Reliable, comparable information about the main causes of disease and injury in populations, and how these are changing, is a critical input for debates about priorities in the health sector. Traditional sources of information about the descriptive epidemiology of diseases, injuries, and risk factors are generally incomplete, fragmented, and of uncertain reliability and comparability. The Global Burden of Disease (GBD) Study has provided a conceptual and methodological framework to quantify and compare the health of populations using a summary measure of both mortality and disability, the disability-adjusted life year (DALY). This article describes key features of the Global Burden of Disease analytic approach, the evolution of the GBD starting from the first study for the year 1990, and summarizes the methodological improvements incorporated into GBD revisions carried out by the World Health Organization. It also reviews controversies and criticisms, and examines priorities and issues for future GBD updates.

Global Burden of Disease

As the global eradication of wild poliovirus nears, the World Health Organization (WHO) is addressing challenges unprecedented in public health. The live, attenuated oral poliovirus vaccine (OPV), used for more than four decades to interrupt poliovirus transmission, and the vaccine of choice for developing countries, is genetically unstable. Reversion of the small number of substitutions conferring the attenuated phenotype frequently occurs during OPV replication in humans and is the underlying cause of the rare cases of vaccine-associated paralytic poliomyelitis (VAPP) in OPV recipients and their close contacts. Whereas VAPP has long been recognized, two other adverse events have been identified more recently: (a) long-term excretion of highly evolved vaccine-derived polioviruses (VDPVs) in persons with primary immunodeficiencies, and (b) polio outbreaks associated with circulating VDPVs in areas with low rates of OPV coverage. Developing a posteradication strategy to minimize the risks of VDPV emergence and spread has become an urgent WHO priority.

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Vaccine-derived polioviruses and the endgame strategy for global polio eradication.

Polioviruses and the Endgame Strategy for Global Polio Eradication

Nanotechnology in vaccine delivery.

Salmonella enterica serovars often have a broad host range, and some cause both gastrointestinal and systemic disease. But the serovars Paratyphi A and Typhi are restricted to humans and cause only systemic disease. It has been estimated that Typhi arose in the last few thousand years. The sequence and microarray analysis of the Paratyphi A genome indicates that it is similar to the Typhi genome but suggests that it has a more recent evolutionary origin. Both genomes have independently accumulated many pseudogenes among their approximately 4,400 protein coding sequences: 173 in Paratyphi A and approximately 210 in Typhi. The recent convergence of these two similar genomes on a similar phenotype is subtly reflected in their genotypes: only 30 genes are degraded in both serovars. Nevertheless, these 30 genes include three known to be important in gastroenteritis, which does not occur in these serovars, and four for Salmonella-translocated effectors, which are normally secreted into host cells to subvert host functions. Loss of function also occurs by mutation in different genes in the same pathway (e.g., in chemotaxis and in the production of fimbriae).

Comparison of genome degradation in Paratyphi A and Typhi, human-restricted serovars of Salmonella enterica that cause typhoid.

The global polio eradication initiative: lessons learned and prospects for success.

In 1988, the World Health Assembly resolved to eradicate poliomyelitis Wild poliovirus (WPV) transmission persists in only two countries (Afghanistan and Pakistan) after the removal of Nigeria from the list of countries with endemic polio in September 2015* Indigenous WPV type 2 has not been detected since 1999 and was declared eradicated by the Global Commission for the Certification of Poliomyelitis Eradication in September 2015(†) Since November 2012, when the last case of WPV type 3 was detected in Nigeria, WPV type 1 has been the sole circulating type of WPV (1) This report summarizes global progress toward polio eradication during 2015-2016 and updates previous reports (2) In 2015, 74 WPV cases were reported in two countries (Afghanistan and Pakistan), a decrease of 79% from the 359 WPV cases reported in 2014 in nine countries; 12 WPV cases have been reported in 2016 (to date), compared with 23 during the same period in 2015 (3) Paralytic polio caused by circulating vaccine-derived poliovirus (cVDPV) remains a risk in areas with low oral poliovirus vaccine (OPV) coverage Seven countries, including Pakistan, reported 32 cVDPV cases in 2015 (4) In four of these countries, ≥6 months have passed since the most recent case or isolate One country (Laos) with VDPV transmission in 2015 has reported three additional cVDPV cases in 2016 to date Encouraging progress toward polio eradication has been made over the last year; however, interruption of WPV transmission will require focus on reaching and vaccinating every missed child through high quality supplementary immunization activities (SIAs) and cross-border coordination between Afghanistan and Pakistan (5,6)

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Progress Toward Polio Eradication - Worldwide, 2015-2016.

