Bad Liver and a Broken Heart: Hepatitis B in the Newborn.

Hepatitis B viral infection is a significant source of morbidity and mortality worldwide. The United States has experienced a precipitous drop in acute hepatitis B infection after the introduction and widespread adoption of recombinant vaccines. Neonates experience significant risk from both vertical and horizontal hepatitis B exposure during a period of immaturity of the innate and adaptive immune systems. Acquisition of hepatitis B virus at or near birth confers the highest lifetime risk of chronic infection and subsequent complications including liver cirrhosis and hepatocellular carcinoma. Pregnant women should be screened for the presence of hepatitis B surface antigen, indicating acute or chronic infection, and, if positive, hepatitis B viral deoxyribonucleic acid, allowing for quantification of viral load. The development of highly effective and safe recombinant vaccines allows partial protection of late preterm and term neonates immediately after birth. Additionally, administration of hepatitis B immune globulin in the setting of suspected or confirmed exposure supplements the immune response and decreases the risk of chronic infection. The optimal timing of vaccination is later in low-birth-weight neonates due to the aforementioned immune system immaturity. Health care providers serving neonates must familiarize themselves with national guidelines regarding hepatitis B vaccination and hepatitis B immune globulin therapy. Understanding the risks of infection and the evidence basis supporting vaccination and immunotherapy will allow providers to educate families and support decision-making, with the potential to eradicate this vaccine-preventable illness in our lifetime.

Uptake of hepatitis B vaccination and associated factors among health sciences students, Mogadishu, Somalia.

Background: Hepatitis B is a potentially fatal liver infection caused by the hepatitis B virus (HBV). It is a serious issue for global health. It considerably raises the risk of cirrhosis and liver cancer-related death and can result in chronic infection. The risk of infection is high among health sciences students due to the risk of occupational contact with fluids of infected patients and the risk of needle stick injury. The most effective way of preventing HBV infection is the vaccination of students prior to their posting to healthcare settings. There is no data available about HBV vaccination uptake among Health Sciences students in Somalia. Therefore, this study aimed to determine HBV vaccination uptake and associated factors toward HBV among health science students in Somalia. Methods: A cross-sectional study was undertaken among health sciences students from August to October 2022. Data were gathered using Kobo Toolbox using a standardized questionnaire with questions on characteristics, knowledge attitude, and HBV prevention practices. A total of 569 students were involved in the study. Stata version 15 was utilized for the analysis. Bivariate and multivariate logistic regression analysis, as well as descriptive statistics, were performed. In order to assess the existence and significance of the relationship between the outcome and risk factors, an adjusted odds ratio with a 95% confidence interval (CI) was used. Statistical significance was considered as a p-value ≤0.05. Results: Of the 569 study participants, 33.4% (95%CI: 29.6-37.4) received a full dose of the HBV vaccine in this study. Participants had good HBV prevention knowledge, attitudes, and practices at 69.6, 37.96, and 50.6%, respectively. The lack of access and the high cost of the vaccine were the reasons for not taking the vaccine. Second-year [AOR: 0.22 (0.12-0.43)]. Positive attitude [AOR: 0.54 (0.31-0.93)], and good practice [AOR: 6.99 (3.62-13.5)]. Discussion: The study indicated that 33.4% of health sciences students had received the required HBV vaccination doses, academic year, attitude, and practice were significantly associated with full-dose vaccination status. The unavailability of the vaccine and the high cost of vaccination were the most common reasons for not taking the vaccine. It is recommended that students receive vaccinations before beginning clinical rotations, and give instruction on infection prevention strategies and general precautions, particularly regarding HBV infection.

The impacts of the COVID-19 pandemic on patients with viral hepatitis B infection: follow-up, compliance with antiviral treatment, and vaccine preferences.

