Interesting case from Argentina: Kidney transplant recipient with skin lesions-A Latin American perspective.

This is a case of a kidney transplant recipient who presented with skin lesions, low-grade fevers, and pancytopenia 2 months after his transplant.

Acquisition of antimicrobial resistance determinants in Enterobacterales by international travelers from a large urban setting in Brazil.

BACKGROUND: Antimicrobial resistance is increased by international mobility. We present data about intestinal colonization of travelers departing from a middle-income country. METHODS: Travelers were recruited from 2015 to 2019, collected an anal stool specimen and answered a questionnaire before and after travel. Enterobacterales isolates were investigated for antimicrobial resistance; extended-spectrum beta-lactamase (ESBL) and carbapenemase production; plasmid-encoded cephalosporinases (pAmpC), plasmid-mediated quinolone resistance (PMQR) and mcr genes by PCR and sequencing; and association with travel related variables. RESULTS: Among 210 travelers, 26 (12%) carried multidrug-resistant Enterobacterales (MDR-E) and 18 (9%) ESBL-producing Enterobacterales (ESBL-E) before travel, with an increased prevalence from 1% to 11% over the study years. Acquisition of MDR-E and ESBL-E occurred in 59 (32%) and 43 (22%) travelers, respectively, mostly blaCTX-M-15 carrying Escherichia coli. One traveler acquired one isolate carrying blaOXA-181 gene, and two others, isolates carrying mcr-1. PMQR were detected in 14 isolates of returning travelers. The risk of MDR-E acquisition was higher in Southeast Asia and the Indian subcontinent, and after using antimicrobial agents. CONCLUSION: We describe an increasing pre-travel prevalence of ESBL-E colonization in subjects departing from this middle-income country over time. Travel to known risk areas and use of antimicrobial agents during travel were associated with acquisition of MDR-E. Travel advice is critical to mitigating this risk, as colonization by MDR-E may raise the chances of antimicrobial-resistant infections.

Neuroinvasive chikungunya in a liver transplant recipient.

The influence of chronic immunosuppression on the course of chikungunya virus (CHIKV) infection in recipients of solid organ transplantation (SOT) is still unsettled. Scarce data suggest that the course of CHIKV infection is generally benign in this population. In addition, the occurrence of severe atypical manifestations associated with CHIKV has not been well documented among SOT recipients. In this report, we describe a 64-year-old male liver transplant recipient who was admitted with fever, headache, arthralgia, left palpebral ptosis, mydriasis, and right hemiparesis. Cranial magnetic resonance imaging did not reveal any alteration suggestive of acute infection. Nevertheless, CHIKV was detected in the cerebrospinal fluid (CSF) with a real-time reverse transcriptase assay. Other PCR assays carried out in CSF were negative for HSV-1 and 2, cytomegalovirus, dengue virus (DENV), and Zika virus (ZIKV). CHIKV viremia was also detected while PCR assays for ZIKV and DENV in the blood were negative. ZIKV viruria was simultaneously present in this case. All neurologic manifestations waned within 2 weeks after the onset. This report shows that chikungunya must be considered in the differential diagnosis of acute neurologic disease in SOT recipients who live in or have recently traveled to endemic areas.

Prevalence of fluoroquinolone-resistant and broad-spectrum cephalosporin-resistant community-acquired urinary tract infections in Rio de Janeiro: Impact of Escherichia coli genotypes ST69 and ST131.

