HDAg-L variants in covert hepatitis D and HBV occult infection among Amerindians of Argentina: new insights.

BACKGROUND: Guidelines suggest that all HBsAg-positive patients should be tested for anti-HDV IgG antibodies and to confirm active hepatitis D virus (HDV) infection by detection of HDV RNA by reverse transcriptase (RT) polymerase chain reaction (PCR). OBJECTIVES: The aim of this study was to determine the serological prevalence and molecular features of HDV within an Amerindian community from Argentina exhibiting positivity for HBsAg and/or anti-HBc total Ig. STUDY DESIGN: Forty-six plasma samples were tested for the detection of total anti-HDV antibodies by ELISA. Concomitantly, a partial RNA region coding for the delta antigen (HDAg) was amplified by RT-nested PCR (RT-nPCR). In silica translation of DNA sequences into the amino acid (aa) sequence of HDAg-S (aa110-195) and HDAg-L (aa110-214) was performed. RESULTS: Out of 46 HDV non-reactive samples by ELISA, 3 were HDV RNA positive by RT-nPCR. These samples were anti-HBc-only positive, 2 of them identified as cases of occult hepatitis B infection (OBI). The 3 cases were HBeAg-negative and showed normal ALT/AST levels. All sequences were ascribed to HDV genotype 1, but exhibited nucleotide differences in HDAg-L coding region, among which, mutations at codons 197 and 201 - reportedly known to promote in vitro an unsuitable interaction with HBsAg - were observed. CONCLUSIONS: These results provide evidence of covert HDV infection even among OBI, highlighting the need to reevaluate the currently applied guidelines for HDV diagnostic algorithms, as well as to explore if the observed mutations promote any effect on HDV pathogenesis.

New natural variants of hepatitis B virus among Amerindians from Argentina with mainly occult infections.

BACKGROUND: Hepatitis B virus infection is frequent among Amerindians. In Argentina HBV genotypes A, B, C, D, E, F and H were described in different populations, while some cases of occult hepatitis B infection (OBI) were reported in human immunodeficiency virus (HIV) coinfected patients. OBJECTIVE: To determine the prevalence, genetic diversity of HBV and to analyze the deduced amino acid sequence of both S and viral polymerase (P) genes among Amerindians of Argentina. STUDY DESIGN: A cross-sectional study including 561 individuals belonging to distinct ethnic groups, the Mbyá-guaraní (MG), the Kolla (K), the Sagua-Huarpe (SH) and the Wichi (W) was performed. RESULTS: The prevalence of HBsAg was 1.7% and 1.4% for the MG and SH, respectively, while anti-HBc was detected in all communities. HBV DNA of S/P and preCore-Core genomic regions were amplified by nested polymerase chain reaction in 59 reactive samples for anti-HBc total Ig and/or HBsAg. Of them, thirteen exhibited detectable HBV DNA, eleven of which were identified as OBI. Genotype F was predominant in the MG community with co-circulation of subgenotypes F4, F1b, A2 and D3, while subgenotype C2 prevailed within the SH community. All cases exhibited the polymorphism rtL217R within the RT domain associated to resistance to adefovir. Mutations rtD206E and rtV207I associated with lamivudine resistance were found in two MG and three SH respectively. Other new substitutions were described within the P sequence. CONCLUSIONS: This study shows for the first time the predominance of OBI, HBV subgenotypes and natural variants in Amerindians from Argentina.

Factores de riesgo asociados a la transmisión intrafamiliar del virus de la hepatitis B en la provincia de Misiones / Risk factors associated with intrafamiliar transmission of hepatitis B virus in Misiones province

INTRODUCCION: Se estima que en el mundo existen 2.000 millones de personas infectadas por el virus de la hepatitis B (VHB), de los cuales 400 millones presentan infección crónica y 1 millón muere anualmente debido a falla hepática. La transmisión del VHB entre los convivientes de un portador crónico es un evento precuente. La seroprevalencia de marcadores de infección por VHB en estos grupos de riesgo supera la esperada para la población general. La importancia de la transmisión horizontal de la hepatitis B en los núcleos familiares radica en el mayor riesgo de que sus integrantes, en particular los niños, adquieran la enfermedad y sufran graves complicaciones.OBJETIVO: Determinar la prevalencia de infección en familiares y convivientes de portadores crónicos del VHB y evaluar los posibles mecanismos de transmisión del virus de la región.METODOS: Se realizó un estudio descriptivo para determinar la prevalencia de la infección en familiares de donantes del Banco de Sangre Central de la Provincia de Misiones (BSCM) con marcadores serológicos de infección crónica (estudio transversal en 40 casos índice y 50 familiares y convivientes). Se obtuvieron datos de interés epidemiológico y muestras de sangre para detectar marcadores serológicos de infección.RESULTADOS: En los familiares y convivientes se reportaron 6% de infecciones crónicas, 22% de infecciones resueltas y 72% de individuos sin exposición al virus.CONCLUSIONES: La prevalencia total de infección por VHB fue mayor a la hallada en la población de referencia, con significancia estadística, lo que evidenció la existencia de transmisión intrafamiliar. Dado que no se logró identificar factores de riesgo, es necesario llevar a cabo más investigaciones para determinar cuáles son los mecanismos de transmisión intrafamiliar en la región y aplicar las medidas de profilaxis adecuadas.

