Global Eradication Of Smallpox Research Articles

Navigating resistance in global health governance: Certification of smallpox eradication in China

ABSTRACT Certification is an essential stage in disease eradication efforts, encompassing epidemiological, managerial, and political complexities. The certification of smallpox eradication in the People’s Republic of China (PRC, or China) exemplifies the multifaceted nature of the certification. Despite eradicating smallpox in the early 1960s, before the Global Smallpox Eradication Programme (SEP) intensified in 1967, China was one of the last countries certified as smallpox-free by the World Health Organization (WHO) in 1979. The WHO encountered notable resistance during the certification of smallpox eradication in China. This article examines the underlying motivations propelling China’s resistance, the factors that contributed to the shifts in its stance, the challenges navigated by the WHO, and the ultimate achievement of certification despite controversies surrounding its transparency and credibility. Through the case of the certification of smallpox eradication, the article provides a historical context of China’s selective engagement in global health governance, emphasising the critical importance of building a trusting relationship between the WHO and its member states. It offers insights for fostering effective collaboration among diverse stakeholders driven by varied political agendas in addressing shared global health challenges such as the coronavirus disease (COVID-19) pandemic.

Clinical features and management of human monkeypox

The COVID-19 pandemic is abating, but the threat of a new epidemic is growing due to the spread of monkeypox in non-endemic regions of the world. In 2022, there were the monkeypox outbreaks throughout Europe, in the Western Hemisphere. With the cessation of the vaccine, due to the global eradication of smallpox, outbreaks of monkeypox have become more common. Currently, there are no exact recommendations for complex treatment and alleviation of the monkeypox symptoms for infected people. Under these conditions, it is especially important to know the pathogenetic mechanisms and epidemiology of the virus for the most effective containment of its spread, especially in view of the negative experience gained in combating the COVID-19 epidemic. The purpose of this study was to summarise the known data on the epidemiology, clinical course and treatment of monkeypox, as well as an attempt to assess the possibility of a new world-spanning pandemic. A targeted search was performed on the keywords "monkeypox", "virology", "Tecovirimat", "Cidofovir", "Brincidofovir" in PubMed, in the period up to July 2022. 661 articles were reviewed, among them as reviews, original research and clinical trials. Preference was given to articles in English that dealt in most detail with cases of monkeypox infection outside the Africa and included comments on the therapy. Seventeen articles were selected and analysed, as well as links within them for additional information on the case. It was revealed that monkeypox is mainly treated with maintenance therapy and the treatment of more complex cases is based on the use of specific antiviral drugs: Tecovirimat, Cidofovir, Brincidofovir. However, there is no widespread therapeutic practice for these drugs. Little is currently known about the monkeypox virus; the transmission of infection, the animal reservoirs, the host range and the prospects for specific treatment are not fully understood. Sharing resources and data with outbreak tracking around the world will greatly facilitate the process of learning about the virus and how to deal with it effectively

Efficacy of smallpox vaccines against Mpox infections in humans.

The Mpox virus (MPXV) is endemic in certain countries in Central and West Africa, where several mammalian species, especially rodents, are natural reservoirs. However, the MPXV can infect nonhuman primates and cause zoonotic infections in humans after close contact with an infected animal. Human-to-human transmission of MPXV can also occur through direct close contact with an infected individual or infected materials. In May 2022 an initial cluster of human Mpox cases was identified in the UK, with the first case confirmed in a patient who had recently travelled to Nigeria. The infection subsequently spread via human-to-human transmission within the UK and Mpox cases began to appear in many other countries around the world where the MPXV is not endemic. No specific treatments for MPXV infection in humans are available. However, data from studies undertaken in Zaire in the 1980s revealed that those with a history of smallpox vaccination during the global smallpox eradication campaign also had good cross-protection against MPXV infection. However, the vaccines used during the global eradication campaign are no longer available. During the 2022 global Mpox outbreak over a million doses of the Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) smallpox vaccine were offered either as pre or postexposure prophylaxis to those at high risk of MPXV infection. Here, we review what has been learned about the efficacy of smallpox vaccines in reducing the incidence of MPXV infections in high-risk close contacts.

