Non/hypo-response to hepatitis B vaccination and influencing factors in HIV-infected patients in the context of different immunization schedules / 中华流行病学杂志

Objective: To study the non/hypo-response to hepatitis B vaccination in HIV-infected patients, identify the influencing factors and provide evidence for the development of hepatitis B prevention and control strategies and measures for special population. Methods: On the basis of the randomized controlled trial of 20 µg hepatitis B vaccine immunization at 0-1-6 month, 0-1-2-6 month and 60 µg hepatitis B vaccine immunization at 0-1-2-6 month, the HIV-infected patients who completed one-month follow-up after the full course vaccination were selected as study subjects. Quantification of antibody to hepatitis B surface antigen (anti-HBs) in serum samples was performed by using chemiluminescent microparticle immunoassay (CMIA) and demographic characteristics, disease history, HIV infection and treatment status of the study subjects were collected. Statistical analysis was conducted by χ2 test, t test, unconditional logistic regression and interaction analyses. Results: The non/hypo-response rates to hepatitis B vaccination were 34.65% (35/101), 24.49% (24/98) and 10.99% (10/91) in 20 µg group at 0-1-6 month or 0-1-2-6 month and 60 µg group at 0-1-2-6 month (P<0.001), respectively. Logistic regression analysis showed that after controlling for confounding factors, the risk for non/hypo-response was 0.22 times higher in HIV-infected patients receiving 60 µg hepatitis B vaccine at 0-1-2-6 month than in patients receiving 20 µg hepatitis B vaccine at 0-1-6 month (95%CI: 0.10-0.50), the risk for non/hypo-response was higher in men than in women (OR=3.65, 95%CI: 1.88-7.07), and the risk for non/hypo-response was 2.64 times higher in those without hepatitis B vaccination history than in those with hepatitis B vaccination history (95%CI: 1.10-6.32). Moreover, there were multiplicative interactions between immunization schedule and gender (OR=2.49, 95%CI: 1.24-5.00). Conclusion: The non/hypo-response rate to hepatitis B vaccination was significantly lower in HIV-infected patients receiving 60 µg hepatitis B vaccine at 0-1-2-6 month than in those receiving 20 µg hepatitis B vaccine at 0-1-6 month and 0-1-2-6 month. Gender, vaccination schedule and history of hepatitis B vaccination were the influencing factors of the non/hypo-response to hepatitis B vaccination. There was a multiplicative interaction between vaccination schedule and gender, and men receiving 20 µg hepatitis B vaccines had a higher risk for non/hypo-response to hepatitis B vaccination.

Hepatitis B Vaccination and Factors Related with Unresponsiveness in Healthy Children

ABSTRACT Background: The aim of this study was to assess the effectiveness of hepatitis B vaccination and factors associated with vaccine unresponsiveness in healthy children. Methods: A total of 141 healthy children aged between two and five years were included in the study. All of the cases had received 20 μg of recombinant DNA vaccine for hepatitis B (0, 1 and 6 months). Demographic features and factors such as duration of breastfeeding, exposure to HBsAg-positive family members, administration of concomitant vaccines and exposure to smoke were determined. Hepatitis B vaccination serological markers were evaluated. Post-vaccination serologic evaluation was performed one month after the last dose of primary vaccination, one month after the booster dose. Human leukocyte antigens typing was performed in non-responders. Results: Only 87.9% of the children achieved seroprotection antibodies to hepatitis B surface antigen (anti-HBsAG titers ≥ 10 mIU/ml) one month after primary vaccination. No difference was observed between vaccine responsiveness and age, gender, birthweight, maturity, duration of breastfeeding, exposure to HBsAg-positive family members, and mid-upper arm circumference (p > 0.05). HLA types, DRB 111 (64.7%), B5 (52.9%), DRB 104 (52.9%) and DRB 11001 (47%) were detected at increased frequency in non-responders. The antibody titers were significantly higher in children who breastfed for the first six months and longer and who were vaccinated concomitantly with other common vaccines. Conclusion: The seroprotection antibodies to hepatitis B surface antigen correlated with breast feeding and hepatitis B vaccination concomitant with other common vaccines. HLA types DRB 111, B5, DRB 104 and DRB 11001 had increased frequency in non-responders.

Reducción en la infección por VHB y VHD en dos poblaciones indígenas de la Amazonia peruana después de la vacunación contra la hepatitis B / Reduction of HBV and HDV infection in two indigenous peoples of Peruvian Amazon after the vaccination against hepatitis B

Resumen: Objetivo: Conocer el resultado de la vacunación contra la hepatitis B en las comunidades hiperendémicas Kandozi y Chapra de la Amazonia Peruana a partir de la prevalencia de infecciones por los virus de la hepatitis B (VHB) y Delta (VHD), ocho años después de iniciada la vacunación. Material y métodos: Se realizó un estudio transversal en 2 944 pobladores de 67 comunidades indígenas Kandozi y Chapra en abril de 2010. El tamizaje serológico para el antígeno de superficie del VHB (HBsAg), anticuerpos anti-HBc IgM e IgG, anticuerpos anti-HBs y anti-VHD se determinaron mediante pruebas de ELISA. Resultados: Las tasas de prevalencia del HBsAg, anti-HBc IgG, anti-HBs ≥10 mlUI/ml y anti-VHD fueron 2.3, 39.13, 50.95 y 2.11%, respectivamente. La prevalencia del HBsAg en niños <11 años fue cero. Entre los portadores del HBsAg, las tasas de prevalencia de sobreinfeccion por el VHD e infección aguda por el VHB fueron 2.11% (todos fueron >14 años) y 11.94%, respectivamente. Conclusiones: Estos hallazgos muestran la eliminación de portadores de VHB en niños <11 años, ocho años después de iniciada la vacunación contra el VHB.

