Low prevalence of hepatitis delta infection in Cuban HBsAg carriers: Prospect for elimination.

Introduction: Infection with hepatitis delta virus (HDV) is one of the most severe hepatitis B virus (HBV) complications, with a more rapid progression to cirrhosis and an increased risk of hepatic decompensation and death. Data on HDV infection in Cuba are limited. The aims of our study were to determine the HDV prevalence in HBsAg carriers and to characterize the HDV strains circulating. The data were used to assess the possibility of HDV elimination in the Cuban HBV epidemiological setting. Methods: Five hundred and two serum samples from the same number of HBsAg carriers collected in the period 2006-2019 from all over the country were tested for anti-HDV total antibodies. If positive, the samples were analyzed for HDV-RNA using Real-Time RT-PCR targeting the ribozyme and HD antigen domains followed by genotyping based on phylogenetic analysis. Results: Two samples were anti-HDV positive [0.39% (95% CI 0.11-1.44)]. One of them was also HDV-RNA positive. Clinically, the patient with active HDV infection had compensated liver cirrhosis. Phylogenetic analysis showed that the virus belonged to genotype 1 and thus clustered with contemporary strains from North America, Europe, Middle East, and Asia. Discussion: This is the first HDV study, including molecular detection and virus characterization, done after the introduction of the universal childhood anti-hepatitis B vaccination. The very low prevalence of HDV infection in HBsAg carriers combined with the high HBV vaccination coverage of all newborn children, of previously identified risk groups, and of the general population currently under 40 years of age suggests that HDV elimination is feasible in Cuba if the success in HBV control is maintained.

HCV genotype determination in monoinfected and HIV co-infected patients in Cuba.

With the aim to characterize the HCV genotype distribution in Cuba, sera were collected from two subgroups: HCV-monoinfected and HCV/HIV co-infected patients. A combination of reverse transcription-PCR using genotype-specific primers, restriction fragment length polymorphism and sequencing was used to determine the genotype of 84 samples. Seventy-nine (94%) showed single infections (10 [12%] were genotype 1a and 69 [82%] genotype 1b) and 5 (6%) samples corresponded to mixed infections (2 [2%] with genotypes 1a/3a and 1 sample [1%] each with 1b/3a, 1b/4a and 1a/1b/3a). HCV/HIV co-infected subjects had a higher frequency of mixed infections (p=0.08), infection with genotype 3a (p=0.18) and for the first time genotype 4a was found. There was no association of any demographic characteristics with any specific genotype although HCV/HIV co-infected patients showed a tendency to have mixed genotypes in those older than 45 years of age (p=0.11). Phylogenetic analysis showed that HCV isolates clustered with subtypes 1b (n=15, maximal genetic distance 2.51%) and 1a (n=2, maximal genetic distance 0.35%). This report presents the prevalence of HCV genotypes in monoinfected and HIV co-infected patients, mixed HCV infections in HCV/HIV co-infected men who have sex with men with high-risk sexual practices and for the first time identifies that the uncommon genotype 4a can be present in a patient co-infected with HIV.

Molecular characterization of hepatitis E virus in patients with acute hepatitis in Venezuela.

Hepatitis E virus (HEV) causes a common infection in developing countries. HEV infection occurs as outbreaks, as sporadic clinical cases and as large epidemics in endemic areas. The objective of this study was to determine the presence of HEV infection in patients with clinical suspicion of hepatitis A virus (HAV) infection, referred to the Instituto Nacional de Higiene "Rafael Rangel" in Venezuela. Seventy-four sera were tested for anti-HAV and anti-HEV IgM antibodies. HEV-RNA was amplified from anti-HEV IgM positive sera using nested reverse transcription polymerase chain reaction for ORF1 (RNA dependent RNA polymerase region) and the amplicons sequenced for phylogenetic analysis. The frequency of anti-HEV IgM was 22/74 (30%) in the samples tested. Dual infection with HAV and HEV was found in 31% (12/39) of anti-HAV IgM positive patients. Viremia was detected in 3/22 (14%) of sera positive for anti-HEV IgM. Two HEV strains were classified as genotype 1 and one as genotype 3, which were closely related to Yam 67 (north of India) and US1 isolates from the USA, respectively. These findings suggest that HEV is an important cause of acute viral hepatitis in Venezuela as a single infection or co-infection with HAV, with high morbidity in children and young adults suggesting that this infection is endemic in Venezuela.

Dual infection with hepatitis A and E viruses in outbreaks and in sporadic clinical cases: Cuba 1998-2003.

Viral hepatitis ranks as the fifth cause of morbidity for infectious diseases in Cuba. Epidemics are observed frequently in the population, the hepatitis A virus being the main agent responsible for such epidemics. Previous reports also confirmed the circulation of the hepatitis E virus. From 1998 to 2003, 258 serum samples were collected by the Reference Laboratory on Viral Hepatitis during 33 outbreaks of acute viral hepatitis as well as from 39 sporadic clinical cases. Sera were tested for anti-HAV and anti-HEV IgM by EIA. Overall of the 33 outbreaks studied sera from 12 (36.4%) were positive for anti-HAV IgM only, from 7 (21.2%) were positive for anti-HEV IgM only, and from 14 (42.4%) were positive for antibodies to both viruses. Individually of the 258 sera collected, 137 (53.1%) were positives for anti-HAV IgM, 20 (7.8%) were positives for anti-HEV IgM, 33 (12.8%) were positives for both markers and 68 (26.4%) were negative to both. Of the clinical cases, 4 (10.3%) were positives for anti-HAV IgM, 13 (33.3%) were positives for anti-HEV IgM and 5 (12.8%) were positives for both markers. Seventeen (43.6%) sera were negatives for all viral hepatitis markers available (A-E). A high positivity for HEV was found in outbreaks tested with the kit produced by CIGB. In particular HEV seems to infect individuals of all ages. The results demonstrate the co-circulation of and co-infection with two enterically transmitted viruses; however a higher positivity was observed for anti-HAV than to anti-HEV (53.1% vs. 7.8%) in outbreaks.