Anti-Aspergillus fumigatus IgG in patients with bronchiectasis and its relationship with clinical outcome

Aspergillosis is a mycosis, most commonly afecting the airways. This mycosis can worsen the clinical condition of patients with concurrent lung diseases. We assayed for the presence of serum anti-A. fumigatus IgG in bronchiectasis patients from a tertiary hospital in south Brazil and evaluated the relationship with clinical outcome. Thirty-one patients with bronchiec tasis, without cystic fbrosis, were included. Clinical and epidemiological data were collected from all participants. Positive serological tests were detected in 13% (4/31) of the patients. The mortality rate for the year following the assay was, in the seropositive group, 75% (3/4), whereas in the seronegative group, 15% (4/27). An illustrative case is also shown and discussed. Our study highlights the diagnostic challenge and the possible impact of Aspergillus infection on these patients, indicating the necessity of more and larger investigations in the feldinfo:eu-repo/semantics/publishedVersio

PCR ESPÉCIE-ESPECÍFICO PARA O DIAGNÓSTICO DE ESPOROTRICOSE CAUSADA POR S. BRASILIENSIS

Despite thousands of sporotrichosis cases related to the zoonotic transmission of Sporothrix brasiliensis have been described, the diagnostic gold standard is still the classical culturing methods. The mycological culture results are available afterseven to 30 days of incubation. Since an early diagnosis contributes to improving thetreatment and to the spread control of this mycosis, studies evaluating faster diagnosticmethods are needed. Therefore, we aimed to evaluate the species-specific PCR for thesporotrichosis diagnosis caused by S. brasiliensis, using samples collected with a noninvasive technique. Seventy-four swabs from feline (n=64), canine (n=5), and human(n=5) suspect sporotrichosis cases were included. All samples were submitted to classicalmethods for diagnosis and to S. brasiliensis-specific PCR. Using mycological culture asthe gold standard, the diagnosis of S. brasiliensis-caused infection was confirmed in 69%(51/74) of the cases. PCR was positive in 30 out of these 51 cases, showing 59%sensitivity, 100% specificity, 72% accuracy, 100% positive predictive value, and 52%negative predictive value. Consequently, more studies are needed to elucidate theinterference factors that culminated with the high rate of false-negative results and thenoptimize this molecular test for the accurate diagnosis of infections caused by S.brasiliensis.Apesar de milhares de casos de esporotricose relacionados a transmissão zoonótica por Sporothrix brasiliensis venham sendo descritos, o diagnóstico padrão-ouro ainda é a partir do método clássico de cultura. O resultado da cultura micológica demora de sete a trinta dias para ficar disponível. Considerando que o diagnóstico precoce contribuiria para um tratamento prematuro e com isso, com o controle na disseminação desta micose, estudos avaliando um diagnóstico precoce são necessários. Portanto, o objetivo do presente estudo foi avaliar o PCR espécie-específico para o diagnóstico da esporotricose causada por S. brasiliensis, utilizando amostras coletas por uma técnica não invasiva. Foram incluídas setenta e quatro amostras de casos suspeitos de esporotricose (swabs) oriundos de felinos (n=64), caninos (n=5) e humanos (n=5). Todas as amostras foram submetidas ao método clássico de diagnóstico e ao PCR específico para S. brasiliensis. Utilizando a cultura micológica como padrão-ouro, o diagnóstico da infecção causada por S. brasiliensis foi confirmado em 69% (51/74) dos casos. O PCR foi positivo em 30 dos 51 casos, demonstrando 59% de sensibilidade, 100% de especificidade, 72% de acurácia, 100% de valor preditivo positivo e 52% de valor preditivo negativo. Consequentemente, mais estudos são necessários para elucidar os fatores de transferência que culminaram com a alta taxa de resultados falsos negativos e então otimizar este teste molecular para a acurácia diagnóstica para infecções causadas por S. brasiliensis

Aspergilose pulmonar crónica: os desafios para o diagnóstico e aplicabilidade de ferramentas auxiliares - relato de caso