OBJECTIVE: Elimination programs and interventions for patients with viral hepatitis B (HBV) have been disrupted during the COVID-19 pandemic. This study aimed to evaluate the effects of the COVID-19 pandemic on patients with HBV infection in terms of COVID-19 vaccine preferences, follow-up visits, and antiviral treatment compliance. PATIENTS AND METHODS: In this retrospective single-center cross-sectional study, 129 patients with viral hepatitis B infection were evaluated. The patients were surveyed at the time of admission. A special form was created for patients with viral hepatitis B infection, and the form contained information about the patients at admission to collect the study data. RESULTS: A total of 129 participants were included in the study. Of the participants, 49.6% were males and the median age was 50 years. In total, 73 (56.6%) patients had their follow-up visits disrupted because of the COVID-19 pandemic. No newly diagnosed case of HBV infection was detected. Among the 129 patients, 46 had inactive hepatitis B, and 83 had chronic hepatitis B infection and were receiving antiviral treatment. None of the patients had trouble reaching antiviral treatments during the COVID-19 pandemic. A liver biopsy was recommended for 8 patients. Half of these 8 patients did not have follow-up visits during the COVID-19 pandemic. Most of the patients (123/129, 95.3%) received the COVID-19 vaccine and the most frequent vaccine that was used was the Pfizer-BioNTech (n: 92, 71.3%) vaccine. Serious side effects of the COVID-19 vaccines were not detected. Mild side effects were found in 41.9% (13/31) of the patients. The COVID antibody level was found to be statistically and significantly higher in the patients who received the Pfizer-BioNTech vaccine than in those that received the CoronoVac vaccine. CONCLUSIONS: It was reported that elimination programs and interventions for HBV infection decreased or stopped because of the COVID-19 pandemic. In the present study, no newly diagnosed case of HBV infection was detected. Most of the patients had their follow-up visits disrupted. There were no patients who could not receive antiviral treatment, the vaccination rate of the patients was high, and the vaccines were well tolerated.

Impact and cost-effectiveness of hepatitis B virus prophylaxis in pregnancy: a dynamic simulation modelling study.

BACKGROUND: In 2020, WHO recommended the addition of peripartum antiviral prophylaxis (PAP) to hepatitis B birth dose vaccination (HepB-BD) and hepatitis B infant vaccination (HepB3) to reduce mother-to-child transmission of hepatitis B virus (HBV) infection in pregnant women who have a marker of high infectivity (ie, HBV DNA ≥200 000 international units per mL or HBeAg-positive). We aimed to evaluate the impact and cost-effectiveness of this recommendation and of a theoretical simplified strategy whereby PAP is given to all pregnant women who are HBsAg-positive without risk stratification. METHODS: This modelling study used a dynamic simulation model of the HBV epidemic in 110 countries in all WHO regions, structured by age, sex, and country. We assessed three strategies of scaling up PAP for pregnant women: PAP for those with high viral load (PAP-VL); PAP for those who are HBeAg-positive (PAP-HBeAg); and PAP for all pregnant women who are HBsAg-positive (PAP-universal), in comparison with neonatal vaccination alone (HepB-BD). We investigated how different diagnostic and antiviral drug costs affected the cost-effectiveness of the strategies evaluated. Using a health-care provider perspective, we calculated incremental cost-effectiveness ratios in cost (US$) per disability-adjusted life-year (DALY) averted in each country's population and compared these with country-specific cost-effectiveness thresholds. We also calculated new neonatal infections averted for each of the strategies. FINDINGS: Adding PAP-VL to HepB-BD could avert around 1·1 million (95% uncertainty interval 1·0 million-1·2 million) new neonatal infections by 2030 and around 3·2 million (95% uncertainty interval 3·0 million-3·4 million) new neonatal infections and approximately 8·8 million (7·8 million-9·7 million) DALYs by 2100 across all the countries modelled. This strategy would probably be cost-effective up to 2100 in 28 (26%) of 106 countries analysed (which included some of the countries that have the greatest HBV burden) if costs are as currently expected to be, and in 74 (70%) countries if diagnostic and monitoring costs were lowered (by about 60-75%). The relative cost-effectiveness of PAP-VL and PAP-HBeAg was finely balanced and depended on the respective diagnostic and monitoring costs. The PAP-universal strategy could be more cost-effective than either of these strategies in most countries, but the use of antiviral treatment could be five times as high than with PAP-VL. INTERPRETATION: PAP can provide substantial health benefits, and, although the current approach might already be cost-effective in some high-burden settings, decreased diagnostic costs would probably be needed for PAP to be cost-effective in most countries. Therefore, careful consideration needs to be given about how such a strategy is implemented, and securing reduced costs for diagnostics should be a priority. The theoretical strategy of offering PAP to all women who are HBsAg-positive (eg, if diagnostic tests to identify mothers at risk of transmission are not available) could be a cost-effective alternative, depending on prevailing costs of diagnostics and antiviral therapy. FUNDING: UK Medical Research Council, UK National Institute for Health and Care Research, and the Vaccine Impact Modelling Consortium.

