Young caregivers in the context of the HIV/AIDS pandemic in sub-Saharan Africa

Against a background of rising adult mortality and morbidity in the context of the HIV/AIDS pandemic in sub-Saharan Africa, this paper provides both quantitative and qualitative evidence for the existence of a largely neglected group of young people with increased responsibility for caregiving. Using questionnaire surveys, focus groups, storyboards and in-depth interviews in three studies across Southern and Eastern Africa some young people in Lesotho, Tanzania and Zimbabwe are found to devote considerable time and energy to caring for sick members of their households. Examination of the tasks carried out by these youngsters finds them to be burdened beyond usual familial and societal expectations of children's 'normal' contributions to the reproduction of households via domestic chores and suchlike. It is concluded that these young people can be described as 'young carers'. The three studies are presented to illuminate different sociospatial aspects of caregiving by young people. First, using qualitative data from Lesotho the range of caring tasks young caregivers; perform for care recipients - usually a grandmother, parent, or sibling - is identified. Second, the impact caregiving responsibilities have on children's primary school attendance is examined using survey data from Tanzania. Third, the wider negative and positive impacts of caregiving including loss of friends and gaining of emotional maturity for young carers and their households is explored with in-depth individual interviews from Zimbabwe. Finally, suggestions are made for further research to deepen understanding of the geographies of caring within the context of the population geographies of the HIV/AIDS pandemic in sub-Saharan Africa and beyond. Copyright (c) 2006 John Wiley & Sons, Ltd.

Investment in preventing and preparing for biological emergencies and disasters: social and economic costs of disasters versus costs of surveillance and response preparedness

Biological emergencies such as the appearance of an exotic transboundary or emerging disease can become disasters. The question that faces Veterinary Services in developing countries is how to balance resources dedicated to active insurance measures, such as border control, surveillance, working with the governments of developing countries, and investing in improving veterinary knowledge and tools, with passive measures, such as contingency funds and vaccine banks. There is strong evidence that the animal health situation in developed countries has improved and is relatively stable. In addition, through trade with other countries, developing countries are becoming part of the international animal health system, the status of which is improving, though with occasional setbacks. However, despite these improvements, the risk of a possible biological disaster still remains, and has increased in recent times because of the threat of bioterrorism. This paper suggests that a model that combines decision tree analysis with epidemiology is required to identify critical points in food chains that should be strengthened to reduce the risk of emergencies and prevent emergencies from becoming disasters.

Generation of candidate human influenza vaccine strains in cell culture: rehearsing the European response to an H7N1 pandemic threat

Background: Although H5N1 avian influenza viruses pose the most obvious imminent pandemic threat, there have been several recent zoonotic incidents involving transmission of H7 viruses to humans. Vaccines are the primary public health defense against pandemics, but reliance on embryonated chickens eggs to propagate vaccine and logistic problems posed by the use of new technology may slow our ability to respond rapidly in a pandemic situation. Objectives: We sought to generate an H7 candidate vaccine virus suitable for administration to humans whose generation and amplification avoided the use of eggs. Methods: We generated a suitable H7 vaccine virus by reverse genetics. This virus, known as RD3, comprises the internal genes of A/Puerto Rico/8/34 with surface antigens of the highly pathogenic avian strain A/Chicken/Italy/13474/99 (H7N1). The multi-basic amino acid site in the HA gene, associated with high pathogenicity in chickens, was removed. Results: The HA modification did not alter the antigenicity of the virus and the resultant single basic motif was stably retained following several passages in Vero and PER. C6 cells. RD3 was attenuated for growth in embryonated eggs, chickens, and ferrets. RD3 induced an antibody response in infected animals reactive against both the homologous virus and other H7 influenza viruses associated with recent infection by H7 viruses in humans. Conclusions: This is the first report of a candidate H7 vaccine virus for use in humans generated by reverse genetics and propagated entirely in mammalian tissue culture. The vaccine has potential use against a wide range of H7 strains.