Podiel českých a slovenských lekárov pri dosiahnutí globálnej eradikácie varioly

Bifurkované ihly používané v Programe globálnej eradikácie varioly. Zaviedli sa v roku 1968 a výrazne zjednodušili proces očkovania. Ihly boli v plastovej nádobke s kónickým vrchnákom s otvorom, ktorým prešla len jedna ihla. Vakcinátor ju vytiahol a bifurkovanú časť namočil do ampulky s vakcínou. V medzere medzi ihlami sa zachytilo potrebné množstvo vakcíny. Následne sa očkovalo opakovanými vpichmi do pokožky. Použité ihly sa vložili do prázdnej nádobky a sterilizovali. Tento postup mohli vykonávať aj miestni vakcinátori po krátkom zaučení. Foto: Prof. MUDr. Tibor Baška, PhD.

Smallpox, Monkeypox and Other Human Orthopoxvirus Infections.

Considering that vaccination against smallpox with live vaccinia virus led to serious adverse effects in some cases, the WHO, after declaration of the global eradication of smallpox in 1980, strongly recommended to discontinue the vaccination in all countries. This led to the loss of immunity against not only smallpox but also other zoonotic orthopoxvirus infections in humans over the past years. An increasing number of human infections with zoonotic orthopoxviruses and, first of all, monkeypox, force us to reconsider a possible re-emergence of smallpox or a similar disease as a result of natural evolution of these viruses. The review contains a brief analysis of the results of studies on genomic organization and evolution of human pathogenic orthopoxviruses, development of modern methods for diagnosis, vaccination, and chemotherapy of smallpox, monkeypox, and other zoonotic human orthopoxvirus infections.

Monkeypox Emergence and the Eradication of Smallpox: An Historical Review.

Human monkeypox infection was first identified in 1970 in African. Small rodents were the natural reservoir of this orthopoxvirus, with humans and primates as incidental hosts. Smallpox vaccination induces cross protection against monkeypox. In Africa monkeypox overlapped with the Global Smallpox Eradication Program (GSEP) six decades ago. The 2022 human monkeypox epidemic prompted literature review re potential impact of monkeypox upon GSEP efforts. Literature review from 1960 to present related to GSEP launched in 1969 with particular focus on monkeypox epidemiology during planning of GSEP in the 1960's through 1989 including surveillance years later. Establishing the lack of a non-human reservoir of smallpox was essential to assessing the GSEP because of the similarity of the two orthopoxviruses. It was found that a non-human smallpox reservoir was highly remote. Human monkeypox did not occur in smallpox-vaccinated humans and was limited to non-vaccinees. Surveillance in Democratic Republic of the Congo (DRC) until 1989 found monkeypox was very unlikely to persist in humans and unlikely to become a major public health problem. From 2005-2007, decades after cessation of smallpox vaccination, monkeypox surveillance in DRC revealed 20-fold higher incidence of human monkeypox correlated with much lower rates of prior smallpox vaccination. Human monkeypox rates in DRC were 20-fold higher decades after cessation of smallpox vaccination compared to when smallpox vaccination was still used. The resultant decreased cross-protection against monkeypox contributed to the 2022 multinational outbreak of human monkeypox.

Monkey Pox Pathogenesis, Diagnosis, Treatment: A Comprehensive Review

Human monkeypox is a zoonotic Orthopoxvirus with a presentation similar to smallpox. Clinical differentiation of the disease from smallpox and varicella is difficult. Laboratory diagnostics are principal components to identification and surveillance of disease, and new tests are needed for a more precise and rapid diagnosis. The majority of human infections occur in Central Africa, where surveillance in rural areas with poor infrastructure is difficult but can be accomplished with evidence-guided tools and educational materials to inform public health workers of important principles. As the fear of the coronavirus disease 2019 (COVID-19) pandemic subsides, countries around the globe are now dealing with a fear of the epidemic surrounding the prevalence of monkeypox cases in various regions. Previously endemic to regions of Africa, the majority of monkeypox cases associated with the 2022 outbreak are being noted in countries around Europe and in the western hemisphere. While contact-tracing projects are being conducted by various organizations, it is unknown how this outbreak began. Monkeypox virus is one of the many zoonotic viruses that belong to the Orthopoxvirus genus of the Poxviridae family. Monkeypox cases received global attention during the 1970s, after the global eradication of smallpox. The smallpox vaccine provided cross-immunity to the monkeypox virus. Upon the cessation of smallpox vaccine administration, monkeypox cases became more prevalent. It was not until the 2003 US outbreak that monkeypox truly gained global attention. Despite the virus being named monkeypox, monkeys are not the origin of the virus. Several rodents and small mammals have been attributed as the source of the virus; however, it is unknown what the true origin of monkeypox is. The name monkeypox is due to the viral infection being first witnessed in macaque monkeys. Though human-to-human transmission of monkeypox is very rare, it is commonly attributed to respiratory droplets or direct contact with mucocutaneous lesions of an infected individual. Currently, there is no treatment allocated for infected individuals, however, supportive treatments can be administered to provide symptom relief to individuals; Medications such as tecovirimat may be administered in very severe cases. These treatments are subjective, as there are no exact guidelines for symptom relief. Contemporary epidemiological studies are needed now that populations do not receive routine smallpox vaccination. New therapeutics and vaccines offer hope for the treatment and prevention of monkeypox; however, more research must be done before they are ready to be deployed in an endemic setting. There is a need for more research in the epidemiology, ecology, and biology of the virus in endemic areas to better understand and prevent human infections.