Universal Adult Hepatitis B Screening and Vaccination as the Path to Elimination.

This Viewpoint describes new recommendations from the CDC regarding universal screening of adults for hepatitis B virus infection.

Loss of protective anti-HBs titers and seroconversion to hepatitis B vaccination in children during chemotherapy for acute lymphoblastic leukemia.

BACKGROUND: This study aimed to evaluate loss of protective anti-hepatitis B (HBs) titers and seroconversion to hepatitis B vaccine (HBV) during chemotherapy in children with acute lymphoblastic leukemia (ALL). METHODS: Anti-HBs titers were done at diagnosis. Patients were divided into two groups. Group I (protective titers >10 mIU/ml) received single double dose of HBV as booster. Titers were repeated at three time points: end of phase 1b, beginning of re-induction, and start of maintenance chemotherapy. Group II (nonprotective titers <10 mIU/L) received hepatitis B immunoglobulin (HBIG), prior to start of chemotherapy, followed by three double doses of HBV as booster. Titers were repeated at two time points: prior to first dose, and 4 weeks after third dose of vaccine. RESULTS: Total 125 patients were included: 88 in group I; 37 in group II. Among group I patients, 98.7%, 90%, and 84% retained protective titers at the three points, respectively. Subgroup analysis showed that those with initial titers greater than 100 mIU/L retained protective titers better than those with titers between 11 and 100 mIU/L (p = .0001). Among group II patients, 62% and 64% attained protective titers at the two points, respectively. CONCLUSIONS: HBV boosters helped maintain protective titers during intensive ALL chemotherapy in immunized children having titers more than 10 mIU/L, and more so if titer was more than 100 mIU/L. Therefore, we propose that cut off for protective anti-HBs titers be changed to greater than or equal to 100 mIU/L. Titers between 11 and 100 mIU/L may require combined active and passive immunization. Around one-third of group II patients who fail to attain protective titers may need frequent doses of HBIG.

An Evidence-based Practical Guide to Vaccination for Hepatitis B Virus.

The hepatitis B virus (HBV) is highly infectious, with over 292 million chronically infected people worldwide and up to 2.4 million in the United States. Following infection, clinically silent liver damage can ensue, but symptoms or signs of advanced disease, including cirrhosis and hepatocellular carcinoma, can take decades to emerge. HBV has the heaviest public health burden of all hepatitis viruses and has now surpassed other major communicable diseases (eg, HIV, diarrheal disease, malaria, tuberculosis) as a leading cause of death globally. Preventing transmission is essential, and efforts are in place to reinforce screening, vaccination, and routine follow-up. Three safe and effective vaccines are available in the United States and other countries for HBV prevention, and the benefits of vaccination in preventing infection and its sequelae have been substantiated. For the first time in over 25 years, a new Food and Drug Administration-approved vaccine is available that offers a high degree of immunogenicity after 2, rather than 3, injections. Persistent challenges include the underutilization of vaccination, choice of vaccine, incomplete vaccinations, varying needs in different populations, management of nonresponders or those with undocumented or incompletely documented vaccination courses, and questions about whether and when booster injections may be needed. A panel of US academic hepatologists with expertise and experience in preventing and managing HBV infection have collaborated to write this practical clinical paper intended to guide clinicians in vaccinating for HBV and address questions that regularly arise in the clinic.

Long term outcome of prevention of liver cancer by hepatitis B vaccine: Results from an RCT with 37 years.