Abstract: Objective: To determine the outcome of the vaccination against hepatitis, we determined the prevalence of hepatitis B virus (HBV) and hepatitis D virus (HDV) infections, eight years after introduction of the vaccination. Materials and methods: A cross-sectional study was performed in 2 944 participants of 67 Kandozi and Chapra indigenous peoples in April 2010. Serological screening for hepatitis B surface antigen (HBsAg), antibody anti-HBc IgM and IgG, antibody anti-HBs and anti-HDV were determined by ELISA tests. Results: The prevalence rates of HBsAg, anti-HBc total, anti-HBs ≥10 mlUI/ml and anti-HDV were 2.3, 39.13, 50.95 and 2.11%, respectively. The prevalence rate of HBsAg in children <11 years was 0%. Among carriers of HBsAg, the prevalence rates of HDV and acute HBV infections were 2.11% (all were >14 years) and 11.94%, respectively. HBsAg and anti-HBc total were associated with individuals ≥10 years (p<0.001). Conclusions: These findings show the elimination of HBV carriers in children <11 years, eight years following introduction of the vaccination against HBV.

Análise da soroconversão após esquema habitual de vacinação contra hepatite B em pacientes com doenças inflamatórias intestinais / Seroconversion analysis after habitual hepatitis b vaccination scheme in patients with inflammatory bowel diseases

ABSTRACT BACKGROUND: Patients with inflammatory bowel disease (IBD) vaccinated for hepatitis B have a low success rate in achieving protective antibody levels. The main factors suggested for this are IBD itself and the use of immunosuppressive drugs. OBJECTIVE: To evaluate the concentration of anti-HBs antibodies and to verify factors associated with the effectiveness of hepatitis B vaccination in patients with IBD. METHODS: This is a prospective, consecutive, observational, descriptive and analytical, non-randomized, qualitative study that evaluated the levels of anti-HBs antibodies in IBD patients at the Interdisciplinary Inflammatory Bowel Disease Clinic of the Family and Community Health Unit of UNIVALI - Itajaí, Santa Catarina. RESULTS: Thirty-six patients were vaccinated against hepatitis B virus (HBV), of which 29 were female. The average age was 46.2 years. Regarding the type of IBD, twenty-four patients had Crohn's disease and the duration of inflammatory bowel disease was 74 months. Fifteen patients were on concomitant immunosuppressive therapy. The effective response rate to HBV vaccine was 72.2%, verified by anti-HBs titration ≥10 UI/L. Statistical analysis revealed a negative response to vaccination in patients with Crohn's disease and immunosuppressive drugs. CONCLUSION: The success rate of HBV immunization in IBD patients is low compared to the general population. Type of disease and use of immunosuppressive drugs appear to influence the vaccine response.

RESUMO CONTEXTO: Os pacientes com doenças inflamatórias intestinais (DII) vacinados para hepatite B possuem baixa taxa de sucesso em alcançar níveis protetores de anticorpos. Os principais fatores sugeridos para isso são a própria DII e o uso de medicamentos imunossupressores. OBJETIVO: Avaliar a titulação de anticorpos anti-HBs e verificar fatores associados a efetividade da vacinação contra hepatite B em pacientes com DII. MÉTODOS: Trata-se de um estudo prospectivo e consecutivo, de caráter observacional, descritivo e analítico, não-randomizado, qualiquantitativo, que avaliou a titulação de anticorpos anti-HBs em pacientes portadores de DII no Ambulatório Interdisciplinar de Doença Inflamatória Intestinal da Unidade de Saúde da Família e Comunitária da UNIVALI - Itajaí, Santa Catarina. RESULTADOS: Trinta e seis pacientes foram vacinados contra o vírus da hepatite B (VHB), destes, 29 eram do sexo feminino. A média de idade foi de 46,2 anos. Em relação ao tipo de DII, 24 pacientes eram portadores de doença de Crohn e o tempo médio de doença inflamatória intestinal encontrado foi de 74 meses. Quinze pacientes estavam em uso de terapia imunossupressora concomitante à vacinação. A taxa de resposta à vacina contra o VHB foi de 72,2%, verificada através de titulação de anti-HBs ≥10 UI/L. A análise estatística revelou uma resposta negativa à vacinação em pacientes em uso de medicamentos imunossupressores e portadores de doença de Crohn. CONCLUSÃO: A taxa de sucesso na imunização contra o VHB em pacientes com DII é baixo quando comparado à população em geral. Tipo de doença e uso de medicamentos imunossupressores parecem desempenhar influência na resposta vacinal.

The effectiveness of the national hepatitis B vaccination program 25 years after its introduction in Iran: a historical cohort study

ABSTRACT Introduction: Hepatitis B virus (HBV) is responsible for one of the most common human viral infections. An estimated 257 million people are living with chronic HBV infection worldwide, and mortality has reached 900,000 deaths in recent years. In 2001, the World Health Organization reported a prevalence of chronic hepatitis B infection in Iran between 2-7%. Objective: To assess the effect of the national HBV mass vaccination program after 25 years. Methods: A retrospective cohort study was conducted in vaccinated and unvaccinated people according to the year of birth. Blood samples were obtained from each enrolled person and data about demographic variables, and medical and vaccination history were collected using a standardized questionnaire. Persons were considered uninfected if they were negative for both HBsAg and anti-HBc. Also, Vaccine effectiveness was measured by calculating the risk of disease among vaccinated and unvaccinated persons and defining the percentage risk reduction of infection in the vaccinated group. Results: A total of 2720 persons were interviewed. The rate of HBV breakthrough infection among the vaccinated group was significantly lower than in unvaccinated group. One hundred ninety-four cases with positive HBV markers of infection were identified. The risk ratio of HBV infection was 0.71, 95% CI: 0.54-0.94 (vaccinated/unvaccinated). The estimated vaccination effectiveness against Hepatitis B infection was 29% (95% CI: 6%-46%). Conclusions: Iran has successfully combined hepatitis B vaccination into regular immunization programs. The WHO goal of reducing HBsAg prevalence to an equivalent of 1% by 2020 has been reached. With respect to vaccination effectiveness and low prevalence of the disease in the country, catch-up hepatitis B vaccination programs for adolescents can guarantee the immunity of the population.

