Effects of Extreme Precipitation to the Distribution of Infectious Diseases in Taiwan, 1994–2008

The incidence of extreme precipitation has increased with the exacerbation of worldwide climate disruption. We hypothesize an association between precipitation and the distribution patterns that would affect the endemic burden of 8 infectious diseases in Taiwan, including water- and vector-borne infectious diseases. A database integrating daily precipitation and temperature, along with the infectious disease case registry for all 352 townships in the main island of Taiwan was analysed for the period from 1994 to 2008. Four precipitation levels, <130 mm, 130–200 mm, 200–350 mm and >350 mm, were categorized to represent quantitative differences, and their associations with each specific disease was investigated using the Generalized Additive Mixed Model and afterwards mapped on to the Geographical Information System. Daily precipitation levels were significantly correlated with all 8 mandatory-notified infectious diseases in Taiwan. For water-borne infections, extreme torrential precipitation (>350 mm/day) was found to result in the highest relative risk for bacillary dysentery and enterovirus infections when compared to ordinary rain (<130 mm/day). Yet, for vector-borne diseases, the relative risk of dengue fever and Japanese encephalitis increased with greater precipitation only up to 350 mm. Differential lag effects following precipitation were statistically associated with increased risk for contracting individual infectious diseases. This study’s findings can help health resource sector management better allocate medical resources and be better prepared to deal with infectious disease outbreaks following future extreme precipitation events

Analysis of Epitopes on Dengue Virus Envelope Protein Recognized by Monoclonal Antibodies and Polyclonal Human Sera by a High Throughput Assay

Dengue virus is the leading cause of arboviral diseases worldwide. The envelope protein is the major target of neutralizing antibodies and vaccine development. While previous studies have reported several epitopes on envelope protein, the possibility of interdomain epitopes and the relationship of epitopes to neutralizing potency remain unexplored. We developed a high throughput dot blot assay by using 67 alanine mutants of surface-exposed envelope residues as a systematic approach to identify epitopes recognized by mouse monoclonal antibodies and polyclonal human sera. Our results suggested the presence of interdomain epitopes more frequent than previously appreciated. Compared with monoclonal antibodies generated by traditional protocol, the potent neutralizing monoclonal antibodies generated by a new protocol showed several unique features of their epitopes. Moreover, the predominant epitopes of antibodies against envelope protein in polyclonal sera can be identified by this assay. These findings have implications for future development of epitope-specific diagnostics and epitope-based dengue vaccine, and add to our understanding of humoral immune responses to dengue virus at the epitope level

Regulation of dendritic cell interleukin-12 secretion by tumour cell necrosis

Dendritic cells (DCs) play a key role in the induction and regulation of antigen-specific immunity. Studies have shown that, similar to infection, cellular necrosis can stimulate DC maturation. However, the ability of necrotic cell death to modulate DC cytokine secretion has yet to be explored. We investigated the regulation of interleukin (IL)-12 secretion by human DCs in response to tumour cell necrosis in an in vitro culture model. Two human tumour cell lines (K562 and JAr) were induced to undergo necrosis using heat injury and repeated cycles of freezing and thawing. Both types of tumour cells tested in this study, when injured, induced secretion of monomeric IL-12p40 by monocyte-derived DCs. Furthermore, priming DCs with necrotic cells augmented IL-12p70 secretion significantly in conjunction with CD40 cross-linking. This was physiologically relevant because cell death-pulsed DCs were more potent than non-pulsed DCs at stimulating T cells to proliferate and secrete interferon (IFN)-γ. The Toll-like receptor 4 (TLR4) played a role in mediating the DC response to heat-killed, but not freeze/thaw-killed necrotic cells. For both methods of injury, proteins contributed to the effect of necrosis on dendritic cells, whereas DNA was involved in the effect of freeze/thawed cells only. These findings indicate that necrotic tumour cell death is not sufficient to induce bioactive IL-12p70, the Th1 promoting cytokine, but acts to augment its secretion via the CD40/CD40L pathway. The results also highlight that the mode of cell death may determine the mechanism of dendritic cell stimulation

Field trial on a novel control method for the dengue vector, Aedes aegypti by the systematic use of Olyset® Net and pyriproxyfen in Southern Vietnam

BackgroundJars, tanks, and drums provide favorable rearing/breeding sites for Aedes aegypti in Vietnam. However, the use of insecticides to control mosquitoes at such breeding sites has not been approved in Vietnam since they are also often sources of drinking water, making larval vector control difficult. Mosquito nets pre-treated with long-lasting insecticide treated nets (LLITNs) form an effective measure for malaria control. We examined changes in the abundance of immature Aedes aegypti to evaluate the efficacy of covering ceramic jars with lids comprising one type of LLITN, Olyset® Net, in inhibiting oviposition by adult females, and to evaluate the effect of treating other breeding containers, such as flower vases, inside and around the outside of houses with a slow-release pyriproxyfen formulation to kill pupae.MethodsWe selected 313 households for the trial and 363 households for the control in Tan Chanh, Long An province, Vietnam. In the trial area, Olyset® Net lids were used to cover five major types of water container (ceramic jars, cylindrical concrete tanks, other concrete tanks, plastic drums, and plastic buckets), while pyriproxyfen was used to treat flower vases and ant traps. We also monitored dengue virus transmission by measuring anti-dengue IgM and IgG levels in healthy residents in both control and trial areas to estimate the effectiveness of Olyset® Net at controlling the dengue vector, Aedes aegypti.ResultsThe container-index and house-index for immature Ae. aegypti fell steeply one month after treatment in the trial area. Lids with Olyset® Net that fit container openings clearly seemed to reduce the presence of immature Ae. aegypti as the density of pupae decreased 1 month after treatment in the trial area. Pyriproxyfen was also effective at killing pupae in the water containers in the trial area. Although the dengue seroconversion rate was not influenced by Olyset® Net, it was lower in two-five year old children when compared to older children and adults in both control and trial areas.ConclusionsOur study showed that the treatment by Olyset® Net and pyriproxyfen had a strong negative effect on the prevalence of immature Ae. aegypti, which persisted for at least 5 months after treatment

Water level flux in household containers in Vietnam - a key determinant of Aedes aegypti population dynamics

We examined changes in the abundance of immature Aedes aegypti at the household and water storage container level during the dry-season (June-July, 2008) in Tri Nguyen village, central Vietnam. We conducted quantitative immature mosquito surveys of 171 containers in the same 41 households, with replacement of samples, every two days during a 29-day period. We developed multi-level mixed effects regression models to investigate container and household variability in pupal abundance. The percentage of houses that were positive for I/II instars, III/IV instars and pupae during any one survey ranged from 19.5-43.9%, 48.8-75.6% and 17.1-53.7%, respectively. The mean numbers of Ae. aegypti pupae per house ranged between 1.9-12.6 over the study period. Estimates of absolute pupal abundance were highly variable over the 29-day period despite relatively stable weather conditions. Most variability in pupal abundance occurred at the container rather than the household level. A key determinant of Ae. aegypti production was the frequent filling of the containers with water, which caused asynchronous hatching of Ae. aegypti eggs and development of cohorts of immatures. We calculated the probability of the water volume of a large container (>500L) increasing or decreasing by ≥20% to be 0.05 and 0.07 per day, respectively, and for small containers