Genetic variability of hepatitis B virus in acute and in different phases of chronic infection in Brazil.

The selection pressure imposed by the host immune system impacts on hepatitis B virus (HBV) variability. This study evaluates HBV genetic diversity, nucleos(t)ide analogs resistance and HBsAg escape mutations in HBV patients under distinct selective pressures. One hundred and thirteen individuals in different phases of HBV infection were included: 13 HBeAg-positive chronic infection, 9 HBeAg-positive chronic hepatitis, 47 HBeAg-negative chronic infection (ENI), 29 HBeAg-negative chronic hepatitis (ENH) and 15 acute infected individuals. Samples were PCR amplified, sequenced and genetically analyzed for the overlapping POL/S genes. Most HBV carriers presented genotype A (84/113; 74.3%), subgenotype A1 (67/84; 79.7%), irrespective of group, followed by genotypes D (20/113; 17.7%), F (8/113; 7.1%) and E (1/113; 0.9%). Clinically relevant mutations in polymerase (tL180M/M204V) and in the Major Hydrophilic Region of HBsAg (sY100C, T118A/M, sM133T, sD144A and sG145R) were observed. Our findings, however, indicated that most polymorphic sites were located in the cytosolic loops (CYL1-2) and transmembrane domain 4 (TMD4) of HBsAg. Lower viral loads and higher HBV genetic diversity were observed in ENI and ENH groups (p < 0.001), suggesting that these groups are subjected to a higher selective pressure. Our results provide information on the molecular characteristics of HBV in a diverse clinical setting, and may guide future studies on the balance of HBV quasispecies at different stages of infection.

Differences in risky sexual behaviors and HIV prevalence between men who have sex with men and transgender women in the Midwest Brazil.

Men who have sex with men (MSM) and transgender women (TW) are disproportionally affected by HIV infection. This cross-sectional study evaluated the HIV-1/2 prevalence, risk factors and HIV molecular features of MSM and TW from Midwest Brazil. Four hundred and thirty participants (278 MSM and 152 TW) from Mato Grosso do Sul, Brazil, were interviewed and tested for HIV-1/2 infection between November 2011 and September 2013. Participants who were assigned male at birth, older than 18 years old and self-declared as MSM or TW were recruited from LGBT+ associations, as well as public (parks, square, streets, etc) and private [nightclubs, saunas, brothels, etc] places. The prevalence of HIV-1 was 14.4% (9.0% among MSM and 24% among TW; p<0.001). The factor independently associated with HIV-1 infection among MSM was being 30 years-old or older. Among TW, having suffered sexual coercion, lifetime syphilis infection and hepatitis C virus exposure were associated with HIV-1 infection. Phylogenetic analyses classified 65% sequences as subtype B and 35% as possible recombinants. All but one recombinant sample were from TW individuals. High HIV-1 prevalences were observed in both groups, highlighting the urgent need to devise specific HIV interventions targeting these key populations. Notably, TWs are more vulnerable to HIV infection, which was associated with sexual violence and co-infection with other STIs. With regard to MSM, being 30 years old or older was significanty associated to HIV, reinforcing the idea that MSM are less exposed [or exposed later] to STIs than TWs, although MSM are clearly more vulnerable than the general population.

SARS-CoV-2 and dialysis: humoral response, clinical and laboratory impacts before vaccination.

BACKGROUND: Patients with kidney disease on Hemodialysis (HD) are susceptible to Coronavirus Disease (COVID-19) due to multiple risk factors. AIM: This study aims to report the prevalence of antibodies against SARS-CoV-2 among patients on hemodialysis before vaccination in Brazil and to compare with clinical, demographic, and laboratory data. METHODS: Blood samples from 398 Chronic Kidney Disease (CKD) patients treated in three different private institutions in Rio de Janeiro State, Brazil were submitted to the total anti-SARS-CoV-2 testing. Kidney, liver, and hematological markers were also determined. Respiratory samples were tested by real-time PCR for SARS-CoV-2 RNA and positive samples were subjected to high-throughput sequencing on the MinION device. RESULTS: Overall, anti-SARS-CoV-2 prevalence was 54.5 % (217/398) and two individuals had SARS-CoV-2 RNA with variant B.1.1. High anti-SARS-CoV-2 seroprevalence was found in male gender and those with hospital admission in the last 3-months before the inclusion in the study. Lower red blood cell count was observed in the anti-SARS-CoV-2 seropositive group. High levels of anti-SARS-CoV-2 were found in those who reported symptoms, had low levels of eosinophils and low hematocrit, and who practiced physical activity. CONCLUSION: High prevalence of anti-SARS-CoV-2 was found in CKD patients before the universal immunization in Brazil suggesting that dialysis patients were highly exposed to SARS-CoV-2.

