Stability testing of vaccines: Developing Countries Vaccine Manufacturers' Network (DCVMN) perspective

Stability testing is an integral part of the vaccine manufacturing process and is crucial for the success of immunization programs. WHO (World Health Organization) has recently published guidelines on the stability testing of vaccines. These guidelines enlist scientific basis and principles for stability testing at various stages like development, pre-clinical, clinical, licensing, lot release and post-licensure monitoring. DCVMN (Developing Countries Vaccine Manufacturers' Network) is an international body of developing countries vaccine manufacturers and has viewpoints on technical and administrative issues in stability testing of vaccines. We here highlight viewpoints, possible roles and global expectations of DCVMN in the area of stability testing of vaccines.     

Ethical issues in medical research in the developing world: a report on a meeting organised by Fondation Mérieux

This paper reports on a multidisciplinary meeting held to discuss ethical issues in medical research in the developing world. Many studies, including clinical trials, are conducted in developing countries with a high burden of disease. Conditions under which this research is conducted vary because of differences in culture, public health, political, legal and social contexts specific to these countries. Research practices, including standards of care for participants, may vary as a result. It is therefore not surprising that ethical issues emerge. This meeting sought to identify and discuss these issues from the perspectives of the many actors in such research, including community representatives, with a view to finding ethical and pragmatic solutions to these issues. Dialogue between these actors was also promoted, with a view to identifying the need to develop such dialogue in future.
Drawing from the experiences of the speakers, the colloquium attempted to outline some answers to several key questions characterising the field today. Experiences related to epidemiologic research, vaccine trials, drug trials, diagnostic tests and to some fundamental ethical issues in health research. Speakers were from different countries, disciplines and professions. The meeting provided a forum for consultation and debate between different ethics actors. Both encouraging findings and challenges emerged.     

Brucellosis in India — a review

Brucellosis is an important re-emerging zoonosis with a worldwide distribution. It is still an uncontrolled serious public health problem in many developing countries including India. Brucellosis in India is yet a very common but often neglected disease. Currently, Brucella melitensis accounts for most recorded cases globally with cattle emerging as a important reservoir with the few cases of B. suis. Isolated cases of non-terrestrial brucellosis and continuing transmission from wild animals have raised important epidemiological issues. Routine serological surveillance along with high clinical suspicion and screening of family members of index cases would be essential in delineating the real magnitude of human brucellosis in endemic countries. Increased business and leisure travel to endemic countries have led to diagnostic challenge in non-endemic areas. Laboratory testing is indispensable for diagnosis. Advances in newer rapid, sensitive, and specific testing methodologies and alternate treatment strategies are urgently needed. A safe and effective vaccine in human is not yet available. Prevention is dependent upon increasing public awareness through health education programmes and safe livestock practices. Active co-operation between health and veterinary services should be promoted. This review collates world literature and its impact to the discovery, isolation and diagnosis and epidemiology along with the control measures adapted in the Indian scenario.     

Helicobacter in the developing world

Helicobacter pylori in the developing world is associated with many unique challenges not encountered in an industrialized setting. The 20% prevalence of infection with H. pylori among adolescents in the United States pales in comparison to infection rates exceeding 90% by 5 years of age in parts of the developing world. While H. pylori within the developed world is associated with gastritis, which may lead to peptic ulcer and gastric carcinoma, the infection in the developing world appears to also be linked with chronic diarrhea, malnutrition and growth faltering as well as predisposition to other enteric infections, including typhoid fever and cholera. Once identified, treatment of H. pylori within the developing world presents increased difficulties due to the frequency of antibiotic resistance as well as the frequency of recurrence after successful treatment. Control, and possibly eradication, of H. pylori could likely be achieved through increased standards of living and improved public health, as it has in the industrialized world. However, these measures are distant objectives for most developing countries, making long-term control of the organism dependent on the development and administration of an effective vaccine.     