We aimed to evaluate the long-term efficacy of the hepatitis B vaccine in China. In an initial efficacy study, participants were collected from a cluster-randomized clinical trial conducted in 1983-90 in Qidong. All the participants in the vaccination group were vaccinated at birth, 1 and 6 months of age, and no intervention was implemented to the control group. In this 37-year extended follow-up study, the Poisson regression method was employed to derive rates per 105 person-years. The frailty Cox proportional hazard regression models obtained the hazard ratio (HR). Cumulative incidence/mortality rates were calculated and compared with log-rank tests. 41,136 in the vaccination and 41,730 in the control group were recorded. The incidence rate of liver cancer was significantly lower in the vaccinated group than in the control group [HR, 0.28; 95% confidence interval (CI) 0.11-0.70, P = 0.007]. The vaccine offers 72% (95% CI, 30-89) protection to prevent the occurrence of liver cancer. There is 70% (95% CI, 23-88) protective efficacy against liver cancer deaths and 64% (95% CI, 27-82) benefits in the prevention of deaths associated with liver diseases. Hepatitis B vaccine given at birth shows excellent protective effects in preventing the development of liver cancer and reducing mortality from liver cancer and liver diseases.

Hepatitis B Screening, Vaccination, and Linkage to Care: Lessons Learned from a Mississippi Vietnamese Community.

BACKGROUND: Asian-Americans and Pacific Islanders are disproportionately impacted by chronic hepatitis B infection (CHBI). The long-term effects of untreated CHBI include cirrhosis of the liver, hepatocellular carcinoma, and liver failure. Approximately two-thirds of those living with CHBI are unaware of their HBV status. OBJECTIVES: Plan, implement, and evaluate a culturally and linguistically appropriate screening, vaccination, and linkage-to-care initiative that used Vietnamese-speaking community health workers for care navigation among Vietnamese-Americans residing in the Mississippi coastal counties of Hancock, Harrison, and Jackson. METHODS: The initiative employed a community-based participatory framework to plan and implement the program. An active community advisory board was established and was representative of all the partners that worked together to make the initiative a success.Results and Lessons Learned: Before program implantation, results from focus groups indicated that the Vietnamese community had low knowledge about the risk of CHBI. Additionally, there were no Vietnamese-speaking health care providers, nor primary care providers treating CHBI in the prioritized counties. A total of 505 Vietnamese individuals were screened. One-half were immune by infection (n = 235 [46.5%]), 83 (16.4%) were immune by vaccination, 46 (9.1%) had CHBI, 130 (25.7%) were vaccine naïve, and 40 (7.9%) were undetermined, (n = 130), 101 (77.7%) received the complete three-injection vaccine series. Five new primary care providers now provide treatment for those with CHBI. Cultural competency and community/medical interpreter training were also provided to reduce language barriers during medical encounters. CONCLUSIONS: To ensure success, it is paramount that community input is not only solicited but that partnerships provide a space where the input informs all aspects of the program.

The Possible Protective Effect of Hepatitis B Vaccine against Lymphomas: A Systematic Review.

BACKGROUND: In the last few years, the possible etiological role of the Hepatitis B virus (HBV) in the outbreak of extrahepatic pathologies has been studied, including lymphomas. The World Health Organization (WHO) estimates that around 257 million people live with chronic HBV infection, and to date, the vaccine is the most effective means of prevention. OBJECTIVE: The aim of this review was to evaluate whether the vaccination against Hepatitis B can lead to a reduction in lymphoma cases and has a protective role. METHODS: A literature search was conducted in April 2020 using the databases Scopus, PubMed, and ISI Web of Science. Search terms included: "Hepatitis B vaccination AND lymphoma." All articles evaluating the association between Hepatitis B vaccination and the prevention of lymphoma were selected. No limits were applied. RESULTS: Eight studies were eligible to be included in the review. Data showed that association between lymphoma and HBV infection is not the same for all types of lymphomas, but it appears to be more significant for Non-Hodgkin Lymphoma (NHL). The results from all the considered articles were not unitary. This is because studies were conducted in different countries with different endemicity of Hepatitis B, different vaccination coverage, treatment of chronic Hepatitis, and prevention of its complications, as well as the availability of data for researchers. No statistically significant association was found between HBV vaccination and the development of lymphomas. CONCLUSION: Although the literature is still largely lacking regarding the protective effect of anti- HBV vaccination on lymphoma subtypes, the association between HBV infection and lymphoma has been confirmed in several studies. Vaccination programs eliminate the risk of HBV infection and prevent liver disease but can also indirectly reduce the risk of lymphomas.

