Prediction of Dengue Incidence Using Search Query Surveillance

Improvements in surveillance, prediction of outbreaks and the monitoring of the epidemiology of dengue virus in countries with underdeveloped surveillance systems are of great importance to ministries of health and other public health decision makers who are often constrained by budget or man-power. Google Flu Trends has proven successful in providing an early warning system for outbreaks of influenza weeks before case data are reported. We believe that there is greater potential for this technique for dengue, as the incidence of this pathogen can vary by a factor of ten in some settings, making prediction all the more important in public health planning. In this paper, we demonstrate the utility of Google search terms in predicting dengue incidence in Singapore and Bangkok, Thailand using several regression techniques. Incidence data were provided by the Singapore Ministry of Health and the Thailand Bureau of Epidemiology. We find our models predict incident cases well (correlation greater than 0.8) and periods of high incidence equally well (AUC greater than 0.95). All data and analysis code used in our study are available free online and can be adapted to other settings

Infection and Transmission of Rift Valley Fever Viruses Lacking the NSs and/or NSm Genes in Mosquitoes: Potential Role for NSm in Mosquito Infection

Rift Valley fever virus is transmitted mainly by mosquitoes and causes disease in humans and animals throughout Africa and the Arabian Peninsula. The impact of disease is large in terms of human illness and mortality, and economic impact on the livestock industry. For these reasons, and because there is a risk of this virus spreading to Europe and North America, it is important to develop a vaccine that is stable, safe and effective in preventing infection. Potential vaccine viruses have been developed through deletion of two genes (NSs and NSm) affecting virus virulence. Because this virus is normally transmitted by mosquitoes we must determine the effects of the deletions in these vaccine viruses on their ability to infect and be transmitted by mosquitoes. An optimal vaccine virus would not infect or be transmitted. The viruses were tested in two mosquito species: Aedes aegypti and Culex quinquefasciatus. Deletion of the NSm gene reduced infection of Ae. aegypti mosquitoes indicating a role for the NSm protein in mosquito infection. The virus with deletion of both NSs and NSm genes was the best vaccine candidate since it did not infect Ae. aegypti and showed reduced infection and transmission rates in Cx. quinquefasciatus

High Seroprevalence of Rift Valley Fever and Evidence for Endemic Circulation in Mbeya Region, Tanzania, in a Cross-Sectional Study

We describe a high seropositivity rate for Rift Valley fever virus, in up to 29.3% of tested individuals from the shore of Lake Malawi in southwestern Tanzania, and much lower rates from areas distant to the lake. Rift Valley fever disease or outbreaks have not been observed there in the past, which suggests that the virus is circulating under locally favorable conditions and is either a non-pathogenic strain, or that occasional occurrence of disease is missed. We were able to identify a low socio-economic status and cattle ownership as possible socio-economic risk factors for an individual to be seropositive. Environmental risk factors associated with seropositivity include dense vegetation, and ambient land surface temperatures which may be important for breeding success of the mosquitoes which transmit Rift Valley fever, and for efficient multiplication of the virus in the mosquito. Low elevation of the home, and proximity to Lake Malawi probably lead to abundant surface water collections, which serve as breeding places for mosquitoes. These findings will inform patient care in the areas close to Lake Malawi, and may help to design models which predict low-level virus circulation

Effects of Irritant Chemicals on Aedes aegypti Resting Behavior: Is There a Simple Shift to Untreated “Safe Sites”?

Aedes aegypti, the primary vector mosquito of dengue virus, typically lives near or inside human dwellings, and feeds preferentially on humans. The control of this mosquito vector remains the most important dengue prevention method. The use of chemicals at levels toxic to mosquitoes is currently the only confirmed effective adult vector control strategy with interventions usually applied following epidemic onset. However, research indicates that sub-lethal chemical approaches to prevent human-vector contact at the house level exist: contact irritancy and spatial repellency. The optimum efficacy of an intervention based on contact irritant actions of chemicals will, however, require full knowledge of variables that will influence vector resting behavior and thereby chemical uptake from treated sources. Here we characterize the resting patterns of female Ae. aegypti on two material types at various dark:light surface area coverage ratios and contrast configurations under chemical-free and treated conditions using a laboratory behavioral assay. Change in resting behavior between baseline and treatment conditions was quantified to determine potential negative effects of untreated surfaces (“safe sites”) when irritant responses are elicited. We show that treatment of preferred resting sites with known irritant compounds do not stimulate mosquitoes to move to safe sites after making contact with treated surfaces

Spatial Dimensions of Dengue Virus Transmission across Interepidemic and Epidemic Periods in Iquitos, Peru (1999–2003)

To target prevention and control strategies for dengue fever, it is essential to understand how the virus travels through the city. We report spatial analyses of dengue infections from a study monitoring school children and adult family members for dengue infection at six-month intervals from 1999–2003, in the Amazonian city of Iquitos, Peru. At the beginning of the study, only DENV serotypes 1 and 2 were circulating. Clusters of infections of these two viruses were concentrated in the northern region of the city, where mosquito indices and previous DENV infection were both high. In 2002, DENV-3 invaded the city, replacing DENV-1 and -2 as the dominant strain. During the invasion process, the virus spread rapidly across the city, at low levels. After this initial phase, clusters of infection appeared first in the northern region of the city, where clusters of DENV-1 and DENV-2 had occurred in prior years. Most of the clusters we identified had radii >100 meters, indicating that targeted or reactive treatment of these high-risk areas might be an effective proactive intervention strategy. Our results also help explain why vector control within 100 m of a dengue case is often not successful for large-scale disease prevention