Eficácia de um novo esquema vacinal contra hepatite B em pacientes submetidos a transplante de fígado / New immunization schedule effectiveness against hepatitis b in liver transplantation patients

ABSTRACT BACKGROUND: Although liver transplantation is considered to be a high-risk procedure, it is well-established as a treatment option for the cure and quality of life enhancement for individuals who suffer from diseases. Preventing an infection by hepatitis B virus through immunization schedules has been the most effective way to reduce complications, since it decreases the number of people who suffer from chronic hepatitis caused by the hepatitis B virus and eradicates its transmission. OBJECTIVE: 1. Analyzing evidence in the literature on various schedules employed for immunization against hepatitis B in patients who have received a liver transplantation. 2. Suggesting potential immunization schedules against hepatitis B in patients who suffer from liver cirrhosis, without previous verifying documentation, using the Child-Turcotte Pugh score, according to evidences found in the literature. METHODS: Systematic review of the literature, conducted on the data bases MedLine, PubMed, and Lilacs, between September, 2017 and January, 2018, by using the following keywords: "Liver Transplantation, "Immunization Schedule", "Hepatitis B Vaccines". In order to analyze the articles, a summary figure was especially designed and both the results and discussion were presented in a descriptive way. RESULTS: We included 24 studies; among them, eight had accelerated immunization schedules, 13 followed the conventional schedules, and three had super accelerated schedules. Regarding immunization, 21 studies were conducted with patients in the pre-transplant period, one with a transplanted patient, one with a pre-transplant group, and one with a post-transplant group. Found articles suggest that, disregarding the chosen immunization schedule, seroconversion rates tended to be lower as the liver disease advanced, compared to the healthy population. CONCLUSION: The studies did not find seroconversion superiority between the different immunization schedules (conventional and unconventional). However, since candidates to liver transplantation are usually very vulnerable, results show that super accelerated immunization schedules are possibly recommended for such group of patients; serologic test results will be higher when the immunization schedule is completed in the pre-transplant period.

RESUMO CONTEXTO: O transplante de fígado, apesar de ser um procedimento de elevado risco, está consolidado como recurso terapêutico para cura e melhoria da qualidade de vida de indivíduos acometidos por doenças. A prevenção da infecção pelo vírus da hepatite B através da vacinação tem sido a medida mais efetiva para reduzir complicações, diminuindo o número de pessoas com hepatite crônica pelo vírus da hepatite B e eliminando a transmissão. OBJETIVO: 1. Analisar as evidências na literatura sobre os diferentes esquemas utilizados para a vacina contra a hepatite B em pacientes submetidos a transplante de fígado. 2. Sugerir possíveis esquemas de vacinação contra hepatite B para pacientes com cirrose hepática, sem documentação comprovatória anterior, em relação à classificação de Child-Turcotte Pugh, segundo evidências encontradas na literatura. MÉTODOS: Revisão sistemática da literatura, realizada nas bases de dados MedLine, PubMed e Lilacs, no período de setembro/2017 a janeiro/2018, com as seguintes palavras chaves: "Liver Transplantation, "Immunization Schedule", "Hepatitis B Vaccines". Para análise dos artigos foi utilizado um quadro sinóptico especialmente construído para esse fim e a apresentação dos resultados e discussão foi feita de forma descritiva. RESULTADOS: Foram incluídos 24 estudos, sendo oito com esquemas vacinais acelerados, 13 com esquemas convencionais e três com esquemas super acelerado. Quanto ao período da vacinação, 21 estudos foram realizados com pacientes no período pré-transplante, um em pacientes transplantados e um com um grupo pré e um grupo pós transplante. Os artigos encontrados sugerem que independente do esquema vacinal escolhido, as taxas de soroconversão tendem a ser menores conforme o avançar da doença hepática, em relação à população saudável. CONCLUSÃO: Os estudos não encontraram superioridade de soroconversão entre os diferentes esquemas de vacinação (convencional e não convencional). Entretanto, sabendo da vulnerabilidade que os candidatos a transplante de fígado estão expostos, os resultados demonstram que o esquema de vacinação superacelerado pode ser indicado para este grupo de pacientes, e que os resultados sorológicos são mais elevados quando o esquema de vacinação é completado no período pré-transplante.

Vaccination coverage and immunity against hepatitis B in public health dentists

Abstract INTRODUCTION: Occupational exposure is a major risk factor for hepatitis B (HB) transmission. METHODS: Vaccination coverage and immunity verification from 64 dentists of the Brazilian Unified Health System were investigated. An immunochromatographic method was used to verify immunity against the disease. RESULTS: Overall, 77.77% of participating dentists completed the vaccination schedule; 37.50% had negative anti-HBs test results. Furthermore, 60.93% of participants never underwent anti-HBs tests and 40% did not know how to correctly interpret results. CONCLUSIONS: Numerous dentists were not immune to the disease. Few participants previously performed the test, with many not knowing how to interpret the results.

Cumplimiento de la vacunación contra el virus de la hepatitis b en recién nacidos de Lima y Callao / Compliance of hepatitis-b virus vaccination in newborns in Lima and Callao

RESUMEN El objetivo del estudio fue determinar el cumplimiento de la vacunación contra el virus de la hepatitis B (VHB) en recién nacidos de Lima y Callao. Estudio de diseño descriptivo, transversal y multicéntrico, realizado en hospitales de alto nivel, públicos y privados. La información sobre la vacunación corresponde a recién nacidos durante una semana del 2015, y fue obtenida mediante consultas a los padres y revisión de reporte de los servicios de salud. El estudio se realizó en 12 establecimientos de salud incluyéndose a 935 madres y recién nacidos. La cobertura de vacunación dentro de las 24 horas de vida fue de 85,1% según el reporte de padres y 88,7% según el reporte de los servicios de salud. Se concluye que la cobertura la vacunación contra el VHB en recién nacidos dentro de las 24 horas de vida fue importante, pero aún alejada de metas ideales propuestas por el Ministerio de Salud y la Organización Mundial de la Salud.

ABSTRACT The objective of the study was to determine compliance with hepatitis-B virus (HBV) in newborns in Lima and Callao. A descriptive, cross-sectional, multicenter-design study was conducted in high level public and private hospitals. Information on vaccination corresponds to newborns during one week of 2015 and was obtained through consultations with parents and review of health service reports. The study was conducted in 12 health facilities including 935 mothers and newborns. Vaccination coverage within 24 hours of life was 85.1%, according to the parents' report; and 88.7%, according to the health services' report. It is concluded that the coverage of HBV vaccination in newborns within 24 hours of life was important, but still far from the ideal goals proposed by the Ministry of Health and the World Health Organization.