Measuring quality of hepatitis B care in a remote Australian Aboriginal community: opportunities for improvement.

BACKGROUND: Chronic hepatitis B (CHB) infection remains a significant public health issue for Indigenous Australians, in particular for remote communities. AIM: To evaluate the spectrum of hepatitis B virus (HBV) care provided to a remote Aboriginal community. Measures studied included screening, seroprevalence, vaccination rates and efficacy, and HCC risk and surveillance adherence. METHODS: A retrospective audit of HBV care received by all permanent residents currently attending a remote Aboriginal Health service. This study was endorsed by both the local Aboriginal Health service and the Aboriginal Health Council of South Australia. RESULTS: A total of 208 patients attended the clinic, of whom 52% (109) were screened for HBV. Of these, 12% (13) had CHB and 20% (22) had evidence of past infection. Similarly, of the 208 attending patients, complete vaccination was documented in 48% (99). Of the 33 patients with post-vaccination serology, 24% (8) had subtherapeutic (<10 IU/mL) levels of HBsAb. Subtherapeutic HBsAb was independently associated with higher Charlson Comorbidity scores (odds ratio = 17.1; 95% confidence interval 1.2-243.3; P = 0.036). Definitive breakthrough infection was identified in 6% (2) patients. One HBsAg positive patient was identified as needing HCC surveillance, but had not undertaken HCC surveillance. CONCLUSION: Opportunities to improve the quality of CHB care through increased HBV vaccination, screening and adherence to HCC surveillance were identified. High rates of subtherapeutic vaccine responses and documented breakthrough infection raises concerns about the effectiveness of current CHB vaccines in this population.

Hepatitis B Vaccination Impact and the Unmet Need for Antiviral Treatment in Blantyre, Malawi.

BACKGROUND: Hepatitis B is the leading cause of cirrhosis and liver cancer in sub-Saharan Africa. To reduce mortality, antiviral treatment programs are needed. We estimated prevalence, vaccine impact, and need for antiviral treatment in Blantyre, Malawi. METHODS: We conducted a household study in 2016-2018. We selected individuals from a census using random sampling and estimated age-sex-standardized hepatitis B surface antigen (HBsAg) seroprevalence. Impact of infant hepatitis B vaccination was estimated by binomial log-linear regression comparing individuals born before and after vaccine implementation. In HBsAg-positive adults, eligibility for antiviral therapy was assessed. RESULTS: Of 97386 censused individuals, 6073 (median age 18 years; 56.7% female) were sampled. HBsAg seroprevalence was 5.1% (95% confidence interval [CI], 4.3%-6.1%) among adults and 0.3% (95% CI, .1%-.6%) among children born after vaccine introduction. Estimated vaccine impact was 95.8% (95% CI, 70.3%-99.4%). Of HBsAg-positive adults, 26% were HIV-positive. Among HIV-negative individuals, 3%, 6%, and 9% were eligible for hepatitis B treatment by WHO, European, and American hepatology association criteria, respectively. CONCLUSIONS: Infant HBV vaccination has been highly effective in reducing HBsAg prevalence in urban Malawi. Up to 9% of HBsAg-positive HIV-negative adults are eligible, but have an unmet need, for antiviral therapy.

