Mpox outbreak in Rio de Janeiro, Brazil: A translational approach.

Mpox is a zoonotic disease historically reported in Africa. Since 2003, limited outbreaks have occurred outside Africa. In 2022, the global spread of cases with sustained interhuman transmission and unusual disease features raised public health concerns. We explore the mpox outbreak in Rio de Janeiro (RJ) state, Brazil, in an observational study of mpox-suspected cases from June to December 2022. Data collection relied on a public healthcare notification form. Diagnosis was determined by MPXV-PCR. In 46 confirmed cases, anti-OPXV IgG was determined by ELISA, and seven MPXV genomes were sequenced. A total of 3095 cases were included, 816 (26.3%) with positive MPXV-PCR results. Most positive cases were men in their 30 s and MSM. A total of 285 (34.9%) MPXV-PCR+ patients live with HIV. Eight were coinfected with varicella-zoster virus. Anogenital lesions and adenomegaly were associated with the diagnosis of mpox. Females and individuals under 18 represented 9.4% and 5.4% of all confirmed cases, respectively, showing higher PCR cycle threshold (Ct) values and fewer anogenital lesions compared to adult men. Anti-OPXV IgG was detected in 29/46 (63.0%) patients. All analyzed sequences belonged to clade IIb. In RJ state, mpox presented a diverse clinical picture, represented mainly by mild cases with low complication rates and prominent genital involvement. The incidence in females and children was higher than usually reported. The observation of a bimodal distribution of Ct values, with few positive results, may suggest the need to review the diagnostic criteria in these groups.

Understanding the Elevated Lethality of COVID-19 in Liver Transplant Recipients: Does Immunosuppression Management Matter? Results from a Brazilian Multicentric Historical Cohort.

BACKGROUND: Infections by SARS-CoV-2 in liver transplant recipients (LT) patients are of particular concern, notably due to perceived added risks related to immunosuppression and comorbidity burden. Current literature on this topic often relies on small, non-standardized, and geographically limited studies. This manuscript describes COVID-19 presentations and causes for elevated mortality in a large cohort of LT recipients. METHODS: This study was designed as a multicentric historical cohort, including LT recipient patients with COVID-19 in 25 study centers, with the primary endpoint being COVID-related death. We also collected demographic, clinical, and laboratory data regarding presentation and disease progression. RESULTS: Two hundred and thirty-four cases were included. The study population was predominantly male and White and had a median age of 60 years. The median time from transplantation was 2.6 years (IQR 1-6). Most patients had at least one comorbidity (189, 80.8%). Patient age (P = .04), dyspnea (P < .001), intensive care unit admission (P < .001), and mechanical ventilation (P < .001) were associated with increased mortality. Modifications of immunosuppressive therapy (P < .001), specifically the suspension of tacrolimus, maintained significance in multivariable analysis. CONCLUSIONS: Attention to risk factors and the individualization of patient care, especially regarding immunosuppression management, is crucial for delivering more precise interventions to these individuals.

Validation of the INCREMENT-SOT-CPE score in a large cohort of liver transplant recipients with carbapenem-resistant Enterobacterales infection.