Uropathogenic Escherichia coli (UPEC) is the leading cause of community-acquired urinary tract infection (CA-UTI). The increasing prevalence of CA-UTI caused by UPEC strains resistant to broad-spectrum drugs complicates clinical management of these infections. Here we assessed the prevalence of antimicrobial drug resistance, genotypes and beta-lactamase genes among UPEC isolated from cases of CA-UTI in Rio de Janeiro, Brazil during November 2015 to determine if the prevalence of drug-resistant CA-UTI is determined by multiple genotypes of resistant UPEC or dissemination of key lineages of UPEC. Among 499 UPEC isolates, 98 (20%) were ciprofloxacin (CIP) resistant and 41 (8%) produced extended-spectrum beta-lactamase (ESBL). Sequence types (ST) 69 and 131 were the most common genotypes, representing 77 (15%) and 42 (8%) of all UPEC isolates, respectively. Of fluoroquinolone-resistant isolates, ST69 and ST131 together accounted for 57%, while of ESBL-producers, ST131 represented 21%. Only 5 (2%) of 255 susceptible isolates belonged to these STs (p < .001). blaCTX-M-15 was detected in 17 (42%) of the 41 ESBL-producing isolates. Comparison with a collection of UPEC isolates obtained a decade earlier from the same community showed that a large proportion (60% and 25%, respectively) of the increase in CA-UTI caused by fluoroquinolone-resistant and ESBL-producing UPEC appears to be due to just two pandemic lineages ST131 and ST69. These findings indicate that much of the prevalence of broad-spectrum drug-resistant CA-UTI in Rio de Janeiro is due to a limited set of pandemic lineages of UPEC circulating in the community instead of multiple genotypes selected by antimicrobial agents.

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.

Screening for BKV-DNAEMIA after renal transplantation in a resource limited setting.

Costs may hinder the implementation of BK polyomavirus (BKV)-DNAemia screening in resource-limited kidney transplant (KT) centers. We analyzed data from two studies to assess the performance and potential cost saving of a dual-step screening strategy based on the use of a preliminary qualitative semi-nested PCR (snPCR) assay followed by BKV-DNAemia quantification after KT. In the preliminary study, in which 130 samples from 33 KT recipients were screened for BKV-DNAemia, the estimated positive and negative predictive values of snPCR, as compared to quantitative PCR (qPCR), were 88% and 99%, respectively. In the second study, which included 84 KT recipients, BKV-DNAemia was detected by snPCR in 28/472 (5.9%) samples and confirmed by qPCR in 26 samples of 21 (25%) subjects. No graft loss occurred among KT recipients who developed BKV-DNAemia. Cost analyses suggested that this strategy might be a cost saving alternative for BKV-DNAemia screening for some resource-limited settings.

Severe Strongyloides stercoralis infection in kidney transplant recipients: A multicenter case-control study.

BACKGROUND: Severe Strongyloides stercoralis infection in kidney transplant recipients is associated with considerable morbidity and mortality, although little is known about the risk factors for such infection. METHODOLOGY/PRINCIPAL FINDINGS: This was a retrospective, multicenter, case-control study in which we assessed the risk factors for and clinical outcomes of severe S. stercoralis infections in kidney transplant recipients in Brazil. We included 138 kidney transplant recipients: 46 cases and 92 controls. Among the cases, the median number of days from transplantation to diagnosis was 117 (interquartile range [IQR], 73.5-965) and the most common clinical findings were gastrointestinal symptoms (in 78.3%) and respiratory symptoms (in 39.1%), whereas fever and eosinophilia were seen in only 32.6% and 43.5%, respectively. The 30-day all-cause mortality among the cases was 28.3% overall and was significantly higher among the cases of infection occurring within the first three months after transplantation (47% vs. 17.2%, P = 0.04). The independent risk factors were receiving a transplant from a deceased donor (odds ratio [OR] = 6.16, 95% confidence interval [CI] = 2.05-18.5), a history of bacterial infection (OR = 3.04, 95% CI = 1.2-7.5), and a cumulative corticosteroid dose (OR = 1.005, 95% CI = 1.001-1.009). The independent predictors of mortality were respiratory failure (OR = 98.33, 95% CI = 4.46-2169.77) and concomitant bacteremia (OR = 413.00, 95% CI = 4.83-35316.61). CONCLUSIONS/SIGNIFICANCE: Severe S. stercoralis infections are associated with considerable morbidity and mortality after kidney transplantation. In endemic areas, such infection may occur late after transplantation, although it seems to be more severe when it occurs earlier after transplantation. Specific risk factors and clinical manifestations can identify patients at risk, who should receive prophylaxis or early treatment.

Diversity of clonal types of Klebsiella pneumoniae causing infections in intensive care neonatal patients in a large urban setting.

