Global Vaccination Programs Research Articles

Mucha-Habermann Disease-like Eruption Following Pandemic Influenza H1N1 Vaccination: Coincidence or Causal Relationship?

Since its emergence reported in April 2009, pandemic influenza H1N1 rapidly spreads among humans all over the world. Although seasonal influenza vaccination has been implicated to occasionally induce skin diseases, extremely rare cases of skin eruption following pandemic influenza H1N1 vaccination have been reported. We here present a case of Mucha-Habermann disease-like eruption following pandemic influenza H1N1 vaccination. With a global H1N1 vaccination program against the pandemic H1N1 influenza, physicians and patients should be appraised of such rare skin reactions that may be induced by pandemic influenza H1N1 vaccination.

PATH Influenza Vaccine Project: accelerating the development of new influenza vaccines for low-resource countries

The 2009 influenza A/H1N1 pandemic demonstrated that a pandemic influenza virus has the potential to spread more rapidly in today’s highly interconnected world than in the past. While pandemic morbidity and mortality are likely to be greatest in low-resource countries, manufacturing capacity and access to influenza vaccines predominantly exist in countries with greater resources and infrastructure. Even with recently expanded manufacturing capacity, the number of doses available within a 6-month timeframe would be inadequate to fully immunize the global population if the decision to implement a global vaccination program were made today. Improved, affordable vaccines are needed to limit the consequences of a global influenza outbreak and protect low-resource populations. PATH’s Influenza Vaccine Project is supporting a range of activities in collaboration with private- and public-sector partners to advance the development of promising influenza vaccines that can be accessible and affordable for people in low-resource countries.

Remaining issues and challenges for rotavirus vaccine in preventing global childhood diarrheal morbidity and mortality

Rotavirus vaccines have had a dramatic impact on morbidity and mortality from diarrhea among children in high- and middle-income countries that have introduced the vaccine into their national immunization programs. Widespread introduction of rotavirus vaccine in developing countries is imminent and their full potential in reducing the global burden from severe childhood diarrhea may soon be realized. The objectives of this paper are to describe the remaining issues and challenges in ensuring the success of the global rotavirus vaccination program and to discuss further research needed to help address them.

Access to Care and Optimal Treatment of Chronic Hepatitis B in Asian Americans: An Evolving Agenda

Chronic hepatitis B (CHB) is an important public health problem and a leading cause of liver-related morbidity and mortality worldwide, particularly in the Asia Pacific region [1]. In the US, it has been estimated that 1.25 million individuals, or 0.4% of the population, are infected with the hepatitis B virus (HBV) [2]. However, during the past two decades, a large number of foreign-born persons have immigrated to the US from areas where the prevalence rate of chronic HBV infection is high, including, in particular, Asia, but, also, the middle East and Africa. This pattern of immigration has contributed to an increased prevalence of chronic HBV infection, which is evident in urban areas and communities with a high Asian immigrant population. Screening programs conducted on Asian Americans in San Francisco and New York City showed that approximately 10% of newly tested persons have chronic HBV infection [3, 4], leading to a revised estimate that 2 million people in the US have chronic HBV infection [5]. A recent encouraging study of trends in the prevalence of HBV infection in the US shows that the HBV prevalence rate decreased among children, which reflects the impact of global and domestic vaccination programs; however, the prevalence rate of chronic HBV infection changed little among adults [6]. Many of these adults are Asian Americans whose cumulative rate of morbidity and mortality from cirrhosis and hepatocellular carcinoma (HCC) is high, based on their infection as neonates or in early childhood [1]. Thus, it is timely that two articles in this issue of Digestive Diseases and Sciences address the challenges of increasing the detection rate of HBV infection in Asian Americans and proposes a consensus recommendation for the treatment of Asian Americans with CHB [7, 8]. Hu et al. [7] point out that the Asian American immigrant population is rapidly expanding in the US and is projected to continue this pace of growth. Routine screening for HBV infection can identify those Asian Americans who are infected and potential candidates for antiviral therapy and/or routine surveillance for HCC, as well as those without infection or immunity, who should undergo vaccination. The excellent review by Hu et al. [7] describes a number of factors that are potential obstacles to screening for hepatitis B in the Asian American population, including patient barriers (lack of knowledge of hepatitis B, limited English language proficiency, cultural beliefs, social stigma, and perceived costs), provider barriers (underestimate of the risk of HBV infection in Asian Americans, incorrect use of screening tests, and lack of knowledge regarding the cost-effectiveness of screening and the availability of safe and effective therapy), and healthcare system barriers (difficulty navigating the healthcare system and lack or underutilization of health insurance). This article also coincides with a burgeoning national awareness of the importance of HBV infection to public health that has led to the publication of a national strategy for the prevention and control of hepatitis B (as well as chronic hepatitis C) by the Institute of Medicine [9]. In response to this report, the US Department of Health and Human Services issued on May 12, 2011 its action plan: Combating the Silent Epidemic of Viral Hepatitis. Action Plan for the Prevention, Care and Treatment of Viral Hepatitis [10]. The preamble to this report emphasizes that 65–75% of infected Americans remain unaware of their viral infection, which is largely preventable. For the first E. B. Keeffe (&) Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, 750 Welch Road, Suite 210, Palo Alto, CA 94304-1509, USA e-mail: ekeeffe@stanford.edu