Rethinking malaria: Governance lessons from other disease programs.

The global disruptions brought about by the COVID-19 pandemic as well as the stagnation of progress of global malaria elimination efforts have provided an opportunity to rethink several aspects of the global malaria program, including its governance at all levels, from the community to the nation and to the world. Approaching this issue requires an examination of the critical governance factors that affect malaria elimination as well as lessons that could be learned from the governance of other global health programs. The paper, therefore, first reviews malaria program governance challenges at the global, national, and sub-national levels. We then conducted a literature review of governance factors that affected four major global disease elimination programs; (1) the global smallpox eradication program; (2) polio eradication efforts (focus on Latin America); (3) the onchocerciasis eradication program; and (4) global COVID-19 pandemic control efforts. Based on this review, we identified eight comment governance themes that impact disease elimination programs. These include 1) International support and coordination; 2) Financing; 3) Data use for engagement and decision making, 4) Country ownership; 5) National program structure and management, 6) Community support/engagement; 7) Multisectoral engagement; and 8) Technology and innovation The paper then illustrates how these eight governance themes were factored in the four disease control programs, draws lessons and insights about the role of governance from these programs and outlines the implications for governance of malaria elimination efforts. The paper concludes by making recommendations for improving governance of malaria elimination programs and how the analyses of other global disease control programs can provide new ideas and inspiration for a more robust push towards malaria eradication.

Monkeypox: Cutaneous clues to clinical diagnosis

Monkeypox: Cutaneous clues to clinical diagnosis

Monkeypox: A Comprehensive Review of Transmission, Pathogenesis, and Manifestation.

As the fear of the coronavirus disease 2019 (COVID-19) pandemic subsides, countries around the globe are now dealing with a fear of the epidemic surrounding the prevalence of monkeypox cases in various regions. Previously endemic to regions of Africa, the majority of monkeypox cases associated with the 2022 outbreak are being noted in countries around Europe and in the western hemisphere. While contact-tracing projects are being conducted by various organizations, it is unknown how this outbreak began. Monkeypox virus is one of the many zoonotic viruses that belong to the Orthopoxvirus genus of the Poxviridae family. Monkeypox cases received global attention during the 1970s, after the global eradication of smallpox. The smallpox vaccine provided cross-immunity to the monkeypox virus. Upon the cessation of smallpox vaccine administration, monkeypox cases became more prevalent. It was not until the 2003 US outbreak that monkeypox truly gained global attention. Despite the virus being named monkeypox, monkeys are not the origin of the virus. Several rodents and small mammals have been attributed as the source of the virus; however, it is unknown what the true origin of monkeypox is. The name monkeypox is due to the viral infection being first witnessed in macaque monkeys. Though human-to-human transmission of monkeypox is very rare, it is commonly attributed to respiratory droplets or direct contact with mucocutaneous lesions of an infected individual. Currently, there is no treatment allocated for infected individuals, however, supportive treatments can be administered to provide symptom relief to individuals; Medications such as tecovirimat may be administered in very severe cases. These treatments are subjective, as there are no exact guidelines for symptom relief.