BACKGROUND: Klebsiella infections are reported from neonatal intensive care units (NICUs) worldwide, but data on their incidence and genetic diversity remain scarce. OBJECTIVE: We determined the incidence and genetic diversity of Klebsiella infections in NICU patients in Rio de Janeiro. METHODS: This was a prospective study including newborns admitted to NICU in three hospitals during April 2005-November 2006 and March 2008-February 2009. Klebsiella pneumoniae isolates were genotyped by multilocus sequence typing (MLST) and extended spectrum ß-lactamases (ESBL) were characterized. RESULTS: Klebsiella infections occurred in 38 of 3984 patients (incidence rate, 9.5/1000 admissions); 14 (37%) of these 38 newborns died. Two clonal groups, CC45 and CC1041, caused 11 cases (42% of K. pneumoniae infection). Ten (32%) of the isolates causing infection produced ESBL, 9 of which (83%) carried blaCTX-M-15, all belonging to clonal complex (CC) 45 and CC1041. Nine of these ESBL-producing isolates were confined to only one of the NICUs. MAJOR CONCLUSIONS: The high incidence of Klebsiella infections in NICU in Rio de Janeiro appeared to be due to a combination of frequent sporadic infections caused by multiple K. pneumoniae genotypes and small outbreaks caused by dominant multidrug-resistant clones.

Adherence to malaria prophylaxis among travelers from a middle-income country.

INTRODUCTION: Malaria is the main cause of death by infection among travelers and is preventable through a combination of chemoprophylaxis and personal protective measures. METHODS: Travelers were interviewed by phone 28-90 days after returning, to assess adherence to pre-travel advice for malaria prevention. RESULTS: A total 57 travelers were included. Adherence to chemoprophylaxis was significantly higher among participants prescribed mefloquine (n=18; 75%) than doxycycline (n=14; 45%). Adherence to mosquito repellent and bed net use was 65% and 67%, respectively. CONCLUSIONS: Adherence to malaria prophylaxis was lower than expected. Further studies testing innovative approaches to motivate travelers' compliance are required.

Hepatitis C virus genotypes in hemodialysis patients in Angola.

To our knowledge, there are no published data on hepatitis C virus (HCV) genotypes in Angola. This study aimed at assessing the distribution of HCV genotypes in seropositive hemodialysis patients in Luanda. Among 51 HCV-positive subjects included, viremia was detected in 27 (53%). HCV genotyping was performed by bidirectional sequencing of the 5'-untranslated region by the Sanger method. HCV genotype 4 was largely predominant (20 cases; 74%), followed by genotypes 1b (5 cases; 18.5%), 1a and 2 (one case each; 3.7%). These results suggest that the distribution of HCV genotypes in Angola is similar to that reported from other Central African countries.

Adherence to malaria prophylaxis among travelers from a middle-income country

Abstract INTRODUCTION: Malaria is the main cause of death by infection among travelers and is preventable through a combination of chemoprophylaxis and personal protective measures. METHODS: Travelers were interviewed by phone 28-90 days after returning, to assess adherence to pre-travel advice for malaria prevention. RESULTS: A total 57 travelers were included. Adherence to chemoprophylaxis was significantly higher among participants prescribed mefloquine (n=18; 75%) than doxycycline (n=14; 45%). Adherence to mosquito repellent and bed net use was 65% and 67%, respectively. CONCLUSIONS: Adherence to malaria prophylaxis was lower than expected. Further studies testing innovative approaches to motivate travelers' compliance are required.

Seroprevalence of antibodies against the three serotypes of poliovirus and IPV vaccine response in adult solid organ transplant candidates.

OBJECTIVES: To assess the prevalence of protective antibody titers to polioviruses in adults candidates for solid organ transplant (SOT), and to assess the immunogenic response to inactivated polio vaccine in this population. METHODS: The study included SOT candidates referred to Immunization Reference Centre of Evandro Chagas National Institute of Infectious Diseases from March 2013 to January 2016. It was conducted in 2 phases. The first one, a cross-sectional seroprevalence study, followed by an uncontrolled analysis of vaccine response among patients without protective antibody titers at baseline. Antibody titers to poliomyelitis were determined by microneutralization assay. RESULTS: Among 206 SOT candidates included, 156 (76%) had protective antibody titers to all poliovirus serotypes (95% CI: 70-81%). Proven history of oral vaccination in childhood was not associated with higher seroprevalence of protective antibody. In 97% of individuals without protective antibody titers at baseline, there was adequate vaccine response with one dose of inactivated polio vaccine. CONCLUSIONS: A relevant proportion of adult candidates for SOT does not have protective titers of antibodies to one or more poliovirus serotype. One dose of inactivated vaccine elicited protective antibody titers in 97% of these subjects and should be routinely prescribed prior to SOT.