Receptor binding profiles of avian influenza virus hemagglutinin subtypes on human cells as a predictor of pandemic potential

The host adaptation of influenza virus is partly dependent on the sialic acid (SA) isoform bound by the viral hemagglutinin (HA). Avian influenza viruses preferentially bind the α-2,3 SA and human influenza viruses the α-2,6 isoform. Each isoform is predominantly associated with different surface epithelial cell types of the human upper airway. Using recombinant HAs and human tracheal airway epithelial cells in vitro and ex vivo, we show that many avian HA subtypes do not adhere to this canonical view of SA specificity. The propensity of avian viruses to adapt to human receptors may thus be more widespread than previously supposed.

Improving flood forecasts for better flood preparedness in the UK (and beyond)

This winter (2013/14) coastal storms and an unprecedented amount of rainfall led to significant and widespread flooding across the southern UK. Despite much criticism and blame surrounding the flood events, the Flood Forecasting Centre, a recent development in national-level flood forecasting capabilities for the government and emergency response communities, has received considerable praise. Here we consider how scientific developments and organisational change have led to improvements in the forecasting and flood preparedness seen in this winter's flooding. Although such improvements are admirable, there are many technical and communication challenges that remain for probabilistic flood forecasts to achieve their full potential.

AIDS, mobility and commercial sex in Ethiopia: Implications for policy

Since the emergence of the AIDS pandemic in sub-Saharan Africa, male mobility has been highlighted as one of the reasons for the spread of the disease with men employing the services of commercial sex workers while away from home. However, sex workers' mobility and the implications of this for their access to prevention services, has largely been ignored. This paper, based on multi-method qualitative research with 60 young sex workers in two Ethiopian towns, reveals that sex workers are highly mobile, moving in order to attract a wider or different client base, for adventure and to conceal illnesses which might be associated with AIDS. In addition, sex workers are affected by restrictions on their movements, with girls working in bars and red-light areas having little free time to access projects. This paper advocates that policy approaches need to take account of this mobility in three ways: first, by exploring ways for girls to access information and maintain contact with support structures while moving between places of work; second, by building the capacity of sex workers to take greater control over decision-making in their day-to-day lives and third, by developing outreach strategies for taking services into bars and red-light areas.

Mutations in H5N1 influenza virus hemagglutinin that confer binding to human tracheal airway epithelium

The emergence in 2009 of a swine-origin H1N1 influenza virus as the first pandemic of the 21st Century is a timely reminder of the international public health impact of influenza viruses, even those associated with mild disease. The widespread distribution of highly pathogenic H5N1 influenza virus in the avian population has spawned concern that it may give rise to a human influenza pandemic. The mortality rate associated with occasional human infection by H5N1 virus approximates 60%, suggesting that an H5N1 pandemic would be devastating to global health and economy. To date, the H5N1 virus has not acquired the propensity to transmit efficiently between humans. The reasons behind this are unclear, especially given the high mutation rate associated with influenza virus replication. Here we used a panel of recombinant H5 hemagglutinin (HA) variants to demonstrate the potential for H5 HA to bind human airway epithelium, the predominant target tissue for influenza virus infection and spread. While parental H5 HA exhibited limited binding to human tracheal epithelium, introduction of selected mutations converted the binding profile to that of a current human influenza strain HA. Strikingly, these amino-acid changes required multiple simultaneous mutations in the genomes of naturally occurring H5 isolates. Moreover, H5 HAs bearing intermediate sequences failed to bind airway tissues and likely represent mutations that are an evolutionary "dead end." We conclude that, although genetic changes that adapt H5 to human airways can be demonstrated, they may not readily arise during natural virus replication. This genetic barrier limits the likelihood that current H5 viruses will originate a human pandemic.