Breast cancer as a global health concern

Public health data indicate that the global burden of breast cancer in women, measured by incidence, mortality, and economic costs, is substantial and on the increase. Worldwide, it is estimated that more than one million women are diagnosed with breast cancer every year, and more than 410,000 will die from the disease. In low- and middle-income countries (LMCs), the infrastructure and resources for routine screening mammography are often unavailable. In such lower resource settings, breast cancers are commonly diagnosed at late stages, and women may receive inadequate treatment, pain relief, or palliative care. There have been an increasing number of global health initiatives to address breast cancer including efforts by Susan G. Komen for the Cure^©, the Breast Health Global Initiative (BHGI), the U.S. Centers for Disease Control and Prevention (CDC), the American Cancer Society, the National Cancer Institute (NCI), and ongoing work by leading oncology societies in different parts of the world. To support such initiatives, and to provide a scientific evidence base for health policy and public health decision making, there is a need for further health services research and program evaluations. Cancer registries can be invaluable in ascertaining the magnitude of cancer disease burden and its distribution in these countries. Additional data are needed for various geographic areas to assess resources required, cost-effectiveness, and humane approaches for preventing or controlling breast cancer in low resource settings in developing countries.     

A Review of the Evidence to Support Influenza Vaccine Introduction in Countries and Areas of WHO's Western Pacific Region

Background

Immunization against influenza is considered an essential public health intervention to control both seasonal epidemics and pandemic influenza. According to the World Health Organization (WHO), there are five key policy and three key programmatic issues that decision-makers should consider before introducing a vaccine. These are (a) public health priority, (b) disease burden, (c) efficacy, quality and safety of the vaccine, (d) other inventions, (e) economic and financial issues, (f) vaccine presentation, (g) supply availability and (h) programmatic strength. We analyzed the body of evidence currently available on these eight issues in the WHO Western Pacific Region.

Methodology/Principal Findings

Studies indexed in PubMed and published in English between 1 January 2000 and 31 December 2010 from the 37 countries and areas of the Western Pacific Region were screened for keywords pertaining to the five policy and three programmatic issues. Studies were grouped according to country income level and vaccine target group. There were 133 articles that met the selection criteria, with most (90%) coming from high-income countries. Disease burden (n = 34), vaccine efficacy, quality and safety (n = 27) and public health priority (n = 27) were most frequently addressed by studies conducted in the Region. Many studies assessed influenza vaccine policy and programmatic issues in the general population (42%), in the elderly (24%) and in children (17%). Few studies (2%) addressed the eight issues relating to pregnant women.

Conclusions/Significance

The evidence for vaccine introduction in countries and areas in this Region remains limited, particularly in low- and middle-income countries that do not currently have influenza vaccination programmes. Surveillance activities and specialized studies can be used to assess the eight issues including disease burden among vaccine target groups and the cost-effectiveness of influenza vaccine. Multi-country studies should be considered to maximize resource utilization for cross-cutting issues such as vaccine presentation and other inventions.     

Evaluation of vaccines against enteric infections: a clinical and public health research agenda for developing countries

Enteric infections are a major cause of morbidity and mortality in developing countries. To date, vaccines have played a limited role in public health efforts to control enteric infections. Licensed vaccines exist for cholera and typhoid, but these vaccines are used primarily for travellers; and there are two internationally licensed vaccines for rotavirus, but they are mainly used in affluent countries. The reasons that enteric vaccines are little used in developing countries are multiple, and certainly include financial and political constraints. Also important is the need for more cogent evidence on the performance of enteric vaccines in developing country populations. A partial inventory of research questions would include: (i) does the vaccine perform well in the most relevant settings? (ii) does the vaccine perform well in all epidemiologically relevant age groups? (iii) is there adequate evidence of vaccine safety once the vaccines have been deployed in developing countries? (iv) how effective is the vaccine when given in conjunction with non-vaccine cointerventions? (v) what is the level of vaccine protection against all relevant outcomes? and (vi) what is the expected population level of vaccine protection, including both direct and herd vaccine protective effects? Provision of evidence addressing these questions will help expand the use of enteric vaccines in developing countries.     