Evaluación del uso en adultos de cuatro vacunas: una encuesta poblacional en Argentina / Assessment of the use in adults of four vaccines: a population survey in Argentina

La vacunación es una de las estrategias más efectivas para la prevención de enfermedades. Argentina inició la transición de la vacunación del niño a la de la familia, incorporando la vacunación del adulto. Una de las dificultades con este último grupo es determinar el porcentaje de utilización (PU) de las vacunas. Con el objetivo de caracterizar el PU de las vacunas en adultos en Argentina, la Encuesta Nacional de Factores de Riesgo que realizó el Ministerio de Salud de la Nación en 2013 incluyó un módulo de vacunación. El diseño muestral fue estratificado y multietápico. Fueron encuestadas 32 365 personas >18 años sobre el uso de cuatro vacunas incluidas en el Calendario Nacional de Vacunación: hepatitis B, tétanos, influenza y neumococo. Se consideró toda la población encuestada para tétanos y hepatitis B y ciertos grupos en riesgo para influenza y neumococo, de acuerdo con las recomendaciones. El PU varió según las vacunas analizadas: tétanos 49.8%, hepatitis B 21.7%, influenza 51.6% y neumococo 16.2%. Las principales fuentes de información sobre vacunas del adulto fueron, en primer lugar los medios públicos de comunicación (televisión, internet, etc.), y en segundo lugar el personal de salud (70.8% y 27.9%, respectivamente). Se concluye que la encuesta es una herramienta útil para evaluar el uso de vacunas por adultos, identificar poblaciones con baja cobertura, así como para planificar e implementar estrategias para mejorar la cobertura.

Vaccination is one of the most effective strategies for disease prevention. Argentina initiated the transition from child vaccination to family vaccination through the incorporation of an adult schedule. One of the difficulties with this last group is to assess the percentage of use (PU) of the vaccines. With the aim of determining the PU of adult vaccines in Argentina, a vaccination module was included in the National Survey of Risk Factors carried out in 2013 by the National Ministry of Health. The sampling had a stratified multistage design. A total of 32 365 people = 18 year-old were surveyed about the use of four vaccines included in the National Vaccination Calendar: hepatitis B, tetanus, influenza, and pneumococcus. The entire population was surveyed for tetanus and hepatitis B while certain groups at risk were evaluated for influenza and pneumococcus, according to current recommendations. PU varied according to the vaccine analyzed: tetanus 49.8%, hepatitis B 21.7%, influenza 51.6% and pneumococcus 16.2%. The main information sources on adult vaccination were media (television, internet, etc.) followed by health personnel (70.8% and 27.9%, respectively). The survey is a suitable tool to assess the use of vaccines by adults, identify low coverage populations, and to plan and implement strategies to improve coverage.

Hepatitis B status in hemodialysis patients / Situação da hepatite B em pacientes em hemodiálise

ABSTRACT BACKGROUND: Patients on chronic dialysis present a high prevalence of hepatitis B virus infection. Despite infection-control practices, surveillance of serological markers, and hepatitis B vaccination, there are still outbreaks of the disease in dialysis centers. OBJECTIVE: This study aims to assess the serologic and vaccination status for hepatitis B in hemodialysis patients. METHODS: This cross-sectional study assessed serologic markers and hepatitis B vaccination status of chronic kidney disease patients on regular dialysis program in São Carlos, SP, Brazil. Patients without information about hepatitis B status (anti-HBc, HBsAg and anti-HBs) were referred for testing. Individuals with uncertain or incomplete immunization status and without serological conversion (anti-HBs <10mIU/mL) were referred to vaccination, with adverse effects monitored. RESULTS: The study included 130 from a total of 181 dialysis patients. The majority were male (63.8%), mean age 53.9 years. All patients were already screened and negative for HBsAg, and 73.8% were vaccinated against hepatitis B (59.2% complete and 14.6% incomplete schedule), with a seroconversion rate of 75.3%. Only 11 (8.5%) patients had prior dosage of anti-HBc (negative). Among the 47 patients referred for anti-HBc testing, four were anti-HBc positive and one indeterminate. Of the total of patients referred to immunization, 34 have actually received HBV vaccine; among them five had mild adverse effects. CONCLUSION: Despite the benefit of dosing of anti-HBc and anti-HBs before admission to dialysis, economic constraints have reduced the screening to only HBsAg. Since occult HBV infection has already been demonstrated in hemodialysis patients, the measure of anti-HBc should be encouraged.

RESUMO CONTEXTO: Pacientes cronicamente em diálise apresentam alta prevalência de infecção por vírus da hepatite B. Apesar de práticas de controle de infecção, vigilância de marcadores sorológicos e vacinação contra a hepatite B, ainda há surtos da doença em centros de diálise. OBJETIVO: Este estudo tem como objetivo avaliar o estado sorológico e a vacinação contra hepatite B em pacientes em hemodiálise. MÉTODOS: Estudo transversal avaliando marcadores sorológicos e vacinação contra a hepatite B em pacientes com doença renal crônica em programa regular de hemodiálise em São Carlos, SP, Brasil. Pacientes sem marcadores sorológicos para hepatite B disponíveis (anti-HBc, HBsAg e anti-HBs) foram encaminhados para testagem. Em caso de situação vacinal desconhecida, incompleta ou sem resposta vacinal (anti-HBs <10mIU/mL), os pacientes foram encaminhados para vacinação, sendo os efeitos adversos monitorados. RESULTADOS: O estudo incluiu 130 de um total de 181 pacientes em diálise. A maioria era do sexo masculino (63,8%), com idade média de 53,9 anos. Todos os pacientes já haviam sido rastreados e eram negativos para HBsAg, e 73,8% foram vacinados contra a hepatite B (59,2% esquema completo e 14,6% esquema incompleto), com uma taxa de soroconversão de 75,3%. Apenas 11 (8,5%) pacientes dispunham de dosagem prévia de anti-HBc (negativo). Entre os 47 pacientes encaminhados para testagem anti-HBc, quatro eram anti-HBc reagentes e um indeterminado. Do total de pacientes encaminhados à imunização, 34 receberam efetivamente a vacina contra o HBV; entre eles, cinco tiveram efeitos adversos leves. CONCLUSÃO: Apesar do benefício da dosagem de anti-HBc e anti-HBs antes da admissão à diálise, restrições econômicas reduziram o rastreio apenas à dosagem de HBsAg. Como a infecção oculta por HBV já foi demonstrada em pacientes em hemodiálise, a dosagem de anti-HBc deve ser incentivada.