Genetic characterization of the parvovirus full-length VP2 gene in domestic cats in Brazil.

Feline parvovirus (FPV) and canine parvovirus (CPV) are over 98% identical in their DNA sequences, and the new variants of CPV (2a/2b/2c) have gained the ability to infect and replicate in cats. The aim of this study was to determine the genetic diversity in the VP2 gene of parvovirus strains circulating in domestic cats in Brazil during a 10-year period (2008-2017). For parvovirus screening, specific PCR was performed, and 25 (34.7%) of 72 cats tested positive. The PCR-positive samples were further subjected to full-length VP2 sequencing (1755 bp), and eight sequences (36%) were characterized as FPV, seven (28%) as CPV-2a and (32%) nine (36%) as CPV-2b. One sequence (RJ1085/11) showing typical CPV amino acid (aa) at residues 80 R, 93 N, 103 A, 232 I, and 323 N could not be characterized at this time. The sequences in this study displayed aa changes previously described for FPV (A14T, A91S, I101T, N564S, and A568G) from cats and CPV-2a/2b (S297N and Y324L) from dogs. However, the Y324L mutation has not yet been reported in any CPV-2a/2b strains from cats. Phylogenetic analysis supported the division of these sequences into two well-defined clades, clade 1 for FPV and clade 2 for CPV2a/2b. Unusually, the sequence RJ1085/11 was grouped separately. Two recombination breakpoints were detected by Bootscan and 3Seq methods implemented in the RDP4. This study is the first report of CPV-2a/2b in cats in Brazil. The detection of FPV strains with mutations characteristic of CPV indicates that Brazilian FPV strains have undergone genetic changes.

Could Herpesviridae be the cause of severe acute hepatitis of unknown origin in children?

INTRODUCTION: Severe acute hepatitis (SAH) is defined by a severe inflammation of hepatocytes in the liver parenchyma which can lead to an acute liver failure, a clinical condition with high mortality rate that can be triggered by several factors but is usually associated to hepatotropic viruses' infection. In 2022, cases of children with severe acute hepatitis of unknown origin hospitalized in Glasgow, Scotland, were reported. Possible causes of this condition include, but are not limited to, undiagnosed viral (and non-viral) infections, autoimmune hepatitis, drug and/or chemical toxicity, mitochondrial chain respiratory and metabolic disorders. AREAS COVERED: Herpesviruses can cause severe acute hepatitis, but little is known about the role and the mechanisms of herpesviruses as a causative agent of this type of hepatitis. We review the role of herpesviruses as causative agent of SAH in children and other possible mechanisms involved in this disease. EXPERT OPINION: Differential diagnosis for herpesvirus in SAH should be implemented in all settings. Alternative fluids, such as saliva and dried blood, could be used in the diagnosis to overwhelm the availability of biological specimens at sufficient volume. In the future, genetic studies could also be added to increase the knowledge about severe acute hepatitis in children.

SARS-CoV-2 and dialysis: humoral response, clinical and laboratory impacts before vaccination