In 1988, the World Health Assembly resolved to eradicate polio worldwide. Since then, four of the six World Health Organization (WHO) regions have been certified as polio-free: the Americas in 1994, the Western Pacific Region in 2000, the European Region in 2002, and the South-East Asia Region in 2014. Currently, nearly 80% of the world's population lives in areas certified as polio-free. Certification may be considered when ≥3 years have passed since the last isolation of wild poliovirus (WPV) in the presence of sensitive, certification-standard surveillance. Although regional eradication has been validated in the European Region and the Western Pacific Region, outbreaks resulting from WPV type 1 (WPV1) imported from known endemic areas were detected and controlled in these regions in 2010 and 2011, respectively. The last reported case associated with WPV type 2 (WPV2) was in India in 1999, marking global interruption of WPV2 transmission. The completion of polio eradication was declared a programmatic emergency for public health in 2012, and the international spread of WPV1 was declared a public health emergency of international concern in May 2014. The efforts needed to interrupt all indigenous WPV1 transmission are now being focused on the remaining endemic countries: Nigeria, Afghanistan, and Pakistan. WPV type 3 (WPV3) has not been detected in circulation since November 11, 2012. This report summarizes the evidence of possible global interruption of transmission of WPV3, based on surveillance for acute flaccid paralysis (AFP) and environmental surveillance.

Possible eradication of wild poliovirus type 3--worldwide, 2012.

Depuis la resolution de l'Assemblee mondiale de la Sante adoptee en 1988 concernant l'eradication de la poliomyelite, l'interruption de la transmission du poliovirus sauvage a considerablement progresse dans le monde entier. Une procedure formelle de certification a ete etablie sur la base de l'experience acquise pour la variole. Des groupes independants d'experts ont ete designes aux niveaux mondial, regional et des pays pour mener cette procedure a bien. En matiere de certification, les principales exigences sont l'absence constatee du poliovirus sauvage dans des echantillons preleves sur des cas suspects, sur des sujets en bonne sante ou dans l'environnement, dans toutes les Regions de l'OMS pendant au moins trois annees consecutives moyennant une surveillance de grande qualite repondant aux normes de certification, et le confinement de tous les stocks de poliovirus sauvages en laboratoire. Trois Regions de l'OMS - les Ameriques (1994), le Pacifique occidental (2000) et la Region europeenne (2002) - ont deja ete certifiees exemptes de poliovirus sauvages autochtones. L'eradication et les activites en vue de la certification progressent dans les trois Regions d'endemie (Afrique, Mediterranee orientale et Asie du Sud-Est). Il reste plusieurs defis a relever pour parvenir a la certification : renforcer la coordination des activites de certification entre les Regions de l'OMS, verifier le confinement des virus en laboratoire, mettre au point un mecanisme pour verifier a l'avenir que les poliovirus derives des souches vaccinales ne circulent pas, maintenir le statut des Regions deja certifiees jusqu'a la certification mondiale.

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Certification of polio eradication: process and lessons learned

In 1988, the World Health Assembly of the World Health Organization (WHO) resolved to interrupt wild poliovirus (WPV) transmission worldwide, and in 2012, the World Health Assembly declared the completion of global polio eradication a programmatic emergency for public health. By 2013, the annual number of WPV cases had decreased by >99% since 1988, and only three countries remained that had never interrupted WPV transmission: Afghanistan, Nigeria, and Pakistan. This report summarizes global progress toward polio eradication during 2013-2014 and updates previous reports. In 2013, a total of 416 WPV cases were reported globally from eight countries, an 86% increase from the 223 WPV cases reported from five countries in 2012. This upsurge in 2013 was caused by a 60% increase in WPV cases detected in Pakistan, and by outbreaks in five previously polio-free countries resulting from international spread of WPV. In 2014, as of May 20, a total of 82 WPV cases had been reported worldwide, compared with 34 cases during the same period in 2013. Polio cases caused by circulating vaccine-derived poliovirus (cVDPV) were detected in eight countries in 2013 and in two countries so far in 2014. To achieve polio eradication in the near future, further efforts are needed to 1) address health worker safety concerns in areas of armed conflict in priority countries, 2) to prevent further spread of WPV and new outbreaks after importation into polio-free countries, and 3) to strengthen surveillance globally. Based on the international spread of WPV to date in 2014, the WHO Director General has issued temporary recommendations to reduce further international exportation of WPV through vaccination of persons traveling from currently polio-affected countries.

Rudolf H. Tangermann

Papers

The global polio eradication initiative: lessons learned and prospects for success.

Progress Toward Polio Eradication - Worldwide, 2015-2016.

Possible eradication of wild poliovirus type 3--worldwide, 2012.

Certification of polio eradication: process and lessons learned

Progress toward polio eradication--Worldwide 2013-2014.