Effects of Interleukin-4 and Interleukin-12b Gene Polymorphisms on Hepatitis B Virus Vaccination

Abstract: Approximately 10% of individuals do not respond to hepatitis B virus (HBV) vaccination, i.e. non-responders (NRs). We aimed to investigate the association of interleukin (IL)-4 and IL-12B gene polymorphisms with responsiveness to the HBV vaccine in Korean infants. Among 300 healthy infants (9-12 month), SNPs for the IL-4 gene (rs2243250, rs2070874, and rs2227284) and for the IL-12B gene (rs3213094 and rs17860508) were compared between subgroups in terms of the response to HBV vaccination. The percentages of NRs (< 10 mIU/mL), low-titer responders (LRs, 10-100 mIU/mL), and high-titer responders (HRs, ≥ 100 mIU/mL) were 20.3%, 37.7% and 42.0%, respectively. No SNPs differed in frequency between NRs and responders or between LRs and HRs. We divided the subjects into two groups according to the time interval from the 3rd dose of HBV vaccination to Ab quantification: > 6 months from the 3rd dose (n = 87) and ≤ 6 months from the 3rd dose (n = 213). In the ≤ 6 month subjects, rs2243250C and rs2227284G were significantly frequent in the lower-titer individuals (NRs + LR) than HRs (40.1 vs. 25.9%, p = 0.014 and 45.1 vs. 33.0%, p = 0.018, respectively), and the rs2243250C and rs2227284G frequencies were significantly different among the three subgroups (13.2 vs. 26.9 vs. 25.9%, p = 0.040 and 15.5 vs. 29.6 vs. 33.0%, p = 0.038, respectively). In conclusion, those results suggest that IL-4 gene polymorphisms may play a role in the response to the HBV vaccine in Korean infants.

Síndrome de Nicolau por la administración de la vacuna séxtuple intramuscular en un lactante de 6 meses / Nicolau syndrome induced by intramuscular injection of a hexavalent vaccine in a 6-month-old girl

El síndrome de Nicolau, también conocido como embolia cutis medicamentosa o dermatitis livedoide, es una reacción cutánea infrecuente, caracterizada por una necrosis de la piel y los tejidos blandos de aparición súbita luego de la aplicación intramuscular de algunas drogas. Presentamos a un bebé de 6 meses de edad que, al recibir la tercera dosis de la vacuna séxtuple intramuscular, desarrolló una lesión necrótica con reticulado violáceo periférico en el sitio de aplicación. Se destaca la importancia del diagnóstico precoz a fin de instaurar un adecuado tratamiento y seguimiento para evitar complicaciones secundarias a la isquemia.

Nicolau syndrome, also known as embolia cutis medicamentosa or livedo-like dermatitis, is a sudden tissue necrosis, a rare complication of intramuscular injection of some drugs. We report a case of a 6-month-old girl who received intramuscularly the third dose of hexavalent vaccine (DTaP-HVB-IPV/HIb), and immediately presented a livedoid lesion around the injection site, progressing to necrosis. We reinforce the importance of early diagnosis to perform a suitable treatment and clinical follow-up to avoid ischemic secondary complications.

Prevalence, risk factors and hepatitis B immunization: helping fill the gap on hepatitis B epidemiology among homeless people, Goiânia, Central Brazil / Prevalência, fatores de risco e imunização contra a hepatite B: ajudando a preencher as lacunas na epidemiologia da hepatite B entre pessoas em situação de rua em Goiânia, Goiás, Brasil / Prevalencia, factores de riesgo e inmunización contra la hepatitis B: ayudando a completar las lagunas en la epidemiología de la hepatitis B entre personas sin techo en Goiânia, Goiás, Brasil

Data are limited in Brazil on hepatitis B infection among homeless individuals, a marginalized population with high risk of sexually transmissible infections (STI), including hepatitis B. The aim of this study was to investigate hepatitis B epidemiology in homeless persons lodged in a public shelter in Goiânia, Central Brazil. From August 2014 to June 2015, 353 individuals were interviewed and tested for markers of HBV infection. Overall HBV prevalence was 21.8% (95%CI: 17,82-26,41), and 19,5% (95%CI: 15,75-24,0) showed a serological profile of previous HBV vaccination. Older individuals (> 50 years), blacks, and homosexuals or bisexuals showed increased exposure to HBV. The low frequency of individuals immunized against HBV, high social vulnerability, and risk behaviors emphasize the need for health services administrators to provide more opportunities for HBV vaccination in this target population.

No Brasil, existem poucos dados sobre a infecção por hepatite B entre pessoas em situação de rua, uma população marginalizada com alto risco para infecções sexualmente transmissíveis (IST), incluindo a hepatite B. O objetivo deste estudo foi investigar a epidemiologia da hepatite B em pessoas alojadas em um abrigo público da cidade de Goiânia, Brasil Central. De agosto de 2014 a junho de 2015, 353 indivíduos foram entrevistados e testados para os marcadores da infecção pelo HBV. Uma prevalência global de 21,8% (IC95%: 17,82-26,41) para HBV foi estimado, e 19,5% (IC95%: 15,75-24,0) apresentaram perfil sorológico de vacinação prévia contra o HBV. Ser mais velho (acima de 50 anos de idade), preto e homossexual ou bissexual foram preditores de exposição ao HBV. A baixa frequência de indivíduos imunizados contra o HBV, bem como de alta vulnerabilidade social e ocorrência de comportamentos de risco reforçam a necessidade dos gestores de saúde proporcionar mais oportunidades de vacinação para esta população-alvo.