Recommendations for Management of Endemic Diseases and Travel Medicine in Solid-Organ Transplant Recipients and Donors: Latin America.

The Recommendations for Management of Endemic Diseases and Travel Medicine in Solid-Organ Transplant Recipients and Donors: Latin America clinical practice guideline is intended to guide clinicians caring for solid-organ transplant (SOT) donors, candidates and recipients regarding infectious diseases (ID) issues related to this geographical region, mostly located in the tropics. These recommendations are based on both systematic reviews of relevant literature and expert opinion from both transplant ID and travel medicine specialists. The guidelines provide recommendations for risk evaluation and laboratory investigation, as well as management and prevention of infection of the most relevant endemic diseases of Latin America. This summary includes a brief description of the guideline recommendations but does not include the complete rationale and references for each recommendation, which is available in the online version of the article, published in this journal as a supplement. The supplement contains 10 reviews referring to endemic or travel diseases (eg, tuberculosis, Chagas disease [ChD], leishmaniasis, malaria, strongyloidiasis and schistosomiasis, travelers diarrhea, arboviruses, endemic fungal infections, viral hepatitis, and vaccines) and an illustrative section with maps (http://www.pmourao.com/map/). Contributors included experts from 13 countries (Brazil, Canada, Chile, Denmark, France, Italy, Peru, Spain, Switzerland, Turkey, United Kingdom, United States, and Uruguay) representing four continents (Asia, the Americas and Europe), along with scientific and medical societies.

BK polyomavirus genotypes Ia and Ib1 exhibit different biological properties in renal transplant recipients.

BK polyomavirus (BKV) is an opportunist agent associated with nephropathy (BKVAN) in 1-10% of kidney transplant recipients. BKV is classified into genotypes or subgroups according to minor nucleotidic variations with unknown biological implications. Studies assessing the possible association between genotypes and the risk of BKVAN in kidney transplant patients have presented conflicting results. In these studies, genotype Ia, which is highly prevalent in Brazil, was less frequently found and, thus, comparative data on the biological properties of this genotype are lacking. In this study, BKV Ia and Ib1 genotypes were compared according to their viral load, genetic evolution (VP1 and NCCR) - in a cohort of renal transplant recipients. The patients infected with Ia (13/23; 56.5%) genotype exhibited higher viral loads in urine [>1.4 log over Ib1 (10/23; 43.5%); p=0.025]. In addition, genotype Ia was associated with diverse mutations at VP1 loops and sites under positive selection outside loops, which were totally absent in Ib1. Although the number of viremic patients was similar, the three patients who had BK nephropathy (BKVAN) were infected with Ia genotype. NCCR architecture (ww or rr) were not distinctive between Ia and Ib1 genotypes. Ia genotype, which is rare in other published BKV cohorts, presented some diverse biological properties in transplanted recipients in comparison to Ib1.

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.

Multidrug-resistant bacterial infections after liver transplantation: an ever-growing challenge.

Bacterial infections are a leading cause of morbidity and mortality among solid organ transplant recipients. Over the last two decades, various multidrug-resistant (MDR) pathogens have emerged as relevant causes of infection in this population. Although this fact reflects the spread of MDR pathogens in health care facilities worldwide, several factors relating to the care of transplant donor candidates and recipients render these patients particularly prone to the acquisition of MDR bacteria and increase the likelihood of MDR infectious outbreaks in transplant units. The awareness of this high vulnerability of transplant recipients to infection leads to the more frequent use of broad-spectrum empiric antibiotic therapy, which further contributes to the selection of drug resistance. This vicious cycle is difficult to avoid and leads to a scenario of increased complexity and narrowed therapeutic options. Infection by MDR pathogens is more frequently associated with a failure to start appropriate empiric antimicrobial therapy. The lack of appropriate treatment may contribute to the high mortality occurring in transplant recipients with MDR infections. Furthermore, high therapeutic failure rates have been observed in patients infected with extensively-resistant pathogens, such as carbapenem-resistant Enterobacteriaceae, for which optimal treatment remains undefined. In such a context, the careful implementation of preventive strategies is of utmost importance to minimize the negative impact that MDR infections may have on the outcome of liver transplant recipients. This article reviews the current literature regarding the incidence and outcome of MDR infections in liver transplant recipients, and summarizes current preventive and therapeutic recommendations.