Synergism and Mutual Collaboration between formal Conventional Medicine and Holistic Medicines Including Homeopathy: An Inevitable Essentiality for Oncoming Sensitive Situations

Background: In general, the subject and treatment of diseases are one of the crucial issues that have always occupied the human mind since ancient times. Main body: For this reason, there are various medical schools in different countries and regions around the world. On the other hand, it should be admitted that formal conventional medicine, especially in the treatment of common infectious diseases, has achieved remarkable success in many cases, which cannot be denied. Global eradication of human smallpox, human plague, and polio in many countries worldwide are successful examples in this regard. In veterinary medicine, FMD and brucellosis, which is a common disease between humans and animals, as well as Glanders, have been successfully eradicated in a significant number of developed countries, and bovine plague (Rinderpest) in some Middle Eastern countries such as Iran. The role of vaccination in controlling influenza in humans and birds, and more recently the Covid 19 pandemic, is undeniable despite the fundamental part of health practices such as adequate indoor ventilation. However, the inability of conventional medicine to treat some chronic diseases and the ability of traditional holistic medicine to satisfy a significant number of patients, as well as issues such as microbial resistance and drug side effects, has led to the continuation of traditional methods. Conclusion: As a result, it seems reasonable to look for a framework for the mutual cooperation and synergy of formal conventional medicine and traditional medicines in the sensitive conditions of the world ahead so that the parties can maximize their capabilities in treating human and animal diseases without increasing tolls and costs.

Adaptive Immune Response to Vaccinia Virus LIVP Infection of BALB/c Mice and Protection against Lethal Reinfection with Cowpox Virus.

Mass vaccination has played a critical role in the global eradication of smallpox. Various vaccinia virus (VACV) strains, whose origin has not been clearly documented in most cases, have been used as live vaccines in different countries. These VACV strains differed in pathogenicity towards various laboratory animals and in reactogenicity exhibited upon vaccination of humans. In this work, we studied the development of humoral and cellular immune responses in BALB/c mice inoculated intranasally (i.n.) or intradermally (i.d.) with the VACV LIVP strain at a dose of 105 PFU/mouse, which was used in Russia as the first generation smallpox vaccine. Active synthesis of VACV-specific IgM in the mice occurred on day 7 after inoculation, reached a maximum on day 14, and decreased by day 29. Synthesis of virus-specific IgG was detected only from day 14, and the level increased significantly by day 29 after infection of the mice. Immunization (i.n.) resulted in significantly higher production of VACV-specific antibodies compared to that upon i.d. inoculation of LIVP. There were no significant differences in the levels of the T cell response in mice after i.n. or i.d. VACV administration at any time point. The maximum level of VACV-specific T-cells was detected on day 14. By day 29 of the experiment, the level of VACV-specific T-lymphocytes in the spleen of mice significantly decreased for both immunization procedures. On day 30 after immunization with LIVP, mice were infected with the cowpox virus at a dose of 46 LD50. The i.n. immunized mice were resistant to this infection, while 33% of i.d. immunized mice died. Our findings indicate that the level of the humoral immune response to vaccination may play a decisive role in protection of animals from orthopoxvirus reinfection.

Mutations in the A34R gene increase the immunogenicity of vaccinia virus

Самым простым и надежным способом защиты от вирусных инфекций является вакцинопрофилактика. При этом наибольшей протективной эффективностью обладают живые вакцины, в основе которых используют слабовирулентные для человека вирусы, близкородственные патогенным, или аттенуированные (ослабленные за счет мутаций/делеций в вирусном геноме) варианты патогенного для человека вируса. Вакцинация против оспы с использованием живого вируса осповакцины (vaccinia virus, VACV), близкородственного вирусу натуральной оспы, сыграла важнейшую роль в успехе программы глобальной ликвидации оспы, которая осуществлялась под эгидой Всемирной организации здравоохранения. Прекращение после 1980 г. противооспенной вакцинации привело к тому, что огромная часть населения Земли в настоящее время не имеет иммунитета не только к оспе, но и любым другим зоонозным ортопоксвирусным инфекциям. Это создает возможность циркуляции зоонозных ортопоксвирусов в человеческой популяции и, как следствие, приводит к изменению экологии и круга чувствительных хозяев для разных видов ортопоксвирусов. При этом использование классической живой вакцины на основе VACV для защиты от этих инфекций в настоящее время не приемлемо, так как она может обусловливать тяжелые побочные реакции. В связи с этим все более актуальной становится разработка новых безопасных вакцин против ортопоксвирусных инфекций человека и животных. Аттенуация (ослабление вирулентности) VACV достигается в результате направленной инактивации определенных генов вируса и обычно приводит к уменьшению эффективности размножения VACV in vivo. Следствием этого может быть снижение иммунного ответа при введении аттенуированного вируса пациентам в стандартных дозах. Часто используемым для встройки/инактивации в геноме VACV является ген тимидинкиназы, нарушение которого приводит к аттенуации вируса. В данной работе изучено, как введение двух точечных мутаций в ген A34R аттенуированного штамма LIVP-GFP (ТК-), увеличивающих выход внеклеточных оболочечных вирионов (EEV), влияет на свойства пато- и иммуногенности варианта VACV LIVP-GFP-A34R при интраназальном заражении лабораторных мышей. Показано, что увеличение продукции EEV рекомбинантным штаммом VACV LIVP-GFP-A34R не меняет аттенуированный фенотип, характерный для родительского штамма LIVP-GFP, но приводит к существенно большей продукции VACV-специфичных антител. Ключевые слова: вирус осповакцины; направленные мутации; аттенуация; иммуногенность.