Parasites, people and policy: infectious diseases and the Millennium Development Goals

Here, I briefly review past history and present patterns in the interactions between parasites (defined broadly to include viruses and bacteria along with protozoan, helminth and arthropod parasites) and human populations in developed and developing countries. Against this background, I offer thoughts on current public health initiatives at national and international levels, with particular reference to the Millennium Development Goals. The news is both good and bad: mortality and morbidity from infectious diseases in the developing world are significantly lower than they were 50 years ago, but we should and could be doing better, particularly in relation to neglected tropical diseases.     

Legacy of implementing industrial health and safety in developing countries

Aiming to develop public attention to the hindrance of national and international efforts on industrial health and safety, this paper explores some important issues, such as the reasons for the lack of motivation to implement necessary measures in developing countries. Examples are likewise given to show why working people are significantly exposed to a number of occupational problems that are reflected in a deterioration of their health, safety and well being. In lieu thereof, an introduction of health and safety is not itself a solution, if certain changes are not rationalised according to the local need. While health and safety intervention is concerned, then local need is of prime importance. If individual situation is not clearly outlined, then preventive and control measures can be treated as a de facto measure. Hence immediate attention, collaboration and co-operation is needed from all the concerned parties such as local government authorities, semi-government or private organisations and international communities for proper implementation of work regulations as well as industrial acts and rules in various workplaces in each of the developing countries.     

Primary prevention of hepatocellular carcinoma in developing countries

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world with 80% of cases occurring in developing countries. The cancer is rapidly fatal in almost all cases with survival generally less than 1 year from diagnosis. The major risk factors for this cancer have been identified as chronic infection with hepatitis B (HBV) and hepatitis C (HCV) viruses and dietary exposure to aflatoxins. There is a safe and effective vaccine to prevent chronic HBV infection. Given estimates that approximately 70% of HCC in developing countries is attributable to HBV then vaccination could prevent more than 250,000 cases per year in these areas of the world. A major challenge now is to ensure the availability of vaccine in countries with endemic infection. Development of a vaccine against HCV is more problematic due to the genetic heterogeniety of the virus. However, with 24% of HCC in developing countries attributable to HCV (approximately 93,000 cases per year) a vaccine would make a major contribution to cancer prevention. Aflatoxins contaminate dietary staple foods (groundnuts, maize), are potent animal hepatocarcinogens and are carcinogenic in humans with particularly high risks in individuals with a concomitant infection with HBV. Reduction of exposure can be addressed at the community level either pre- or post-harvest by limiting fungal contamination of crops; approaches may involve low technology post-harvest measures to limit fungal growth or genetic engineering of crops to be resistant to fungal infection or toxin biosynthesis. An alternative measure is to modulate the metabolism of aflatoxins once ingested using chemopreventive agents e.g., oltipraz. The resources available in countries with endemic hepatitis infection and fungal contamination of foods are often severely limited. Clearly HBV vaccination has to be the priority in the reducing the incidence of HCC. However, there are currently 360 million chronic HBV carriers worldwide and HBV vaccine is still not incorporated into many national immunisation programs. Thus measures to reduce food spoilage by fungi and the associated dietary exposure to aflatoxins is also a desirable public health goal.     

Replicating viral vectors as HIV vaccines: Summary report from the IAVI-sponsored satellite symposium at the AIDS vaccine 2009 conference

In October 2009, The International AIDS Vaccine Initiative (IAVI) convened a satellite symposium entitled ‘Replicating Viral Vectors for use in AIDS Vaccines’ at the AIDS Vaccine 2009 Conference in Paris. The purpose of the symposium was to gather together researchers, representatives from regulatory agencies, and vaccine developers to discuss issues related to advancement of replication-competent viral vector- based HIV vaccines into clinical trials. The meeting introduced the rationale for accelerating the development of replicating viral vectors for use as AIDS vaccines. It noted that the EMEA recently published draft guidelines that are an important first step in providing guidance for advancing live viral vectors into clinical development. Presentations included case studies and development challenges for viral vector-based vaccine candidates. These product development challenges included cell substrates used for vaccine manufacturing, the testing needed to assess vaccine safety, conducting clinical trials with live vectors, and assessment of vaccination risk versus benefit. More in depth discussion of risk and benefit highlighted the fact that AIDS vaccine efficacy trials must be conducted in the developing world where HIV incidence is greatest and how inequities in global health dramatically influence the political and social environment in developing countries.     