En Brasil, existen pocos datos sobre la infección por hepatitis B entre personas sin techo, una población marginalizada con un alto riesgo de infecciones sexualmente transmisibles (IST), incluyendo la hepatitis B. El objetivo de este estudio fue investigar la epidemiología de la hepatitis B en personas alojadas en un albergue público de la ciudad de Goiânia, Brasil Central. De agosto de 2014 a junio de 2015, se entrevistó a 353 individuos y se probaron los marcadores de la infección por HBV. Se estimó una prevalencia global de un 21,8% (IC95%: 17,82-26,41) para HBV, y 19,5% (IC95%: 15,75-24,0) presentaron un perfil serológico de vacunación previa contra el HBV. Ser más viejo (por encima de 50 años de edad), negro y homosexual o bisexual fueron predictores de exposición al HBV. La baja frecuencia de individuos inmunizados contra el HBV, así como la alta vulnerabilidad social y ocurrencia de comportamientos de riesgo refuerzan la necesidad de los gestores de salud de proporcionar más oportunidades de vacunación para esta población-objetivo.

Vacunación frente al virus de la hepatitis B en una unidad de hemodiálisis: comparativa entre 2 pautas de administración / Vaccination against hepatitis B virus in a hemodyalisis unit: comparative analysis between two different schemes

INTRODUCCIÓN: La vacunación frente al virus de la hepatitis B (VHB) es más efectiva en prediálisis pero en ocasiones el paciente llega a diálisis de forma no programada sin realizar vacunación completa previa. Pretendemos determinar el grado de respuesta a inmunización frente a VHB con diferentes esquemas en hemodiálisis. MATERIAL Y MÉTODOS: Estudiamos 30 pacientes en hemodiálisis administrando 2 esquemas de vacunación frente a VHB. Un grupo realiza el esquema de 3 dosis (0, 1, 6 meses) (PAUTA 3) y otro de 4 dosis (0, 1, 2, 6 meses) (PAUTA 4). RESULTADOS: El 56.7% hizo pauta 3 con respuesta del 26.7% y el 43.3% hizo pauta 4 con 23.3% de respuesta, sin diferencias significativas entre ambas (p=0.6). La tasa de AcHBs postvacunacional fue significativamente mayor con pauta 4 (p<0.05) así como en las tasas de anticuerpos mantenidas al año; a los 2 años las tasas de anticuerpos no fueron significativamente diferentes entre ambas pautas. En el resto de análisis estadístico, la vacunación realizada en pacientes con más tiempo en diálisis tuvo mayor respuesta con pauta 4 (p<0.05) aunque con respecto a los niveles de anticuerpos no hubo diferencias en los que respondieron con cada pauta. CONCLUSIONES: No existen diferencias en la respuesta inmunológica a vacunación frente VHB en hemodiálisis entre esquemas de 3 y 4 dosis. Hay mayor respuesta con el esquema de 4 dosis en la vacunación en pacientes con mayor tiempo en diálisis. Por ello, aconsejamos realizar la inmunoprofilaxis con el esquema de 3 dosis en pacientes incidentes en hemodiálisis que no han sido vacunados anteriormente

INTRODUCTION: Vaccination against hepatitis B virus (HBV) is more effective in pre-dialysis, but sometimes the patient has to start treatment in an unscheduled way, without full immunization coverage. We try to establish the immune response rate against HBV in hemodialysis with different vaccination schemes. METHODS: We studied 30 patients in hemodialysis program with 2 different vaccination schemes against HBV. One group performed a 3-doses scheme (0, 1 and 6 months) (PATTERN 3) and the other group performed a 4-doses scheme (0, 1, 2 and 6 months) (PATTERN 4). RESULTS: 56.7% performed pattern 3, with immune response of 26.7%. 43.3% performed pattern 4, with immune response of 23.3%, without significant differences between them (p=0.06). Anti-hepatitis B surface antibodies (anti-HBs) rate after vaccination was significantly higher with pattern 4 (p<0.05) as well as the antibodies counts maintained within 1 year. After 2 years, anti-HBs rates were not significantly different between both patterns. In other statical analysis, vaccination carried out in patients who have been for a long time in hemodialysis treatment, was more responsive with pattern 4 (p<0.05) although anti-HBs levels were similar in patients that had response with each pattern. CONCLUSIONS: There are no differences in immune response between 3-doses scheme and 4-doses scheme in HBV vaccination for hemodialysis patients. There is greater response with 4-doses scheme in hemodialysis patients who have not been vaccinated previously

Avaliação de mutações de resistência ao tratamento com análogos de nucleos(t)ídeos e de escape vacinal do vírus da hepatite B (VHB) em pacientes com hepatite crônica / Evaluation of treatment resistance mutations with nuclei analogues (t) ide and vaccine escape the hepatitis B virus (HBV) in patients with chronic hepatitis