INTRODUCTION: Hepatitis B virus (HBV) affecs an estimated 2 billion persons worldwide, of which 400 million remain chronically infected, and 1 million die of HBV-related liver diseases annually. HBV transmission between household contacts of a chronic carrier is a frequent event. The serological prevalence of HBV infection markeris in these risk groups is higher than the one observed in general population. The horizontal transmission risk is related to the severe forms of the disease, particularly in children.OBJECTIVE: To evaluate the prevalence and the modes of transmission of HBV, within infected subjects and their household in the region.METHODS: A descriptive study was conducted to determine the prevalence of infection in family members of donors of the Central Blood Bank of Misiones Province (BSCM) with serological markers of chronic infection (cross-sectional study performed in 40 index cases and 50 household contacts). Data of epidemiological interest and blood samples were collected to detect serological markers of infection.RESULTS: The prevalence in household contacts was 6% of chronic infections, 22% of resolved infections and 72% of individuals without previous virus exposure.CONCLUSIONS: The overall prevalence of HBV infection was higher than for the reference population, with statistical significance, showing intrafamiliar transmission. Since no risk factors were identified, it is necessary to do more research to clarify the intrafamiliar impact and transmission mechanisms in the region.

Factores de riesgo asociados a la transmisión intrafamiliar del virus de la hepatitis B en la provincia de Misiones / Risk factors associated with intrafamiliar transmission of hepatitis B virus in Misiones province

INTRODUCCION: Se estima que en el mundo existen 2.000 millones de personas infectadas por el virus de la hepatitis B (VHB), de los cuales 400 millones presentan infección crónica y 1 millón muere anualmente debido a falla hepática. La transmisión del VHB entre los convivientes de un portador crónico es un evento precuente. La seroprevalencia de marcadores de infección por VHB en estos grupos de riesgo supera la esperada para la población general. La importancia de la transmisión horizontal de la hepatitis B en los núcleos familiares radica en el mayor riesgo de que sus integrantes, en particular los niños, adquieran la enfermedad y sufran graves complicaciones.OBJETIVO: Determinar la prevalencia de infección en familiares y convivientes de portadores crónicos del VHB y evaluar los posibles mecanismos de transmisión del virus de la región.METODOS: Se realizó un estudio descriptivo para determinar la prevalencia de la infección en familiares de donantes del Banco de Sangre Central de la Provincia de Misiones (BSCM) con marcadores serológicos de infección crónica (estudio transversal en 40 casos índice y 50 familiares y convivientes). Se obtuvieron datos de interés epidemiológico y muestras de sangre para detectar marcadores serológicos de infección.RESULTADOS: En los familiares y convivientes se reportaron 6% de infecciones crónicas, 22% de infecciones resueltas y 72% de individuos sin exposición al virus.CONCLUSIONES: La prevalencia total de infección por VHB fue mayor a la hallada en la población de referencia, con significancia estadística, lo que evidenció la existencia de transmisión intrafamiliar. Dado que no se logró identificar factores de riesgo, es necesario llevar a cabo más investigaciones para determinar cuáles son los mecanismos de transmisión intrafamiliar en la región y aplicar las medidas de profilaxis adecuadas.

INTRODUCTION: Hepatitis B virus (HBV) affecs an estimated 2 billion persons worldwide, of which 400 million remain chronically infected, and 1 million die of HBV-related liver diseases annually. HBV transmission between household contacts of a chronic carrier is a frequent event. The serological prevalence of HBV infection markeris in these risk groups is higher than the one observed in general population. The horizontal transmission risk is related to the severe forms of the disease, particularly in children.OBJECTIVE: To evaluate the prevalence and the modes of transmission of HBV, within infected subjects and their household in the region.METHODS: A descriptive study was conducted to determine the prevalence of infection in family members of donors of the Central Blood Bank of Misiones Province (BSCM) with serological markers of chronic infection (cross-sectional study performed in 40 index cases and 50 household contacts). Data of epidemiological interest and blood samples were collected to detect serological markers of infection.RESULTS: The prevalence in household contacts was 6% of chronic infections, 22% of resolved infections and 72% of individuals without previous virus exposure.CONCLUSIONS: The overall prevalence of HBV infection was higher than for the reference population, with statistical significance, showing intrafamiliar transmission. Since no risk factors were identified, it is necessary to do more research to clarify the intrafamiliar impact and transmission mechanisms in the region.