BACKGROUND: Management of infections due to carbapenemase-resistant Enterobacterales (CRE) in solid organ transplant (SOT) recipients remains a difficult challenge. The INCREMENT-SOT-CPE score has been specifically developed from SOT recipients to stratify mortality risk, but an external validation is lacking. METHODS: Multicenter retrospective cohort study of liver transplant (LT) recipients colonized with CRE infection who developed infection after transplant over 7-year period. Primary endpoint was all-cause 30-day mortality from infection onset. A comparison between INCREMENT-SOT-CPE and other selected scores was performed. A two-level mixed effects logistic regression model with random effects for the center was fitted. Performance characteristics at optimal cut-point were calculated. Multivariable Cox regression analysis of risk factors for all-cause 30-day mortality was carried out. RESULTS: Overall, 250 CRE carriers developed infection after LT and were analyzed. The median age was 55 years (interquartile range [IQR]: 46-62) and 157 were males (62.8%). All-cause 30-day mortality was 35.6%. A sequential organ failure assessment (SOFA) score ≥ 11 showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 69.7%, 76.4%, 62.0%, 82.0%, and 74.0%, respectively. An INCREMENT-SOT-CPE ≥ 11 reported a sensitivity, specificity, PPV, NPV, and accuracy of 73.0%, 62.1%, 51.6%, 80.6% and 66.0%, respectively. At multivariable analysis acute renal failure, prolonged mechanical ventilation, INCREMENT-SOT-CPE score ≥ 11 and SOFA score ≥ 11 were independently associated with all-cause 30-day mortality, while a tigecycline-based targeted regimen was found to be protective. CONCLUSIONS: Both INCREMENT-SOT-CPE ≥ 11 and SOFA ≥ 11 were identified as strong predictors of all-cause 30-day mortality in a large cohort of CRE carriers developing infection after LT.

Effectiveness of Direct-acting Agents After Liver Transplantation A Real-life Study in Rio de Janeiro.

BACKGROUND: Data concerning hepatitis C virus (HCV) treatment using direct-acting agents (DAAs) post liver transplantation (LT) remains scarce in low- and average-income countries. AIM OF THE STUDY: To evaluate the safety and efficacy of post-LT HCV treatment using DAAs in Rio de Janeiro (Brazil), and to assess the course of hepatic biomarkers after sustained virological response (SVR). METHODS: Data from LT recipients with recurrent HCV treated using DAAs was retrospectively analyzed. HCV was defined by detectable HCV-RNA with elevated aminotransferases and/or histological signs of infection on liver biopsy post LT. SVR was defined as undetectable HCV-RNA 12 weeks after the end of treatment. Aspartate-to-Platelet Ratio Index (APRI) and Fibrosis-4 score (FIB-4) were calculated before treatment and after SVR. RESULTS: 116 patients (63% male, median age 62 years, 75% genotype 1 and 62% with hepatocellular carcinoma [HCC] prior to LT) were included. Cirrhosis was identified in the allograft of 21 subjects (18%). The overall SVR was 96.6% without differences in SVR proportion according to clinical/demographic characteristics, genotype or presence of cirrhosis. SVR rates were similar in individuals with and without HCC pre-LT (95.8% [95% CI: 87.6-98.7] vs. 97.7% [95% CI: 85.0-99.7%], p = 0.588). No serious adverse events were observed and the use of ribavirin was associated with at least one adverse event (OR = 8.71 [95% CI: 3.17-23.99]). SVR was associated with regression of APRI (OR = 26.00 [95% CI 4.27-1065.94]) and FIB-4 (OR = 15.00 [95% CI: 2.30-631.47]). CONCLUSION: Post-LT HCV treatment with DAAs was safe and effective and associated with a significant decrease in hepatic biomarker levels after SVR.

Development of a Risk Prediction Model for Carbapenem-resistant Enterobacteriaceae Infection After Liver Transplantation: A Multinational Cohort Study.

BACKGROUND: Patients colonized with carbapenem-resistant Enterobacteriaceae (CRE) are at higher risk of developing CRE infection after liver transplantation (LT), with associated high morbidity and mortality. Prediction model for CRE infection after LT among carriers could be useful to target preventive strategies. METHODS: Multinational multicenter cohort study of consecutive adult patients underwent LT and colonized with CRE before or after LT, from January 2010 to December 2017. Risk factors for CRE infection were analyzed by univariate analysis and by Fine-Gray subdistribution hazard model, with death as competing event. A nomogram to predict 30- and 60-day CRE infection risk was created. RESULTS: A total of 840 LT recipients found to be colonized with CRE before (n = 203) or after (n = 637) LT were enrolled. CRE infection was diagnosed in 250 (29.7%) patients within 19 (interquartile range [IQR], 9-42) days after LT. Pre- and post-LT colonization, multisite post-LT colonization, prolonged mechanical ventilation, acute renal injury, and surgical reintervention were retained in the prediction model. Median 30- and 60-day predicted risk was 15% (IQR, 11-24) and 21% (IQR, 15-33), respectively. Discrimination and prediction accuracy for CRE infection was acceptable on derivation (area under the curve [AUC], 74.6; Brier index, 16.3) and bootstrapped validation dataset (AUC, 73.9; Brier index, 16.6). Decision-curve analysis suggested net benefit of model-directed intervention over default strategies (treat all, treat none) when CRE infection probability exceeded 10%. The risk prediction model is freely available as mobile application at https://idbologna.shinyapps.io/CREPostOLTPredictionModel/. CONCLUSIONS: Our clinical prediction tool could enable better targeting interventions for CRE infection after transplant.