Understanding the alphaviruses: Recent research on important emerging pathogens and progress towards their control

The alphaviruses were amongst the first arboviruses to be isolated, characterized and assigned a taxonomic status. They are globally very widespread, infecting a large variety of terrestrial animals, insects and even fish, and circulate both in the sylvatic and urban/peri-urban environment, causing considerable human morbidity and mortality. Nevertheless, despite their obvious importance as pathogens, there are currently no effective antiviral drugs with which to treat humans or animals infected by any of these viruses. The EU-supported project—VIZIER (Comparative Structural Genomics of Viral Enzymes Involved in Replication, FP6 Project: 2004-511960) was instigated with an ultimate view of contributing to the development of antiviral therapies for RNA viruses, including the alphaviruses [Coutard, B., Gorbalenya, A.E., Snijder, E.J., Leontovich, A.M., Poupon, A., De Lamballerie, X., Charrel, R., Gould, E.A., Gunther, S., Norder, H., Klempa, B., Bourhy, H., Rohayemj, J., L’hermite, E., Nordlund, P., Stuart, D.I., Owens, R.J., Grimes, J.M., Tuckerm, P.A., Bolognesi, M., Mattevi, A., Coll, M., Jones, T.A., Åqvist, J., Unger, T., Hilgenfeld, R., Bricogne, G., Neyts, J., La Colla, P., Puerstinger, G., Gonzalez, J.P., Leroy, E., Cambillau, C., Romette, J.L., Canard, B., 2008. The VIZIER project: preparedness against pathogenic RNA viruses. Antiviral Res. 78, 37–46]. This review highlights some of the major features of alphaviruses that have been investigated during recent years. After describing their classification, epidemiology and evolutionary history and the expanding geographic distribution of Chikungunya virus, we review progress in understanding the structure and function of alphavirus replicative enzymes achieved under the VIZIER programme and the development of new disease control strategies.

Infection of human airway epithelium by human and avian strains of influenza a virus

We describe the characterization of influenza A virus infection of an established in vitro model of human pseudostratified mucociliary airway epithelium (HAE). Sialic acid receptors for both human and avian viruses, alpha-2,6- and alpha-2,3-linked sialic acids, respectively, were detected on the HAE cell surface, and their distribution accurately reflected that in human tracheobronchial tissue. Nonciliated cells present a higher proportion of alpha-2,6-linked sialic acid, while ciliated cells possess both sialic acid linkages. Although we found that human influenza viruses infected both ciliated and nonciliated cell types in the first round of infection, recent human H3N2 viruses infected a higher proportion of nonciliated cells in HAE than a 1968 pandemic-era human virus, which infected proportionally more ciliated cells. In contrast, avian influenza viruses exclusively infected ciliated cells. Although a broad-range neuraminidase abolished infection of HAE by human parainfluenza virus type 3, this treatment did not significantly affect infection by influenza viruses. All human viruses replicated efficiently in HAE, leading to accumulation of nascent virus released from the apical surface between 6 and 24 h postinfection with a low multiplicity of infection. Avian influenza A viruses also infected HAE, but spread was limited compared to that of human viruses. The nonciliated cell tropism of recent human H3N2 viruses reflects a preference for the sialic acid linkages displayed on these cell types and suggests a drift in the receptor binding phenotype of the H3 hemagglutinin protein as it evolves in humans away from its avian virus precursor.

Attenuating mutations in the influenza virus genome which may increase the safety of vaccine production

