALETE, Claudia M.; PIMENTEL, Maria I. F.
Background Meglumine antimoniate (MA) remains the main treatment for cutaneous leishmaniasis (CL). Uncontrolled studies suggest that intralesional MA (IL-MA) may be noninferior and safer than systemic MA (S-MA). Methods Multicenter, randomized, controlled, open-label, phase 3 clinical trial to evaluate the efficacy and toxicity of IL-MA in 3 infiltrations at 14-day intervals compared with S-MA (10-20 mg Sb5+/kg/day, 20 days) for CL, with noninferiority margin of 20%. Primary and secondary outcomes were definitive cure at day 180 and epithelialization rate at day 90 of treatment, respectively. A 2-year follow-up was performed to assess relapses and emergence of mucosal lesions. Adverse events (AEs) were monitored according to the Division of AIDS AE grading system. Results We evaluated 135 patients. The cure rates (95% confidence interval) for IL-MA and S-MA treatment were, respectively, 82.8% (70.5-91.4) and 67.8% (53.3-78.3) per protocol (PP) and 70.6% (58.3-81.0) and 59.7% (47.0-71.5) per intention to treat (ITT). The epithelialization rates of the IL-MA and S-MA treatment were, respectively, 79.3% (66.6-88 + 8) and 71.2% (57.9-82.2) PP and 69.1% (55.2-78.5) and 64.2% (50.0-74.2) ITT. AEs in the IL-MA and S-MA groups were, respectively, clinical, 45.6% and 80.6%; laboratory, 26.5% and 73.1%; and electrocardiogram, 8.8% and 25.4%. Ten participants in the S-MA group and 1 in the IL-MA group were discontinued due to severe or persistent AEs. Conclusions IL-MA provides a similar cure rate and results in less toxicity compared with S-MA and may be used as first-line therapy for CL patients. This multicenter, randomized, controlled, open-label, phase 3 clinical trial, we evaluated the efficacy and toxicity of intralesional infiltration meglumine antimoniate (IL-MA) compared with systemic MA (S-MA) for cutaneous leishmaniasis (CL). IL-MA provides similar cure rate and results in less toxicity compared with S-MA. Clinical Trials Registration. REBEC: RBR-6mk5n4.
Cutaneous Naganishia albida (Cryptococcus albidus) infection: a case report and literature review
(2023) OLIVEIRA, Vitor Falcao de; FUNARI, Alexandre Pereira; TABORDA, Mariane; MAGRI, Adriana Satie Goncalves Kono; LEVIN, Anna Sara; MAGRI, Marcello Mihailenko Chaves
Naganishia albida (Cryptococcus albidus) is considered saprophytic fungi, and is rarely reported as a human pathogen. Cutaneous infections caused by non-neoformans cryptococcus are rare. We describe a case of an immunocompetent older male with cutaneous cryptococcosis caused by Naganishia albida following skin trauma, and conduct a literature review in PubMed, Lilacs, and Embase. Only six previous similar reports were found. The seven cases (including ours) were widely distributed geographically (Brazil, the US, the UK, Hungary, South Korea, and Iran), all males, and their ages varied, ranging from 14 to 86 years. Four individuals had underlying skin diseases (Sezary Syndrome, psoriasis, and skin rash without etiology) plus potentially immunosuppressive underlying conditions (diabetes mellitus, kidney transplantation, and the use of etanercept, adalimumab, and methylprednisolone). Cutaneous presentation was polymorphic, with lesions characterized as warts, ulcers, plaques, and even macules. Two patients presented disseminated disease. Serum cryptococcal antigen was negative in six patients, and diagnosis was made by fungal culture in all. There is a lack of data on optimal antifungal treatment and outcomes.

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