Lack of Impact of Acute Pyelonephritis on Kidney Graft Survival.

BACKGROUND: Urinary tract infection is the most common bacterial infection after kidney transplant. Some studies suggested that urinary tract infection could impair graft survival, but this issue remains debated. The objective of this study was to analyze the association between acute pyelonephritis (APN) and the risk of kidney graft failure. METHODS: We performed a retrospective cohort study including patients who received a kidney transplant from 2001 to 2009 at a university hospital in Rio de Janeiro, Brazil. They were followed until December 2015. The primary outcome was graft failure. Follow-up of patients who died with a functioning graft was censored on the date of death. Cox proportional hazards method was used in multivariable analysis to assess risk factors for graft failure. The occurrence of the first episode of APN and acute rejection were modeled as time-dependent variables. RESULTS: A total of 587 patients were included. Of these, 112 recipients (19%) developed 173 episodes of APN. Graft failure occurred in 150 patients (25%) after a median follow-up of 79 months. The factors associated with graft failure in the multivariate analyses were age of the transplant recipient (hazard ratio [HR], 0.97 per year; 95% confidence interval [CI], 0.96-0.99; P < .01), occurrence of delayed graft function (HR, 2.42; 95% CI, 1.72-3.40; P < .01), and acute rejection (HR, 2.71; 95% CI, 1.92-3.82; P < .01). There was no association between APN and graft failure (HR, 1.05; 95% CI, 0.65-1.68; P = .85). CONCLUSIONS: Our results suggest that the occurrence of APN is not associated with a significant reduction in graft survival after kidney transplant.

Respiratory Tract Infection Caused by Fonsecaea monophora After Kidney Transplantation.

Fonsecaea spp. are melanized fungi which cause most cases of chromoblastomycosis. The taxonomy of this genus has been revised, now encompassing four species, with different pathogenic potential: F. pedrosoi, F. nubica, F. pugnacius, and F. monophora. The latter two species present wider clinical spectrum and have been associated with cases of visceral infection, most often affecting the brain. To our knowledge, this is the first report of proven case of F. monophora respiratory tract infection. A Brazilian 57-year-old-female patient underwent kidney transplantation on January 12, 2013. On the fourth postoperative month, the patient presented with fever, productive cough, and pleuritic pain in the right hemithorax. A thoracic CT scan showed a subpleural 2.2-cm nodular lesion in the right lung lower lobe, with other smaller nodules (0.5-0.7 cm) scattered in both lungs. Bronchoscopy revealed a grayish plaque on the right bronchus which was biopsied. Microscopic examination demonstrated invasion of bronchial mucosa by pigmented hyphae. Culture from the bronchial biopsy and bronchoalveolar lavage samples yielded a melanized mold, which was eventually identified as F. monophora. She started treatment with voriconazole (400 mg q.12h on the first day, followed by 200 mg q.12h). After 4 weeks of therapy, voriconazole dose was escalated to 200 mg q.8h and associated with amphotericin B (deoxycolate 1 mg/kg/day) because of a suspected dissemination to the brain. The patient eventually died of sepsis 8 weeks after the start of antifungal therapy. In conclusion, F. monophora may cause respiratory tract infection in solid organ transplant recipients.

The influence of carbapenem resistance on mortality in solid organ transplant recipients with Acinetobacter baumannii infection.