Influenza virus epidemics occur on an annual basis and cause severe disease in the very young and old. The vaccine administered to high-risk groups is generated by amplifying reassortant viruses, with chronologically relevant viral surface antigens, in eggs. Every 20 years or so, influenza pandemics occur causing widespread fatality in all age groups. These viruses display novel viral surface antigens acquired from a zoonotic source, and vaccination against them poses new issues since production of large amounts of a respiratory virus containing novel surface antigens could be dangerous for those involved in manufacture. To minimise risks, it is advisable to use a virus whose genetic backbone is highly attenuated in man. Traditionally, the A/PR/8/34 strain of virus is used, however, the genetic basis of its attenuation is unclear. Cold-adapted (CA) strains of the influenza virus are all based on the H2N2 subtype, itself a virus with pandemic potential, and again the genetic basis of temperature sensitivity is not yet established. Reverse genetics technology allows us to engineer designer influenza viruses to order. Using this technology, we have been investigating mutations in several different gene segments to effectively attenuate potential vaccine strains allowing the safe production of vaccine to protect against the next pandemic. (C) 2003 Elsevier B.V. All rights reserved.

A single amino acid in the HA of pH1N1 2009 influenza virus affects cell tropism in human airway epithelium, but not transmission in ferrets

The first pandemic of the 21(st) century, pandemic H1N1 2009 (pH1N1 2009), emerged from a swine-origin source. Although human infections with swine-origin influenza have been reported previously, none went on to cause a pandemic or indeed any sustained human transmission. In previous pandemics, specific residues in the receptor binding site of the haemagglutinin (HA) protein of influenza have been associated with the ability of the virus to transmit between humans. In the present study we investigated the effect of residue 227 in HA on cell tropism and transmission of pH1N1 2009. In pH1N1 2009 and recent seasonal H1N1 viruses this residue is glutamic acid, whereas in swine influenza it is alanine. Using human airway epithelium, we show a differential cell tropism of pH1N1 2009 compared to pH1N1 2009 E227A and swine influenza suggesting this residue may alter the sialic acid conformer binding preference of the HA. Furthermore, both pH1N1 2009 E227A and swine influenza multi-cycle viral growth was found to be attenuated in comparison to pH1N1 2009 in human airway epithelium. However this altered tropism and viral growth in human airway epithelium did not abrogate respiratory droplet transmission of pH1N1 2009 E227A in ferrets. Thus, acquisition of E at residue 227 was not solely responsible for the ability of pH1N1 2009 to transmit between humans.

New dimensions in early flood warning across the globe using grand-ensemble weather predictions

Early and effective flood warning is essential to initiate timely measures to reduce loss of life and economic damage. The availability of several global ensemble weather prediction systems through the “THORPEX Interactive Grand Global Ensemble” (TIGGE) archive provides an opportunity to explore new dimensions in early flood forecasting and warning. TIGGE data has been used as meteorological input to the European Flood Alert System (EFAS) for a case study of a flood event in Romania in October 2007. Results illustrate that awareness for this case of flooding could have been raised as early as 8 days before the event and how the subsequent forecasts provide increasing insight into the range of possible flood conditions. This first assessment of one flood event illustrates the potential value of the TIGGE archive and the grand-ensembles approach to raise preparedness and thus to reduce the socio-economic impact of floods.

Deriving global flood hazard maps of fluvial floods through a physical model cascade

Global flood hazard maps can be used in the assessment of flood risk in a number of different applications, including (re)insurance and large scale flood preparedness. Such global hazard maps can be generated using large scale physically based models of rainfall-runoff and river routing, when used in conjunction with a number of post-processing methods. In this study, the European Centre for Medium Range Weather Forecasts (ECMWF) land surface model is coupled to ERA-Interim reanalysis meteorological forcing data, and resultant runoff is passed to a river routing algorithm which simulates floodplains and flood flow across the global land area. The global hazard map is based on a 30 yr (1979–2010) simulation period. A Gumbel distribution is fitted to the annual maxima flows to derive a number of flood return periods. The return periods are calculated initially for a 25×25 km grid, which is then reprojected onto a 1×1 km grid to derive maps of higher resolution and estimate flooded fractional area for the individual 25×25 km cells. Several global and regional maps of flood return periods ranging from 2 to 500 yr are presented. The results compare reasonably to a benchmark data set of global flood hazard. The developed methodology can be applied to other datasets on a global or regional scale.