Discovery of forgotten variola specimens at the National Institutes of Health in the USA.

In early July 2014, the National Institutes of Health in the USA discovered a few vials containing smallpox virus in their Bethesda, Maryland facility. The subsequent investigation, performed by US CDC, documented viable virus in two of the discovered vials that were subjected to tissue culture testing.

The certification of smallpox eradication and implications for guinea worm, poliomyelitis, and other diseases: confirming and maintaining a negative.

Rigorous, independent, confirmation of disease eradication is necessary to assure credibility of the claimed accomplishment. The criteria and procedures for formal certification of global disease freedom are based on the biological and epidemiological features of the pathogen and its manifestations. Certification activities by previously endemic and at-risk countries include comprehensive documentation focusing on surveillance, reports of national independent review groups, and special field surveys. National and regional results are reviewed by authoritative International Commissions (ICs) which verify the findings by field visits. The ICs present their results to an independent WHO-convened group ("Global Commission" for smallpox), members of which participate in field visits. When fully satisfied, the Global Commission makes conclusions and recommendations to the World Health Assembly (WHA). Smallpox was confirmed eradicated in 1980 by the WHA less than three years after the last naturally occurring case was detected. Dracunculiasis (guinea worm) freedom has been certified in 187 countries. Regional commissions have certified the Americas, Asia, and Europe polio-free; however, re-establishment of endemic foci in countries previously declared disease-free has created special challenges for completing this program. Post-eradication activities require attention to surveillance, maximum security of the microbial agent, and essential research to assure maintenance of disease freedom.

Safe landing for global polio eradication: a perspective.

After over two decades of immense efforts, the global polio eradication initiative may be approaching its final phase. With leadership from WHO, great efforts of national programs and support from its collaborators, combined with the recent use of mono and bivalent oral polio vaccines, success may be at hand. For a "safe landing" of this global program, it is important once more to recall the key role of routine vaccination as the foundation on which mass vaccination campaigns can be successful. Continued effective routine vaccination programs are essential to reduce the ill effects of high population density in formerly endemic countries. Considering the large number of subclinical poliovirus infections, failing to reduce the number of unvaccinated persons per km(2) could severely impact the final stage of eradication. Here the authors, from their personal perspectives, discuss how the current program will be viewed from 2012 onwards. The authors will highlight the epidemiological importance of circulating vaccine-derived poliovirus, the problem of biosecurity as well as the use of inactivated polio vaccine and how each of these may affect the post eradication era and how research into each of these must continue to ensure success.

A personal recollection of smallpox eradication with the benefit of hindsight: in commemoration of 30th anniversary.

This year 2010 marks the 30th anniversary of smallpox eradication, as declared by the WHO Assembly in 1980. As someone who worked for this program for many years, I would like to present my recollection of how it succeeded and what lessons can be learnt, with the added benefit of hindsight. The program achieved the global unification of mankind despite differences in race, nationality, religion, and politics, and research contributed significantly to building the effective strategy that ultimately led to success. These lessons should be useful in a designing a planning solution for many of the problems we face in today's changing world, including problems regarding health security and even those in current and future socioeconomic regions.

Road map for polio eradication--establishing the link with Millennium Development Goal no. 4 for child survival.

The global polio eradication program, started in 1988, initially targeted the year 2000 for the worldwide elimination of the disease. Although poliovirus transmission has been markedly reduced, it has not been eliminated. As we enter the 20th year of the campaign, poliovirus continues to infect and cause paralysis in localized areas of South Asia and sub-Saharan Africa. To combat this scourge, the World Health Organization, together with other worldwide partners, has newly committed to worldwide eradication by 2009. It appears that the delay has been caused by a combination of the failure of globalization to deliver the prosperity it initially promised and technical problems specific to polio eradication. We hope that the world can reach zero level status for polio report, but verification would take many years and extended research due to the nature of poliovirus. We propose a scientific joint enterprise by which the polio endgame is accelerate, at the same time that a special immunization program against multiple other vaccine-preventable diseases is initiated. This newly organized collaborative effort, we believe, will maximize the benefits achieved by polio eradication and reduce childhood disease and deaths, namely achieve the Millennium Development Goal no. 4, in sub-Saharan Africa, the region that especially needs such action.

Smallpox vaccine and its stockpile in 2005.

Smallpox vaccine was the most important tool in the successful eradication of smallpox. In 1980, this achievement made it possible for all nations to cease smallpox vaccination. However, the threat of smallpox bioterrorism has made it necessary to reconsider the need for vaccination. Over the past 3 years, many nations have set up action plans for use in the event of such an attack. The setting up of these plans was not simple. Several factors needed to be considered, including the judgement of risk, vaccine complications, conventional vaccines versus new vaccines, optimal stockpile of smallpox vaccine, and its use for different target populations in different emergency situations. Here, I review measures taken by the USA, Japan, and other nations, and discuss likely national and global efforts in 2005 and subsequently, in view of the fact that half of the world's population is now apparently unvaccinated and that this proportion will increase with time.