BACKGROUND: Infection with carbapenem-resistant Acinetobacter baumannii has been associated with high morbidity and mortality in solid organ transplant recipients. The main objective of this study was to assess the influence of carbapenem resistance and other potential risk factors on the outcome of A. baumannii infection after kidney and liver transplantation. METHODS: Retrospective study of a case series of A. baumannii infection among liver and renal transplant recipients. The primary outcome was death associated with A. baumannii infection. Multivariate logistic regression was used to assess the influence of carbapenem resistance and other covariates on the outcome. RESULTS: Forty-nine cases of A. baumannii infection affecting 24 kidney and 25 liver transplant recipients were studied. Eighteen cases (37%) were caused by carbapenem-resistant isolates. There were 17 (35%) deaths associated with A. baumannii infection. In unadjusted analysis, liver transplantation (p = 0.003), acquisition in intensive care unit (p = 0.001), extra-urinary site of infection (p < 0.001), mechanical ventilation (p = 0.001), use of central venous catheter (p = 0.008) and presentation with septic shock (p = 0.02) were significantly related to a higher risk of mortality associated with A. baumannii infection. The number of deaths associated with A. baumannii infection was higher among patients infected with carbapenem-resistant isolates, but the difference was not significant (p = 0.28). In multivariate analysis, the risk of A. baumannii-associated mortality was higher in patients with infection acquired in the intensive care unit (odds ratio [OR] = 34.8, p = 0.01) and on mechanical ventilation (OR = 15.2, p = 0.04). Appropriate empiric antimicrobial therapy was associated with significantly lower mortality (OR = 0.04, p = 0.03), but carbapenem resistance had no impact on it (OR = 0.73, p = 0.70). CONCLUSION: These findings suggest that A. baumannii-associated mortality among liver and kidney transplant recipients is influenced by baseline clinical severity and by the early start of appropriate therapy, but not by carbapenem resistance.

Simultaneous cytomegalovirus and Mycobacterium tuberculosis infection presenting as hemorrhagic colitis 3 years after a kidney transplant.

Cytomegalovirus is an important cause of colonic disease in solid organ transplant recipients. Although several reports have shown that simultaneous infection with other pathogens may aggravate the course of cytomegalovirus colitis, to our knowledge, no case of colitis caused by simultaneous cytomegalovirus and Mycobacterium tuberculosis has been previously reported. We describe a case of hemorrhagic colitis associated with simultaneous cytomegalovirus/ Mycobacterium tuberculosis infection in a 26-year-old woman, 38 months after a kidney transplant. Initial results of histopathologic analyses of gastrointestinal biopsies showed that tuberculosis was the only cause of colitis, as no morphologic alteration suggestive of cytomegalovirus infection was observed on hematoxylin-eosin staining. However, further analysis with immunoperoxidase staining confirmed the clinical suspicion of cytomegalovirus infection. This report shows that cytomegalovirus/tuberculosis coinfection may be a cause of late-onset colitis among solid organ transplant recipients. It also illustrates that coinfection with other pathogens may pose an additional challenge for diagnosing gastrointestinal cytomegalovirus disease.

Paniculite criptocócica em transplantado renal / Cryptococcal panniculitis in a renal transplant recipient

Os autores relatam um caso de paniculite criptocócica em paciente transplantado renal inicialmente tratado como celulite bacteriana. O diagnóstico definitivo só foi possível pela impressão clínica dermatológica confirmada pelo exame micológico. O tratamento foi realizado a princípio com anfotericina B e posteriormente com fluconazol, considerando-se as interações das drogas imunossupressoras utilizadas para evitar rejeição. A regressão clínica foi alcançada no sexto mês de tratamento, que, no entanto, foi mantido por 12 meses. São feitas considerações a respeito dessa forma rara de criptococose cutânea em transplantado de órgão sólido e suas implicações diagnósticas e terapêuticas.