Route-coupled pathogenicity and immunogenicity of vaccinia virus variant inoculated mice

Vaccinia virus had played a key role in the global smallpox eradication. However, in case of mass vaccination with various Vaccinia virus strains severe side effects were revealed sometimes ending up with lethal outcomes, especially in immunocompromised humans. Hence, in 1980 the World Health Organization recommended to cancel smallpox vaccination after declaring about smallpox eradication. Over the last 40 years, human population virtually lost immunity not only against smallpox, but also against other zoonotic orthopoxvirus infections, such as monkeypox, cowpox, buffalopox, and camelpox. All of them pose a represent increasing threat to human health and heighten a risk of emerging highly contagious viruses due to natural evolution of previous zoonotic orthopoxviruses. In order to prevent development of small outbreaks into spreading epidemics and, thus, to decrease a risk of emergence due to natural evolution of highly pathogenic for humans orthopoxviruses, efforts should be applied to develop safe new generation live vaccines based on Vaccinia virus with target virulence genes inactivation. These strains should be examined in laboratory animal models inoculated via different routes. Currently, Vaccinia virus often becomes attenuated to create live recombinant vaccines due to inserting target DNA sequences into the virus virulence genes resulting in their inactivation. Vaccinia virus strain LIVP used in the Russian Federation as smallpox vaccine as well as derivative attenuated variant LIVP-GFP created by using genetic engineering methods with inactivating its thymidine kinase gene were examined. Such viruses were intracerebrally inoculated into suckling mice at doses of 101 or 102 PFU/animal for neurovirulence assessment. Adult mice were infected intranasally, subcutaneously or intradermally at doses of 107 or 108 PFU/animal and clinical manifestations were analyzed for 14 days. On the 28th day after the onset, blood serum samples were collected from individual mice to measure virus specific antibody level by using ELISA. It was shown that recombinant Vaccinia virus strain LIVP-GFP displayed markedly lowered neurovirulence and pathogenicity for mice as compared to parental LIVP. Finally, intradermal route turned out to demonstrate the most safe and effective profile for immunization with both examined Vaccinia virus strains.

Smallpox in the Post-Eradication Era.

Widespread vaccination programmes led to the global eradication of smallpox, which was certified by the World Health Organisation (WHO), and, since 1978, there has been no case of smallpox anywhere in the world. However, the viable variola virus (VARV), the causative agent of smallpox, is still kept in two maximum security laboratories in Russia and the USA. Despite the eradication of the disease smallpox, clandestine stocks of VARV may exist. In a rapidly changing world, the impact of an intentional VARV release in the human population would nowadays result in a public health emergency of global concern: vaccination programmes were abolished, the percentage of immunosuppressed individuals in the human population is higher, and an increased intercontinental air travel allows for the rapid viral spread of diseases around the world. The WHO has authorised the temporary retention of VARV to enable essential research for public health benefit to take place. This work aims to develop diagnostic tests, antiviral drugs, and safer vaccines. Advances in synthetic biology have made it possible to produce infectious poxvirus particles from chemicals in vitro so that it is now possible to reconstruct VARV. The status of smallpox in the post-eradication era is reviewed.

Genes that Control Vaccinia Virus Immunogenicity.