Pityriasis rosea following influenza (H1N1) vaccination

Pityriasis rosea is a distinct papulosquamous skin eruption that has been attributed to viral reactivation, certain drug exposures or rarely, vaccination. Herein, we reported a clinicopathlogically typical case of pityriasis rosea that developed after the H1N1 vaccination. With a global H1N1 vaccination program against the pandemic H1N1 influenza, patients should be apprised of the possibility of such rare but benign skin reaction to avoid unnecessary fear. Furthermore, a brief review of the current reported skin adverse events related to the novel H1N1 vaccination in Taiwan is presented here.

Global safety of vaccines: strengthening systems for monitoring, management and the role of GACVS

Vaccines have contributed enormously in reducing the impact of many infectious diseases, and the expanded use of new and existing vaccines provides unprecedented potential for further reducing the global burden of infectious diseases. Yet, as with the deployment of other technologies, their use may also sometimes be associated with undesirable effects that need to be identified rapidly, understood and minimized. In this article, we review the models and systems that have been developed to monitor and respond to concerns regarding vaccine safety and we give illustrative examples of real or perceived vaccine safety issues. The Global Advisory Committee on Vaccine Safety (GACVS) was set up 10 years ago and charged to provide the WHO with independent advice on vaccine safety issues. The role of the GACVS is both to analyze and to interpret reports of the adverse effects of vaccines that impact on global vaccination programs and strategies, and to foster the development of improved surveillance systems to detect any adverse effects of vaccines, particularly in low- and middle-income countries. It also monitors the development of new vaccines during clinical testing and advises on the safe use of vaccines in immunization programs. As success is achieved with reducing the burden of vaccine-preventable diseases, there will be increasing attention focused on potential adverse effects, on the development of effective surveillance systems to detect adverse effects, and on improved methods to manage and control any harmful consequences of vaccination.

Immune concept of human papillomaviruses and related antigens in local cancer milieu of human cervical neoplasia

It is presently the right time for clarifying human papillomavirus (HPV)-associated cellular immunity and clinical implications before global HPV vaccination programs begin. Infection with oncogenic HPV associates with the progression of cervical neoplasia. Both cellular and humoral immune responses are essential for the clearance of HPV-associated cervical lesions. There is increasing evidence that the immune system plays a pivotal role in determining the outcome of HPV infection. Viruses and associated neoplastic cells are proposed to have evolved mechanisms to avoid immune attack. T-cell-mediated immune responses against oncogenic HPV are believed to play a central role in cervical carcinogenesis. The presence of HPV-specific cytotoxic T lymphocytes (CTL) in a majority of human cervical cancer patients provides an approach for further study of their functional role in modulating this malignancy. Tumor-infiltrating lymphocytes (TIL) develop as manifestations of the recognition and defense against malignant cells by the host immune system. Cancer cells may overcome immune surveillance, either by downregulating the proliferation of HPV-specific CTL, or altering the effector compositions of immune cells against HPV infections. TIL in the tumor microenvironment can be functionally inhibited and lose the ability of clonal proliferation as a result of depressed expression of IL-2Ralpha. The upregulation of inhibitory signaling relates to the modulation of the virus- and/or tumor-specific immune responses. Alteration of host genetic susceptibility may also lead to abnormal immune response as a general genomic instability resulting from virus persistence. Induction of HPV-specific immune responses is anticipated as an intimate point for the treatment of cervical neoplasia.

