Forgotten, not neglected: viral hepatitis in resource-limited settings, recall for action.

In 2010, the World Health Assembly adopted a resolution calling for interventions for the prevention and control of chronic viral hepatitis. These infectious diseases mostly affect resource-limited countries accounting for 80% of the world's population and facing numerous obstacles to contain the epidemic. At a time when morbidity and mortality of chronic liver disease have been considerably improved in wealthy countries by new innovative strategies and new potent antiviral drugs, it is now urgent to recall for concrete actions from stakeholders of global health policy to reduce the burden in resource-limited countries.

Hepatitis C vaccine: supply and demand.

Despite difficulties associated with extreme variability and mutability of hepatitis C virus (HCV), several vaccines that prevent initial infection or viral persistence, or that clear viraemia in individuals with chronic HCV infections, are currently in development. At least one vaccine that may prevent chronic persistent infections will soon be available for testing. We review the widespread importance of HCV infection and disease, the immune response to HCV and correlates of protection, prevention strategies and vaccine candidates, and groups that will need the vaccine and provide suitable populations for assessing vaccine safety and efficacy. The evaluation of prophylactic vaccines is particularly problematic since distribution must focus upon individuals at high risk of exposure-for example, intravenous drug users and health-care providers in areas with high HCV prevalence. Although there is a huge need for therapeutic vaccines, further immunological hurdles must be cleared before one becomes available.

Improving birth dose coverage of hepatitis B vaccine.

Administration of a birth dose of hepatitis B vaccine (HepB vaccine) to neonates is recommended to prevent mother-to-infant transmission and chronic infection with the hepatitis B virus (HBV). Although manufacturers recommend HepB vaccine distribution and storage at 2-8 degrees C, recognition of the heat stability of hepatitis B surface antigen stimulated research into its use after storage at, or exposure to, ambient or high temperatures. Storage of HepB vaccine at ambient temperatures would enable birth dosing for neonates delivered at home in remote areas or at health posts lacking refrigeration. This article reviews the current evidence on the thermostability of HepB vaccine when stored outside the cold chain (OCC). The reports reviewed show that the vaccines studied were safe and effective whether stored cold or OCC. Field and laboratory data also verifies the retained potency of the vaccine after exposure to heat. The attachment of a highly stable variety of a vaccine vial monitor (measuring cumulative exposure to heat) on many HepB vaccines strongly supports policies allowing their storage OCC, when this will benefit birth dose coverage. We recommend that this strategy be introduced to improve birth dose coverage, especially in rural and remote areas. Concurrent monitoring and evaluation should be undertaken to affirm the safe implementation of this strategy, and assess its cost, feasibility and effect on reducing HBV infection rates. Meanwhile, release of manufacturer data verifying the potency of currently available HepB vaccines after exposure to heat will increase confidence in the use of vaccine vial monitors as a managerial tool during storage of HepB vaccine OCC.

Expanding the use of hepatitis vaccines in obstetrics and gynecology.

Current pediatric vaccination schedules in the United States are based on age. In contrast, adults are vaccinated against most infectious diseases, including hepatitis A and B, only when they are identified as at high risk or after a known exposure. There are multiple risk factors for hepatitis A and B of which clinicians often are not aware. Consequently, many persons at high risk are never vaccinated. Universal vaccination against hepatitis A and B is recommended for adults to halt transmission of the virus and prevent long-term sequelae. Women and their offspring are an especially important population to consider in efforts to reduce the incidence of hepatitis. The following recommendations for expanding the use of hepatitis vaccines in obstetrics and gynecology are made in this article: all older adolescents and adults should be vaccinated regardless of risk factors, and greater efforts should be made to educate physicians about the need to vaccinate their patients against hepatitis.

Supplementary statement on hepatitis A prevention.

In a recent statement on the prevention of infections caused by hepatitis A virus (HAV), NACI described the usual indications for use of immune serum globulin (IG) and the newly available inactivated hepatitis A vaccine (HAVRIX, SmithKline Beecham). Subsequently, a more potent vaccine formulation was licensed, permitting a single dose primary immunization of adults. This supplementary statement addresses this development and comments on vaccine use in children.

Hepatitis B: global importance and need for control.

Hepatitis B is a disease of global importance, with greater than 300 million carriers of the virus world-wide. Hepatitis B virus (HBV) is the cause of up to 80% of cases of primary liver cancer, the single most important cause of mortality globally. In countries where HBV carrier rates reach 10%, HBV infection may account for 3% of total mortality, a level which exceeds polio-related mortality before the introduction of polio vaccine. The only means by which hepatitis B can be eventually eliminated is mass vaccination of infants with hepatitis B vaccine as part of the Expanded Programme on Immunization (EPI) in areas of the world where the HBV carrier rate exceeds 2.5%. With recent dramatic increases in hepatitis B vaccine production and decreases in per-dose price, there are grounds for optimism that global HBV infection rates may be reduced by as much as 90% over the next 10 years.

Development and production aspects of a recombinant yeast-derived hepatitis B vaccine.

Any attempt to control or eradicate hepatitis B on a global scale requires the availability of large quantities of effective, safe and affordable hepatitis B vaccine. The drawbacks of the first generation of plasma-derived vaccines--poor acceptance, relatively high cost, limited availability--have led to the search for alternative means of producing hepatitis B vaccines. This article reviews the development and production of a yeast-derived vaccine based on recombinant DNA technology and discusses potency, stability and potential availability for use in the implementation of vaccination programmes.

Vaccines made from recombinant yeast cells.

Production of polypeptide and protein antigens through recombinant DNA technology in prokaryotic and certain eukaryotic cells in culture is facilitating the development of new vaccines that are safe, efficacious, and economically feasible to manufacture. A current example is that of human hepatitis B vaccine that, to the present, has been produced commercially using hepatitis B viral surface antigen (HBsAg) purified from the plasma of human carriers chronically infected with the virus. Production of plasma-derived vaccine is limited by the available supply of suitable carrier plasma and by the need to apply highly technical procedures to purify the antigen as well as to ensure inactivation of all infectious agents that might be present in human plasma.