The live smallpox vaccine was a historical first and highly effective vaccine. However, along with high immunogenicity, the vaccinia virus (VACV) caused serious side effects in vaccinees, sometimes with lethal outcomes. Therefore, after global eradication of smallpox, VACV vaccination was stopped. For this reason, most of the human population worldwide lacks specific immunity against not only smallpox, but also other zoonotic orthopoxviruses. Outbreaks of diseases caused by these viruses have increasingly occurred in humans on different continents. However, use of the classical live VACV vaccine for prevention against these diseases is unacceptable because of potential serious side effects, especially in individuals with suppressed immunity or immunodeficiency (e.g., HIV-infected patients). Therefore, highly attenuated VACV variants that preserve their immunogenicity are needed. This review discusses current ideas about the development of a humoral and cellular immune response to orthopoxvirus infection/vaccination and describes genetic engineering approaches that could be utilized to generate safe and highly immunogenic live VACV vaccines.

Skin lesions caused by Orthopoxvirus in children.

IntroductionThe global eradication of smallpox and abandonment of mandatory smallpox vaccination has led to an increased proportion of the population who are immunologically naïve to infections caused by Orthopoxviruses (OPV).AimTo present the different courses of OPV infection in children and to highlight the diagnostic difficulties in their differentiation from the other inflammatory processes.Material and methodsWe retrospectively evaluated the medical documentation of 5 children with OPV infection. Clinical diagnosis of OPV infection was based on evaluation of animal contact and skin symptoms, characterised by either a single ulcer or disseminated lesions. In all five cases, blood samples and skin swabs were collected from the lesion(s) to identify specific OPV DNA fragments (Vgf, b9R and D11L genes) using PCR.ResultsTwo children presented with high fever, a single ulcer on the skin and local lymphadenopathy. The three other patients were in good general health and their skin lesions presented as a disseminated vesicular rash. Using the Vgf gene as the target for PCR, OPV infection was confirmed in material collected from skin lesions of all children and in blood samples of 4 children. The B9R and d11L genes tested positive in the skin material of 2 children and blood samples of 2 children. All analysed patients presented a history of ineffective antibiotic therapy.ConclusionsIn the case of unclear necrotising skin lesions in children, the primary diagnosis always includes bacterial dermatitis. However, if the patient has come into contact with animals, diagnosis of OPV infection should also be considered.

40 Years without Smallpox

The last case of natural smallpox was recorded in October, 1977. It took humanity almost 20 years to achieve that feat after the World Health Organization had approved the global smallpox eradication program. Vaccination against smallpox was abolished, and, during the past 40 years, the human population has managed to lose immunity not only to smallpox, but to other zoonotic orthopoxvirus infections as well. As a result, multiple outbreaks of orthopoxvirus infections in humans in several continents have been reported over the past decades. The threat of smallpox reemergence as a result of evolutionary transformations of these zoonotic orthopoxviruses exists. Modern techniques for the diagnostics, prevention, and therapy of smallpox and other orthopoxvirus infections are being developed today.

40 лет без оспы

The last case of natural smallpox was recorded in October, 1977. It took humanity almost 20 years to achieve that feat after the World Health Organization had approved the global smallpox eradication program. Vaccination against smallpox was abolished, and, during the past 40 years, the human population has managed to lose immunity not only to smallpox, but to other zoonotic orthopoxvirus infections as well. As a result, multiple outbreaks of orthopoxvirus infections in humans in several continents have been reported over the past decades. The threat of smallpox reemergence as a result of evolutionary transformations of these zoonotic orthopoxviruses exists. Modern techniques for the diagnostics, prevention, and therapy of smallpox and other orthopoxvirus infections are being developed today.

Ethical and legal challenges of vaccines and vaccination: Reflections.

Vaccines and vaccination have emerged as key medical scientific tools for prevention of certain diseases. Documentation of the history of vaccination shows that the initial popular resistance to universal vaccination was based on false assumptions and eventually gave way to acceptance of vaccines and trust in their ability to save lives. The successes of the global eradication of smallpox, and now of polio, have only strengthened the premier position occupied by vaccines in disease prevention. However, the success of vaccines and public trust in their ability to eradicate disease are now under challenge, as increasing numbers of people refuse vaccination, questioning the effectiveness of vaccines and the need to vaccinate.