Distribution of HBV genotypes among HBV carriers in Benin:phylogenetic analysis and virological characteristics of HBV genotype E.

AIM: To determine the distribution of Hepatitis B virus (HBV) genotypes in Benin, and to clarify the virological characteristics of the dominant genotype. METHODS: Among 500 blood donors in Benin, 21 HBsAg-positive donors were enrolled in the study. HBV genotypes were determined by enzyme immunoassay and restriction fragment length polymorphism. Complete genome sequences were determined by PCR and direct sequencing. RESULTS: HBV genotype E (HBV/E) was detected in 20/21 (95.2%), and HBV/A in 1/21 (4.8%). From the age-specific prevalence of HBeAg to anti-HBe seroconversion (SC) in 19 HBV/E subjects, SC was estimated to occur frequently in late teens in HBV/E. The comparison of four complete HBV/E genomes from HBeAg-positive subjects in this study and five HBV/E sequences recruited from the database revealed that HBV/E was distributed throughout West Africa with very low genetic diversity (nucleotide homology 96.7-99.2%). Based on the sequences in the basic core promoter (BCP) to precore region of the nine HBV/E isolates compared to those of the other genotypes, a nucleotide substitution in the BCP, G1757A, was observed in HBV/E. CONCLUSION: HBV/E is predominant in the Republic of Benin,and SC is estimated to occur in late teens in HBV/E. The specific nucleotide substitution G1757A in BCP,which might influence the virological characteristics, is observed in HBV/E.

Role of a sentinel surveillance system in the context of global surveillance of infectious diseases.

In some nation states, sustained integrated global epidemiological surveillance has been weakened as a result of political unrest, disinterest, and a poorly developed infrastructure due to rapidly increasing global inequality. The emergence of severe acute respiratory syndrome has shown vividly the importance of sensitive worldwide surveillance. The Agency for Cooperation in International Health, a Japanese non-governmental organisation, has developed on a voluntary basis a sentinel surveillance system for selected target infectious diseases, covering South America, Africa, and Asia. The system has uncovered unreported infectious diseases of international importance including cholera, plague, and influenza; current trends of acute flaccid paralysis surveillance in polio eradication; and prevalence of HIV, syphilis, hepatitis B, and hepatitis C in individual areas covered by the sentinels. Despite a limited geographical coverage, the system seems to supplement disease information being obtained by global surveillance. Further development of this sentinel surveillance system would be desirable to contribute to current global surveillance efforts, for which, needless to say, national surveillance and alert system takes principal responsibility.

Eradication of infectious diseases: its concept, then and now.

The concept of disease eradication emerged as recently as the mid-20th century. The successful eradication of smallpox resulted in the concept of the extinction of the causative agent in man as well as in the environment, leading to the cessation of all control measures including vaccination. Subsequently, world resources have been invested in global polio eradication and measles eradication in the Western Hemisphere. The former is apparently now at the "end game", the latter, after successful campaign in the Americas, aims at program development worldwide. However, both endeavors are being challenged by delays in schedules, unexpected technical problems, lack of global coordination, and ever-increasing political unrest. It is proposed that disease eradication be redefined as the extinction of the pathogen in man, not in nature, making for a more flexible approach in the post-eradication period. Smallpox eradication was a rare event. That concept is unrealistic in today's world.

Distribution of hepatitis B virus (HBV) genotypes among HBV carriers in the Cote d'Ivoire: complete genome sequence and phylogenetic relatedness of HBV genotype E.

The characteristics of hepatitis B virus (HBV) genotype E are not well known because only a few studies have been carried out by complete genome analysis. The aim of this study was to elucidate the distribution of HBV genotypes in Cote d'Ivoire, and to clarify the genotype-related characteristics of genotype E. The distribution of HBV genotypes among 48 HBV carriers in Cote d'Ivoire was determined using serological and genetic methods. The characteristics of genotype E were evaluated by complete genome sequences, and further investigations of small S gene, basic core promoter (BCP) mutation, and precore mutation were undertaken. HBV genotype distribution among the 48 carriers was 6.3% for genotype A, 6.3% for genotype D, and 87.4% for genotype E. Complete genomes of two genotype E strains were sequenced, and found to have 98.2% to 99.2% homology at the nucleotide level when compared with genotype E strains reported previously. In 24 genotype E carriers, the precore mutation was detected in 75% of the patients without HBeAg, in contrast to only 25% of the patients with HBeAg (P < 0.05). All 24 strains have T at nucleotide 1858 in the precore region. In contrast, BCP double mutation was detected in 17% of the patients with HBeAg, and 33% of the patients without HBeAg. These results indicated as the following: (1) genotypes A, D, and E of HBV exist in Cote d'Ivoire and genotype E is the most prevalent; (2) genotype E spread with low genetic diversity over the complete genome in West Africa; (3) HBV precore and/or BCP double variants were common among the patients with genotype E infections.