Suicide prevention in Nepal: a comparison to Australia-a personal view

Suicide is a crisis of unknown proportions in much of the developing world. The majority of research into suicide has been done in high-resource countries such as Australia, and most intervention protocols have been drawn up using Western models. There appear to be a number of differences in the aetiology, presentation and treatment options for mental health problems between high-resource and low-resource countries. This review compares suicide in a high-resource country, Australia, and low-resource country, Nepal.Many low-resource countries such as Nepal struggle to address barriers to mental health care due to limited mental health resources and issues such as stigma, workforce and mental health literacy. Issues relating to suicide prevention are raised, contrasting a low-resource country, Nepal, with a high-resource country, Australia.     

Changing Patterns of Infant Mortality and Maternal Fertility among Pumé Foragers and Horticulturalists

National census data show that the modern demographic transition—the recent trend toward declining mortality and fertility—is well underway in most countries. A different picture emerges when data from small-scale societies in unindustrialized parts of the world are considered. Many of these small-scale societies are also adapting to rapid changes in their subsistence economies. In this article, we examine the relationship between the pace of acculturation, infant mortality, and fertility levels among Pumé foragers and horticulturalists, two related groups of native South Americans. During the earliest stages of acculturation, Pumé horticulturalists experience not only a rapid drop in infant mortality but also a rise in birth rates. An anthropological view of demographic transitions provides important insight into how small-scale societies are affected by exposure to the labor market economy and has practical applications to effective development initiatives and public health policies.     

Worldwide human zoonotic cryptosporidiosis caused by Cryptosporidium felis

Cryptosporidium is an important enteric pathogen worldwide distributed causing diarrhoeal illness in humans and animals. Identifying Cryptosporidium species using conventional criteria, such as oocyst morphology, is inadequate. The advent of molecular techniques has conducted to characterize different species and genotypes of Cryptosporidium infecting humans. The vast majority of human cases of cryptosporidiosis in the world are caused by both species, Cryptosporidium hominis and Cryptosporidium parvum. However other species including Cryptosporidium felis can infect humans too. In this review, we analyse 58 reported cases of human C. felis infection in different parts of the world. To date this emerging protozoan disease is present in humans around the world, except in Australia and Oceania. Adults and children are infected, more often when immunocompromised by HIV infection (83 % of reported cases). Apparently immunocompetent individuals are also infected by C. felis. In developing countries, inhabitants are more likely infected by C. felis probably through the oocyst contamination of drinking or recreational water. The public health importance of C. felis infection in tropical countries remains to be evaluated.     

Public vaccine manufacturing capacity in the Latin American and Caribbean region: Current status and perspectives

The vaccine global market is currently growing at a rate of 16.52%. Nowadays the vaccine manufacturing industry is limited in the sense that not all vaccine manufacturers have the capacity to execute all the steps necessary to produce a successful product. The biological variation inherent to vaccine manufacturing and the initial investment required to bring a vaccine to the market are some of the factors that discourage vaccine manufacturing initiatives.Given the current global context in vaccine innovation and production, and the increasing participation of vaccine manufacturers from developing countries in global markets, this paper aims to review vaccine manufacturing capacity in Latin American and Caribbean (LAC) countries with specific focus on trends in national or public sector manufacturing, presenting current challenges and future opportunities for the sector in meeting national and regional (LAC) needs.Despite the overall low vaccine manufacturing capacity reported within the LAC region within this paper, it is considered that the relatively high and concentrated capacity that exists within a number of countries, combined with political commitment of all countries within the Region, can provide the necessary platform for the continued development of capacity in vaccine development and manufacture within LAC.     