INTRODUÇÃO: A hepatite B (VHB) é uma infecção dinâmica crônica, que apesar de existir programas de imunização e tratamento antiviral disponível, existe o risco de emergência de mutações de resistência aos análogos de núcleos(t)ídeos (AN) que devem ser rastreadas, devido as suas implicações clínicas. O Brasil disponibiliza pelo SUS cinco drogas para o tratamento antiviral: IFN, LAM, ADF, ETV e TDF e um guia de conduta clínica para orientar o tratamento no território nacional, o Protocolo de Diretrizes Terapêuticas para Hepatite B e co-infecções. OBJETIVO: O objetivo do presente estudo foi avaliar as mutações de resistência aos AN, mutações de escape vacinal e genótipos circulantes em pacientes com hepatite B crônica em dois centros de referencia em Hepatites, na Bahia (região Nordeste) e no Acre (região Norte) do Brasil. MATERIAL E MÉTODOS: Foi utilizadas ferramentas de biologia molecular e bioinformática, através de nested PCR e sequenciamento direto das amostras, para rastrear as mutações de resistência, a região alvo foi a transcriptase reversa (RT) do gene P e as mutações de escape vacinal foi a região do gene S do VHB, como também os genótipos e subgenotipos do VHB. RESULTADOS: Foram incluídos 527 pacientes durante o período de 2011-2015, sendo 320 pacientes do HUPES/BA e 207 do FUNDHACRE/AC. Os pacientes que representam a região Nordeste foram 59,3 % do sexo masculino e uma média de idade de 44,75±12,4 DP, os pacientes da região Norte 42% foram do sexo masculino e a média de idade foi de 40,36±13,9 DP. Todos os pacientes incluídos apresentaram AgHBs persistente por mais de seis meses e 86,1% apresentaram AgHBe negativo. Foram sequenciadas 296 amostras dos pacientes com VHB crônica. Foram encontradas mutações de resistência aos AN na Região Norte 1,2% (2), Região Nordeste 7,4%(8) e no global 3,8%(20). Os padrões de mutações de resistência primária encontrados foram: rtA194T, (3) rtL180M+M204V, rtL180M+M204I, rtS202I, rtM204I, rtA181S, rtA181E e rtA184S. Em relação ao escape vacinal a frequencia para a Região Norte foi de 7,1% (11), Região Nordeste 8,4% (9) e no global 7,6% (20). Nos pacientes virgens de tratamento (n=189), a frequência de mutações de resistência foi de 6%, somente nas amostras da região Nordeste. Não houve diferença estatisticamente significante entre o grupo com ou sem mutação dos pacientes virgens de tratamento. Não foram encontradas mutações de resistência nas amostras da região Norte. Os genótipos circulantes nas duas regiões foram A, D e F, e a região Nordeste foi encontrada o genótipo C (C2). CONCLUSÃO: Os resultados demonstram a importância de rastrear e monitorar as mutações de resistência aos AN e de escape vacinal devido a importância epidemiológica e clínica na conduta terapêutica.

INTRODUTION: Hepatitis B virus (HBV) is a chronic dynamic infection, which although there immunization programs and antiviral therapy available, there is a risk of emergence of resistance mutations cores analogs (t) ide to be screened, because of their implications clinics. The Brazil offers the SUS five drugs for antiviral treatment: IFN, LAM, ADF, ETV and TDF and clinical guide of conduct to guide treatment in the country, the Therapeutic Guidelines Protocol for Hepatitis B and coinfections. AIM: The aim of this study was to evaluate the resistance mutations core analogues (t) ide, vaccine escape mutations and circulating genotypes in patients with chronic hepatitis B in two reference centers in Hepatitis, Bahia (Northeast) and Acre (Northern region) of Brazil. MATERIAL AND METHODS: Was used tools of molecular biology and bioinformatics by nested PCR and direct sequencing of samples to track resistance changes, the target region is the reverse transcriptase (RT) P gene and vaccine escape mutations was region of the gene S of HBV, as well as the HBV genotypes and subgenotipos. RESULTS: 527 patients were included during the period 2011-2015, with 320 patients HUPES / BA and 207 FUNDHACRE / AC. Patients representing the Northeast were 59.3% male and an average age of 44.75 ± 12.4 PD patients in the northern region 42% were male and the average age was 40, 36 ± 13.9 DP. All patients had persistent HBsAg for more than six months and 86.1% were HBeAg negative. We were sequenced 296 samples from patients with chronic HBV. the cores of similar resistance mutations were found (t) ide in the North 1.2% (2), Northeast 7.4% (8) and 3.8% overall (20). The patterns of primary resistance mutations were: rtA194T (3) rtL180M + M204V, M204I + rtL180M, rtS202I, rtM204I, rtA181S, and rtA181E rtA184S. Regarding vaccine escape the frequency for the Northern Region was 7.1% (11), Northeast 8.4% (9) and the global 7.6% (20). In treatment-naïve patients (n = 189), the frequency of resistance mutations was 6%, only the samples in the Northeast. There was no statistically significant difference between the groups with or without mutation of naive patients. There were no resistance mutations in samples from the North. Circulating genotypes in the two regions A, D and F, and the Northeast found the C genotype (C2). CONCLUSION: The results demonstrate the importance of tracking and monitoring the resistance mutations similar cores (t) ide and vaccine escape due to epidemiological and clinical importance in the therapeutic approach.

Vaccination coverage and immunity against hepatitis B among HIV-infected patients in South Brazil

Evidence-based strategies to improve the hepatitis B virus (HBV) vaccination coverage rates might help to reduce the burden caused by co-infection with HBV and human immuno-deficiency virus (HIV). In this study, the aim was to evaluate the vaccination coverage and immunity against HBV among HIV-infected individuals in South Brazil, and identify factors that are associated with compliance patterns and antibody reactivity. Three hundred HIV-infected men and women were included in this survey. The patients answered a standardized questionnaire, and vaccination cards were checked in order to assess hepatitis B vaccine status. A blood sample was collected for quantitative determination of antibody to hepatitis B virus surface antigen (anti-HBs). Participants were also evaluated for their CD4 cell count and HIV viral load. The overall vaccination coverage of HBV vaccination found in this study (57.4%) was lower than that was previously reported in South Brazil. Anti-HBs levels >10 IU/L were observed in 47.0% of the studied population. A significant inequality in the coverage rates and antibody reactivity was found in favor of patients with better economic status. In conclusion, the results indicate the need for improvement in the HBV vaccination coverage among HIV carriers, in particular focusing on low-income individuals.

Fighting Hepatitis B in North Korea: Feasibility of a Bi-modal Prevention Strategy

In North Korea, the prevalence of hepatitis B is high due to natural factors, gaps in vaccination, and the lack of antiviral treatment. Aid projects are urgently needed, however impeded by North Korea's political and economical situation and isolation. The feasibility of a joint North Korean and German humanitarian hepatitis B prevention program was assessed. Part 1: Hepatitis B vaccination catch-up campaign. Part 2: Implementation of endoscopic ligation of esophageal varices (EVL) by trainings in Germany and North Korea. By vaccinating 7 million children between 2010 and 2012, the hepatitis B vaccination gap was closed. Coverage of 99.23% was reached. A total of 11 hepatitis B-induced liver cirrhosis patients (mean age 41.1 yr) with severe esophageal varices and previous bleedings were successfully treated by EVL without major complications. A clinical standard operating procedure, a feedback system and a follow-up plan were developed. The bi-modal preventive strategy was implemented successfully. Parts of the project can serve as an example for other low-income countries, however its general transferability is limited due to the special circumstances in North Korea.