Abstract Background Patients with kidney disease on Hemodialysis (HD) are susceptible to Coronavirus Disease (COVID-19) due to multiple risk factors. Aim This study aims to report the prevalence of antibodies against SARS-CoV-2 among patients on hemodialysis before vaccination in Brazil and to compare with clinical, demographic, and laboratory data. Methods Blood samples from 398 Chronic Kidney Disease (CKD) patients treated in three different private institutions in Rio de Janeiro State, Brazil were submitted to the total anti-SARS-CoV-2 testing. Kidney, liver, and hematological markers were also determined. Respiratory samples were tested by real-time PCR for SARS-CoV-2 RNA and positive samples were subjected to high-throughput sequencing on the MinION device. Results Overall, anti-SARS-CoV-2 prevalence was 54.5 % (217/398) and two individuals had SARS-CoV-2 RNA with variant B.1.1. High anti-SARS-CoV-2 seroprevalence was found in male gender and those with hospital admission in the last 3-months before the inclusion in the study. Lower red blood cell count was observed in the anti-SARS-CoV-2 seropositive group. High levels of anti-SARS-CoV-2 were found in those who reported symptoms, had low levels of eosinophils and low hematocrit, and who practiced physical activity. Conclusion High prevalence of anti-SARS-CoV-2 was found in CKD patients before the universal immunization in Brazil suggesting that dialysis patients were highly exposed to SARS-CoV-2.

High prevalence of hepatitis A and E viruses in environmental and clinical samples from West Argentina

ABSTRACT Environmental surveillance of water sources is important to monitoring viral hepatitis transmission in clinical settings. This study investigated the circulation of hepatitis A (HAV) and E (HEV) viruses in sewage and clinical samples from Argentina. Between 2016 and 2017, 80 raw sewage samples and 86 clinical samples (stool and serum) from suspected cases of hepatitis A and hepatitis E were obtained. HAV and HEV were tested by both real-time and nested PCR. Positive samples were sequenced for genotype determination and phylogenetic analysis. Overall, HAV was recovered in 39% of sewage samples and 61.1% of clinical samples. HEV was detected in 22.5% of sewage samples and 15.9% of clinical samples. HAV was found more frequently in sewage during the winter and in clinical samples in spring; HEV was more prevalent in sewage during summer and in clinical samples in autumn. All HAV isolates belonged to genotype IA and HEV isolates belonged to genotype 3, the most prevalent genotypes in South America. High prevalence of HAV and HEV in environmental and clinical samples in Mendoza, Argentina was observed. These findings reinforce the importance of environmental surveillance and implementation of health strategies to control the spread of HAV and HEV in developing countries.

Os genótipos do vírus da hepatite B na África e no Brasil: evolução, disseminação e associação com a rota de escravos / The genotypes of hepatitis B virus in Africa and in Brazil: evolution, spread and association with the route of slaves

A infecção pelo vírus da hepatite B (HBV) representa um grave problema de saúde públicamundial, apesar da existência de uma vacina eficiente. Estima-se que cerca de 350 milhõesde indivíduos no mundo estejam cronicamente infectados, dos quais a maior parte seencontra em países em desenvolvimento. A heterogeneidade das sequências dos isoladosdo HBV permite a sua classificação em oito genótipos, A a H, baseada na divergência do genoma completo de mais de 7,5 por cento. A presente tese é composta principalmente de três manuscritos, sendo um trabalho publicado e dois outros em submissão, além de cinco trabalhos como colaboradora. Esses estudos se propuseram a investigar a evolução dos genótipos do HBV entre África e Brasil e associar a dispersão dos genótipos no Brasil com a rota de escravos. No primeiro trabalho, entitulado Analysis of Complete NucleotideSequences of Angolan Hepatitis B Virus Isolates Reveals the Existence of a SeparateLineage within Genotype E, realizamos a caracterização filogenética viral dos isolados circulantes em Angola e sua associação com os perfis sorológicos e moleculares existentes naquela população. Através dessas análises, identificamos a separação das amostrasangolanas como pertencentes a uma nova linhagem, composta por Angola, Namibia eRepublica Democratica do Congo, provisoriamente denominada pela nossa equipe, SWL(Southwest African Lineage). No segundo trabalho, entitulado HBV subgenotype A1:Relationships between Brazilian, African and Asian isolates, fomos em busca das históriaevolutiva do HBV/A1, e suas suas rotas de dispersão entre África e Brasil durante o período do tráfico negreiro. Surpreendentemente, observamos que todas as amostras brasileiras estão geneticamente relacionadas às amostras da Ásia, ao invés da África. Esse fato sugere quer que o HBV/A1 possa ter sido introduzino no Brasil a partir dos portos de Moçambique,no sudeste africano, ou diretamente atravpés da Índia por navegantes portugueses...

