HCMV UL97 phosphotransferase gene mutations may be associated with antiviral resistance in immunocompromised patients in Belém, PA, Northern Brazil

Abstract INTRODUCTION: Human cytomegalovirus is one of the causes of opportunist infections in immunocompromised patients, and is triggered by factors such as state of viral latency, weakened immune responses, and development of antiviral resistance to ganciclovir, the only drug offered by the public health system in Brazil to treat the infection. The goal of this study was to identify mutations that may be associated with antiviral resistance in immunocompromised patients. METHODS: Molecular analysis was performed in 82 blood samples and subjected to genomic DNA extraction by a silica-based method. Three sequences of the HCMV UL97 gene, which encodes a phosphotransferase protein required for activation of ganciclovir, were amplified by polymerase chain reaction. Pyrosequencing methods were applied to one external 2096-bp segment DNA and two internal sequences between nucleotides 1087 to 1828 to detect mutations in this gene. RESULTS: Approximately 10% of sequences contained mutations between nucleotides 377 and 594, in conserved regions of the UL97 gene, leading to amino acid changes. Eleven coding mutations were identified, including changes leading to amino acid substitutions, E596K and S604F, which were observed in 100% of samples and are described for the first time in Brazil. In addition, one mutation (A594V) that is associated with ganciclovir resistance was detected in a kidney transplant patient. CONCLUSIONS: Further studies to detect mutations associated with HCMV resistance to antiviral drugs are required to demonstrate the need to increase the variety and availability of drugs used to treat viral infections in the public health care system in Brazil.

Myocarditis associated with Plasmodium vivax malaria: a case report

Malaria remains a major public health problem in Brazil where Plasmodium vivax is the predominant species, responsible for 82% of registered cases in 2013. Though benign, P. vivax infection may sometimes evolve with complications and a fatal outcome. Here, we report a severe case of P. vivax malaria in a 35-year-old Brazilian man from a malaria endemic area, who presented with reversible myocarditis.

Association between histological findings, aminotransferase levels and viral genotype in chronic hepatitis C infection

Introduction: The genomic heterogeneity of hepatitis C virus (HCV) influences liver disorders. This study aimed to determine the prevalence of HCV genotypes and to investigate the influence of these genotypes on disease progression. Methods: Blood samples and liver biopsies were collected from HCV-seropositive patients for serological analysis, biochemical marker measurements, HCV genotyping and histopathological evaluation. Results: Hepatitis C virus-ribonucleic acid (HCV-RNA) was detected in 107 patients (90.6% with genotype 1 and 9.4% with genotype 3). Patients infected with genotype 1 exhibited higher mean necroinflammatory activity and fibrosis. Conclusions: HCV genotype 1 was the most prevalent and was associated with greater liver dysfunction. .

Colonização por Pseudomonas aeruginosa em pacientes com fibrose cística na região amazônica: efeito na função respiratória / Colonization by Pseudomonas aeruginosa in patients with cystic fibrosis in Amazonregion: effect on respiratory function

Objetivo: descrever as características espirométricas e clínicas dos pacientes com fibrose císticacolonizados por Pseudomonas aeruginosa atendidos no Hospital Universitário João de BarrosBarreto (HUJBB), no estado do Pará, Brasil. Método: estudo retrospectivo nos prontuários de 44pacientes, período de 1997-2007, que atenderam aos critérios de inclusão, sendo 14 colonizadospor P. aeruginosa. Resultados: no grupo colonizado 10 eram do sexo feminino; a idade média dossintomas iniciais foi de 0.3±0.6 anos, com diferença significativa quando comparado com pacientesnão colonizados (p<0.05). A idade média ao diagnóstico foi de 13.1±10.8 nos colonizados, todosapresentando sintomas respiratórios persistentes ao diagnóstico. A média dos valores percentuaispreditos das espirometrias, referentes à avaliação inicial e final, do grupo colonizado foiVEF1(60.0± 25.0%) e (47,82±16.1%) e FEF25-75%(42.5± 22.9%) e (26,5±17.9%) e no grupo nãocolonizado foi VEF1(79.2± 21.0%) e (79,6±18.0%) e FEF25-75%(69.2± 26.7%) e (68,9±26.8%),respectivamente (p<0.005). A média do escore de Shwachman inicial nos colonizados foi de42.9±13.5 e nos não colonizados foi de 68.4±15.1(p<0.0001) e na avaliação final foi de 36.6±18.7 e73.6±12.3 (p<0.0001), respectivamente. Os fatores relacionados aos óbitos foram: colonização porP. aeruginosa, estado nutricional deficiente e VEF1 reduzido. Conclusões: o comprometimento dafunção pulmonar foi maior entre os pacientes com fibrose cística colonizados por P. aeruginosa,apresentando idade média mais elevada ao diagnóstico do que em outros estados brasileiros. Hánecessidade de ações para diagnóstico precoce no estado do Pará, propiciando abordagemterapêutica eficaz com aumento da sobrevida e qualidade de vida destes indivíduos.

Objective: to evaluate spirometric and clinic characteristics of patients who present cystic fibrosisand who are attended at João de Barros Barreto University Hospital (HUJBB), in the State of Pará,Brazil. Methods: a retrospective study was performed with 44 patient records that were attended atHUJBB during the 1997 to 2007; these patients fit into inclusion criteria, in which 14 presented P.aeruginosa bacteria colony. Results: within the group, who was colonized by P. aeruginosa, tenpatients were women and the median age for their initial symptoms was of 0.3 ± 0.6 year which wassignificantly different when compared with patients who didn?t present the bacteria colony (p?0.05). The median age for diagnosis was of 13.1 ± 10.8 in colonized patients and all of thempresented respiratory symptoms pertaining to the diagnosis. The median of the predicted percentagevalues of spirometries for initial and final evaluation of the colonized group was VEF1 (60.0 ±25.0%) and (47,82 ± 16.1%) and FEF 25-75% (42.5 ± 22.9%) and (26.5 ± 17.9%), and in the noncolonizedgroup, the median was VEF1 (79.2 ± 21.0%) and (79,6 ± 18.0%) and FEF 25-75% (69.2± 26.7%) and (68.9 ± 26.8%), respectively (p? 0.005). The median initial Shwachman score in thecolonized patients was 42.9 ± 13.5 and in the non-colonized patients it was 68.4 ± 15.1 (p? 0.0001),and at the final evaluation the median was 36.6 ± 18.7 and 73.6 ± 12.3 (p? 0.0001), respectively.Factors related to deaths found in the study were related to P. aeruginosa colonization, inadequatenutritional status and reduced VEF1. Conclusions: in the studied casuistry, a larger damage torespiratory function in P. aeruginosa colonized group and older median age for diagnosis werefound in the State of Pará when compared to other Brazilian States. There is the need for actiontowards precocious diagnosis in the State of Pará so that an efficient therapeutic approach is put intopractice guiding to survival increase and quality of life for these individuals.