Acesso à vacina contra a hepatite B entre parturientes que realizaram o pré-natal em Pelotas, Rio Grande do Sul / Access to hepatitis B vaccine by pregnant women attending antenatal care in Pelotas, Rio Grande do Sul State, Brazil / Acceso a la vacuna contra la hepatitis B entre parturientas que realizaron el prenatal en Pelotas, Rio Grande do Sul

Objetivo: avaliar a falta de acesso à vacina contra a hepatite B, motivos e fatores associados, entre parturientes que realizaram pré-natal no município de Pelotas, Rio Grande do Sul, Brasil. Métodos: estudo transversal de base populacional, incluindo todas as parturientes internadas nas maternidades do município por ocasião do parto, em período de 30 dias, no ano de 2013. Resultados: foram entrevistadas 352 parturientes; a falta de acesso à vacina foi de 23,1 (IC95 por cento: 18,5-27,6) e o principal motivo foi não indicação pelo médico (70,1 por cento); não foi encontrada associação entre falta de acesso e os fatores sociodemográficos estudados. Conclusões: o acesso à vacina contra a hepatite B entre parturientes foi limitado, principalmente devido a sua não recomendação por parte do médico; os resultados evidenciam a necessidade de estabelecer medidas e ações que proporcionem melhorias na atenção pré-natal, no que se refere às estratégias de vacinação contra o vírus da hepatite B.

Objective: to evaluate lack of access to hepatitis B vaccination, its reasons and associated factors in pregnant women attending antenatal care in Pelotas. Methods: this was a cross-sectional population-based study using primary data at the municipality maternity facilities, including all women giving birth during a 30 day period in 2013. Results: 352 women were interviewed. There was 23.1 percent (95 percent CI, 18.5-27.6) lack of access to hepatitis B vaccine and the main reason for non-vaccination was the absence of the doctor's recommendation (70.1 percent). No association was found between lack of access and the sociodemographic factors studied. Conclusions: the study found limited access to hepatitis B vaccine among pregnant women in Pelotas- RS, due mainly to the lack of the physician recommendation. The results highlight the need for measures and actions to improve prenatal care regarding HBV vaccination strategies.

Objetivo: evaluar la falta de acceso a la vacuna contra la hepatitis B, motivos y factores asociados, entre parturientas que realizaron el prenatal en el municipio de Pelotas, Rio Grande do Sul, Brasil.Métodos: estudio transversal de base poblacional, incluyendo a todas las parturientes internadas en las maternidades del municipio por ocasión del parto, en un período de 30 días, en el año de 2013.Resultados: se entrevistaron 352 parturientes; la falta de acceso a la vacuna fue de un 23,1% (IC95%: 18,5-27,6) y el principal motivo fue la no indicación por parte del médico (70,1%); no se encontró asociación entre la falta de acceso y los factores sociodemográficos estudiados.Conclusiones: el acceso a la vacuna contra la hepatitis B entre parturientes fue limitado, principalmente debido a la no recomendación por parte del médico; los resultados ponen en evidencia la necesidad de establecer medidas y acciones que proporcionen mejorías en la atención prenatal, en lo referente a las estrategias de vacunación contra el virus de la hepatitis B.

Hepatitis b vaciination coverage and postvaccintion serologic testing among meedical students at a public university in Brazil / Cobertura vacinal para a hepatite B e teste sorológico pós-vacinal entre estudantes de medicina de universidade pública no Brasil

The aim of this cross-sectional study was to determine the hepatitis B vaccination coverage among medical students at a public university in Rio de Janeiro, Brazil, and their compliance with the postvaccination serologic testing recommendations. Of the total of 858 students, 675 (78.7%) participated in the study. Among the participants, 48.9% (95% CI: 45.1% to 52.7%) were vaccinated against hepatitis B (received ≥ 3 doses of the vaccine), 31.6% were not (received 0, 1 or 2 doses), and 19.6% did not know their vaccination status. Hepatitis B vaccination coverage increased from 26.0% among first-year students to 70.6% among sixth-year students while the prevalence of unknown vaccination status decreased from 39.7% among first-year students to 2.4% among sixth-year students. The frequency of unvaccinated students ranged from 23.7% among fifth-year students to 34.4% among first-year students. Only 34.8% of the vaccinated students performed the anti-HBs testing after vaccination. Among these medical students, we found a low adherence to the hepatitis B vaccination and to the postvaccination serologic testing. A comprehensive hepatitis B immunization program should be offered to students at this medical school.

O objetivo deste estudo transversal foi determinar a cobertura vacinal para a hepatite B entre estudantes de medicina de uma universidade pública no Rio de Janeiro, Brasil e a sua adesão às recomendações sobre o teste sorológico pós-vacinal. De um total de 858 estudantes, 675 (78,7%) participaram do estudo. Entre os participantes, 48,9% (IC de 95%: 45,1% a 52,7%) eram vacinados contra a hepatite B (receberam ≥ 3 doses da vacina), 31,6% não eram (receberam zero, uma ou duas doses) e 19,6% não sabiam o seu status vacinal. A cobertura vacinal para a hepatite B aumentou de 26,0% entre os estudantes do primeiro ano para 70,6% entre os estudantes do sexto ano, enquanto a prevalência de status vacinal ignorado diminuiu de 39,7% entre os estudantes do primeiro ano para 2,4% entre os estudantes do sexto ano. A frequência de estudantes não vacinados variou de 23,7% entre os estudantes do quinto ano a 34,4% entre os estudantes do primeiro ano. Apenas 34,8% dos estudantes vacinados realizaram o teste anti-HBs após a vacinação. Entre esses estudantes de medicina encontramos uma baixa adesão à vacinação contra a hepatite B e ao teste sorológico pós-vacinal. Um amplo programa de imunização contra a hepatite B deveria ser oferecido aos estudantes, nessa escola médica.