Usos de la levadura Pichia pastoris en la producción de proteínas recombinantes / Uses of Pichia pastoris yeast in the production of recombinant proteins

La levadura metilotrófica Pichia pastoris (clasificada actualmente como Komagataella phaffii) es una de las más importantes para la producción de proteínas heterólogas. En el trabajo se presenta un análisis de las principales características que se ponen de manifiesto en la expresión de proteínas recombinantes expresadas en este microorganismo. Se describen las cepas disponibles para la transformación y producción de proteínas recombinantes expresadas en Pichia pastoris, los principales vectores comerciales para la expresión, los promotores más eficientes, los marcadores seleccionables, la señal de secreción, los métodos usados en las transformaciones genéticas y los patrones de glicosilación que se presentan. Se brindan recomendaciones generales acerca de los parámetros de bioprocesos como la composición del medio, el pH, la temperatura, la velocidad de aireación, la inducción y las estrategias de alimentación para alcanzar altos valores de productividad. Se presentan los resultados de las aplicaciones de Pichia pastoris en la producción de dos vacunas en Cuba, la vacuna contra la hepatitis B y la vacuna para el control de la garrapata(AU)

Pichia pastoris metylotrofic yeast (currently classified as Komagataella phaffii) is one of the most important yeast for the production of heterologous proteins. The work presents an analysis of the main characteristics that are marked in the production of recombinant proteins expressed in Pichia pastoris. It describes the strains available for the transformation and production of recombinant proteins expressed in P. pastoris, the main commercial vectors for expression, the most efficient promoters, selectable markers, the secretion signal, the methods used in genetic transformations and glycosylation patterns that occur. General recommendations are provided on bioprocess parameters such as media composition, pH, temperature, aeration velocity, induction, and feeding strategies to achieve high productivity values. The results of Pichia pastoris applications for the production of two vaccines in Cuba, the hepatitis B vaccine and the tick control vaccine are shown(AU)

Hepatitis B Before and After Hepatocellular Carcinoma.

Hepatitis B virus (HBV) is the one of most common causes of the hepatocellular carcinoma (HCC), especially in eastern world. The aim of this review is to try to understand the relationship between HBV and HCC and to reveal the role of prevention and treatment of HBV infection in reducing the incidence of HCC. Strategies to prevent HCC due to HBV can be classified into three categories. These are primary, secondary, and tertiary preventions. Hepatitis B vaccine is now in the most vital position in preventing HBV-associated HCC. In patients with chronic hepatitis B infection, suppressing viral load with potent antivirals such as tenofovir disoproxil fumarate (TDF) and entecavir (ETV) prevents the development of HCC and improves prognosis by reducing recurrence after HCC treatments. There is currently no clear consensus on which of these drugs should be preferred. Although data on tenofovir alafenamide (TAF) are scarce, available data with TDF suggest that TAF therapy will also be a strong actor for HCC.

Immunotherapy and therapeutic vaccines for chronic HBV infection.

Chronic hepatitis B virus (HBV) infection is a major global health burden causing severe complications like liver cirrhosis or hepatocellular carcinoma. Curative treatment options are lacking. Therefore, there is an urgent need for new therapeutic options. Immunotherapy with the goal to restore dysfunctional HBV-specific T cell immunity is an interesting new therapeutic strategy. Based on current evidence on dysfunction of the HBV-specific CD8+ T cell response in chronic HBV infection, we will review the growing field of immunotherapeutic approaches for treatment of chronic HBV infection. The review will focus on therapies targeting T cells and will cover checkpoint inhibitors, T cell engineering, Toll-like receptor agonists and therapeutic vaccination.

Hepatitis B Vaccines.

Hepatitis B is caused by the hepatitis B virus (HBV), which infects the liver and may lead to chronic liver disease, including cirrhosis and hepatocellular carcinoma. HBV represents a worldwide public health problem, causing major morbidity and mortality. Affordable, safe, and effective, hepatitis B vaccines are the best tools we have to control and prevent hepatitis B. In 2019, coverage of 3 doses of the hepatitis B vaccine reached 85% worldwide compared to around 30% in 2000. The effective implementation of hepatitis B vaccination programs has resulted in a substantial decrease in the HBV carrier rate and hepatitis B-related morbidity and mortality. This article summarizes the great triumphs of the hepatitis B vaccine, the first anticancer and virus-like-particle-based vaccine. In addition, existing unresolved issues and future perspectives on hepatitis B vaccination required for global prevention of HBV infection are discussed.

Therapeutic vaccination for treatment of chronic hepatitis B.