Abstract publicado em: Braz J Infect Dis. 2021 Jan;25(S1):101078. doi:10.1016/j.bjid.2020.101446.Introdução: Estima‐se que anualmente 3 milhões de pessoas em todo o mundo desenvolvam aspergilose pulmonar crônica (CPA), no entanto, seu diagnóstico é desafiador. Objetivo: Relatar o caso de um paciente com repetidos isolamentos de A. fumigatus em amostras respiratórias desde 2013, e diagnóstico de CPA confirmado somente em 2019. Metodologia: Homem, 73 anos, diagnóstico de HIV em 2000 (desde 2010 supressão virológica), ex‐usuário de drogas, tabaco e álcool (abstêmio desde 2008), timoma em 2002, com ressecção cirúrgica. Em 2006 e 2009, apresentou infecção por Mycobacterium avium. Desde 2010, em uso de corticóide inalatório e β2‐agonista para DPOC, infecções respiratórias de repetição e deterioração progressiva de parênquima pulmonar em exames de imagem. Realizadas cerca de 10 investigações para micobacteriose, após tratamento, todas negativas. Em 2013 e 2015, A. fumigatus foi isolado de escarro e LBA, respectivamente. Interpretado como colonização, não houve tratamento antifúngico em ambas ocasiões. Em 2018, A. fumigatus foi novamente isolado de escarro, sendo realizada investigação sorológica, que permitiu o diagnóstico por detecção de anticorpos (IDGA ‐ IMMY®; e ELISA IgG Aspergillus Bio‐Rad®) e antígeno (LFA Aspergillus GM, IMMY®). Paciente não tolerou a terapia com anfo B, recebendo itraconazol (ITC) (200 mg; 12/12 h). Após 6 meses de tratamento, teve melhora clínica e estabilização do quadro radiológico; e IDGA negativou, sendo indicada manutenção do ITC por mais 6 meses. A análise genotípica pela técnica de microssatélites (alto poder discriminatório: 0,9968), comprovou que três isolados de A. fumigatus obtidos em diferentes momentos eram a mesma estirpe. Discussão/Conclusão: O diagnóstico da CPA é um desafio pela dificuldade em interpretar o isolamento de A. fumigatus de amostra respiratória, podendo ser contaminação, colonização ou, de fato, uma infecção ativa. Nosso caso ilustra este contexto, no qual esse diagnóstico foi considerado somente após diversos isolamentos fúngicos. O fato de tratar‐se de mesma cepa fúngica isolada nos diferentes anos, sugere a associação deste agente com a deterioração progressiva do parênquima pulmonar; ou ainda uma colonização prévia que culminou com progressão para doença ativa após danos por outras etiologias e/ou uso de corticóide. Em ambos os casos, cabe ressaltar a importância de investigar um paciente com comprometimento pulmonar crônico cujas amostras respiratórias resultem em isolamento de A. fumigatus.info:eu-repo/semantics/publishedVersio

Treatment of Human Sporotrichosis Caused by <i>Sporothrix brasiliensis</i>

We describe the successful treatment of a series of 30 zoonotic sporotrichosis cases from southern Brazil. Sporothrix brasiliensis was the species genotypically identified in all 25 confirmed cases. Five other cases were classified as probable, without laboratory confirmation, but with clinical and epidemiological data of cat-transmitted sporotrichosis. Two isolates were sequenced by translation elongation factor-1 alpha (EF1α) loci in order to compare their sequences, and both of them showed distinct genotypes from S. brasiliensis strains from other Brazilian states. Itraconazole (ITZ) or potassium iodide (KI) were the first choice treatment in 28 and 2 cases, respectively. Microdilution assay showed a wild-type profile of S. brasiliensis isolates to ITZ. However, a lack of clinical response occurred in 42% of cases, especially those treated with ITZ 100 mg/day, and treatment needed modifications, by either increased doses or antifungal combinations. Clinical cure required a mean of 187 days of treatment, which was dependent on the clinical form of the disease and age of patients. Therapy, including dosages and durations, for cutaneous forms of sporotrichosis requires re-evaluation, since cases caused by S. brasiliensis may influence treatment efficacy

Genetic markers associated to dyslipidemia in HIV-infected individuals on HAART

This study evaluated the impact of 9 single nucleotide polymorphisms (SNPs) in 6 candidate genes (APOB, APOA5, APOE, APOC3, SCAP, and LDLR) over dyslipidemia in HIV-infected patients on stable antiretroviral therapy (ART) with undetectable viral loads. Blood samples were collected from614 patients at reference services in the cities of Porto Alegre, Pelotas, and Rio Grande in Brazil. The SNPs were genotyped by conventional polymerase chain reaction (PCR) and real-time PCR. The prevalence of dyslipidemia was particularly high among the protease inhibitors-treated patients (79%). APOE (rs429358 and rs7412) genotypes and APOA5 −1131T>C (rs662799) were associated with plasma triglycerides (TG) and low-density-lipoprotein cholesterol levels (LDL-C). The APOA5 −1131T>C (rs662799) and SCAP 2386A>G (rs12487736) polymorphisms were significantly associated with high-densitylipoprotein cholesterol levels. The mean values of the total cholesterol and LDL-C levels were associated with both the APOB SP Ins/Del (rs17240441) and APOB XbaI (rs693) polymorphisms. In conclusion, our data support the importance of genetic factors in the determination of lipid levels in HIV-infected individuals. Due to the relatively high number of carriers of these risk variants, studies to verify treatment implications of genotyping before HAART initiation may be advisable to guide the selection of an appropriate antiretroviral therapy regimen