Preventing a surgical complication during cesarean delivery in a morbidly obese patient: a simple apparatus to retract the abdominal panniculus

Obesity is no longer just a "Western" problem, as evidenced by an increase in prevalence of up to 75% in parts of the developing world. It is important to transfer experience from the developed world to developing countries in an attempt to prepare for the inevitable health and economic problems. This case report highlights an unusual intraoperative complication that has medical and medico-legal implications. A simple apparatus designed to retract the panniculus of an obese patient might reduce complications when performing abdominal surgery in such cases.     

肺炎链球菌疫苗研制进展

肺炎链球菌导致的疾病已成为全球一个重要的公共卫生问题。疫苗开发及使用成为重要的预防策略,目前肺炎球菌疫苗主要有多糖疫苗和多糖蛋白结合疫苗二类。对肺炎链球菌病原学、流行病学、所致疾病、疫苗研发进展及疫苗使用情况进行了综述。     

Vaccination: the present and the future

Vaccines have undoubtedly saved the lives of millions, and along with improved sanitation, they remain one of the cornerstones of modern medicine. Many diseases that were once widespread are now eradicated, but vaccine programs face ongoing challenges. Safety concerns as well as limited funding have led to pockets of reduced vaccine coverage around the world - including in developed countries. Chronic and recurrent diseases such as human immunodeficiency virus (HIV), tuberculosis, and malaria remain without effective vaccines. This review will briefly describe vaccines and the two major issues faced by modern vaccination programs: insufficient vaccine coverage and developing effective vaccines for chronic and recurrent diseases.     

Pandemic management and developing world bioethics: bird flu in West Bengal

This paper examines the case of a recent H5N1virus (avian influenza) outbreak in West Bengal, an eastern state of India, and argues that poorly executed pandemic management may be viewed as a moral lapse. It further argues that pandemic management initiatives are intimately related to the concept of health as a social 'good' and to the moral responsibility of protection from foreseeable social harm from an infectious disease. The initiatives, therefore, have to be guided by special moral obligations towards biorisk reduction, obligations which remain unfulfilled when a public body entrusted with the responsibility fails to manage satisfactorily the prevention and control of the infection. The overall conclusion is that pandemic management has a moral dimension. The gravity of the threat that fatal infectious diseases pose for public health creates special moral obligations for public bodies in pandemic situations. However, the paper views the West Bengal case as a learning opportunity, and considers the lapses cited as challenges that better, more effectively conducted pandemic management can prepare for. It is hoped that this paper will provoke constructive bioethical deliberations, particularly pertinent to the developing world, on how to ensure that the obligations towards health are fulfilled ethically and more effectively.     

Neglected tropical disease vaccines

The neglected tropical diseases or ‘NTDs’ represent the most common infections of the world's one billion poorest people. Unlike the better known acute or emerging infections, the NTDs are generally chronic and disabling (and often disfiguring) conditions. The long-term disability they cause has been revealed as a major reason why poor people in developing countries cannot escape the poverty trap. Because NTDs are associated with poverty, vaccines against these conditions are sometimes referred to as antipoverty vaccines. However, despite their global public health and economic importance, such vaccines have largely been ignored by industry and today are predominantly being produced through the activities of non-profit product development partnerships (PDPs). The Human Hookworm Vaccine Initiative based at the Sabin Vaccine Institute is one such PDP developing two antipoverty vaccines for hookworm and schistosomiasis, respectively. It has been proposed to combine these vaccines in order to target polyparasitic co-infections leading to severe anemia. Ultimately, to ensure global access of a multivalent anthelminthic vaccine, it may be linked to deworming programs through vaccine-linked chemotherapy. This would be an important step towards achieving the Millennium Development Goals for sustainable poverty reduction by 2015.