[Seroprevalence of HTLV-1/2 in blood donors from Misiones Province]. / Seroprevalencia de HTLV-1/2 en donantes de sangre de la Provincia de Misiones.

Human T-cell Lymphotropic viruses type 1 (HTLV-1), the first human oncoretrovirus to be discovered, is the etiologic agent of Adult T-cell Leukemia (ATL) and HTLV-1 Associated Mielopathy or Tropical Spastic Paraparesis (HAM/TSP). It is endemic worldwide, including the North of Argentina where both associated diseases have also been detected. No etiologic role has been described for HTLV-2, although it has been associated with HAM/TSP-like neurologic syndromes. Both retroviruses are endemic in native populations of The Americas, Africa and at-risk populations. They are transmitted through sex contact, parenterally and from mother to child. The aim of this study was to estimate the seroprevalence of HTLV-1/2 in a blood donor population from Misiones province. A total of 6912 accepted blood donations in 2008 were analyzed. HTLV-1/2 screening was performed with ELISA and particle agglutination, and reactive samples were confirmed by Western Blot. From the total, 5 samples resulted seropositive with a final prevalence of 0.00072. Out of the 5 positive samples, one was an HTLV, three HTLV-1 and one HTLV-2. These blood donors were residents of Posadas, Eldorado and Oberá, with no risk antecedents. This study demonstrates the presence of HTLV-1/2 in a population of Misiones with a prevalence rate similar to those reported among blood donors from non-endemic areas.

Seroprevalencia de HTLV-1/2 en donantes de sangre de la Provincia de Misiones / Seroprevalence of HTLV-1/2 in blood donors from Misiones Province

El Virus Linfotrópico T Humano tipo 1 (HTLV-1), primer oncorretrovirus humano descubierto, es el causante etiológico de la leucemia de células T del adulto (ATL) y de la mielopatía asociada al HTLV-1 o paraparesia espástica tropical (HAM/TSP). Es endémico en distintas partes del mundo, inclusive en el noroeste argentino, donde ambas enfermedades fueron detectadas. El HTLV-2, no tiene un rol etiológico definido, si bien ha sido asociado con síndromes neurológicos similares a la HAM/TSP. Ambos virus son endémicos en comunidades originarias del continente americano, tribus de Africa y poblaciones en riesgo. Ambos retrovirus se transmiten por vía sexual, parenteral y de madre a hijo. El objetivo de este trabajo fue determinar la seroprevalencia de HTLV-1/2 en una población de donantes de sangre de la provincia de Misiones. Se analizaron 6912 donaciones de sangre recibidas en el Banco de Sangre Central de la Provincia de Misiones durante 2008. La detección de anticuerpos se realizó por ELISA y aglutinación de partículas, y las muestras reactivas fueron confirmadas por Western Blot. Del total de muestras, 5 resultaron seropositivas con una prevalencia final de 0.00072. De ellas, una era HTLV, tres HTLV-1 y una HTLV-2 positiva. Los donantes positivos provenían de Posadas, Eldorado y Oberá, sin antecedentes de riesgo. Este estudio demuestra la presencia de HTLV-1/2 en donantes de sangre de Misiones, con cifras similares a las notificadas en donantes de sangre de zonas no endémicas.

Human T-cell Lymphotropic viruses type 1 (HTLV-1), the first human oncoretrovirus to be discovered, is the etiologic agent of Adult T-cell Leukemia (ATL) and HTLV-1 Associated Mielopathy or Tropical Spastic Paraparesis (HAM/TSP). It is endemic worldwide, including the North of Argentina where both associated diseases have also been detected. No etiologic role has been described for HTLV-2, although it has been associated with HAM/TSP-like neurologic syndromes. Both retroviruses are endemic in native populations of The Americas, Africa and at-risk populations. They are transmitted through sex contact, parenterally and from mother to child. The aim of this study was to estimate the seroprevalence of HTLV-1/2 in a blood donor population from Misiones province. A total of 6912 accepted blood donations in 2008 were analyzed. HTLV-1/2 screening was performed with ELISA and particle agglutination, and reactive samples were confirmed by Western Blot. From the total, 5 samples resulted seropositive with a final prevalence of 0.00072. Out of the 5 positive samples, one was an HTLV, three HTLV-1 and one HTLV-2. These blood donors were residents of Posadas, Eldorado and Oberá, with no risk antecedents. This study demonstrates the presence of HTLV-1/2 in a population of Misiones with a prevalence rate similar to those reported among blood donors from non-endemic areas.