Hepatitis B virus (HBV) infection is one of the major global human health problems, despitethe existence of an effective vaccine. It is estimated that around 350 million people worldwideare chronically infected; most of them is in developing countries. The sequenceheterogeneity of HBV isolates has led to the classification of HBV into eight genotypes, A toH, based on full-length genomic divergence of more than 7.5 percent. This thesis is composedmainly of three manuscripts: One of them is already published and two others are insubmission. Five other manuscripts are listed as complementary production. These studieshave set out to understand the evolution of HBV genotypes between Africa and Brazil andassociate its dispersion with slave routes. In the first study, entitled Analysis of CompleteNucleotide Sequences of Hepatitis B Virus Isolates Angolan Reveals the Existence of aSeparate Lineage Within Genotype E , performed the phylogenetic characterization of viralisolates circulating in Angola and its association with serological and molecular profiles.Through these analyzes, we characterized a separated lineage composed by Angolan,Namibia and Democratic Republic of Congo, provisionally named by our team as SWL(Southwest African Lineage). In the second paper, entitled Hepatitis B virus subgenotypeA1: Relationships between Brazilian, African and Asian isolates we aimed investigate theevolutionary history and migration patterns of HBV/A1 from Africa to Brazil during the slavetrade. Surprisingly, was observed that all Brazilian samples are genetically related to Asianisolates, rather than the African ones. These finds suggest that Asia was the source ofHBV/A1 infection in Brazil, probably through Mozambique in southeastern Africa, or directlythrough India by Portuguese sailors...

Epidemiology and molecular characterization of hepatitis B virus in Luanda, Angola

An estimated 360 million people are infected with hepatitis B virus (HBV) worldwide. Among these, 65 million live in Africa. Despite the high levels of hepatitis B in Africa, HBV epidemiology is still poorly documented in most African countries. In this work, the epidemiological and molecular characteristics of HBV infection were evaluated among the staff, visitors and adult patients (n = 508) of a public hospital in Luanda, Angola. The overall prevalence of hepatitis B core antibody (anti-HBc) and hepatitis B surface antigen was 79.7 percent and 15.1 percent, respectively. HBV infection was higher in males and was more prevalent in individuals younger than 50 years old. HBV-DNA was detected in 100 percent of HBV "e" antigen-positive serum samples and in 49 percent of anti-hepatitis Be antibody-positive samples. Thirty-five out of the 40 HBV genotypes belonged to genotype E. Circulation of genotypes A (4 samples) and D (1 sample) was also observed. The present study demonstrates that HBV infection is endemic in Luanda, which has a predominance of genotype E. This genotype is only sporadically found outside of Africa and is thought to have emerged in Africa at a time when the trans-Atlantic slave trade had stopped.

Fulminant hepatitis failure in adults and children from a Public Hospital in Rio de Janeiro, Brazil

Fulminant hepatic failure (FHF) is characterized by massive hepatocellular injury, whose physiopathology is still unclear. Hepatitis B (HBV) is probably the most common viral cause of FHF, while hepatitis A (HAV) virus seem occurs less frequently. However, the host and viral factors that determine the outcome of these infections are poorly understood. In the present study, viral load and genotyping determining regions of HAV and HBV genomes were sequenced. Eight FHF patients and one patient with severe acute hepatitis (SAH) were included. Liver and blood samples were collected during liver transplantation or necropsy procedures. HAV-RNA and HBV-DNA were extracted from serum, biopsy and paraffin liver. Nucleotide sequencing of HAV-RNA was performed from VP1/2A and HBV-DNA from PreS/S region. The amplified samples were quantified by Real-Time PCR. The cases of HAV infection were due to subgenotype IA. The cases of HBV infection were due to genotype A2 and D4. The case of HAV/HBV coinfection was infected by genotype IA and D3. Hepatitis A and B infection were associated with genotypes most prevalent in Brazil. In hepatitis A infection the mean of period evolution was 13 days. In hepatitis B, FHF patients infected by genotype D have a shorter period of evolution than FHF patients infected by genotype A (mean 15 v. 53 days). There was no association with genotype-determining region with the severity of hepatitis, however nucleotide differences and high viral load could be observed among FHF.