Genetic markers associated to dyslipidemia in HIV-infected individuals on HAART

This study evaluated the impact of 9 single nucleotide polymorphisms (SNPs) in 6 candidate genes (APOB, APOA5, APOE, APOC3, SCAP, and LDLR) over dyslipidemia in HIV-infected patients on stable antiretroviral therapy (ART) with undetectable viral loads. Blood samples were collected from614 patients at reference services in the cities of Porto Alegre, Pelotas, and Rio Grande in Brazil. The SNPs were genotyped by conventional polymerase chain reaction (PCR) and real-time PCR. The prevalence of dyslipidemia was particularly high among the protease inhibitors-treated patients (79%). APOE (rs429358 and rs7412) genotypes and APOA5 −1131T>C (rs662799) were associated with plasma triglycerides (TG) and low-density-lipoprotein cholesterol levels (LDL-C). The APOA5 −1131T>C (rs662799) and SCAP 2386A>G (rs12487736) polymorphisms were significantly associated with high-densitylipoprotein cholesterol levels. The mean values of the total cholesterol and LDL-C levels were associated with both the APOB SP Ins/Del (rs17240441) and APOB XbaI (rs693) polymorphisms. In conclusion, our data support the importance of genetic factors in the determination of lipid levels in HIV-infected individuals. Due to the relatively high number of carriers of these risk variants, studies to verify treatment implications of genotyping before HAART initiation may be advisable to guide the selection of an appropriate antiretroviral therapy regimen

Short communication : UGT1A1*28 variant allele is a predictor of severe hyperbilirubinemia in HIV-infected patients on HAART in Southern Brazil

Highly active antiretroviral therapy (HAART) has increased the survival of HIV-infected patients. However, adverse effects play a major role in adherence to HAART. Some protease inhibitors (mainly atazanavir and indinavir) act as inhibitors of uridine diphosphate-glucuronosyltransferase (UGT1A1), the enzyme responsible for hepatic conjugation of bilirubin. Variations in the promoter region of the UGT1A1 gene (UGT1A1*28, rs8175347) can influence bilirubin plasma levels, modulating the susceptibility to hyperbilirubinemia. Aiming to analyze the association between UGT1A1*28 allele and hyperbilirubinemia in individuals exposed to HAART, we evaluated 375 HIV-positive individuals on antiretroviral therapy. Individuals carrying the UGT1A1*28 allele had a higher risk of developing severe hyperbilirubinemia [prevalence ratio (PR) = 2.43, 95% confidence interval (CI) 1.08–5.45, p = 0.032] as well as atazanavir users (PR = 7.72, 95% CI = 3.14–18.98, p < 0.001). This is the first description of such an association in Brazilian HIV patients, which shows that in African-American and Euroamerican HAART users, the UGT1A1*28 allele also predisposes to severe hyperbilirubinemia, especially in those exposed to atazanavir

Short communication : UGT1A1*28 variant allele is a predictor of severe hyperbilirubinemia in HIV-infected patients on HAART in Southern Brazil

Highly active antiretroviral therapy (HAART) has increased the survival of HIV-infected patients. However, adverse effects play a major role in adherence to HAART. Some protease inhibitors (mainly atazanavir and indinavir) act as inhibitors of uridine diphosphate-glucuronosyltransferase (UGT1A1), the enzyme responsible for hepatic conjugation of bilirubin. Variations in the promoter region of the UGT1A1 gene (UGT1A1*28, rs8175347) can influence bilirubin plasma levels, modulating the susceptibility to hyperbilirubinemia. Aiming to analyze the association between UGT1A1*28 allele and hyperbilirubinemia in individuals exposed to HAART, we evaluated 375 HIV-positive individuals on antiretroviral therapy. Individuals carrying the UGT1A1*28 allele had a higher risk of developing severe hyperbilirubinemia [prevalence ratio (PR) = 2.43, 95% confidence interval (CI) 1.08–5.45, p = 0.032] as well as atazanavir users (PR = 7.72, 95% CI = 3.14–18.98, p < 0.001). This is the first description of such an association in Brazilian HIV patients, which shows that in African-American and Euroamerican HAART users, the UGT1A1*28 allele also predisposes to severe hyperbilirubinemia, especially in those exposed to atazanavir