SUMMARY: Notified cases of dengue infections in Singapore reached historical highs in 2004 (9459 cases) and 2005 (13 817 cases) and the reason for such an increase is still to be established. We apply a mathematical model for dengue infection that takes into account the seasonal variation in incidence, characteristic of dengue fever, and which mimics the 2004–2005 epidemics in Singapore. We simulated a set of possible control strategies and confirmed the intuitive belief that killing adult mosquitoes is the most effective strategy to control an ongoing epidemic. On the other hand, the control of immature forms was very efficient in preventing the resurgence of dengue epidemics. Since the control of immature forms allows the reduction of adulticide, it seems that the best strategy is to combine both adulticide and larvicide control measures during an outbreak, followed by the maintenance of larvicide methods after the epidemic has subsided. In addition, the model showed that the mixed strategy of adulticide and larvicide methods introduced by the government seems to be very effective in reducing the number of cases in the first weeks after the start of control.

Human respiratory syncytial virus (HRSV) is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a “flip-flop” phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites. As part of the Viral Genetic Diversity Network (VGDN), we sequenced the second variable region (G2) of the G protein of human respiratory syncytial virus (HRSV) A and B from 568 patients sampled during 11 consecutive HRSV seasons (1995–2005) in the state of São Paulo, Brazil. A total of 933 HRSVA and 673 HRSB time-stamped sequences, including those sampled here and globally, was used for phylogenetic inference and the analysis of selection pressures. We identified 18 positively selected sites in both HRSVA (9 sites) and HRSVB (9 sites) that tended to revert in time to their previous codon state (i.e. exhibited a “flip-flop” pattern). We argue that these common evolutionary reversals are indicative of frequent positive selection, reflecting the changing immune status of the human population, coupled with a limited repertoire of functional viable amino acids at specific sites. This information is of particular importance since the ectodomain of the G protein is also a target site in vaccines that have so far proven unsuccessful and because it constitutes a significant step towards describing and understanding the immune-escape repertoire of this major human pathogen.

Yellow fever and dengue are viral infections that in urban centres are transmitted by the same arthropod vector, a mosquito of the genus Aedes. In order to estimate the risk of an epidemic of urban yellow fever in a dengue-infested area we calculated the threshold in the basic reproduction number, R0, of dengue, above which any single sylvatic yellow fever-infected individual will trigger an urban yellow fever epidemic. Specifically, we analysed the relationship between the extrinsic incubation period and the duration of viraemia, from which it is possible to define the R0 for dengue that would also suggest an outbreak potential for yellow fever. We also calculated the critical proportion of people to vaccinate against yellow fever in order to prevent an epidemic in a dengue-endemic area. The theory proposed is illustrated by the case of São Paulo State in southern Brazil, where dengue is endemic and the risk of urban yellow fever is already imminent.

Dengue, the most common arbovirus infection globally, is transmitted by mosquito vectors. Healthcare-related transmission, including transmission by blood products, has been documented, although the frequency of these occurrences is unknown. Dengue is endemic to Singapore, a city-state in Asia. Using mathematical modeling, we estimated the risk for dengue-infected blood transfusions in Singapore in 2005 to be 1.625–6/10,000 blood transfusions, assuming a ratio of asymptomatic to symptomatic infections of 2:1 to 10:1. However, the level of viremia required to cause clinical dengue cases is person-dependent and unknown. Further studies are needed to establish the magnitude of the threat that dengue poses to blood safety in countries where it is endemic. It will then be possible after this information is obtained to assess whether screening is feasible and to identify approaches that are most cost-effective on the basis of characteristics of local populations and seasonality of dengue.

Dengue fever is a mosquito-borne viral disease estimated to cause about 230 million infections worldwide every year, of which 25,000 are fatal. Global incidence has risen rapidly in recent decades with some 3.6 billion people, over half of the world's population, now at risk, mainly in urban centres of the tropics and subtropics. Demographic and societal changes, in particular urbanization, globalization, and increased international travel, are major contributors to the rise in incidence and geographic expansion of dengue infections. Major research gaps continue to hamper the control of dengue. The European Commission launched a call under the 7th Framework Programme with the title of ‘Comprehensive control of Dengue fever under changing climatic conditions’. Fourteen partners from several countries in Europe, Asia, and South America formed a consortium named ‘DengueTools’ to respond to the call to achieve better diagnosis, surveillance, prevention, and predictive models and improve our understanding of t...