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Influenza pandemic preparedness in France: modelling the impact of interventions.

BACKGROUND: Influenza pandemics result in excess mortality and social disruption. To assist health authorities update the French pandemic plan, the authors estimated the number of health events (cases, hospitalisations, and deaths) in a pandemic and compared interventions in terms of impact and efficiency. METHOD: A Monte Carlo simulation model, incorporating probability distributions of key variables, provided estimates of health events (HE) by age and risk group. Input variables were set after literature and expert consultation. The impact of targeted influenza vaccination and antiviral prophylaxis/treatment (oseltamivir) in high risk groups (elderly, chronic diseases), priority (essential professionals), and total populations was compared. Outcome measures were HE avoided, number of doses needed, and direct cost per HE avoided. RESULTS: Without intervention, an influenza pandemic could result in 14.9 million cases, 0.12 million deaths, and 0.6 million hospitalisations in France. Twenty four per cent of deaths and 40% of hospitalisations would be among high risk groups. With a 25% attack rate, 2000-86,000 deaths could be avoided, depending on population targeted and intervention. If available initially, vaccination of the total population is preferred. If not, for priority populations, seasonal prophylaxis seems the best strategy. For high risk groups, antiviral treatment, although less effective, seems more feasible and cost effective than prophylaxis (respectively 29% deaths avoided; 1800 doses/death avoided and 56% deaths avoided; 18,500 doses/death avoided) and should be chosen, especially if limited drug availability. CONCLUSION: The results suggest a strong role for antivirals in an influenza pandemic. While this model can compare the impact of different intervention strategies, there remains uncertainty surrounding key variables.

Adolescent↗

An online operational rainfall-monitoring resource for epidemic malaria early warning systems in Africa.

Periodic epidemics of malaria are a major public health problem for many sub-Saharan African countries. Populations in epidemic prone areas have a poorly developed immunity to malaria and the disease remains life threatening to all age groups. The impact of epidemics could be minimized by prediction and improved prevention through timely vector control and deployment of appropriate drugs. Malaria Early Warning Systems are advocated as a means of improving the opportunity for preparedness and timely response. Rainfall is one of the major factors triggering epidemics in warm semi-arid and desert-fringe areas. Explosive epidemics often occur in these regions after excessive rains and, where these follow periods of drought and poor food security, can be especially severe. Consequently, rainfall monitoring forms one of the essential elements for the development of integrated Malaria Early Warning Systems for sub-Saharan Africa, as outlined by the World Health Organization. The Roll Back Malaria Technical Resource Network on Prevention and Control of Epidemics recommended that a simple indicator of changes in epidemic risk in regions of marginal transmission, consisting primarily of rainfall anomaly maps, could provide immediate benefit to early warning efforts. In response to these recommendations, the Famine Early Warning Systems Network produced maps that combine information about dekadal rainfall anomalies, and epidemic malaria risk, available via their Africa Data Dissemination Service. These maps were later made available in a format that is directly compatible with HealthMapper, the mapping and surveillance software developed by the WHO's Communicable Disease Surveillance and Response Department. A new monitoring interface has recently been developed at the International Research Institute for Climate Prediction (IRI) that enables the user to gain a more contextual perspective of the current rainfall estimates by comparing them to previous seasons and climatological averages. These resources are available at no cost to the user and are updated on a routine basis.

Africa↗

Establishment of multiple sublineages of H5N1 influenza virus in Asia: implications for pandemic control.

Preparedness for a possible influenza pandemic caused by highly pathogenic avian influenza A subtype H5N1 has become a global priority. The spread of the virus to Europe and continued human infection in Southeast Asia have heightened pandemic concern. It remains unknown from where the pandemic strain may emerge; current attention is directed at Vietnam, Thailand, and, more recently, Indonesia and China. Here, we report that genetically and antigenically distinct sublineages of H5N1 virus have become established in poultry in different geographical regions of Southeast Asia, indicating the long-term endemicity of the virus, and the isolation of H5N1 virus from apparently healthy migratory birds in southern China. Our data show that H5N1 influenza virus, has continued to spread from its established source in southern China to other regions through transport of poultry and bird migration. The identification of regionally distinct sublineages contributes to the understanding of the mechanism for the perpetuation and spread of H5N1, providing information that is directly relevant to control of the source of infection in poultry. It points to the necessity of surveillance that is geographically broader than previously supposed and that includes H5N1 viruses of greater genetic and antigenic diversity.

Animals↗

The waiting time for inter-country spread of pandemic influenza.

BACKGROUND: The time delay between the start of an influenza pandemic and its subsequent initiation in other countries is highly relevant to preparedness planning. We quantify the distribution of this random time in terms of the separate components of this delay, and assess how the delay may be extended by non-pharmaceutical interventions. METHODS AND FINDINGS: The model constructed for this time delay accounts for: (i) epidemic growth in the source region, (ii) the delay until an infected individual from the source region seeks to travel to an at-risk country, (iii) the chance that infected travelers are detected by screening at exit and entry borders, (iv) the possibility of in-flight transmission, (v) the chance that an infected arrival might not initiate an epidemic, and (vi) the delay until infection in the at-risk country gathers momentum. Efforts that reduce the disease reproduction number in the source region below two and severe travel restrictions are most effective for delaying a local epidemic, and under favourable circumstances, could add several months to the delay. On the other hand, the model predicts that border screening for symptomatic infection, wearing a protective mask during travel, promoting early presentation of cases arising among arriving passengers and moderate reduction in travel volumes increase the delay only by a matter of days or weeks. Elevated in-flight transmission reduces the delay only minimally. CONCLUSIONS: The delay until an epidemic of pandemic strain influenza is imported into an at-risk country is largely determined by the course of the epidemic in the source region and the number of travelers attempting to enter the at-risk country, and is little affected by non-pharmaceutical interventions targeting these travelers. Short of preventing international travel altogether, eradicating a nascent pandemic in the source region appears to be the only reliable method of preventing country-to-country spread of a pandemic strain of influenza.