The unexpected outcomes of medical research: serendipity and the Australia antigenBlumberg BS, Alter HJ, Visnich S. A new antigen in leukemia sera [J Am Med Assoc 1965;191:541–546

The 'Australia Antigen' is found in the sera of some normal individuals from foreign populations. The total absence of the antigen from the sera of normal United States' subjects and its relatively high frequency in acute leukemia suggests that the presence of the antigen maybe of value in the diagnosis of early acute leukemia. Whether the antigen results from or precedes the leukemia process remains to be seen. (Abstract reproduced by permission of J Am Med Assoc 1965;191:541 - 546.) Many of the major discoveries in science have been the product of chance observations that were pursued by the curious mind to their plausible and provable explanation. Mendel's peas and, at least apocryphally, Newton's apple, come to mind as paradigm shifting observations that respectively opened the fields of genetics and established the laws of gravitation. Fleming's chance observation of the inhibition of bacterial growth in the presence of bread mold ultimately produced the first antibiotic. The unexpected link between the Australia antigen and the hepatitis B virus may be less encompassing than genetics or gravitation, but nonetheless is a classic example of a serendipitous observation pursued to major unexpected payoffs, including the prevention of post-transfusion hepatitis, the development of a vaccine, the prevention of hepatocellular carcinoma and laying the foundation for

Risk factors for hepatitis B virus infection in Rio de Janeiro, Brazil.

BackgroundDespite international efforts to prevent hepatitis B virus (HBV) infection through global vaccination programs, new cases are still being reported throughout the world.MethodsTo supply data that might assist in improving preventive measures and national surveillance for HBV infection, a cross-sectional study was conducted among individuals referred to the Brazilian National Reference Center for Viral Hepatitis (Rio de Janeiro) during a two-year period. Reported risk factors among infected subjects ("HBV-positive") were compared to those of subjects never exposed ("HBV-negative") to HBV. Two subgroups were further identified within the HBV-positive group, "acute" infection and "non-acute" infection.ResultsA total of 1,539 subjects were tested for HBV, of which 616 were HBV-positive (79 acute infection and 537 non-acute infection). HBV-positive subjects were more likely to be of male gender (63% versus 47%); and to report multiple sexual partners (12% versus 6%) and illicit drug use (IDU and/or intranasal cocaine use) (6% versus 3%). Among the HBV-positive subgroups, age differed significantly, with 48% being under 30 years of age in subjects acutely infected compared to 17% in those with non-acute infection.ConclusionsThe association of multiple sexual partners with past HBV infection and the age distribution of currently infected subjects suggest that sexual transmission played a major role in the transmission of HBV in this study population. Thus, vaccination during adolescence should be considered.

Reduced Antigenicity of the Hepatitis B Virus HBsAg Protein Arising as a Consequence of Sequence Changes in the Overlapping Polymerase Gene That Are Selected by Lamivudine Therapy

The prevalence of hepatitis B virus vaccine escape mutants has increased as a consequence of the introduction of global vaccination programs. Furthermore and as a consequence of the organization of the genome of hepatitis B virus (HBV) into overlapping reading frames, the selection of polymerase mutants during long-term lamivudine therapy can select viruses with changes in the overlapping S gene coding for the hepatitis B small antigen (HBsAg). We have investigated the role of lamivudine in selecting HBV mutants with antigenically altered HBsAg protein using pooled human vaccinee sera in enzyme immunosorbent assays and radioimmunoassays. HBsAg proteins containing the vaccine escape mutations G145R and D144E/G145R demonstrated markedly reduced binding to anti-HBs antibody. HBsAg mutants including E164D, W196S, I195M, M198I, and E164D/I195M (corresponding to the polymerase protein changes of V519L, M550I, L526M/M550V V553I, and V519L/L526M/M550V) selected during lamivudine treatment also demonstrated reduced binding to anti-HBs antibody. These findings raise the possibility of lamivudine-resistant mutants arising that possess antigenically distinct HBsAg proteins.

Protein expression in yeast as an approach to production of recombinant malaria antigens.

The selection of a system suitable for expression of recombinant malaria antigens for vaccine development is, in the final analysis, empirical. However, experience gained with both malaria antigens and other recombinant proteins has provided helpful guidelines. Recombinant DNA technology has been successfully applied to the development of vaccines against a number of human diseases. For example, recombinant DNA-derived hepatitis B virus surface antigen has been produced from both prokaryotic and eukaryotic systems. Yeast has been demonstrated to be an excellent host for the expression of recombinant proteins with uses in diagnostics, therapeutics, and vaccine production. Both intracellular and secretory systems have been developed and optimized for the production of high levels of recombinant proteins. Recombinant DNA technology, and in particular yeast expression systems, have been successfully used to produce malaria antigens, several of which have been protective in various animal models. In contrast, attempts to produce sufficient quantities of antigens for a malaria vaccine from in vitro cultures of the malaria parasite have been unsuccessful. Recombinant proteins can be produced and purified from yeast in large quantities and at low cost, each being requirements for a vaccine to be used in a global vaccination program against malaria.