Perfil epidemiológico de pacientes com Hemofilia A e doenças associadas ao uso do fator VIII/recombinante / Epidemiological profile of patients with Hemophilia A and diseases associated with the use of factor VIII/recombinant

Introdução: o Brasil é o quarto país em casos de Hemofilia A. O tratamento é infundir o fator de coagulação ausente. Reações ao uso do fator podem incluir manifestações alérgicas, doenças virais transfusionais e aloanticorpos. Objetivo: analisar o perfil epidemiológico de pacientes com Hemofilia A, e as doenças associadas ao uso do fator VIII e fator VIII recombinante. Metodologia: estudo transversal descritivo e retrospectivo. A coleta de dados foi realizada nos prontuários de pacientes com diagnóstico de hemofilia A, preenchidos com mais de 70% das informações, na Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas, Brasil. Resultados: o Ministério da Saúde identificou no Estado do Amazonas, o registro de 276 indivíduos com diagnóstico de Hemofilia A. Incluídos para análise neste estudo 164 prontuários. Características sociodemográficas: homens 99,4%, adolescentes (28%) e jovens (26,8%); de cor parda 67,1%, ensino fundamental incompleto 28,6% e, exercendo a ocupação de estudante 42,7%. Condição clínica: 36,6% classificados com hemofilia A grave. Todos os pacientes tiveram diagnóstico clínico e laboratorial. O parentesco mais comum é o de irmãos com 35,3%. Sintomas predominantes: hemartrose 45,4%; dor 31,9%; edema 24% e artropatia 8,5%. O fator VIII recombinante, administrado em 34,8% dos pacientes, enquanto o fator VIII plasmático em 28,0%. Administrados doses de 2000UI a 2999UI. As complicações: artralgia 77,4% e hemorragia 77,4%. Conclusão: cuidados qualificados dos profissionais de saúde auxiliam na prevenção de complicações sérias, resultando em qualidade de vida ao hemofílico.

Introduction: Brazil is the fourth country in cases of Hemophilia A. The treatment is to infuse the missing clotting factor. Reactions to the use of the factor can include, allergic manifestations, transfusion viral diseases and alloantibodies. Objective: analyze the epidemiological profile of patients with Hemophilia A, and the diseases associated with the use of factor VIII and recombinant factor VIII. Methodology: descriptive and retrospective cross-sectional study. Data collection was carried out in the medical records of patients diagnosed with hemophilia A, filled with more than 70% of the information, at the Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas, Brazil. Results: in the Ministry of Health of Brazil, it was identified, for the State from Amazonas, the registry of 276 individuals diagnosed with Hemophilia A. Included in the analysis for this study, 164 medical records. Sociodemographic characteristics: male, 99.4%, adolescents (28%) and young people (26.8%), brown skin color, 67.1%, incomplete elementary school, 28.6%, and working as a student, 42.7%. Clinical condition: 36.6% classified with severe hemophilia A. All patients had a clinical and laboratory diagnosis. The most common kinship is that of brothers, 35.3%. Predominant symptoms: hemarthrosis 45.4%, pain 31.9%, edema 24% and arthropathy 8.5%. Recombinant factor VIII, administered in 34.8% of patients, while plasma factor VIII in 28.0%. Doses of 2000 IU to 2999 IU were administered. Complications: arthralgia 77.4% and hemorrhage 77.4%. Conclusion: qualified care by health professionals helps to prevent serious complications, resulting in quality of life for the hemophiliac.

HIV-1 genetic diversity and drug resistance mutations in the northern Brazilian region.