Disease Outbreaks↗

Pandemic preparedness: lessons learnt from H2N2 and H9N2 candidate vaccines.

Vaccination against influenza is considered to be one of the key interventions in case of a pandemic. Unfortunately, shortages in vaccine supplies will occur because of the substantial increase in vaccine demands worldwide and the limited available supply resources. The recommended use of monovalent--instead of current trivalent--vaccines containing 15 micro g hemagglutinin (HA) per dose can theoretically triple vaccine volumes but is unlikely to meet the demand. Furthermore, previous experiences demonstrated that one dose of 15 micro g HA will not be sufficient to elicit protective antibody levels in unprimed individuals. Modified formulation approaches were investigated, that would be suitable to provide significantly higher volumes of potent vaccine within a given period of time. Low doses of HA combined with aluminum (Al) adjuvants and the use of whole virus instead of split or subunit antigens can lead to substantial increases in process yield. In addition, production of whole virus vaccines will reduce manufacturing complexity. In a dose-finding study in healthy adults and elderly, immune responses after administration of Al-adjuvanted low-dose formulations were compared to a standard split virus vaccine (Fluarix, GlaxoSmithKline Biologicals, Rixensart, Belgium). All vaccines were safe and well tolerated. Antigen concentrations as low as 1.9 micro g HA/strain per dose of adjuvant-containing experimental vaccines induced protective antibody levels in primed populations. Reactogenicity profiles of Al-adjuvanted low-dose vaccines were investigated in a feasibility trial. Neither the use of Al-adjuvant nor of whole virus had a significant effect on general reactions. Studies in unprimed populations with H2N2 and H9N2 candidate vaccines showed different results, with a potential need for a two-dose schedule. Indeed, hemagglutination inhibition titers did not reach protective levels after a single vaccine dose but could be met following administration of a second dose. The same is true for Al-adjuvanted whole virus formulations with an up to eightfold-reduced antigen content. It may be concluded that the use of Al-adjuvanted whole virus vaccines with low HA content can raise protective antibody levels after two vaccine doses, which may, in turn, result in significant increases of vaccine supplies in the case of a pandemic.

Adjuvants, Immunologic↗

The next influenza pandemic: lessons from Hong Kong.

Pandemic influenza is a zoonosis. Studies on influenza ecology conducted in Hong Kong since the 1970s in which Hong Kong essentially functioned as an influenza sentinel post indicated that it might be possible, for the first time, to have influenza preparedness at the baseline avian level. This appreciation of influenza ecology facilitated recognition of the H5N1 'bird flu' incident in Hong Kong in 1997 in what was considered to be an incipient pandemic situation, the chicken being the source of virus for humans and, if so, was the first instance where a pandemic may have been averted. The 2001 and 2002 H5N1 incidents demonstrated that it was possible to have an even higher order of baseline preparedness with the recognition in chicken of a range of genotypes of H5N1-like viruses before they had the opportunity to infect humans. Investigations of these incidents revealed a complex ecology involving variously precursor avian H5N1 virus in geese and ducks, and H9N2 and H6N1 viruses in quail, the quail possibly functioning as an avian 'mixing vessel' for key genetic reassortment events for onward transmission of H5N1 viruses highly pathogenic for chicken and humans. These findings highlight the importance of systematic virus surveillance of domestic poultry in recognizing changes in virus occurrence, host range and pathogenicity as signals at the avian level that could presage a pandemic. For example, there is now an increasing prevalence of avian influenza viruses in terrestrial (in contrast to aquatic) poultry. Prior to 1997, no particular virus subtype other than H4N6 would have been considered a candidate for pandemicity and this was based, in the absence of any other data, on its high frequency of occurrence in ducks in southern China. Now,with the isolation of H5N1 and H9N2 viruses from humans supported by genetic, molecular and biological studies on these and other avian isolates, there is credible evidence for the candidacy, in order, of H5N1, H9N2 and H6N1 viruses. These viruses have been made available for the production of diagnostic reagents and exploratory vaccines. The 1997 incident upheld the hypothesis that southern China is an epicentre for the emergence of pandemic influenza viruses. However, the intensification of the poultry (chicken) industry worldwide coupled with the spread of viruses such as the Eurasian lineage of H9N2 suggest that the genesis of a pandemic could take place elsewhere in the world. This re-emphasizes the importance of systematic virus surveillance of poultry globally for international public health and for economic and food concerns. Faced with an incipient pandemic in 1997, Hong Kong brought in international experts to join the investigative effort. Good teamwork at all levels is essential in dealing with the many facets. The threat of a pandemic should not be minimized, nor should governments be lulled into a sense of false security. The media is a powerful channel and has the responsibility and the avenues to convey and influence public perception of events. Close liaison between the media and those on the operational side ensures effective, accurate and timely dissemination of information. This will enhance public confidence in the investigative process and in steps taken for its safety and health.

Animals↗