Chronic hepatitis B infection remains a serious global health threat, contributing to a large number of deaths through liver cirrhosis and hepatocellular carcinoma. Current treatment does not eradicate disease, and therefore new treatments are urgently needed. In acute hepatitis B virus (HBV) a strong immune response is necessary to clear the virus, but in chronic infection the immune response is weakened and dysfunctional. Therapeutic vaccination describes the process of inoculating individuals with a non-infective form of viral antigen with the aim of inducing or boosting existing HBV-specific immune responses, resulting in sustained control of HBV infection. In this review we outline the rationale for therapeutic vaccination in chronic HBV infection, discuss previous and ongoing trials of novel HBV therapeutic vaccine candidates and outline strategies to improve vaccine efficacy going forward.

Cuban Prophylactic and Therapeutic Vaccines for Controlling Hepatitis B.

Hepatitis B causes liver failure, cirrhosis and cancer. It has an estimated global prevalence of 6%, and 700,000 to 1 million persons die every year of hepatitis B-related causes. In 1989, hepatitis B incidence in Cuba was 14.9 per 100,000 population. To control infection, the Genetic Engineering and Biotechnology Center and the Ministry of Public Health, both in Havana, collaborated on a joint project that first produced natural interferon and recombinant interferon alpha-2b, and later a polyethylene glycolconjugated interferon. As part of the Cuban biotechnology development strategy, the project produced a vaccine against hepatitis B in 1985. At that time, hepatitis B vaccines available elsewhere in the world were costly and inaccessible to Cubans due to the US economic and trade embargo. The Heberbiovac HB preventive vaccine was approved by the Cuban regulatory authority and added to the Cuban newborn vaccination program in 1992 after phase 1-3 clinical trials demonstrated its safety and immunogenicity. From 2001 to 2003, PAHO/WHO qualified and requalified the vaccine four times. When associated with other antigens or molecules, Heberbiovac HB provides a common platform of virus-like particles that can be used in different ways, such as in the pentavalent vaccine containing Bordetella pertussis and Haemophilus infl uenzae type b antigens and tetanus and diptheria toxoids. Thanks to this vaccine, annual incidence of acute hepatitis in Cuba has dropped from more than 2000 cases to fewer than 100, and no infections in children aged 0-15 years have been reported since 2007. It is now used in more than 30 countries, providing protective, long-lasting antibody levels with no reports of serious adverse events. Yet, hepatitis B cannot be eliminated until there are no chronic patients. The comprehensive hepatitis B control project therefore included development of a therapeutic vaccine based on Heberbiovac HB. Using its platform, researchers designed an innovative version of the vaccine that was the precursor of a therapeutic nasal/subcutaneous vaccine for chronic hepatitis B, HeberNasvac. This precursor vaccine, which combines Heberbiovac HB with a recombinant antigen from the virus nucleocapsid (rHBcAg), was patented and licensed in 2015 by the Cuban regulatory authority. This article provides an overview of the progress-to-date on the development of this therapeutic vaccine, including clinical trials (some completed and others ongoing) to determine safety, efficacy and therapeutic benefits.

HIV Infection in Adults: Initial Management.

The HIV epidemic is an important public health priority. Transmissions continue to occur despite effective therapies that make HIV preventable and treatable. Approximately one-half of people with HIV are not receiving suppressive antiretroviral therapy (ART). Starting ART early, followed by continuous lifetime treatment, most effectively achieves durable virologic suppression and restoration of immune function that can improve clinical outcomes and prevent transmission to partners who are seronegative. National treatment guidelines include ART options that can be offered immediately after diagnosis, even before the results of baseline HIV drug-resistance testing are available. Initial ART selection should be guided by co-occurring conditions, including viral hepatitis, medications, and other factors such as pregnancy. Identifying and addressing psychosocial barriers to care is a key element of ensuring long-term adherence to treatment. The initial physical examination typically reveals no clinical manifestations of HIV in the absence of advanced disease. A comprehensive laboratory evaluation, including HIV viral load and CD4 lymphocyte monitoring, is necessary to guide decision-making for treatment, opportunistic infection prophylaxis, and vaccinations. The initial management of people with HIV presents a unique opportunity for family physicians to improve patients' long-term health care and reduce HIV transmissions.