Dengue virus, the causative agent of dengue fever and its more serious manifestation dengue hemorrhagic fever, is widespread throughout tropical and subtropical regions. The virus exists as four distinct serotypes, all of which have cocirculated in Bangkok for several decades with epidemic outbreaks occurring every 8 -10 years. We analyze time-series data of monthly infection incidence, revealing a distinctive pattern with epidemics of serotypes 1, 2, and 3 occurring at approximately the same time and an isolated epidemic of serotype 4 occurring in the intervening years. Phylogenetic analysis of virus samples collected over the same period shows that clade replacement events are linked to the epidemic cycle and indicates that there is an interserotypic immune reaction. Using an epidemic model with stochastic seasonal forcing showing 8-to 10-year epidemic oscillations, we demonstrate that moderate cross-protective immunity gives rise to persistent out-of-phase oscillations similar to those observed in the data, but that strong or weak cross-protection or cross-enhancement only produces in-phase patterns. This behavior suggests that the epidemic pattern observed in Bangkok is the result of cross-protective immunity and may be significantly altered by changes in the interserotypic immune reaction.cross-immunity ͉ mathematical model ͉ phylogenetics ͉ rsv ͉ phase pattern
In many regions dengue incidence fluctuates seasonally with few if any infections reported in unfavourable periods. It has been hypothesized that vertical transmission within the mosquito population allows the virus to persist at these times. A review of the literature shows that vertical infection efficiencies are 1-4%. Using a mathematical model we argue that at these infection rates vertical transmission is not an important factor for long term virus persistence. In endemic situations, increases in reproductive number, half-life and persistence times of the disease only become significant when vertical infection efficiency exceeds 20-30%. In epidemic situations vertical infection accelerates the course of the outbreak and may actually reduce persistence time. These results stem from the fact that the mosquito life-cycle is relatively rapid and vertically acquired infections are multiplicatively diluted with every generation. When the efficiency of vertical infection is as low as reported from empirical studies, the virus is rapidly lost unless there is regular amplification in the human population. Processes such as asymptomatic human dengue cases are therefore more likely to be important in persistence than transmission within the vector population. The empirical data are not, however, unequivocal and we identify several areas of research that would further clarify the role of vertical transmission in the epidemiology of dengue.
In metropolitan areas people travel frequently and extensively but often in highly structured commuting patterns. We investigate the role of this type of human movement in the epidemiology of vector-borne pathogens such as dengue. Analysis is based on a metapopulation model where mobile humans connect static mosquito subpopulations. We find that, due to frequency dependent biting, infection incidence in the human and mosquito populations is almost independent of the duration of contact. If the mosquito population is not uniformly distributed between patches the transmission potential of the pathogen at the metapopulation level, as summarized by the basic reproductive number, is determined by the size of the largest subpopulation and reduced by stronger connectivity. Global extinction of the pathogen is less likely when increased human movement enhances the rescue effect but, in contrast to classical theory, it is not minimized at an intermediate level of connectivity. We conclude that hubs and reservoirs of infection can be places people visit frequently but briefly and the relative importance of human and mosquito populations in maintaining the pathogen depends on the distribution of the mosquito population and the variability in human travel patterns. These results offer an insight in to the paradoxical observation of resurgent urban vector-borne disease despite increased investment in vector control and suggest that successful public health intervention may require a dual approach. Prospective studies can be used to identify areas with large mosquito populations that are also visited by a large fraction of the human population. Retrospective studies can be used to map recent movements of infected people, pinpointing the mosquito subpopulation from which they acquired the infection and others to which they may have transmitted it.
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