Brazil is a huge continental country with striking geographic differences which are well illustrated in the HIV/AIDS epidemic. Contrasting with the significant decline in the national AIDS detection rate in the last decade, a linear growth has been reported in the Northern region. Despite its public health and epidemiologic importance, there is scarce HIV-1 molecular data from Northern Brazil. This scoping review summarizes recent epidemiologic data with special emphasis on HIV-1 genetic diversity and antiretroviral drug resistance mutations in patients from the seven Northern states of Brazil. Studies from the Northern Brazil on different HIV-1 genomic regions, mostly pol (protease/reverse transcriptase) sequences of naïve/antiretroviral treated adults/children were retrieved from PubMed/MEDLINE electronic database. These studies indicate a consistent molecular profile largely dominated by HIV-1 subtype B with minor contribution of subtypes F1 and C and infrequent detection of other subtypes (A1, D, K), recombinants (BF1, BC), circulating recombinant forms (CRF) as the new CRF90_BF1 and CRF02_AG-like, CRF28-29_BF-like, CRF31_BC-like, and a potential new CRF_BF1. This pattern indicates a founder effect of subtype B and the introduction of non-B-subtypes and recombinants probably generated in the Southern/Southeastern regions. In naïve populations transmitted drug resistance (TDR) can impact the outcome of first-line antiretroviral treatment and prophylactic/preventive regimens. In the Northern region TDR rates are moderate while patients failing highly active antiretroviral therapy (HAART) showed high prevalence of acquired drug resistance mutations. The limited HIV-1 molecular data from Northern Brazil reflects the great challenges to generate comprehensive scientific data in isolated, underprivileged areas. It also highlights the need to invest in local capacity building which supported by adequate infrastructure and funding can promote robust research activities to help reduce the scientific asymmetries in the Northern region. Currently the impacts of the overwhelming COVID-19 pandemic on the expanding HIV/AIDS epidemic in Northern Brazil deserves to be closely monitored.

HIV-1 genetic diversity and drug resistance mutations in the northern Brazilian region

ABSTRACT Brazil is a huge continental country with striking geographic differences which are well illustrated in the HIV/AIDS epidemic. Contrasting with the significant decline in the national AIDS detection rate in the last decade, a linear growth has been reported in the Northern region. Despite its public health and epidemiologic importance, there is scarce HIV-1 molecular data from Northern Brazil. This scoping review summarizes recent epidemiologic data with special emphasis on HIV-1 genetic diversity and antiretroviral drug resistance mutations in patients from the seven Northern states of Brazil. Studies from the Northern Brazil on different HIV-1 genomic regions, mostly pol (protease/reverse transcriptase) sequences of naïve/antiretroviral treated adults/children were retrieved from PubMed/MEDLINE electronic database. These studies indicate a consistent molecular profile largely dominated by HIV-1 subtype B with minor contribution of subtypes F1 and C and infrequent detection of other subtypes (A1, D, K), recombinants (BF1, BC), circulating recombinant forms (CRF) as the new CRF90_BF1 and CRF02_AG-like, CRF28-29_BF-like, CRF31_BC-like, and a potential new CRF_BF1. This pattern indicates a founder effect of subtype B and the introduction of non-B-subtypes and recombinants probably generated in the Southern/Southeastern regions. In naïve populations transmitted drug resistance (TDR) can impact the outcome of first-line antiretroviral treatment and prophylactic/preventive regimens. In the Northern region TDR rates are moderate while patients failing highly active antiretroviral therapy (HAART) showed high prevalence of acquired drug resistance mutations. The limited HIV-1 molecular data from Northern Brazil reflects the great challenges to generate comprehensive scientific data in isolated, underprivileged areas. It also highlights the need to invest in local capacity building which supported by adequate infrastructure and funding can promote robust research activities to help reduce the scientific asymmetries in the Northern region. Currently the impacts of the overwhelming COVID-19 pandemic on the expanding HIV/AIDS epidemic in Northern Brazil deserves to be closely monitored.

Homogenous HIV-1 subtype B from the Brazilian Amazon with infrequent diverse BF1 recombinants, subtypes F1 and C among blood donors.