The authors report a case of cryptococcal panniculitis in a renal transplant recipient,which was initially mistaken for bacterial cellulitis. Dermatological evaluation and laboratory studies led to the definitive diagnosis. Treatment was started with amphotericin B, followed by oral fluconazol, taking into consideration their interactions with the immunossupressive drugs. Even though clinical improvement was attained after six months, treatment was maintained during a whole year. We discuss this rare presentation of cutaneous cryptococcosis in a solid organ transplant recipient, as well as its diagnosis and therapy.

Selection of donors for living donor liver transplantation in a single center of a developing country: lessons learned from the first 100 cases.

The selection of donors for living donor liver transplantation (LDLT) is one of the most important features in this kind of surgery. The aim of this study is to describe our initial experience in the donor evaluation process. From December 2001 to January 2005, 104 donors were evaluated for 70 recipients (65 potential donors were evaluated for 39 adult recipients, and 39 donors for 31 pediatric recipients). Only 30 donors were able to donate: 13 for the adult group, and 17 for the pediatric one. In general, the utilization rate of potential donors was 28.8% (30/104). For the adult patients, 65 potential donors were seen to perform 13 LDLT, which represents a utilization rate of potential donors of 20%. For the pediatric patients, this rate was 43.6%. The exclusion criteria were clinical in 22 cases (21%), anatomical in 13 cases (13%), psychosocial in nine cases (9%), and others in 12 (12%). Death of recipients led to exclusion 18 of donors (17%). Thirty-three percent of adults and 55% of pediatric recipients who had at least one potential donor to start the evaluation process were able to identify a living donor. In conclusion, the first limit for LDLT is the rigorous donor evaluation.

Perinephric abscess caused by Streptococcus agalactiae after renal transplantation.

We describe the case of a 37 year-old diabetic woman who presented with a multiloculated perinephric abscess caused by Streptococcus agalactiae 12 months after receiving a living-related kidney graft. Infection was successfully treated with surgical drainage and a four-week course of antibiotic therapy. To our knowledge, this is the first report of a perinephric abscess caused by this agent in a renal transplant recipient.

Colonization with methicillin-resistant Staphylococcus aureus after liver transplantation.

Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of infection after orthotopic liver transplantation (OLT). Colonization with MRSA is associated with a higher risk of infection. Previous studies have shown a high prevalence of MRSA colonization among OLT candidates. However, the risk of colonization with MRSA after OLT is still unclear. The objective of this study was to estimate the incidence and the factors associated with colonization with MRSA after OLT. This was a prospective cohort study including patients submitted to OLT between the years 2000 and 2002. Surveillance cultures of nasal swab specimens were performed within the 1st 72 hours of hospital admission and, subsequently, on weeks 2, 6, 13, and 26. Patients whose baseline cultures revealed nasal carriage of MRSA were excluded. A total of 60 patients were included in the study. The median follow-up was 72 days. A total of 9 patients (15%) became colonized. In multiple logistic regression analyses, the use of a urinary catheter for > or =5 days (P = .006), postoperative bleeding at the surgical site (P = .009), and preoperative use of fluoroquinolones (P = .08) were associated with a higher risk of colonization. Patients without any of these risk factors did not become colonized. In conclusion, nasal carriage of MRSA is frequently acquired after OLT. Periodic postoperative screening for MRSA carriage should be an integral component in programs designed to reduce nosocomial MRSA transmission in these patients. Further studies are needed to set up and validate a predictive model that could allow targeting postoperative screening to high-risk OLT recipients.

Liver transplantation with monosegment from a living donor.

The shortage of organ donors for low-weight liver transplant recipients, especially for small children, has led to the development of new surgical techniques to increase the donor pool. Almost all of these techniques use the left lateral segment (Couinaud's segments II and III), but even this graft could be too large for children under 10 kg. We report here the case of an 8-month-old boy, weighing 6.1 kg, who received a monosegmental graft (segment III) from his grandmother weighing 68 kg. The graft was reduced at the donor surgery, before clamping of the vessels. The donor was discharged on the fourth post-operative day; the recipient had an uneventful post-operative period and was discharged after 22 days.