Seasonal pulses of Marburg virus circulation in juvenile Rousettus aegyptiacus bats coincide with periods of increased risk of human infection

Marburg virus (family Filoviridae) causes sporadic outbreaks of severe hemorrhagic disease in sub-Saharan Africa. Bats have been implicated as likely natural reservoir hosts based most recently on an investigation of cases among miners infected in 2007 at the Kitaka mine, Uganda, which contained a large population of Marburg virus-infected Rousettus aegyptiacus fruit bats. Described here is an ecologic investigation of Python Cave, Uganda, where an American and a Dutch tourist acquired Marburg virus infection in December 2007 and July 2008. More than 40,000 R. aegyptiacus were found in the cave and were the sole bat species present. Between August 2008 and November 2009, 1,622 bats were captured and tested for Marburg virus. Q-RT-PCR analysis of bat liver/spleen tissues indicated ,2.5% of the bats were actively infected, seven of which yielded Marburg virus isolates. Moreover, Q-RT-PCR-positive lung, kidney, colon and reproductive tissues were found, consistent with potential for oral, urine, fecal or sexual transmission. The combined data for R. aegyptiacus tested from Python Cave and Kitaka mine indicate low level horizontal transmission throughout the year. However, Q-RT-PCR data show distinct pulses of virus infection in older juvenile bats (,six months of age) that temporarily coincide with the peak twiceyearly birthing seasons. Retrospective analysis of historical human infections suspected to have been the result of discrete spillover events directly from nature found 83% (54/65) events occurred during these seasonal pulses in virus circulation, perhaps demonstrating periods of increased risk of human infection. The discovery of two tags at Python Cave from bats marked at Kitaka mine, together with the close genetic linkages evident between viruses detected in geographically distant locations, are consistent with R. aegyptiacus bats existing as a large meta-population with associated virus circulation over broad geographic ranges. These findings provide a basis for developing Marburg hemorrhagic fever risk reduction strategies.The Department of Health and Human Serviceshttp://www.plospathogens.or

Tissue Tropism and Target Cells of NSs-Deleted Rift Valley Fever Virus in Live Immunodeficient Mice

Rift Valley fever, caused by a member of the Bunyaviridae family, has spread during recent years to most sub-Saharan African countries, in Egypt and in the Arabian peninsula. The virus can be transmitted by insect vectors or by direct contacts with infectious tissues. The analysis of virus replication and dissemination in laboratory animals has been hampered by the need to euthanize sufficient numbers of animals and to assay appropriate organs at various time points after infection to evaluate the viral replication. By following the bioluminescence and fluorescence of Rift Valley fever viruses expressing light reporters, we were able to track the real-time dissemination of the viruses in live immunodeficient mice. We showed that the first infected organs were the thymus, spleen and liver, but the liver rapidly became the main location of viral replication. Phagocytes also appeared as important targets, and their systemic depletion by use of clodronate liposomes decreased the number of viruses in the blood, delayed the viral dissemination and prolonged the survival of the infected mice

Reverse genetics-generated RVF viruses used in this study.

1<p>Vero E6 cell, passage 2 titer expressed as log₁₀ PFU/ml.</p

Replication of rRVF mutant viruses in <i>Culex quinquefasciatus</i> mosquitoes.

1<p>Number of mosquitoes containing detectable virus by plaque assay divided by number of mosquitoes exposed to infectious bloodmeal.</p>2<p>D_e = number of mosquitoes with RVFV antigen in head tissues divided by number of mosquitoes exposed to infectious bloodmeal.</p>3<p>D_i = number of mosquitoes with RVFV antigen in head tissues divided by number of infected mosquitoes.</p>4<p>T_e = number of mosquitoes with positive saliva by plaque assay divided by number of mosquitoes exposed to infectious bloodmeal.</p>5<p>T_d = number of mosquitoes with positive saliva by plaque assay divided by number of mosquitoes with disseminated infection.</p>6<p>Titer expressed as log₁₀ PFU/mL.</p>7<p>n = 3, titer expressed as log₁₀ PFU/ml; avg is log₁₀ geometric mean; sd is standard deviation.</p>*<p>value differs significantly from rRVF-wt values; see <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001639#pntd.0001639.s002" target="_blank">Table S2</a> for statistical analysis results.</p

Replication of rRVF mutant viruses in <i>Aedes aegypti</i> mosquitoes.

1<p>Number of mosquitoes containing detectable virus by plaque assay divided by number of mosquitoes exposed to infectious bloodmeal.</p>2<p>D_e = number of mosquitoes with RVFV antigen in head tissues divided by number of mosquitoes exposed to infectious bloodmeal.</p>3<p>D_i = number of mosquitoes with RVFV antigen in head tissues divided by number of infected mosquitoes.</p>4<p>T_e = number of mosquitoes with positive saliva by plaque assay divided by number of mosquitoes exposed to infectious bloodmeal.</p>5<p>T_d = number of mosquitoes with positive saliva by plaque assay divided by number of mosquitoes with disseminated infection.</p>6<p>Titer expressed as log₁₀ PFU/mL.</p>7<p>n = 3, titer expressed as log₁₀ PFU/ml; avg is log₁₀ geometric mean; sd is standard deviation.</p>8<p>nd = not done.</p>*<p>value differs significantly from rRVF-wt values; see <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001639#pntd.0001639.s002" target="_blank">Table S2</a> for statistical analysis results.</p