In the last decade a growing HIV/AIDS epidemic with increased incidence and AIDS-related mortality has been reported in Northern Brazil from which molecular data are scarce. Also, apparently healthy, adult blood donors, recently diagnosed with HIV-1 represent important sentinel populations for molecular studies. This cross-sectional study describes HIV-1 subtypes in blood donors from three reference public blood centers located in three States in Northern Brazil. HIV-1 pol sequencing (protease/PR, reverse transcriptase/RT) was performed on plasma samples of HIV-1 positive donors from HEMOAM, Manaus, Amazonas (n = 198), HEMERON, Porto Velho, Rondônia (n = 20) and HEMORAIMA, Boa Vista, Roraima (n = 9) collected from 2011-2017. HIV-1 subtypes were identified by REGA, phylogenetic inference; recombinant viruses were characterized by SIMPLOT. Young, single, males predominated, around half was first-time donors. Syphilis co-infection was detected in 17% (39 out of 227), 8% (18 out of 227) was anti-HBc positive. Subtype B represented ≥ 90% in Amazonas, Rondônia and Roraima, subtype C (3.1%) was found in Amazonas and Rondônia; subtype F1 (0.9%) and BF1 recombinants (5.3%) were only detected in Amazonas. Subtype B sequences from Amazonas (n = 179), Rondônia (n = 18) and Roraima (n = 9) were combined with viral strains representative of the BPANDEMIC (n = 300) and BCARIBBEAN/BCAR (n = 200) lineages. The BPANDEMIC lineage predominated (78%) although BCAR lineages were frequent in Roraima (56%) and Amazonas (22%). Subtype C and subtype F1 sequences identified here clustered within Brazilian CBR and F1BR lineages, respectively. Twelve BF1 mosaics showed 11 different recombination profiles: six were singleton unique-recombinant-forms/URFs, one displays a CRF28/29_BF-like recombinant pattern and the remaining four BF1 isolates branched with other Brazilian BF1 viruses previously described and may represent putative new CRF_BF1 from Northern Brazil. Our study shows a highly homogeneous molecular pattern with prevalent subtype B, followed by BF1, and sporadic subtype C and F1 in blood donors from the Northern region. Surveillance studies are important to monitor HIV-1 diversity which can reveal patterns of viral dissemination, especially in a highly endemic, remote and geographically isolated region as Northern Brazil.

Molecular epidemiology of hepatitis B and hepatitis delta viruses circulating in the Western Amazon region, North Brazil.

BACKGROUND: Hepatitis B virus (HBV) and hepatitis D virus (HDV) represent important public health problems in the Western Amazon region with reported cases of fulminant hepatitis. This cross sectional study describes HBV and HDV genotypes circulating in the Brazilian Amazon region. METHODS: HBsAg positive individuals (n = 224) were recruited in Manaus/Amazonas State (130 blood donors from the Hematology and Hemotherapy Foundation from Amazonas/HEMOAM; 60 subjects from outpatient clinic) and in Eirunepe city (n = 34) from 2003-2009. Most participants (n = 153) lived in Manaus, 63 were from 20 remote isolated municipalities, 8 lived outside Amazonas State. Genotyping was based on PCR products: HBV genotype A-F specific primers, restricted length polymorphism for HDV. HDV isolates were directly sequenced (delta antigen 405 nucleotide fragment) and phylogenetic analysis performed (MEGA; neighbor-joining, Kimura's two parameter). RESULTS: Most participants were young adult males and HBV mono-infection predominated (70.5%, 158/224). Among blood donors, outpatient subjects and individuals from Eirunepe, HBV/A prevailed followed by HBV/D and F (p > 0.05). HBV/A was more frequent in blood donors (p < 0.05). HBV-HDV coinfection rate was 8.5% in blood donors (11/130), 65.0% (39/60) in outpatient subjects and 47.0% (16/34) in individuals from Eirunepe. Compared to blood donors, coinfection was higher in outpatient subjects (65.0% versus 8.5%; RR = 5.0; CI 3.4-7.9; p < 0.0001) and in subjects from Eirunepe (47.0% versus 8.5%; RR = 5.5; CI 3.0-9.9; p < 0.0001). HBV-HDV coinfection rates were higher in patients from highly endemic remote cities. Only HDV genotype 3 was detected, HBV/F-HDV/3 predominated (20/38; 52.7%), followed by HBV/A-HDV/3 (31.6%; 12/38) and HBV/D-HDV/3 (15.8%; 6/38). CONCLUSIONS: The description of HBV and HDV genotypes circulating in the western Amazon can contribute to a better understanding of their relevance on the regional epidemics. These infections are highly endemic in the Amazon where their control is challenged by its vast territorial dimension with small, hard-to-reach municipalities dispersed into the jungle and populated by diverse ethnic groups.