O aprendizado melhorado por provas / Test-enhanced learning

Provas não são neutras em termos de aprendizagem. Não têm apenas caráter avaliativo. A utilização de testes repetidamente traz um benefício mnemônico, estudado em psicologia cognitiva no chamado "efeito de ser testado". A utilização de testes repetidos em cenários de educação caracteriza a metodologia do "aprendizado melhorado por provas". Estudos experimentais e aplicados em cursos extracurriculares têm demonstrado melhor desempenho na retenção de conteúdos e em habilidades de alunos submetidos a testes repetidos em comparação aos de grupos controle. Embora caracterize uma metodologia ativa e o incremento de conteúdo factual seja necessário ao desenvolvimento do raciocínio clínico, a crítica que se faz ao método é de ser baseado em memorização e retenção, na era das evidências. Os estudos aplicados não podem, até o momento, estabelecer se há melhor organização dos conteúdos adquiridos para utilização na resolução de problemas e se isto interfere positivamente no cuidado aos pacientes.

Tests are not neutral in terms of learning. They are not only evaluative, but summative too. There is a mnemonic benefit of testing - called the testing effect, in cognitive psychology studies. In educational settings, test-enhanced learning methodology has been associated with improved cognitive skills and performance of students repetitively tested on a specific content. Although it is an active learning method and despite the fact that the development of clinical reasoning depends upon increased factual contents, there has been criticism of memorization and retention in the era of evidence-based medicine. In fact, available studies have been unable to prove the benefits of using this method in problem solving abilities and patient care.

From hepatic diseases and jaundice to viral hepatitis: the configuration of a kaleidoscope.

Viral hepatitis A, B, C, D and E--systemic hepatotropic viral infections--present as acute hepatitis that, depending on the etiological agent, viral load and host conditions, may evolve into chronic hepatitis, cirrhosis, liver cancer and acute fulminant disease. The ecological versatility of these viruses, their spectrum of transmission in time and space, potentialized by the sub-clinical course of a large proportion of infections, comprise an epidemiological challenge. This essay describes scenarios and tendencies in the socioepidemiologic profile, based on the history of these infections, and indicates the need to overcome patterns, models, and protocols and instead investigate each particular situation. In other words, it highlights the need to explore singularities in order to be able to develop new proposals for general actions tailored to local specificities.

A qualitative seminested PCR assay as an alternative to urine cytology for BK polyomavirus screening after renal transplantation.

OBJECTIVE: Polyomavirus-associated nephropathy (PVAN) is a major cause of graft dysfunction after kidney transplantation. Therefore, routine screening for BK polyomavirus (BKV) infection with urine cytology or quantitative PCR-based assays has been recommended. Although less expensive than quantitative tests, qualitative PCR assays are not recommended for screening based on the assumption that their diagnostic accuracy is inferior to urine cytology. However, studies comparing the performance of both methods are scarce. METHODS: We compared the accuracy between a qualitative seminested PCR (snPCR) assay and urine cytology for the screening of BKV viruria in 104 renal transplant recipients. RESULTS: The snPCR assay was more sensitive than cytology (100 and 61%, respectively), yielding better negative predictive value (100 vs. 90%). In 7 (39%) of the 18 PVAN cases, BKV infection was detected exclusively by snPCR. Although the specificity of snPCR (63%) was lower than cytology (74%), their positive predictive values were similar (36 vs. 33%, respectively). In ROC curve analysis, the accuracy of snPCR was significantly higher (p = 0.03). CONCLUSION: This qualitative snPCR assay was more accurate than urine cytology for the detection of BKV viruria in renal transplant patients.